The most important product of the sequencing of a genome is a complete, accurate catalogue of genes and their products, primarily messenger RNA transcripts and their cognate proteins. Such a ...catalogue cannot be constructed by computational annotation alone; it requires experimental validation on a genome scale. Using 'exon' and 'tiling' arrays fabricated by ink-jet oligonucleotide synthesis, we devised an experimental approach to validate and refine computational gene predictions and define full-length transcripts on the basis of co-regulated expression of their exons. These methods can provide more accurate gene numbers and allow the detection of mRNA splice variants and identification of the tissue- and disease-specific conditions under which genes are expressed. We apply our technique to chromosome 22q under 69 experimental condition pairs, and to the entire human genome under two experimental conditions. We discuss implications for more comprehensive, consistent and reliable genome annotation, more efficient, full-length complementary DNA cloning strategies and application to complex diseases.
The Swift Gamma-Ray Burst Mission Gehrels, N; Chincarini, G; Giommi, P ...
The Astrophysical journal,
08/2004, Letnik:
611, Številka:
2
Journal Article
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The Swift mission, scheduled for launch in 2004, is a multiwavelength observatory for gamma-ray burst (GRB) astronomy. It is a first-of-its-kind autonomous rapid-slewing satellite for transient ...astronomy and pioneers the way for future rapid-reaction and multiwavelength missions. It will be far more powerful than any previous GRB mission, observing more than 100 bursts yr super(-1) and performing detailed X-ray and UV/optical afterglow observations spanning timescales from 1 minute to several days after the burst. The objectives are to (1) determine the origin of GRBs, (2) classify GRBs and search for new types, (3) study the interaction of the ultrarelativistic outflows of GRBs with their surrounding medium, and (4) use GRBs to study the early universe out to z > 10. The mission is being developed by a NASA-led international collaboration. It will carry three instruments: a new-generation wide-field gamma-ray (15-150 keV) detector that will detect bursts, calculate 1arcmin-4arcmin positions, and trigger autonomous spacecraft slews; a narrow-field X-ray telescope that will give 5arc sec positions and perform spectroscopy in the 0.2-10 keV band; and a narrow-field UV/optical telescope that will operate in the 170-600 nm band and provide 0!!3 positions and optical finding charts. Redshift determinations will be made for most bursts. In addition to the primary GRB science, the mission will perform a hard X-ray survey to a sensitivity of approx1 mcrab (approx2 x 10 super(-11) ergs cm super(-2) s super(-1) in the 15-150 keV band), more than an order of magnitude better than HEAO 1 A-4. A flexible data and operations system will allow rapid follow-up observations of all types of high-energy transients, with rapid data downlink and uplink available through the NASA TDRSS system. Swift transient data will be rapidly distributed to the astronomical community, and all interested observers are encouraged to participate in follow- up measurements. A Guest Investigator program for the mission will provide funding for community involvement. Innovations from the Swift program applicable to the future include (1) a large-area gamma-ray detector using the new CdZnTe detectors, (2) an autonomous rapid-slewing spacecraft, (3) a multiwavelength payload combining optical, X-ray, and gamma-ray instruments, (4) an observing program coordinated with other ground-based and space-based observatories, and (5) immediate multiwavelength data flow to the community. The mission is currently funded for 2 yr of operations, and the spacecraft will have a lifetime to orbital decay of approx8 yr.
Cancer diagnostics and surgery have been disrupted by the response of health care services to the coronavirus disease 2019 (COVID-19) pandemic. Progression of cancers during delay will impact on ...patients' long-term survival.
We generated per-day hazard ratios of cancer progression from observational studies and applied these to age-specific, stage-specific cancer survival for England 2013–2017. We modelled per-patient delay of 3 and 6 months and periods of disruption of 1 and 2 years. Using health care resource costing, we contextualise attributable lives saved and life-years gained (LYGs) from cancer surgery to equivalent volumes of COVID-19 hospitalisations.
