The Contribution of Particle Impact to the Production of Fe K Emission from Accreting Black Holes

The iron K line is perhaps the most important spectral diagnostic available in the study of accreting black holes. The line is thought to result from the reprocessing of external X-rays by the surface of the accretion disk. However, as is observed in the solar corona, illumination by energetic particles may also produce line emission. In principle, such a process may be uncorrelated with the observed X-rays and could explain some of the unexpected variability behavior of the Fe line. This paper compares predictions of iron K flux generated by impacting electrons and protons to that from photoionization. Non-thermal power-laws of electrons are considered as well as thermal distributions of electrons and virialized protons. The electrons are thought to originate in a magnetically dominated accretion disk corona, while the protons are considered in the context of a two phase (hot/cold) accretion scenario. In each case, the Fe K flux from particle impact is found to be < 1% of that produced by photoionization by a hard X-ray power-law (normalized to the same energy flux as the particles). Thus, the electrons or protons must strike the disk with 100--10,000 times more energy flux than radiation for particle impact to be a significant producer of Fe K flux. This situation is difficult to reconcile with the observations of hard X-ray spectra, or the proposed particle acceleration mechanisms in the accretion disk corona. Truncated accretion flows must be externally illuminated by hard X-rays in order to produce the Fe line, as proton impact is very inefficient in generating line emission. In contrast to the Sun, our conclusion is that, with the possible exception for localized regions around magnetic footpoints, particle impact will not be an important contributor to the X-ray emission in accreting black holes.Comment: 27 pages, 6 figures, ApJ accepte

Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients

Ifosfamide and cisplatin cause urinary loss of carnitine, which is a fundamental molecule for energy production in mammalian cells. We investigated whether restoration of the carnitine pool might improve chemotherapy-induced fatigue in non-anaemic cancer patients. Consecutive patients with low plasma carnitine levels who experienced fatigue during chemotherapy were considered eligible for study entry. Patients were excluded if they had anaemia or other conditions thought to be causing asthenia. Fatigue was assessed by the Functional Assessment of Cancer Therapy-Fatigue quality of life questionnaire. Treatment consisted of oral levocarnitine 4 g daily, for 7 days. Fifty patients were enrolled; chemotherapy was cisplatin-based in 44 patients and ifosfamide-based in six patients. In the whole group, baseline mean Functional Assessment of Cancer Therapy-Fatigue score was 19.7 (±6.4; standard deviation) and the mean plasma carnitine value was 20.9 μM (±6.8; standard deviation). After 1 week, fatigue ameliorated in 45 patients and the mean Functional Assessment of Cancer Therapy-Fatigue score was 34.9 (±5.4; standard deviation) (P<.001). All patients achieved normal plasma carnitine levels. Patients maintained the improved Functional Assessment of Cancer Therapy-Fatigue score until the next cycle of chemotherapy. In selected patients, levocarnitine supplementation may be effective in alleviating chemotherapy-induced fatigue. This compound deserves further investigations in a randomised, placebo-controlled study

Circumbinary disks and cataclysmic variable evolution

The influence of a circumbinary (CB) disk on the evolution of cataclysmic variable (CV) binary systems is investigated. We show that CB mass surface densities sufficient to influence the evolution rate are plausibly provided by the outflows observed in CVs, if the net effect of these winds is to deliver $10^{-4}$--$10^{-3}$ of the mass transfer rate to the CB disk. The torque exerted by the CB disk provides a positive feedback between mass transfer rate and CB disk mass which can lead to mass transfer rates of \sim 10^{-8} -10^{-7} \mpy. This mechanism may be responsible for causing the range of variation of mass transfer rates in CV's. In particular, it may explain rates inferred for the novalike variables and the supersoft X-ray binary systems observed near the upper edge of the period gap ($P \sim 3 - 4$ hr), as well as the spread in mass transfer rates above and below the period gap. Consquences and the possible observability of such disks are discussed.Comment: submitted to Ap

Common variation in NCAN, a risk factor for bipolar disorder and schizophrenia, influences local cortical folding in schizophrenia

Background Recent studies have provided strong evidence that variation in the gene neurocan (NCAN, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance of NCAN variation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls. Method Sixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer). Results In patients, NCAN risk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (p>0.05). For cortical thickness, there was no significant effect in either patients or controls. Conclusions This study is the first to describe an effect of the NCAN risk variant on brain structure. Our data show that the NCAN risk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest that NCAN is involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophreni

A search for radio emission from Galactic supersoft X-ray sources

We have made a deep search for radio emission from all the northern hemisphere supersoft X-ray sources using the VLA and MERLIN telescopes, at 5 and 8.4 GHz. Three previously undetected sources: T Pyx, V1974 Cygni and RX J0019.8+2156 were imaged in quiescence using the VLA in order to search for any persistent emission. No radio emission was detected in any of the VLA fields down to a typical 1 sigma RMS noise of 20 uJy/beam, however, 17 new point sources were detected in the fields with 5 GHz fluxes between 100 and 1500 uJy giving an average 100 uJy-source density of around 200 per square degree, comparable to what was found in the MERLIN HDF survey. The persistent source AG Draconis was observed by MERLIN to provide a confirmation of previous VLA observations and to investigate the source at a higher resolution. The core is resolved at the milliarcsec scale into two components which have a combined flux of around 1 mJy. It is possible that we are detecting nebulosity which is becoming resolved out by the higher MERLIN resolution. We have investigated possible causes of radio emission from a wind environment, both directly from the secondary star, and also as a consequence of the high X-ray luminosity from the white dwarf. There is an order of magnitude discrepancy between observed and modelled values which can be explained by the uncertainty in fundamental quantities within these systems.Comment: Accepted for publication in MNRAS, 7 pages, 1 figur

Excess mid-IR emission in Cataclysmic Variables

We present a search for excess mid-IR emission due to circumbinary material in the orbital plane of cataclysmic variables (CVs). Our motivation stems from the fact that the strong braking exerted by a circumbinary (CB) disc on the binary system could explain several puzzles in our current understanding of CV evolution. Since theoretical estimates predict that the emission from a CB disc can dominate the spectral energy distribution (SED) of the system at wavelengths > 5 microns, we obtained simultaneous visible to mid-IR SEDs for eight systems. We report detections of SS Cyg at 11.7 microns and AE Aqr at 17.6 microns, both in excess of the contribution from the secondary star. In AE Aqr, the IR likely originates from synchrotron-emitting clouds propelled by the white dwarf. In SS Cyg, we argue that the observed mid-IR variability is difficult to reconcile with simple models of CB discs and we consider free-free emission from a wind. In the other systems, our mid-IR upper limits place strong constraints on the maximum temperature of a putative CB disc. The results show that if any sizeable CB disc are present in these systems, they must be self-shadowed or perhaps dust-free, with the peak thermal emission shifted to far-IR wavelengths.Comment: 14 pages, 6 figures, accepted for publication in MNRA

Allele-specific differences in ryanodine receptor 1 mRNA expression levels may contribute to phenotypic variability in malignant hyperthermia

<p>Abstract</p> <p>Background</p> <p>Malignant hyperthermia (MH) is a dominantly inherited skeletal muscle disorder that can cause a fatal hypermetabolic reaction to general anaesthetics. The primary locus of MH (MHS1 locus) in humans is linked to chromosome 19q13.1, the position of the gene encoding the ryanodine receptor skeletal muscle calcium release channel (RyR1).</p> <p>Methods</p> <p>In this study, an inexpensive allele-specific PCR (AS-PCR) assay was designed that allowed the relative quantification of the two RyR1 transcripts in heterozygous samples found to be susceptible to MH (MHS). Allele-specific differences in RyR1 expression levels can provide insight into the observed variable penetrance and variations in MH phenotypes between individuals. The presence/absence of the H4833Y mutation in <it>RYR</it>1 transcripts was employed as a marker that allowed discrimination between the two alleles.</p> <p>Results</p> <p>In four skeletal muscle samples and two lymphoblastoid cell lines (LCLs) from different MHS patients, the wild type allele was found to be expressed at higher levels than the mutant RyR1 allele. For both LCLs, the ratios between the wild type and mutant <it>RYR</it>1 alleles did not change after different incubation times with actinomycin D. This suggests that there are no allele-specific differences in RyR1 mRNA stability, at least in these cells.</p> <p>Conclusion</p> <p>The data presented here revealed for the first time allele-specific differences in <it>RYR</it>1 mRNA expression levels in heterozygous MHS samples, and can at least in part contribute to the observed variable penetrance and variations in MH clinical phenotypes.</p

A spastic paraplegia mouse model reveals REEP1-dependent ER shaping

Axonopathies are a group of clinically diverse disorders characterized by the progressive degeneration of the axons of specific neurons. In hereditary spastic paraplegia (HSP), the axons of cortical motor neurons degenerate and cause a spastic movement disorder. HSP is linked to mutations in several loci known collectively as the spastic paraplegia genes (SPGs). We identified a heterozygous receptor accessory protein 1 (REEP1) exon 2 deletion in a patient suffering from the autosomal dominantly inherited HSP variant SPG31. We generated the corresponding mouse model to study the underlying cellular pathology. Mice with heterozygous deletion of exon 2 in Reep1 displayed a gait disorder closely resembling SPG31 in humans. Homozygous exon 2 deletion resulted in the complete loss of REEP1 and a more severe phenotype with earlier onset. At the molecular level, we demonstrated that REEP1 is a neuron-specific, membrane-binding, and membrane curvature-inducing protein that resides in the ER. We further show that Reep1 expression was prominent in cortical motor neurons. In REEP1-deficient mice, these neurons showed reduced complexity of the peripheral ER upon ultrastructural analysis. Our study connects proper neuronal ER architecture to long-term axon survival

Malignant hyperthermia

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. Thanks to the dramatic progress in understanding the clinical manifestation and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5%