29 research outputs found
Logarithmic Corrections to Schwarzschild and Other Non-extremal Black Hole Entropy in Different Dimensions
Euclidean gravity method has been successful in computing logarithmic
corrections to extremal black hole entropy in terms of low energy data, and
gives results in perfect agreement with the microscopic results in string
theory. Motivated by this success we apply Euclidean gravity to compute
logarithmic corrections to the entropy of various non-extremal black holes in
different dimensions, taking special care of integration over the zero modes
and keeping track of the ensemble in which the computation is done. These
results provide strong constraint on any ultraviolet completion of the theory
if the latter is able to give an independent computation of the entropy of
non-extremal black holes from microscopic description. For Schwarzschild black
holes in four space-time dimensions the macroscopic result seems to disagree
with the existing result in loop quantum gravity.Comment: LaTeX, 40 pages; corrected small typos and added reference
Truncating and missense BMPR2 mutations differentially affect the severity of heritable pulmonary arterial hypertension
<p>Abstract</p> <p>Background</p> <p>Autosomal dominant inheritance of germline mutations in the bone morphogenetic protein receptor type 2 (<it>BMPR2</it>) gene are a major risk factor for pulmonary arterial hypertension (PAH). While previous studies demonstrated a difference in severity between <it>BMPR2 </it>mutation carriers and noncarriers, it is likely disease severity is not equal among <it>BMPR2 </it>mutations. We hypothesized that patients with missense <it>BMPR2 </it>mutations have more severe disease than those with truncating mutations.</p> <p>Methods</p> <p>Testing for <it>BMPR2 </it>mutations was performed in 169 patients with PAH (125 with a family history of PAH and 44 with sporadic disease). Of the 106 patients with a detectable <it>BMPR2 </it>mutation, lymphocytes were available in 96 to functionally assess the nonsense-mediated decay pathway of RNA surveillance. Phenotypic characteristics were compared between <it>BMPR2 </it>mutation carriers and noncarriers, as well as between those carriers with a missense versus truncating mutation.</p> <p>Results</p> <p>While there was a statistically significant difference in age at diagnosis between carriers and noncarriers, subgroup analysis revealed this to be the case only for females. Among carriers, there was no difference in age at diagnosis, death, or survival according to exonic location of the <it>BMPR2 </it>mutation. However, patients with missense mutations had statistically significant younger ages at diagnosis and death, as well as shorter survival from diagnosis to death or lung transplantation than those with truncating mutations. Consistent with this data, the majority of missense mutations were penetrant prior to age 36 years, while the majority of truncating mutations were penetrant after age 36 years.</p> <p>Conclusion</p> <p>In this cohort, <it>BMPR2 </it>mutation carriers have more severe PAH disease than noncarriers, but this is only the case for females. Among carriers, patients with missense mutations that escape nonsense-mediated decay have more severe disease than those with truncating mutations. These findings suggest that treatment and prevention strategies directed specifically at <it>BMPR2 </it>pathway defects may need to vary according to the type of mutation.</p
Function and Assembly of a Chromatin-Associated RNase P that Is Required for Efficient Transcription by RNA Polymerase I
Background: Human RNase P has been initially described as a tRNA processing enzyme, consisting of H1 RNA and at least ten distinct protein subunits. Recent findings, however, indicate that this catalytic ribonucleoprotein is also required for transcription of small noncoding RNA genes by RNA polymerase III (Pol III). Notably, subunits of human RNase P are localized in the nucleolus, thus raising the possibility that this ribonucleoprotein complex is implicated in transcription of rRNA genes by Pol I. Methodology/Principal Findings: By using biochemical and reverse genetic means we show here that human RNase P is required for efficient transcription of rDNA by Pol I. Thus, inactivation of RNase P by targeting its protein subunits for destruction by RNA interference or its H1 RNA moiety for specific cleavage causes marked reduction in transcription of rDNA by Pol I. However, RNase P restores Pol I transcription in a defined reconstitution system. Nuclear run on assays reveal that inactivation of RNase P reduces the level of nascent transcription by Pol I, and more considerably that of Pol III. Moreover, RNase P copurifies and associates with components of Pol I and its transcription factors and binds to chromatin of the promoter and coding region of rDNA. Strikingly, RNase P detaches from transcriptionally inactive rDNA in mitosis and reassociates with it at G1 phase through a dynamic and stepwise assembly process that is correlated with renewal of transcription
Function and Assembly of a Chromatin-Associated RNase P that Is Required for Efficient Transcription by RNA Polymerase I