Per year, 94 912 resections for major cancers result in 80 406 long-term survivors and 1 717 051 LYGs. Per-patient delay of 3/6 months would cause attributable death of 4755/10 760 of these individuals with loss of 92 214/208 275 life-years, respectively. For cancer surgery, average LYGs per patient are 18.1 under standard conditions and 17.1/15.9 with a delay of 3/6 months (an average loss of 0.97/2.19 LYGs per patient), respectively. Taking into account health care resource units (HCRUs), surgery results on average per patient in 2.25 resource-adjusted life-years gained (RALYGs) under standard conditions and 2.12/1.97 RALYGs following delay of 3/6 months. For 94 912 hospital COVID-19 admissions, there are 482 022 LYGs requiring 1 052 949 HCRUs. Hospitalisation of community-acquired COVID-19 patients yields on average per patient 5.08 LYG and 0.46 RALYGs.
Modest delays in surgery for cancer incur significant impact on survival. Delay of 3/6 months in surgery for incident cancers would mitigate 19%/43% of LYGs, respectively, by hospitalisation of an equivalent volume of admissions for community-acquired COVID-19. This rises to 26%/59%, respectively, when considering RALYGs. To avoid a downstream public health crisis of avoidable cancer deaths, cancer diagnostic and surgical pathways must be maintained at normal throughput, with rapid attention to any backlog already accrued.
•Lockdown and re-deployment due to the COVID-19 pandemic have caused significant disruption to cancer diagnosis and management.•A 3-month delay to surgery across all stage 1–3 cancers is estimated to cause >4700 attributable deaths per year in England.•The impact on life-years lost of 3–6-month delay to surgery for stage 1–3 disease varies widely between tumour types.•Strategic prioritisation of patients for diagnostics and surgery has potential to mitigate deaths attributable to delays.•The resource-adjusted benefit in avoiding delay in cancer management compares favourably with admission for COVID-19 infection.
ABSTRACT
Historically, it has often been asserted that most stars form in compact clusters. In this scenario, present-day gravitationally unbound OB associations are the result of the expansion of ...initially gravitationally bound star clusters. However, this paradigm is inconsistent with recent results, both theoretical and observational, that instead favour a hierarchical picture of star formation in which stars are formed across a continuous distribution of gas densities and most OB associations never were bound clusters. Instead they are formed in situ as the low-density side of this distribution, rather than as the remnants of expanding clusters. We utilize the second Gaia data release to quantify the degree to which OB associations are undergoing expansion and, therefore, whether OB associations are the product of expanding clusters, or whether they were born in situ, as the large-scale globally unbound associations that we see today. We find that the observed kinematic properties of associations are consistent with highly substructured velocity fields and additionally require some degree of localized expansion from subclusters within the association. While most present-day OB associations do exhibit low levels of expansion, there is no significant correlation between radial velocity and radius. Therefore, the large-scale structure of associations is not set by the expansion of clusters, rather it is a relic of the molecular gas cloud from which the association was formed. This finding is inconsistent with a monolithic model of association formation and instead favours a hierarchical model, in which OB associations form in situ, following the fractal structure of the gas from which they form.
