4,998 research outputs found

    Whirling of the single mass rotor

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    Motion equations for whirling mass rotor on damped elastic shaf

    Utility of serum biomarker indices for staging of hepatic fibrosis before and after venesection in patients with hemochromatosis caused by variants in HFE

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    Background & Aims Hemochromatosis that is associated with variants in the homeostatic iron regulator gene (HFE) is characterized by intestinal absorption of iron and excessive body and hepatic iron stores; it can lead to hepatic fibrosis and cirrhosis. Fibrosis has been staged by analysis of liver biopsies, but non-invasive staging methods are available. We evaluated the ability of aspartate aminotransferase:platelet ratio index (APRI), the fibrosis-4 (FIB-4) index, and gamma-glutamyl transferase:platelet ratio (GPR) to assess hepatic fibrosis staging in subjects with HFE-associated hemochromatosis, using liver biopsy-staged fibrosis as the reference standard. Methods We performed a retrospective, cross-sectional analysis of 181 subjects with HFE-associated hemochromatosis and hepatic fibrosis staged by biopsy analysis and available serum samples. We calculated APRI, FIB-4, and GPR at diagnosis for all 181 subjects and following venesection therapy in 64 of these subjects (7 subjects had follow-up biopsy analysis). We used area under the receiver operating characteristic curve (AUROC) analysis to assess the relationships between APRI score, FIB-4 score, and GPR and advanced (F3–F4) fibrosis and to select cut-off values. Results Hepatic fibrosis stage correlated with APRI score (r = 0.54; P \u3c .0001), FIB-4 score (r = 0.35; P \u3c .0001), and GPR (r = 0.36, P \u3c .0001). An APRI score above 0.44 identified patients with advanced fibrosis with an AUROC of 0.88, 79.4% sensitivity, 79.4% specificity, and 81% accuracy. A FIB-4 score above 1.1 identified patients with advanced fibrosis with an AUROC of 0.86, 80% sensitivity, 80.3% specificity, and 81% accuracy. A GPR above 0.27 identified patients with advanced fibrosis with an AUROC of 0.76, 67.7% sensitivity, 70.3% specificity, and 69% accuracy. APRI score was significantly more accurate than GPR (P = .05) in detecting advanced fibrosis; there was no difference between APRI and FIB-4. Venesection treatment was associated with significant reductions in APRI (P \u3c .0001) and GPR (P\u3c .001), paralleling fibrosis regression observed in available liver biopsies. Post-venesection APRI identified 87% of subjects with advanced fibrosis that decreased to levels that indicate stage F1–F2 fibrosis. Conclusions In a retrospective study of 181 subjects with HFE-associated hemochromatosis, we found that APRI and FIB-4 scores identified patients with advanced hepatic fibrosis with 81% accuracy. APRI scores might also be used to monitor fibrosis regression following venesection

    Doing gender locally: The importance of ‘place’ in understanding marginalised masculinities and young men’s transitions to ‘safe’ and successful futures

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    Observable anxieties have been developing about the position of boys and young men in contemporary society in recent years. This is expressed as a crisis of masculinity, in which place is often implicitly implicated, but is rarely considered for its role in the shaping of young men’s practices, trajectories and aspirations. Drawing on research conducted with young people who accessed a range of social care support services, this article argues that transition means different things for young men in different locales and that local definitions of masculinity are required to better understand young men’s lives and the opportunities available to them. The authors argue that home life, street life, individual neighbourhoods, regions and nations all shaped the young men’s identities and the practices they (and the staff working with them) drew on in order to create successful futures and ‘safe’ forms of masculinity. It is suggested that this place-based approach has the potential to re-shape the ‘crisis’ discourse surrounding masculinity and the anxieties associated with young men

    Quasi-normal modes of charged, dilaton black holes

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    In this paper we study the perturbations of the charged, dilaton black hole, described by the solution of the low energy limit of the superstring action found by Garfinkle, Horowitz and Strominger. We compute the complex frequencies of the quasi-normal modes of this black hole, and compare the results with those obtained for a Reissner-Nordstr\"{o}m and a Schwarzschild black hole. The most remarkable feature which emerges from this study is that the presence of the dilaton breaks the \emph{isospectrality} of axial and polar perturbations, which characterizes both Schwarzschild and Reissner-Nordstr\"{o}m black holes.Comment: 15 pages, 5 figure

    Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder

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    Background: Mitochondrial disease is often suspected in cases of severe epileptic encephalopathy especially when a complex movement disorder, liver involvement and progressive developmental regression are present. Although mutations in either mitochondrial DNA or POLG are often present, other nuclear defects in mitochondrial DNA replication and protein translation have been associated with a severe epileptic encephalopathy. Methods: and results We identified a proband with an epileptic encephalopathy, complex movement disorder and a combined mitochondrial respiratory chain enzyme deficiency. The child presented with neurological regression, complex movement disorder and intractable seizures. A combined deficiency of mitochondrial complexes I, III and IV was noted in liver tissue, along with increased mitochondrial DNA content in skeletal muscle. Incomplete assembly of complex V, using blue native polyacrylamide gel electrophoretic analysis and complex I, using western blotting, suggested a disorder of mitochondrial transcription or translation. Exome sequencing identified compound heterozygous mutations in CARS2, a mitochondrial aminoacyl-tRNA synthetase. Both mutations affect highly conserved amino acids located within the functional ligase domain of the cysteinyl-tRNA synthase. A specific decrease in the amount of charged mt-tRNACys was detected in patient fibroblasts compared with controls. Retroviral transfection of the wild-type CARS2 into patient skin fibroblasts led to the correction of the incomplete assembly of complex V, providing functional evidence for the role of CARS2 mutations in disease aetiology. Conclusions: Our findings indicate that mutations in CARS2 result in a mitochondrial translational defect as seen in individuals with mitochondrial epileptic encephalopathy

    Relaxation and Landau-Zener experiments down to 100 mK in ferritin

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    Temperature-independent magnetic viscosity in ferritin has been observed from 2 K down to 100 mK, proving that quantum tunneling plays the main role in these particles at low temperature. Magnetic relaxation has also been studied using the Landau-Zener method making the system crossing zero resonant field at different rates, alpha=dH/dt, ranging from 10^{-5} to 10^{-3} T/s, and at different temperatures, from 150 mK up to the blocking temperature. We propose a new Tln(Delta H_{eff}/tau_0 alpha) scaling law for the Landau-Zener probability in a system distributed in volumes, where Delta H_{eff} is the effective width of the zero field resonance.Comment: 13 pages, 4 postscript figure

    Dynamic Group Diffie-Hellman Key Exchange under Standard Assumptions

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    Authenticated Diffie-Hellman key exchange allows two principals communicating over a public network, and each holding public /private keys, to agree on a shared secret value. In this paper we study the natural extension of this cryptographic problem to a group of principals. We begin from existing formal security models and refine them to incorporate major missing details (e.g., strong-corruption and concurrent sessions). Within this model we define the execution of a protocol for authenticated dynamic group Diffie-Hellman and show that it is provably secure under the decisional Diffie-Hellman assumption. Our security result holds in the standard model and thus provides better security guarantees than previously published results in the random oracle model

    Changing times in England: the influence on geography teachers’ professional practice

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    School geography in England has been characterised as a pendulum swinging between policies that emphasise curriculum and pedagogy alternately. In this paper, I illustrate the influence of these shifts on geography teacher's professional practice, by drawing on three “moments” from my experience as a student, teacher and teacher educator. Barnett's description of teacher professionalism as a continuous project of “being” illuminates how geography teachers can adapt to competing influences. It reflects teacher professionalism as an unfinished project, which is responsive, but not beholden, to shifting trends, and is informed by how teachers frame and enact policies. I argue that recognising these contextual factors is key to supporting geography teachers in “being” geography education professionals. As education becomes increasingly competitive on a global scale, individual governments are looking internationally for “solutions” to improve educational rankings. In this climate, the future of geography education will rest on how teachers react locally to international trends. Geography teacher educators can support this process by continuing to inform the field through meaningful geography education research, in particular in making the contextual factors of their research explicit. This can be supported through continued successful international collaboration in geography education research

    A 5-Enolpyruvylshikimate 3-Phosphate Synthase Functions as a Transcriptional Repressor in Populus.

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    Long-lived perennial plants, with distinctive habits of inter-annual growth, defense, and physiology, are of great economic and ecological importance. However, some biological mechanisms resulting from genome duplication and functional divergence of genes in these systems remain poorly studied. Here, we discovered an association between a poplar (Populus trichocarpa) 5-enolpyruvylshikimate 3-phosphate synthase gene (PtrEPSP) and lignin biosynthesis. Functional characterization of PtrEPSP revealed that this isoform possesses a helix-turn-helix motif in the N terminus and can function as a transcriptional repressor that regulates expression of genes in the phenylpropanoid pathway in addition to performing its canonical biosynthesis function in the shikimate pathway. We demonstrated that this isoform can localize in the nucleus and specifically binds to the promoter and represses the expression of a SLEEPER-like transcriptional regulator, which itself specifically binds to the promoter and represses the expression of PtrMYB021 (known as MYB46 in Arabidopsis thaliana), a master regulator of the phenylpropanoid pathway and lignin biosynthesis. Analyses of overexpression and RNAi lines targeting PtrEPSP confirmed the predicted changes in PtrMYB021 expression patterns. These results demonstrate that PtrEPSP in its regulatory form and PtrhAT form a transcriptional hierarchy regulating phenylpropanoid pathway and lignin biosynthesis in Populus
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