Human RNase P has been initially described as a tRNA processing enzyme, consisting of H1 RNA and at least ten distinct protein subunits. Recent findings, however, indicate that this catalytic ribonucleoprotein is also required for transcription of small noncoding RNA genes by RNA polymerase III (Pol III). Notably, subunits of human RNase P are localized in the nucleolus, thus raising the possibility that this ribonucleoprotein complex is implicated in transcription of rRNA genes by Pol I.By using biochemical and reverse genetic means we show here that human RNase P is required for efficient transcription of rDNA by Pol I. Thus, inactivation of RNase P by targeting its protein subunits for destruction by RNA interference or its H1 RNA moiety for specific cleavage causes marked reduction in transcription of rDNA by Pol I. However, RNase P restores Pol I transcription in a defined reconstitution system. Nuclear run on assays reveal that inactivation of RNase P reduces the level of nascent transcription by Pol I, and more considerably that of Pol III. Moreover, RNase P copurifies and associates with components of Pol I and its transcription factors and binds to chromatin of the promoter and coding region of rDNA. Strikingly, RNase P detaches from transcriptionally inactive rDNA in mitosis and reassociates with it at G1 phase through a dynamic and stepwise assembly process that is correlated with renewal of transcription.Our findings reveal that RNase P activates transcription of rDNA by Pol I through a novel assembly process and that this catalytic ribonucleoprotein determines the transcription output of Pol I and Pol III, two functionally coordinated transcription machineries
The Static Maxwell System in Three Dimensional Axially Symmetric Inhomogeneous Media and Axially Symmetric Generalization of the Cauchy–Riemann System
In this paper we discuss different generalizations of the Cauchy–Riemann system and their connection with the static Maxwell system. In particular, this allows us to present relations between slice-monogenic functions and hypermonogenic functions, as well as to provide a physical interpretation of slice-monogenic functions. Furthermore, we present an explicit and complete set of basic solutions of a new class of axial-hypermonogenic functions in R^3. In the end we determine the symmetry operators for the class of axial-hypermonogenic functions
3-Aminopropylsilane-modified iron oxide nanoparticles for contrast-enhanced magnetic resonance imaging of liver lesions induced by Opisthorchis felineus
Alexander M Demin,1,* Alexandra G Pershina,2,3,* Vladimir V Ivanov,2 Kseniya V Nevskaya,2 Oleg B Shevelev,4 Artyom S Minin,5 Iliya V Byzov,5 Alexey E Sazonov,2 Victor P Krasnov,1 Ludmila M Ogorodova2 1Postovsky Institute of Organic Synthesis of RAS (Ural Branch), Yekaterinburg, 2Siberian State Medical University, 3Russian National Research Tomsk Polytechnic University, Tomsk, 4Institute of Cytology and Genetics SB RAS, Novosibirsk, 5Miheev Institute of Metal Physics of RAS (Ural Branch), Yekaterinburg, Russia *These authors contributed equally to this work Purpose: Liver fluke causes severe liver damage in an infected human. However, the infection often remains neglected due to the lack of pathognomonic signs. Nanoparticle-enhanced magnetic resonance imaging (MRI) offers a promising technique for detecting liver lesions induced by parasites.Materials and methods: Surface modification of iron oxide nanoparticles produced by coprecipitation from a solution of Fe3+ and Fe2+ salts using 3-aminopropylsilane (APS) was carried out. The APS-modified nanoparticles were characterized by transmission electron microscopy, fourier transform infrared spectroscopy, and thermogravimetric analysis . Magnetic resonance properties of MNPs were investigated in vitro and in vivo.Results: The amount of APS grafted on the surface of nanoparticles (0.60±0.06 mmol g-1) was calculated based on elemental analysis and infrared spectroscopy data. According to transmission electron microscopy data, there were no essential changes in the structure of nanoparticles during the modification. The APS-modified nanoparticles exhibit high magnetic properties; the calculated relaxivity r2 was 271 mmol-1 s-1. To obtain suspension with optimal hydrodynamic characteristics, amino groups on the surface of nanoparticles were converted into an ionic form with HCl. Cellular uptake of modified nanoparticles by rat hepatoma cells and human monocytes in vitro was 74.1±4.5 and 10.0±3.7 pg [Fe] per cell, respectively. Low cytotoxicity of the nanoparticles was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Annexin V/7-aminoactinomycin D flow cytometry assays. For the first time, magnetic nanoparticles were applied for contrast-enhanced MRI of liver lesions induced by Opisthorchis felineus.Conclusion: The synthesized APS-modified iron oxide nanoparticles showed high efficiency as an MRI contrast agent for the evaluation of opisthorchiasis-related liver damage. Keywords: magnetic nanoparticles, alkoxysilane, magnetic resonance imaging, liver fluk