236 research outputs found
Nse2, a component of the Smc5-6 complex, is a SUMO ligase required for the response to DNA damage
The Schizosaccharomyces pombe SMC proteins Rad18 (Smc6) and Spr18 (Smc5) exist in a high-M(r) complex which also contains the non-SMC proteins Nse1, Nse2, Nse3, and Rad62. The Smc5-6 complex, which is essential for viability, is required for several aspects of DNA metabolism, including recombinational repair and maintenance of the DNA damage checkpoint. We have characterized Nse2 and show here that it is a SUMO ligase. Smc6 (Rad18) and Nse3, but not Smc5 (Spr18) or Nse1, are sumoylated in vitro in an Nse2-dependent manner, and Nse2 is itself autosumoylated, predominantly on the C-terminal part of the protein. Mutations of C195 and H197 in the Nse2 RING-finger-like motif abolish Nse2-dependent sumoylation. nse2.SA mutant cells, in which nse2.C195S-H197A is integrated as the sole copy of nse2, are viable, whereas the deletion of nse2 is lethal. Smc6 (Rad18) is sumoylated in vivo: the sumoylation level is increased upon exposure to DNA damage and is drastically reduced in the nse2.SA strain. Since nse2.SA cells are sensitive to DNA-damaging agents and to exposure to hydroxyurea, this implicates the Nse2-dependent sumoylation activity in DNA damage responses but not in the essential function of the Smc5-6 complex
Available Coal Resoures of the Handshoe 7.5–Minute Quadrangle, Knott County, Kentucky
Coal resources available for mining have been estimated for the Handshoe Quadrangle within the Hazard Coal Reserve District of the Eastern Kentucky Coal Field. Twelve coal beds within the quadrangle are potentially mineable and comprise the basis of these resource estimates. Seven of these beds have been commercially developed, but only four have produced more than 1 million tons: the Tiptop, Hazard No. 8, Hazard No. 4, and Upper Elkhorn No. 3. A computerized Geographic Information System was used to calculate estimates of original, mined-out, and remaining resources, restrictions to mining, and available resources
Available Coal Resources of the Salyersville South 7.5-Minute Quadrangle, Magoffin County, Kentucky
Coal resources available for mining have been estimated for the Salyersville South Quadrangle, which is located in the Licking River Coal Reserve District of the Eastern Kentucky Coal Field. Nine coal beds within the quadrangle are potentially mineable and constitute the basis of these resource estimates. Seven of these beds have been commercially developed, but only five have produced more than 1 million tons: from youngest to oldest, the Skyline A, Lower Broas, Lower Peach Orchard, Middle Peach Orchard, and Upper Peach Orchard. A computerized Geographic Information System was used to calculate estimates of original, mined-out, and remaining resources, as well as restrictions to mining and available resources
Geology of the Fire Clay Coal in Part of the Eastern Kentucky Coal Field
Coal beds mined in Kentucky often are not laterally continuous in thickness, quality, or roof condition. Regional and local variation is common. Because thickness, quality, and roof conditions are the result of geologic processes that were active when the coal was deposited as a peat swamp, a better understanding of the relationships between geology and major coal resources can aid in identifying geologic trends, which can be extrapolated beyond areas of present mining. The focus of this study is on the Fire Clay (Hazard No. 4) coal, one of the leading producers in the Eastern Kentucky Coal Field with 20 million short tons of annual production. More than 3,800 thickness measurements, highwall and outcrop descriptions, borehole and geophysical-log descriptions, and proximate analyses from 97 localities were used in conjunction with previous palynologic and petrographic studies to investigate the geology of the Fire Clay coal in a 15-quadrangle area of the Eastern Kentucky Coal Field.
The Fire Clay coal is commonly separated into two distinct layers or benches by a flint-clay and shale parting called the “jackrock parting” by miners. Maps of coal benches above and below the parting show that the lower bench is limited in extent and variable in thickness. In contrast, the coal above the jackrock parting occurs across most of the study area and is characterized by rectangular patterns of coal thickness.
Multiple coal benches resulted from the accumulation of multiple peat deposits, each with different characteristics. The lower bench of the coal was deposited when a peat accumulated above an irregular topographic surface. Because the peat was being deposited at or below the water table, it was often flooded by sediment from lateral sources, resulting in moderate to locally high ash yields. This peat was drowned and then covered by volcanic ash, which formed the flint clay in the jackrock parting. The upper coal bench accumulated above the ash deposit, after irregularities in the topography had been filled. The relatively flat surface allowed the swamps to spread outward and dome upward above the water table in some areas. Doming of the peat resulted in areas of coal with generally low ash yields and sulfur contents. Sharp, angular changes in the upper coal bench are inferred to represent subtle fault influence on upper peat accumulation.
The upper peat was buried by a series of river channels, which were bounded by levees, flood plains, and elongate bays. Several of the rivers eroded through the Fire Clay peats, forming cutouts in the coal. These cutouts often follow orientations similar to the angular trends of coal thinning, suggesting a relationship that can be extended beyond the present limits of mining. Also, additional peat swamps accumulated above the levees and flood plains bounding the channels. Along the thinning margins of these deposits, the peats came near or merged with the top of the Fire Clay coal, resulting in local areas of increased coal thickness.
