2,993 research outputs found
Nucleosynthesis in Advective Accretion Disks Around Galactic and Extra-Galactic Black Holes
We compute the nucleosynthesis of materials inside advective disks around
black holes. We show that composition of incoming matter can change
significantly depending on the accretion rate and accretion disks. These works
are improvements on the earlier works in thick accretion disks of Chakrabarti,
Jin & Arnett (1987) in presence of advection in the flow.Comment: Latex pages including figures. Kluwer Style files included. Appearing
in `Observational Evidence for Black Holes in the Universe', ed. Sandip K.
Chakrabarti, Kluwer Academic Publishers (DORDRECHT: Holland
High failure rate of the Duraloc Constrained Inlay
Background and purpose After total hip arthroplasty, dislocations are a frequent complication and are difficult to treat in some patients. A great variety of implants and antiluxation mechanisms are used in surgical therapy
Cosmic Hydrogen Was Significantly Neutral a Billion Years After the Big Bang
The ionization fraction of cosmic hydrogen, left over from the big bang,
provides crucial fossil evidence for when the first stars and quasar black
holes formed in the infant universe. Spectra of the two most distant quasars
known show nearly complete absorption of photons with wavelengths shorter than
the Ly-alpha transition of neutral hydrogen, indicating that hydrogen in the
intergalactic medium (IGM) had not been completely ionized at a redshift z~6.3,
about a billion years after the big bang. Here we show that the radii of
influence of ionizing radiation from these quasars imply that the surrounding
IGM had a neutral hydrogen fraction of tens of percent prior to the quasar
activity, much higher than previous lower limits of ~0.1%. When combined with
the recent inference of a large cumulative optical depth to electron scattering
after cosmological recombination from the WMAP data, our result suggests the
existence of a second peak in the mean ionization history, potentially due to
an early formation episode of the first stars.Comment: 14 Pages, 2 Figures. Accepted for publication in Nature. Press
embargo until publishe
Hsp90 governs dispersion and drug resistance of fungal biofilms
Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections
On completeness of logic programs
Program correctness (in imperative and functional programming) splits in
logic programming into correctness and completeness. Completeness means that a
program produces all the answers required by its specification. Little work has
been devoted to reasoning about completeness. This paper presents a few
sufficient conditions for completeness of definite programs. We also study
preserving completeness under some cases of pruning of SLD-trees (e.g. due to
using the cut).
We treat logic programming as a declarative paradigm, abstracting from any
operational semantics as far as possible. We argue that the proposed methods
are simple enough to be applied, possibly at an informal level, in practical
Prolog programming. We point out importance of approximate specifications.Comment: 20 page
Controlling spin relaxation with a cavity
Spontaneous emission of radiation is one of the fundamental mechanisms by
which an excited quantum system returns to equilibrium. For spins, however,
spontaneous emission is generally negligible compared to other non-radiative
relaxation processes because of the weak coupling between the magnetic dipole
and the electromagnetic field. In 1946, Purcell realized that the spontaneous
emission rate can be strongly enhanced by placing the quantum system in a
resonant cavity -an effect which has since been used extensively to control the
lifetime of atoms and semiconducting heterostructures coupled to microwave or
optical cavities, underpinning single-photon sources. Here we report the first
application of these ideas to spins in solids. By coupling donor spins in
silicon to a superconducting microwave cavity of high quality factor and small
mode volume, we reach for the first time the regime where spontaneous emission
constitutes the dominant spin relaxation mechanism. The relaxation rate is
increased by three orders of magnitude when the spins are tuned to the cavity
resonance, showing that energy relaxation can be engineered and controlled
on-demand. Our results provide a novel and general way to initialise spin
systems into their ground state, with applications in magnetic resonance and
quantum information processing. They also demonstrate that, contrary to popular
belief, the coupling between the magnetic dipole of a spin and the
electromagnetic field can be enhanced up to the point where quantum
