893 research outputs found
CARETS: A prototype regional environmental information system. Volume 2, parts A and B: Norfolk and environs; a land use perspective
The author has identified the following significant results. The Norfolk-Portsmouth metropolitan statistical area in southeastern Virginia was the site of intensive testing of a number of land resources assessment methods. Land use and land cover data at three levels of detail were derived by manual image interpretation from both aircraft and satellite sources and used to characterize the 1,766 sq km (682 sq mi) area from the perspective of its various resource-related activities and problems. Measurements at level 1 from 1:100, 000 scale maps revealed 42 percent of the test area (excluding bays and estuaries) to be forest, 28 percent agriculture, 23 percent urban and built-up, 4 percent nonforested wetlands, and 2 percent water. At the same scale and level of detail, 10 percent of the area underwent change from one land use category to another in the period 1959-70, 62 percent of which involved the relatively irreversible change from forest or agriculture to urban uses
Coupling Transcriptional State to Large-Scale Repeat Expansions in Yeast
SummaryExpansions of simple DNA repeats cause numerous hereditary disorders in humans. Replication, repair, and transcription are implicated in the expansion process, but their relative contributions are yet to be distinguished. To separate the roles of replication and transcription in the expansion of Friedreich’s ataxia (GAA)n repeats, we designed two yeast genetic systems that utilize a galactose-inducible GAL1 promoter but contain these repeats in either the transcribed or nontranscribed region of a selectable cassette. We found that large-scale repeat expansions can occur in the lack of transcription. Induction of transcription strongly elevated the rate of expansions in both systems, indicating that active transcriptional state rather than transcription through the repeat per se affects this process. Furthermore, replication defects increased the rate of repeat expansions irrespective of transcriptional state. We present a model in which transcriptional state, linked to the nucleosomal density of a region, acts as a modulator of large-scale repeat expansions
Shared Control Individuals in Health Policy Evaluations with Application to Medical Cannabis Laws
Health policy researchers often have questions about the effects of a policy
implemented at some cluster-level unit, e.g., states, counties, hospitals, etc.
on individual-level outcomes collected over multiple time periods. Stacked
difference-in-differences is an increasingly popular way to estimate these
effects. This approach involves estimating treatment effects for each
policy-implementing unit, then, if scientifically appropriate, aggregating them
to an average effect estimate. However, when individual-level data are
available and non-implementing units are used as comparators for multiple
policy-implementing units, data from untreated individuals may be used across
multiple analyses, thereby inducing correlation between effect estimates.
Existing methods do not quantify or account for this sharing of controls. Here,
we describe a stacked difference-in-differences study investigating the effects
of state medical cannabis laws on treatment for chronic pain management that
motivated this work, discuss a framework for estimating and managing this
correlation due to shared control individuals, and show how accounting for it
affects the substantive results
Modelling chemistry and biology after implantation of a drug-eluting stent. Part I: Drug transport
Drug-eluting stents have been used widely to prevent restenosis of arteries following percutaneous balloon angioplasty. Mathematical modelling plays an important role in optimising the design of these stents to maximise their efficiency. When designing a drug-eluting stent system, we expect to have a sufficient amount of drug being released into the artery wall for a sufficient period to prevent restenosis. In this paper, a simple model is considered to provide an elementary description of drug release into artery tissue from an implanted stent. From the model, we identified a parameter regime to optimise the system when preparing the polymer coating. The model provides some useful order of magnitude estimates for the key quantities of interest. From the model, we can identify the time scales over which the drug traverses the artery wall and empties from the polymer coating, as well as obtain approximate formulae for the total amount of drug in the artery tissue and the fraction of drug that has released from the polymer. The model was evaluated by comparing to in-vivo experimental data and good agreement was found
Visualising apoptosis in live zebrafish using fluorescence lifetime imaging with optical projection tomography to map FRET biosensor activity in space and time
Fluorescence lifetime imaging (FLIM) combined with optical projection tomography (OPT) has the potential to map Förster resonant energy transfer (FRET) readouts in space and time in intact transparent or near transparent live organisms such as zebrafish larvae, thereby providing a means to visualise cell signalling processes in their physiological context. Here the first application of FLIM OPT to read out biological function in live transgenic zebrafish larvae using a genetically expressed FRET biosensor is reported. Apoptosis, or programmed cell death, is mapped in 3-D by imaging the activity of a FRET biosensor that is cleaved by Caspase 3, which is a key effector of apoptosis. Although apoptosis is a naturally occurring process during development, it can also be triggered in a variety of ways, including through gamma irradiation. FLIM OPT is shown here to enable apoptosis to be monitored over time, in live zebrafish larvae via changes in Caspase 3 activation following gamma irradiation at 24 hours post fertilisation. Significant apoptosis was observed at 3.5 hours post irradiation, predominantly in the head region
Dynamics of Sleep-Wake Transitions During Sleep
We study the dynamics of the awakening during the night for healthy subjects
and find that the wake and the sleep periods exhibit completely different
behavior: the durations of wake periods are characterized by a scale-free
power-law distribution, while the durations of sleep periods have an
exponential distribution with a characteristic time scale. We find that the
characteristic time scale of sleep periods changes throughout the night. In
contrast, there is no measurable variation in the power-law behavior for the
durations of wake periods. We develop a stochastic model which agrees with the
data and suggests that the difference in the dynamics of sleep and wake states
arises from the constraints on the number of microstates in the sleep-wake
system.Comment: Final form with some small corrections. To be published in
Europhysics Letters, vol. 57, issue no. 5, 1 March 2002, pp. 625-63
In-line monitoring of particle size and shape from image-based measurements
Within the pharmaceutical industry, particle size and shape distributions are crucial properties of crystalline particles produced in crystallisation processes. They determine the success or otherwise of processes such as granulation, suspension treatment and drying, all involved in the manufacture of the final pharmaceutical product. Some properties of the final pharmaceutical product such as dissolution behaviour are also influenced by the particle size and shape distribution of its ingredients. Therefore, crystallisation processes need to be controlled in order to produce particles with the desired attributes (size and shape). This in turn requires an accurate characterisation of the particle attributes during the crystallisation processes. Traditionally, particle size and shape are determined by means of off-line measurements. However, these techniques only provide information on the final state of the process and involve intermediate processing steps (e.g. sampling, dissolution, drying) that can alter the properties of the particles before the measurement. In recent years, a range of in-line techniques has been developed to obtain in-situ and real-time information on the state of the process in a non-disruptive manner
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Can explicit convection improve modelled dust in summertime West Africa?
