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DNA Methylation Analysis Validates Organoids as a Viable Model for Studying Human Intestinal Aging.
Background & aimsThe epithelia of the intestine and colon turn over rapidly and are maintained by adult stem cells at the base of crypts. Although the small intestine and colon have distinct, well-characterized physiological functions, it remains unclear if there are fundamental regional differences in stem cell behavior or region-dependent degenerative changes during aging. Mesenchyme-free organoids provide useful tools for investigating intestinal stem cell biology in vitro and have started to be used for investigating age-related changes in stem cell function. However, it is unknown whether organoids maintain hallmarks of age in the absence of an aging niche. We tested whether stem cell-enriched organoids preserved the DNA methylation-based aging profiles associated with the tissues and crypts from which they were derived.MethodsTo address this, we used standard human methylation arrays and the human epigenetic clock as a biomarker of age to analyze in vitro-derived, 3-dimensional, stem cell-enriched intestinal organoids.ResultsWe found that human stem cell-enriched organoids maintained segmental differences in methylation patterns and that age, as measured by the epigenetic clock, also was maintained in vitro. Surprisingly, we found that stem cell-enriched organoids derived from the small intestine showed striking epigenetic age reduction relative to organoids derived from colon.ConclusionsOur data validate the use of organoids as a model for studying human intestinal aging and introduce methods that can be used when modeling aging or age-onset diseases in vitro
Ningaloo coast region visitor statistics: collected for the Ningaloo destination modelling project
This Ningaloo Destination Modelling Project report provides the latest information about the characteristics and behaviours of visitors for the tourism industry, managers, and other research projects based in the Ningaloo Coastal Region. This region is defined as the coastal areas between Exmouth town site and Carnarvon town site in the Gascoyne region in the northwest of Western Australia. The Ningaloo Destination Modelling (NDM) project is a collaborative project between researchers from seven Australian universities and the Sustainable Tourism Cooperative Research Centre that will deliver a scenario planning tool that assesses the social, environmental and economic impact of tourism planning strategies in order to assist tourism planning in a region that relies on its unique natural attractions. The project is part of the Ningaloo Collaboration Cluster of projects and sits within the CSIRO Wealth from Oceans Flagship. The Ningaloo Destination Modelling project is cofounded by the STCRC and the CSIRO.
The scenario planning tool is a numerical model of tourism, run through the computer modelling program Vensim, that relies on statistics that were gathered both through collaboration with other projects and collected by researchers affiliated with the project. This includes statistics from 1574 visitor surveys distributed between July 2007 and September 2008. While the visitor surveys were primarily collected for the purpose of providing reliable statistics for the model, they are also the most comprehensive resource available on visitorsā characteristics and behaviour in the region. This technical report provides access to these statistics.
Statistics are provided for the region as a whole and also divided into six subregions. The report includes an introductory chapter outlining the broader research program, the methodology employed to collect the statistics and background information on tourism to the region. The final two chapters provide information on three broad visitor types identified through factor analysis, and an estimation of tourism expenditure in the region. Based on the surveys, we estimate that expenditure in the region for the year ending September 2008 was 79.46. This is consistent with Carlson and Woodās (2004) earlier study in the region that estimated annual expenditure to be $127 million
TK: The Twitter Top-K Keywords Benchmark
Information retrieval from textual data focuses on the construction of
vocabularies that contain weighted term tuples. Such vocabularies can then be
exploited by various text analysis algorithms to extract new knowledge, e.g.,
top-k keywords, top-k documents, etc. Top-k keywords are casually used for
various purposes, are often computed on-the-fly, and thus must be efficiently
computed. To compare competing weighting schemes and database implementations,
benchmarking is customary. To the best of our knowledge, no benchmark currently
addresses these problems. Hence, in this paper, we present a top-k keywords
benchmark, TK, which features a real tweet dataset and queries with
various complexities and selectivities. TK helps evaluate weighting
schemes and database implementations in terms of computing performance. To
illustrate TK's relevance and genericity, we successfully performed
tests on the TF-IDF and Okapi BM25 weighting schemes, on one hand, and on
