Ensemble prediction for nowcasting with a convection-permitting model - II: forecast error statistics

A 24-member ensemble of 1-h high-resolution forecasts over the Southern United Kingdom is used to study short-range forecast error statistics. The initial conditions are found from perturbations from an ensemble transform Kalman filter. Forecasts from this system are assumed to lie within the bounds of forecast error of an operational forecast system. Although noisy, this system is capable of producing physically reasonable statistics which are analysed and compared to statistics implied from a variational assimilation system. The variances for temperature errors for instance show structures that reflect convective activity. Some variables, notably potential temperature and specific humidity perturbations, have autocorrelation functions that deviate from 3-D isotropy at the convective-scale (horizontal scales less than 10 km). Other variables, notably the velocity potential for horizontal divergence perturbations, maintain 3-D isotropy at all scales. Geostrophic and hydrostatic balances are studied by examining correlations between terms in the divergence and vertical momentum equations respectively. Both balances are found to decay as the horizontal scale decreases. It is estimated that geostrophic balance becomes less important at scales smaller than 75 km, and hydrostatic balance becomes less important at scales smaller than 35 km, although more work is required to validate these findings. The implications of these results for high-resolution data assimilation are discussed

An ultrastructural and molecular analysis of neuronal degeneration in Huntington's disease.

Huntington's disease (HD) is an inherited, progressive, neurodegenerative disorder for which there is no effective treatment. It is one of nine disorders known to be caused by the expansion of a genomic CAG repeat sequence, producing a protein with an expanded array of polyglutamine residues. The mechanisms underlying the degeneration and death of neurons in HD remain unclear, and are the subjects of this investigation. Several animal models have been generated to investigate the pathogenic mechanisms underlying HD, of which this thesis uses two: the Bates R6/2 mouse, which has the affected region of the human gene inserted into its genome; and the Shelboume Hdh 'knock-in' mice, in which the CAG repeat sequence of the murine huntingtin gene homologue has been expanded into the pathogenic range. Ultrastructural analyses have been undertaken on the CNS from each of the mouse models, detailing the subcellular changes that occur. This has been furthered by analyses of the molecular machinery of apoptosis in an attempt to identify factors involved in neurodegeneration. Affected neurons in each of the HD models, and in aged wild-type mice, exhibit very similar morphologies: a condensation of cytoplasm and nucleoplasm, disturbances in the nuclear membrane, dilation and disruption of cell organelles and increased autophagic activity. These morphologic changes do not correlate with those reported to occur during apoptosis. Furthermore, molecular analyses reveal the involvement of none of the components of apoptosis. In relating each of the mice, it is clear that neurodegenerative changes do not correlate with phenotypic changes; rather the early and most pronounced symptoms of HD are a result of neuronal dysfunction. It is also concluded that the increased autophagic activity and cell condensation occur in adult neurons under stress and thus may be indicative of a common process by which adult neurons die

The roles of DNA, RNA and histone methylation in ageing and cancer.

Chromatin is a macromolecular complex predominantly comprising DNA, histone proteins and RNA. The methylation of chromatin components is highly conserved as it helps coordinate the regulation of gene expression, DNA repair and DNA replication. Dynamic changes in chromatin methylation are essential for cell-fate determination and development. Consequently, inherited or acquired mutations in the major factors that regulate the methylation of DNA, RNA and/or histones are commonly observed in developmental disorders, ageing and cancer. This has provided the impetus for the clinical development of epigenetic therapies aimed at resetting the methylation imbalance observed in these disorders. In this Review, we discuss the cellular functions of chromatin methylation and focus on how this fundamental biological process is corrupted in cancer. We discuss methylation-based cancer therapies and provide a perspective on the emerging data from early-phase clinical trial therapies that target regulators of DNA and histone methylation. We also highlight promising therapeutic strategies, including monitoring chromatin methylation for diagnostic purposes and combination epigenetic therapy strategies that may improve immune surveillance in cancer and increase the efficacy of conventional and targeted anticancer drugs

High-velocity OH megamasers in IRAS 20100-4156: Evidence for a Supermassive Black Hole

We report the discovery of new, high-velocity narrow-line components of the OH megamaser in IRAS 20100-4156. Results from the Australian Square Kilometre Array Pathfinder (ASKAP)'s Boolardy Engineering Test Array (BETA) and the Australia Telescope Compact Array (ATCA) provide two independent measurements of the OH megamaser spectrum. We found evidence for OH megamaser clumps at $-$409 and $-$562 km/s (blue-shifted) from the systemic velocity of the galaxy, in addition to the lines previously known. The presence of such high velocities in the molecular emission from IRAS 20100$-$4156 could be explained by a ~50 pc molecular ring enclosing an approximately 3.8 billion solar mass black hole. We also discuss two alternatives, i.e. that the narrow-line masers are dynamically coupled to the wind driven by the active galactic nucleus or they are associated with two separate galactic nuclei. The comparison between the BETA and ATCA spectra provides another scientific verification of ASKAP's BETA. Our data, combined with previous measurements of the source enabled us to study the variability of the source over a twenty-six year period. The flux density of the brightest OH maser components has reduced by more than a factor of two between 1988 and 2015, whereas a secondary narrow-line component has more than doubled in the same time. Plans for high-resolution VLBI follow-up of this source are discussed, as are prospects for discovering new OH megamasers during the ASKAP early science program.Comment: Accepted to MNRAS. Seven pages, three figure

The comparative clinical course of pregnant and non-pregnant women hospitalised with influenza A(H1N1)pdm09 infection