Rider coal benches exhibit high to moderate sulfur contents and ash yields, so that although they may increase coal thickness, total coal quality generally decreases where riders combine with the Fire Clay coal
Clinicians approaches to management of background treatment in patients with SLE in clinical remission:results of an international observational survey
Available Resources of the Fire Clay Coal in Part of the Eastern Kentucky Coal Field
Available resources for the Fire Clay coal were calculated for a 15-quadrangle area in the Eastern Kentucky Coal Field. Original coal resources were estimated to be 1.8 billion tons (BT). Coal mined or lost in mining was estimated at 449 million tons (MT), leaving 1.3 BT of remaining Fire Clay resources in the study area. Of the remaining resources, 400 MT is restricted from mining, primarily because the coal is less than 28 in. thick, normally considered too thin to mine underground using present technology. The total coal available for mining in the study area is 911 MT, or 52 percent of the original resource. Of the 911 MT, 14.9 percent is thicker than 42 in., and only 6.1 percent is accessible by surface-mining methods. The largest block of available coal is in the Leatherwood quadrangle, is less than 42 in. thick, and mostly occurs below drainage
Available Coal Resources of the Booneville 7.5–Minute Quadrangle, Owsley County, Kentucky
The Booneville Quadrangle lies within the Southwestern Reserve District of the Eastern Kentucky Coal Field. Six coal beds in the quadrangle have been commercially developed, mainly by surface mining methods, and comprise the basis of this Coal Availability Study. These beds are, in descending stratigraphic order, Copland, Whitesburg, Amburgy, Upper Elkhorn No. 3, Jellico and Manchester. A computerized Geographic Information System (GRASS) was used to calculate estimates of original, mined-out and remaining resources, restrictions to mining and available resources
Post-outbreak African horse sickness surveillance : a scenario tree evaluation in South Africa’s controlled area
An African horse sickness (AHS) outbreak occurred in March and April 2016 in the controlled area of South Africa. This extended an existing trade suspension of live equids from South Africa to the European Union. In the post‐outbreak period ongoing passive and active surveillance, the latter in the form of monthly sentinel surveillance and a stand‐alone freedom from disease survey in March 2017, took place. We describe a stochastic scenario tree analysis of these surveillance components for 24 months, starting July 2016, in three distinct geographic areas of the controlled area. Given that AHS was not detected, the probability of being free from AHS was between 98.3% and 99.8% assuming that, if it were present, it would have a prevalence of at least one infected animal in 1% of herds. This high level of freedom probability had been attained in all three areas within the first 9 months of the 2‐year period. The primary driver of surveillance outcomes was the passive surveillance component. Active surveillance components contributed minimally (<0.2%) to the final probability of freedom. Sensitivity analysis showed that the probability of infected horses showing clinical signs was an important parameter influencing the system surveillance sensitivity. The monthly probability of disease introduction needed to be increased to 20% and greater to decrease the overall probability of freedom to below 90%. Current global standards require a 2‐year post‐incursion period of AHS freedom before re‐evaluation of free zone status. Our findings show that the length of this period could be decreased if adequately sensitive surveillance is performed. In order to comply with international standards, active surveillance will remain a component of AHS surveillance in South Africa. Passive surveillance, however, can provide substantial evidence supporting AHS freedom status declarations, and further investment in this surveillance activity would be beneficial.http://wileyonlinelibrary.com/journal/tbed2021-04-08hj2020Production Animal StudiesVeterinary Tropical Disease
Collecting Symptoms and Sensor Data With Consumer Smartwatches (the Knee OsteoArthritis, Linking Activity and Pain Study):Protocol for a Longitudinal, Observational Feasibility Study
BACKGROUND: The Knee OsteoArthritis, Linking Activity and Pain (KOALAP) study is the first to test the feasibility of using consumer-grade cellular smartwatches for health care research. OBJECTIVE: The overall aim was to investigate the feasibility of using consumer-grade cellular smartwatches as a novel tool to capture data on pain (multiple times a day) and physical activity (continuously) in patients with knee osteoarthritis. Additionally, KOALAP aimed to investigate smartwatch sensor data quality and assess whether engagement, acceptability, and user experience are sufficient for future large-scale observational and interventional studies. METHODS: A total of 26 participants with self-diagnosed knee osteoarthritis were recruited in September 2017. All participants were aged 50 years or over and either lived in or were willing to travel to the Greater Manchester area. Participants received a smartwatch (Huawei Watch 2) with a bespoke app that collected patient-reported outcomes via questionnaires and continuous watch sensor data. All data were collected daily for 90 days. Additional data were collected through interviews (at baseline and follow-up) and baseline and end-of-study questionnaires. This study underwent full review by the University of Manchester Research Ethics Committee (#0165) and University Information Governance (#IGRR000060). For qualitative data analysis, a system-level security policy was developed in collaboration with the University Information Governance Office. Additionally, the project underwent an internal review process at Google, including separate reviews of accessibility, product engineering, privacy, security, legal, and protection regulation compliance. RESULTS: Participants were recruited in September 2017. Data collection via the watches was completed in January 2018. Collection of qualitative data through patient interviews is still ongoing. Data analysis will commence when all data are collected; results are expected in 2019. CONCLUSIONS: KOALAP is the first health study to use consumer cellular smartwatches to collect self-reported symptoms alongside sensor data for musculoskeletal disorders. The results of this study will be used to inform the design of future mobile health studies. Results for feasibility and participant motivations will inform future researchers whether or under which conditions cellular smartwatches are a useful tool to collect patient-reported outcomes alongside passively measured patient behavior. The exploration of associations between self-reported symptoms at different moments will contribute to our understanding of whether it may be valuable to collect symptom data more frequently. Sensor data-quality measurements will indicate whether cellular smartwatch usage is feasible for obtaining sensor data. Methods for data-quality assessment and data-processing methods may be reusable, although generalizability to other clinical areas should be further investigated. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/10238
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