1,537 research outputs found

    The transcript cleavage factor paralogue TFS4 is a potent RNA polymerase inhibitor

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    TFIIS-like transcript cleavage factors enhance the processivity and fidelity of archaeal and eukaryotic RNA polymerases. Sulfolobus solfataricus TFS1 functions as a bona fide cleavage factor, while the paralogous TFS4 evolved into a potent RNA polymerase inhibitor. TFS4 destabilises the TBP-TFB-RNAP pre-initiation complex and inhibits transcription initiation and elongation. All inhibitory activities are dependent on three lysine residues at the tip of the C-terminal zinc ribbon of TFS4; the inhibition likely involves an allosteric component and is mitigated by the basal transcription factor TFEα/β. A chimeric variant of yeast TFIIS and TFS4 inhibits RNAPII transcription, suggesting that the molecular basis of inhibition is conserved between archaea and eukaryotes. TFS4 expression in S. solfataricus is induced in response to infection with the S ulfolobus turreted icosahedral virus. Our results reveal a compelling functional diversification of cleavage factors in archaea, and provide novel insights into transcription inhibition in the context of the host-virus relationship

    Consequentialism and Virtue

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    We examine the following consequentialist view of virtue: a trait is a virtue if and only if it has good consequences in some relevant way. We highlight some motivations for this basic account, and offer twelve choice points for filling it out. Next, we explicate Julia Driver’s consequentialist view of virtue in reference to these choice points, and we canvass its merits and demerits. Subsequently, we consider three suggestions that aim to increase the plausibility of her position, and critically analyze them. We conclude that one of those proposed revisions would improve her account. NOTE: I will self-archive the paper after the 24 month embargo period ends. If you want a copy, just email me

    Microscopic Realization of the Kerr/CFT Correspondence

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    Supersymmetric M/string compactifications to five dimensions contain BPS black string solutions with magnetic graviphoton charge P and near-horizon geometries which are quotients of AdS_3 x S^2. The holographic duals are typically known 2D CFTs with central charges c_L=c_R=6P^3 for large P. These same 5D compactifications also contain non-BPS but extreme Kerr-Newman black hole solutions with SU(2)_L spin J_L and electric graviphoton charge Q obeying Q^3 \leq J_L^2. It is shown that in the maximally charged limit Q^3 -> J_L^2, the near-horizon geometry coincides precisely with the right-moving temperature T_R=0 limit of the black string with magnetic charge P=J_L^{1/3}. The known dual of the latter is identified as the c_L=c_R=6J_L CFT predicted by the Kerr/CFT correspondence. Moreover, at linear order away from maximality, one finds a T_R \neq 0 quotient of the AdS_3 factor of the black string solution and the associated thermal CFT entropy reproduces the linearly sub-maximal Kerr-Newman entropy. Beyond linear order, for general Q^3<J_L^2, one has a finite-temperature quotient of a warped deformation of the magnetic string geometry. The corresponding dual deformation of the magnetic string CFT potentially supplies, for the general case, the c_L=c_R=6J_L CFT predicted by Kerr/CFT.Comment: 18 pages, no figure

    Pulsar Results with the Fermi Large Area Telescope

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    The launch of the Fermi Gamma-ray Space Telescope has heralded a new era in the study of gamma-ray pulsars. The population of confirmed gamma-ray pulsars has gone from 6-7 to more than 60, and the superb sensitivity of the Large Area Telescope (LAT) on Fermi has allowed the detailed study of their spectra and light curves. Twenty-four of these pulsars were discovered in blind searches of the gamma-ray data, and twenty-one of these are, at present, radio quiet, despite deep radio follow-up observations. In addition, millisecond pulsars have been confirmed as a class of gamma-ray emitters, both individually and collectively in globular clusters. Recently, radio searches in the direction of LAT sources with no likely counterparts have been highly productive, leading to the discovery of a large number of new millisecond pulsars. Taken together, these discoveries promise a great improvement in the understanding of the gamma-ray emission properties and Galactic population of pulsars. We summarize some of the results stemming from these newly-detected pulsars and their timing and multi-wavelength follow-up observations.Comment: 21 pages, 9 figures, to appear in Proceedings of ICREA Workshop on The High-Energy Emission from Pulsars and their Systems, Sant Cugat, Spain, 2010 April 12-16 (Springer

    Weakened magnetic braking as the origin of anomalously rapid rotation in old field stars

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    A knowledge of stellar ages is crucial for our understanding of many astrophysical phenomena, and yet ages can be difficult to determine. As they become older, stars lose mass and angular momentum, resulting in an observed slowdown in surface rotation. The technique of 'gyrochronology' uses the rotation period of a star to calculate its age. However, stars of known age must be used for calibration, and, until recently, the approach was untested for old stars (older than 1 gigayear, Gyr). Rotation periods are now known for stars in an open cluster of intermediate age (NGC 6819; 2.5 Gyr old), and for old field stars whose ages have been determined with asteroseismology. The data for the cluster agree with previous period-age relations, but these relations fail to describe the asteroseismic sample. Here we report stellar evolutionary modelling, and confirm the presence of unexpectedly rapid rotation in stars that are more evolved than the Sun. We demonstrate that models that incorporate dramatically weakened magnetic braking for old stars can---unlike existing models---reproduce both the asteroseismic and the cluster data. Our findings might suggest a fundamental change in the nature of ageing stellar dynamos, with the Sun being close to the critical transition to much weaker magnetized winds. This weakened braking limits the diagnostic power of gyrochronology for those stars that are more than halfway through their main-sequence lifetimes.Comment: 25 pages, 3 figures in main paper, 6 extended data figures, 1 table. Published in Nature, January 2016. Please see https://youtu.be/O6HzYgP5uyc for a video description of the resul