Introduction: The Influenza Clinical Information Network (FLU-CIN) was established to gather detailed clinical and epidemiological information about patients with laboratory confirmed A(H1N1)pdm09 infection in UK hospitals. This report focuses on the clinical course and outcomes of infection in pregnancy.Methods: A standardised data extraction form was used to obtain detailed clinical information from hospital case notes and electronic records, for patients with PCR-confirmed A(H1N1)pdm09 infection admitted to 13 sentinel hospitals in five clinical 'hubs' and a further 62 non-sentinel hospitals, between 11th May 2009 and 31st January 2010.Outcomes were compared for pregnant and non-pregnant women aged 15-44 years, using univariate and multivariable techniques.Results: Of the 395 women aged 15-44 years, 82 (21%) were pregnant; 73 (89%) in the second or third trimester. Pregnant women were significantly less likely to exhibit severe respiratory distress at initial assessment (OR?=?0.49 (95% CI: 0.30-0.82)), require supplemental oxygen on admission (OR?=?0.40 (95% CI: 0.20-0.80)), or have underlying co-morbidities (p-trend <0.001). However, they were equally likely to be admitted to high dependency (Level 2) or intensive care (Level 3) and/or to die, after adjustment for potential confounders (adj. OR?=?0.93 (95% CI: 0.46-1.92). Of 11 pregnant women needing Level 2/3 care, 10 required mechanical ventilation and three died.Conclusions: Since the expected prevalence of pregnancy in the source population was 6%, our data suggest that pregnancy greatly increased the likelihood of hospital admission with A(H1N1)pdm09. Pregnant women were less likely than non-pregnant women to have respiratory distress on admission, but severe outcomes were equally likely in both groups

The early and late-time spectral and temporal evolution of GRB 050716

We report on a comprehensive set of observations of Gamma Ray Burst 050716, detected by the Swift satellite and subsequently followed-up rapidly in X-ray, optical and near infra-red wavebands. The prompt emission is typical of long-duration bursts, with two peaks in a time interval of T90 = 68 seconds (15 - 350 keV). The prompt emission continues at lower flux levels in the X-ray band, where several smaller flares can be seen, on top of a decaying light curve that exhibits an apparent break around 220 seconds post trigger. This temporal break is roughly coincident with a spectral break. The latter can be related to the extrapolated evolution of the break energy in the prompt gamma-ray emission, and is possibly the manifestation of the peak flux break frequency of the internal shock passing through the observing band. A possible 3 sigma change in the X-ray absorption column is also seen during this time. The late-time afterglow behaviour is relatively standard, with an electron distribution power-law index of p = 2 there is no noticable temporal break out to at least 10 days. The broad-band optical/nIR to X-ray spectrum indicates a redshift of z ~> 2 for this burst, with a host-galaxy extinction value of E(B-V) ~ 0.7 that prefers an SMC-like extinction curve.Comment: Accepted to MNRAS. 8 pages, 5 figure

OSSOS XXV: Large Populations and Scattering-Sticking in the Distant Transneptunian Resonances

There have been 77 TNOs discovered to be librating in the distant transneptunian resonances (beyond the 2:1 resonance, at semimajor axes greater than 47.7~AU) in four well-characterized surveys: the Outer Solar System Origins Survey (OSSOS) and three similar prior surveys. Here we use the OSSOS Survey Simulator to measure their intrinsic orbital distributions using an empirical parameterized model. Because many of the resonances had only one or very few detections, $j$:$k$ resonant objects were grouped by $k$ in order to have a better basis for comparison between models and reality. We also use the Survey Simulator to constrain their absolute populations, finding that they are much larger than predicted by any published Neptune migration model to date; we also find population ratios that are inconsistent with published models, presenting a challenge for future Kuiper Belt emplacement models. The estimated population ratios between these resonances are largely consistent with scattering-sticking predictions, though further discoveries of resonant TNOs with high-precision orbits will be needed to determine whether scattering-sticking can explain the entire distant resonant population or not.Comment: Accepted for publication in Planetary Sciences Journal (PSJ

A Sample of Very Young Field L Dwarfs and Implications for the Brown Dwarf "Lithium Test" at Early Ages

Using a large sample of optical spectra of late-type dwarfs, we identify a subset of late-M through L field dwarfs that, because of the presence of low-gravity features in their spectra, are believed to be unusually young. From a combined sample of 303 field L dwarfs, we find observationally that 7.6+/-1.6% are younger than 100 Myr. This percentage is in agreement with theoretical predictions once observing biases are taken into account. We find that these young L dwarfs tend to fall in the southern hemisphere (Dec < 0 deg) and may be previously unrecognized, low-mass members of nearby, young associations like Tucana-Horologium, TW Hydrae, beta Pictoris, and AB Doradus. We use a homogeneously observed sample of roughly one hundred and fifty 6300-10000 Angstrom spectra of L and T dwarfs taken with the Low-Resolution Imaging Spectrometer at the W. M. Keck Observatory to examine the strength of the 6708-A Li I line as a function of spectral type and further corroborate the trends noted by Kirkpatrick et al. (2000). We use our low-gravity spectra to investigate the strength of the Li I line as a function of age. The data weakly suggest that for early- to mid-L dwarfs the line strength reaches a maximum for a few 100 Myr, whereas for much older (few Gyr) and much younger (<100 Myr) L dwarfs the line is weaker or undetectable. We show that a weakening of lithium at lower gravities is predicted by model atmosphere calculations, an effect partially corroborated by existing observational data. Larger samples containing L dwarfs of well determined ages are needed to further test this empirically. If verified, this result would reinforce the caveat first cited in Kirkpatrick et al. (2006) that the lithium test should be used with caution when attempting to confirm the substellar nature of the youngest brown dwarfs.Comment: 73 pages with 22 figures; to appear in ApJ (Dec 20, 2008, v689n2 issue