In this paper, we present the first observations of the Ophiuchus molecular cloud performed as part of the James Clerk Maxwell Telescope (JCMT) Gould Belt Survey (GBS) with the SCUBA-2 instrument. We ...demonstrate methods for combining these data with previous HARP CO, Herschel, and IRAM N2H+ observations in order to accurately quantify the properties of the SCUBA-2 sources in Ophiuchus. We produce a catalogue of all of the sources found by SCUBA-2. We separate these into protostars and starless cores. We list all of the starless cores and perform a full virial analysis, including external pressure. This is the first time that external pressure has been included in this level of detail. We find that the majority of our cores are either bound or virialized. Gravitational energy and external pressure are on average of a similar order of magnitude, but with some variation from region to region. We find that cores in the Oph A region are gravitationally bound prestellar cores, while cores in the Oph C and E regions are pressure-confined. We determine that N2H+ is a good tracer of the bound material of prestellar cores, although we find some evidence for N2H+ freeze-out at the very highest core densities. We find that non-thermal linewidths decrease substantially between the gas traced by C18O and that traced by N2H+, indicating the dissipation of turbulence at higher densities. We find that the critical Bonnor–Ebert stability criterion is not a good indicator of the boundedness of our cores. We detect the pre-brown dwarf candidate Oph B-11 and find a flux density and mass consistent with previous work. We discuss regional variations in the nature of the cores and find further support for our previous hypothesis of a global evolutionary gradient across the cloud from south-west to north-east, indicating sequential star formation across the region.
Globally, collapse of ecosystems—potentially irreversible change to ecosystem structure, composition and function—imperils biodiversity, human health and well‐being. We examine the current state and ...recent trajectories of 19 ecosystems, spanning 58° of latitude across 7.7 M km2, from Australia's coral reefs to terrestrial Antarctica. Pressures from global climate change and regional human impacts, occurring as chronic ‘presses’ and/or acute ‘pulses’, drive ecosystem collapse. Ecosystem responses to 5–17 pressures were categorised as four collapse profiles—abrupt, smooth, stepped and fluctuating. The manifestation of widespread ecosystem collapse is a stark warning of the necessity to take action. We present a three‐step assessment and management framework (3As Pathway Awareness, Anticipation and Action) to aid strategic and effective mitigation to alleviate further degradation to help secure our future.
Global climate pressures and regional human impacts are causing increasing collapse of ecosystems across Australia and reaching to Antarctica. Ecosystems are experiencing multiple pressures simultaneously, either chronically (e.g. increasing air temperatures) and/or as extreme, short events (e.g. storms, fires), with their deterioration exhibiting a range of patterns. Knowing these patterns can alert conservation managers to impending collapse. We provide a new framework (the 3As) to use in conservation that focuses on preventing collapse (Awareness of ecosystem values; Anticipation of the range of pressure; Action to stop pressures), as well as guidance as to the types of conservation options available.
The Laser Interferometer Gravitational Wave Observatory (LIGO) consists of two widely separated 4 km laser interferometers designed to detect gravitational waves from distant astrophysical sources in ...the frequency range from 10 Hz to 10 kHz. The first observation run of the Advanced LIGO detectors started in September 2015 and ended in January 2016. A strain sensitivity of better than 10 super(-23)/radicalHz was achieved around 100 Hz. Understanding both the fundamental and the technical noise sources was critical for increasing the astrophysical strain sensitivity. The average distance at which coalescing binary black hole systems with individual masses of 30Mmiddot could be detected above a signal-to-noise ratio (SNR) of 8 was 1.3 Gpc, and the range for binary neutron star inspirals was about 75 Mpc. With respect to the initial detectors, the observable volume of the Universe increased by a factor 69 and 43, respectively. These improvements helped Advanced LIGO to detect the gravitational wave signal from the binary black hole coalescence, known as GW150914.
Transient ischemic attack (TIA) patients are at high risk of recurrent vascular events; timely management can reduce that risk by 70%. The Protocol-guided Rapid Evaluation of Veterans Experiencing ...New Transient Neurological Symptoms (PREVENT) developed, implemented, and evaluated a TIA quality improvement (QI) intervention aligned with Learning Healthcare System principles.
This stepped-wedge trial developed, implemented and evaluated a provider-facing, multi-component intervention to improve TIA care at six facilities. The unit of analysis was the medical center. The intervention was developed based on benchmarking data, staff interviews, literature, and electronic quality measures and included: performance data, clinical protocols, professional education, electronic health record tools, and QI support. The effectiveness outcome was the without-fail rate: the proportion of patients who receive all processes of care for which they are eligible among seven processes. The implementation outcomes were the number of implementation activities completed and final team organization level. The intervention effects on the without-fail rate were analyzed using generalized mixed-effects models with multilevel hierarchical random effects. Mixed methods were used to assess implementation, user satisfaction, and sustainability.