Global and regional models have large systematic errors in their modelled dust fields over West Africa. It is well established that cold-pool outflows from moist convection (haboobs) can raise over 50% of the dust over parts of the Sahara and Sahel in summer, but parameterised moist convection tends to give a very poor representation of this in models. Here, we test the hypothesis that an explicit representation of convection in the Met Office Unified Model (UM) improves haboob winds and so may reduce errors in modelled dust fields. The results show that despite varying both grid spacing and the representation of convection there are only minor changes in dust aerosol optical depth (AOD) and dust mass loading fields between simulations. In all simulations there is an AOD deficit over the observed central Saharan dust maximum and a high bias in AOD along the west coast: both features are consistent with many climate (CMIP5) models. Cold-pool outflows are present in the explicit simulations and do raise dust. Consistent with this, there is an improved diurnal cycle in dust-generating winds with a seasonal peak in evening winds at locations with moist convection that is absent in simulations with parameterised convection. However, the explicit convection does not change the AOD field in the UM significantly for several reasons. Firstly, the increased windiness in the evening from haboobs is approximately balanced by a reduction in morning winds associated with the breakdown of the nocturnal low-level jet (LLJ). Secondly, although explicit convection increases the frequency of the strongest winds, they are still weaker than observed, especially close to the observed summertime Saharan dust maximum: this results from the fact that, although large mesoscale convective systems (and resultant cold pools) are generated, they have a lower frequency than observed and haboob winds are too weak. Finally, major impacts of the haboobs on winds occur over the Sahel, where, although dust uplift is known to occur in reality, uplift in the simulations is limited by a seasonally constant bare-soil fraction in the model, together with soil moisture and clay fractions which are too restrictive of dust emission in seasonally varying vegetated regions. For future studies, the results demonstrate (1) the improvements in behaviour produced by the explicit representation of convection, (2) the value of simultaneously evaluating both dust and winds and (3) the need to develop parameterisations of the land surface alongside those of dust-generating winds
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Crosstalk among Set1 complex subunits involved in H2B ubiquitylation-dependent H3K4 methylation
H2B ubiquitylation (H2Bub)-dependent H3K4 methylation is mediated by the multisubunit Set1 complex (Set1C) in yeast, but precisely how Set1C subunits contribute to this histone modification remains unclear. Here, using reconstituted Set1Cs and recombinant H2Bub chromatin, we identified Set1C subunits and domains involved in the H2Bub-dependent H3K4 methylation process, showing that the Spp1 PHDL domain, in conjunction with the Set1 n-SET domain, interacts with Swd1/Swd3 and that this interaction is essential for H2Bub-dependent H3K4 methylation. Importantly, Set1C containing an Spp1-Swd1 fusion bypasses the requirement for H2Bub for H3K4 methylation, suggesting that the role of H2Bub is to induce allosteric rearrangements of the subunit-interaction network within the active site of Set1C that are necessary for methylation activity. Moreover, the interaction between the Set1 N-terminal region and Swd1 renders the Spp1-lacking Set1C competent for H2Bub-dependent H3K4 methylation. Collectively, our results suggest that H2Bub induces conformational changes in Set1C that support H3K4 methylation activity
In vivo fluorescence lifetime tomography of a FRET probe expressed in mouse
Förster resonance energy transfer (FRET) is a powerful biological tool for reading out cell signaling processes. In vivo use of FRET is challenging because of the scattering properties of bulk tissue. By combining diffuse fluorescence tomography with fluorescence lifetime imaging (FLIM), implemented using wide-field time-gated detection of fluorescence excited by ultrashort laser pulses in a tomographic imaging system and applying inverse scattering algorithms, we can reconstruct the three dimensional spatial localization of fluorescence quantum efficiency and lifetime. We demonstrate in vivo spatial mapping of FRET between genetically expressed fluorescent proteins in live mice read out using FLIM. Following transfection by electroporation, mouse hind leg muscles were imaged in vivo and the emission of free donor (eGFP) in the presence of free acceptor (mCherry) could be clearly distinguished from the fluorescence of the donor when directly linked to the acceptor in a tandem (eGFP-mCherry) FRET construct
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