fluctuations have a dramatic effect on the spin dynamics; as such our work
represents an important step towards the coherent magnetic coupling of
individual spins to microwave photons.Comment: 8 pages, 6 figures, 1 tabl
Metformin:historical overview
Metformin (dimethylbiguanide) has become the preferred first-line oral blood glucose-lowering agent to manage type 2 diabetes. Its history is linked to Galega officinalis (also known as goat's rue), a traditional herbal medicine in Europe, found to be rich in guanidine, which, in 1918, was shown to lower blood glucose. Guanidine derivatives, including metformin, were synthesised and some (not metformin) were used to treat diabetes in the 1920s and 1930s but were discontinued due to toxicity and the increased availability of insulin. Metformin was rediscovered in the search for antimalarial agents in the 1940s and, during clinical tests, proved useful to treat influenza when it sometimes lowered blood glucose. This property was pursued by the French physician Jean Sterne, who first reported the use of metformin to treat diabetes in 1957. However, metformin received limited attention as it was less potent than other glucose-lowering biguanides (phenformin and buformin), which were generally discontinued in the late 1970s due to high risk of lactic acidosis. Metformin's future was precarious, its reputation tarnished by association with other biguanides despite evident differences. The ability of metformin to counter insulin resistance and address adult-onset hyperglycaemia without weight gain or increased risk of hypoglycaemia gradually gathered credence in Europe, and after intensive scrutiny metformin was introduced into the USA in 1995. Long-term cardiovascular benefits of metformin were identified by the UK Prospective Diabetes Study (UKPDS) in 1998, providing a new rationale to adopt metformin as initial therapy to manage hyperglycaemia in type 2 diabetes. Sixty years after its introduction in diabetes treatment, metformin has become the most prescribed glucose-lowering medicine worldwide with the potential for further therapeutic applications
Social functioning and behaviour in Mucopolysaccharidosis IH [Hurlers Syndrome]
Background: Mucopolysaccharidosis type IH (MPS-IH) [Hurlers Syndrome] is a developmental genetic disorder characterised by severe physical symptoms and cognitive decline. This study aimed to investigate the behavioural phenotype of MPS-IH treated by haematopoietic cell transplantation, focusing on social functioning and sleep. Parental stress was also measured.
Methods: Participants were 22 children with MPS-IH (mean age 9 years 1 month), of whom 10 were male (45%). Parents completed the Social Responsiveness Scale (SRS), Child Behaviour Checklist (CBCL), Children’s Sleep Habit Questionnaire and Parent Stress Index, Short Form (PSI-SF).
Results: Twenty-three per cent of children with MPS-IH scored in the severe range of the SRS, suggesting significant difficulties in social functioning. Children with MPS-IH were more than 30 times more likely to receive scores in the severe range than typically developing children. Thirty-six per cent scored in the mild-to-moderate range, suggesting milder, but marked, difficulties in social interaction. Although children with MPS-IH did not show significantly higher rates of internalising, externalising or total behaviour problems than the normative sample, they received scores that were significantly higher on social, thought and attention problems and rule-breaking behaviour, and all the competence areas of the CBCL. Parents of children with MPS-IH did not score significantly higher on parental stress than parents in a normative sample.
Conclusions: Parents of children with MPS-IH rate their children as having problems with social functioning and various areas of competence more frequently than previously thought, with implications for clinical support
First-principles design and subsequent synthesis of a material to search for the permanent electric dipole moment of the electron
We describe the first-principles design and subsequent synthesis of a new
material with the specific functionalities required for a solid-state-based
search for the permanent electric dipole moment of the electron. We show
computationally that perovskite-structure europium barium titanate should
exhibit the required large and pressure-dependent ferroelectric polarization,
local magnetic moments, and absence of magnetic ordering even at liquid helium
temperature. Subsequent synthesis and characterization of
EuBaTiO ceramics confirm the predicted desirable
properties.Comment: Nature Materials, in pres
- …