PREVENT advanced three aspects of a Learning Healthcare System. Learning from Data: teams examined and interacted with their performance data to explore hypotheses, plan QI activities, and evaluate change over time. Learning from Each Other: Teams participated in monthly virtual collaborative calls. Sharing Best Practices: Teams shared tools and best practices. The approach used to design and implement PREVENT may be generalizable to other clinical conditions where time-sensitive care spans clinical settings and medical disciplines.
clinicaltrials.gov: NCT02769338 May 11, 2016.
ALMA observations have revealed nuclear dusty molecular disks or tori with characteristic sizes 15−40 pc in the few Seyferts and low -luminosity AGN that have been studied so far. These structures ...are generally decoupled both morphologically and kinematically from the host galaxy disk. We present ALMA observations of the CO(2–1) and CO(3–2) molecular gas transitions and associated (sub-) millimeter continua of the nearby Seyfert 1.5 galaxy NGC 3227 with angular resolutions 0.085 − 0.21″ (7–15 pc). On large scales, the cold molecular gas shows circular motions as well as streaming motions on scales of a few hundred parsecs that are associated with a large-scale bar. We fit the nuclear ALMA 1.3 mm emission with an unresolved component and an extended component. The 850 μm emission shows at least two extended components, one along the major axis of the nuclear disk, and the other along the axis of the ionization cone. The molecular gas in the central region (1″ ∼ 73 pc) shows several CO clumps with complex kinematics that appears to be dominated by noncircular motions. While we cannot conclusively demonstrate the presence of a warped nuclear disk, we also detected noncircular motions along the kinematic minor axis. They reach line-of-sight velocities of v − vsys = 150 − 200 km s−1. Assuming that the radial motions are in the plane of the galaxy, we interpret them as a nuclear molecular outflow due to molecular gas in the host galaxy that is entrained by the AGN wind. We derive molecular outflow rates of 5 M⊙ yr−1 and 0.6 M⊙ yr−1 at projected distances of up to 30 pc to the northeast and southwest of the AGN, respectively. At the AGN location we estimate a mass in molecular gas of 5 × 105 M⊙ and an equivalent average column density N(H2) = 2 − 3 × 1023 cm−2 in the inner 15 pc. The nuclear CO(2–1) and CO(3–2) molecular gas and submillimeter continuum emission of NGC 3227 do not resemble the classical compact torus. Rather, these emissions extend for several tens of parsecs and appear connected with the circumnuclear ring in the host galaxy disk, as found in other local AGN.
ABSTRACT
The great power offered by photoionization models of active galactic nuclei emission line regions has long been mitigated by the fact that very little is known about the spectral energy ...distribution (SED) between the Lyman limit, where intervening absorption becomes a problem, and 0.3 keV, where soft X-ray observations become possible. The emission lines themselves can, to some degree, be used to probe the SED, but only in the broadest terms. This paper employs a new generation of theoretical SEDs that are internally self-consistent, energy conserving, and tested against observations, to infer properties of the emission-line regions. The SEDs are given as a function of the Eddington ratio, allowing emission-line correlations to be investigated on a fundamental basis. We apply the simplest possible tests, based on the foundations of photoionization theory, to investigate the implications for the geometry of the emission-line region. The SEDs become more far-ultraviolet bright as the Eddington ratio increases, so the equivalent widths of recombination lines should also become larger, an effect that we quantify. The observed lack of correlation between Eddington ratio and equivalent width shows that the cloud covering factor must decrease as Eddington ratio increases. This would be consistent with recent models proposing that the broad-line region is a failed dusty wind off the accretion disc.
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