    The Entropy for General Extremal Black Holes

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    We use the Kerr/CFT correspondence to calculate the entropy for all known extremal stationary and axisymmetric black holes. This is done with the help of two ansatzs that are general enough to cover all such known solutions. Considering only the contribution from the Einstein-Hilbert action to the central charge(s), we find that the entropy obtained by using Cardy's formula exactly matches with the Bekenstein-Hawking entropy.Comment: Minor corrections, section 5 refined, references added

    Abusive Head Trauma and Mortality-An Analysis From an International Comparative Effectiveness Study of Children With Severe Traumatic Brain Injury

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    Objectives: Small series have suggested that outcomes after abusive head trauma are less favorable than after other injury mechanisms. We sought to determine the impact of abusive head trauma on mortality and identify factors that differentiate children with abusive head trauma from those with traumatic brain injury from other mechanisms. Design: First 200 subjects from the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial—a comparative effectiveness study using an observational, cohort study design. Setting: PICUs in tertiary children’s hospitals in United States and abroad. Patients: Consecutive children (age < 18 yr) with severe traumatic brain injury (Glasgow Coma Scale ≤ 8; intracranial pressure monitoring). Interventions: None. Measurements and Main Results: Demographics, injury-related scores, prehospital, and resuscitation events were analyzed. Children were dichotomized based on likelihood of abusive head trauma. A total of 190 children were included (n = 35 with abusive head trauma). Abusive head trauma subjects were younger (1.87 ± 0.32 vs 9.23 ± 0.39 yr; p < 0.001) and a greater proportion were female (54.3% vs 34.8%; p = 0.032). Abusive head trauma were more likely to 1) be transported from home (60.0% vs 33.5%; p < 0.001), 2) have apnea (34.3% vs 12.3%; p = 0.002), and 3) have seizures (28.6% vs 7.7%; p < 0.001) during prehospital care. Abusive head trauma had a higher prevalence of seizures during resuscitation (31.4 vs 9.7%; p = 0.002). After adjusting for covariates, there was no difference in mortality (abusive head trauma, 25.7% vs nonabusive head trauma, 18.7%; hazard ratio, 1.758; p = 0.60). A similar proportion died due to refractory intracranial hypertension in each group (abusive head trauma, 66.7% vs nonabusive head trauma, 69.0%). Conclusions: In this large, multicenter series, children with abusive head trauma had differences in prehospital and in-hospital secondary injuries which could have therapeutic implications. Unlike other traumatic brain injury populations in children, female predominance was seen in abusive head trauma in our cohort. Similar mortality rates and refractory intracranial pressure deaths suggest that children with severe abusive head trauma may benefit from therapies including invasive monitoring and adherence to evidence-based guidelines

    String Theory on Warped AdS_3 and Virasoro Resonances

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    We investigate aspects of holographic duals to time-like warped AdS_3 space-times--which include G\"odel's universe--in string theory. Using worldsheet techniques similar to those that have been applied to AdS_3 backgrounds, we are able to identify space-time symmetry algebras that act on the dual boundary theory. In particular, we always find at least one Virasoro algebra with computable central charge. Interestingly, there exists a dense set of points in the moduli space of these models in which there is actually a second commuting Virasoro algebra, typically with different central charge than the first. We analyze the supersymmetry of the backgrounds, finding related enhancements, and comment on possible interpretations of these results. We also perform an asymptotic symmetry analysis at the level of supergravity, providing additional support for the worldsheet analysis.Comment: 24 pages + appendice

    Mitoxantrone pleurodesis to palliate malignant pleural effusion secondary to ovarian cancer

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    BACKGROUND: Advanced ovarian cancer is the leading non-breast gynaecologic cause of malignant pleural effusion. Aim of this study was to assess the efficacy of mitoxantrone sclerotherapy as a palliative treatment of malignant pleural effusions due to ovarian cancer. METHODS: Sixty women with known ovarian cancer and malignant recurrent symptomatic pleural effusion were treated with chest tube drainage followed by intrapleural mitoxantrone sclerotherapy. Survival, complications and response to pleurodesis were recorded. The data are expressed as the mean ± SEM and the median. RESULTS: The mean age of the entire group was 64 ± 11,24 years. The mean interval between diagnosis of ovarian cancer and presentation of the effusion was 10 ± 2,1 months. Eighteen patients (30%) had pleural effusion as the first evidence of recurrence. The mean volume of effusion drained was 1050 ± 105 ml and chest tube was removed within 4 days in 75% of patients. There were no deaths related to the procedure. Side effects of chemical pleurodesis included fever (37–38,5°C) chest pain, nausea and vomiting. At 30 days among 60 treated effusions, there was an 88% overall response rate, including 41 complete responses and 12 partial responses. At 60 days the overall response was 80% (38 complete responses and 10 partial responses). The mean survival of the entire population was 7,5 ± 1,2 months. CONCLUSIONS: Mitoxantrone is effective in the treatment of malignant pleural effusion secondary to ovarian cancer without causing significant local or systemic toxicity
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