different relational (Oracle, PostgreSQL) and document-oriented (MongoDB)
database implementations, on the other hand
Optimisation of Grease Application to Railway Track
Trackside lubricators are designed to deliver grease to passing wheel flanges to reduce wheel and rail wear on curves. Ensuring that they are set up to deliver sufficient grease for the range of vehicles passing a site can be a challenge. For example, vehicle dynamics modelling and site investigations have shown that the wheels of passenger vehicles do not run as close to the rail face as those of freight vehicles, meaning that they are less likely to contact the grease and lubricate subsequent curves. To investigate the effects of different trackside devices, and the influence of parameters governing grease pickup, including lateral wheel displacement and pump durations, a bespoke test rig was built at the University of Sheffield. The rig used a scaled wheel, a short section of rail and a modern trackside lubricator set-up. Experiments involving different lateral wheel displacements and pumping durations were carried out, in addition to the visualisation of the size of the grease bulb. This showed how a grease bulb grows. It also indicated that a worn profile is likely to require greater wheel displacement to make contact with grease bulbs when compared to a new wheel profile. The experimental results showed that increasing pickup of grease can be expected when an additional component called a GreaseGuideā¢ was fitted to a regular grease delivery unit (GDU) on the rail. The efficiency of grease pickup was investigated, and test results exploring increasing pump durations have indicated a relationship between pickup and bulb size. To validate the use of the scaled rig, similar tests were carried out using a full-scale test rig. The full-scale results were compared to the experimental results of the scaled wheel rig. This showed that whilst there were differences between the two test rigs in absolute values and anomalous results, overall trends were the same on both test scales. The effect of temperature on bulb size and pumpability of grease was also investigated. This work can be extended further by using the same method to investigate other parameters that affect the lubrication of curves. This can lead to optimised lubricator set-up to ensure that the track is fully lubricated all the time
Precision cosmography with stacked voids
We present a purely geometrical method for probing the expansion history of
the Universe from the observation of the shape of stacked voids in
spectroscopic redshift surveys. Our method is an Alcock-Paczynski (AP) test
based on the average sphericity of voids posited on the local isotropy of the
Universe. It works by comparing the temporal extent of cosmic voids along the
line of sight with their angular, spatial extent. We describe the algorithm
that we use to detect and stack voids in redshift shells on the light cone and
test it on mock light cones produced from N-body simulations. We establish a
robust statistical model for estimating the average stretching of voids in
redshift space and quantify the contamination by peculiar velocities. Finally,
assuming that the void statistics that we derive from N-body simulations is
preserved when considering galaxy surveys, we assess the capability of this
approach to constrain dark energy parameters. We report this assessment in
terms of the figure of merit (FoM) of the dark energy task force and in
particular of the proposed EUCLID mission which is particularly suited for this
technique since it is a spectroscopic survey. The FoM due to stacked voids from
the EUCLID wide survey may double that of all other dark energy probes derived
from EUCLID data alone (combined with Planck priors). In particular, voids seem
to outperform Baryon Acoustic Oscillations by an order of magnitude. This
result is consistent with simple estimates based on mode-counting. The AP test
based on stacked voids may be a significant addition to the portfolio of major
dark energy probes and its potentialities must be studied in detail.Comment: 16 pages, 12 figures, 2 tables; accepted by ApJ; this version
reflects the accepted version, conclusions unchange
GsĪ± signalling suppresses PPARĪ³2 generation and inhibits 3T3L1 adipogenesis
Since TSH receptor (TSHR) expression increases during adipogenesis and signals via cAMP/phospho-cAMP-response element binding protein (CREB), reported to be necessary and sufficient for adipogenesis, we hypothesised that TSHR activation would induce preadipocyte differentiation. Retroviral vectors introduced constitutively active TSHR (TSHR*) into 3T3L1 preadipocytes; despite increased cAMP (RIA) and phospho-CREB (western blot) there was no spontaneous adipogenesis (assessed morphologically, using oil red O and QPCR measurement of adipogenesis markers). We speculated that GĪ²Ī³ signalling may be inhibitory but failed to induce adipogenesis using activated GsĪ± (gsp*). Inhibition of phosphodiesterases did not promote adipogenesis in TSHR* or gsp* populations. Furthermore, differentiation induced by adipogenic medium with pioglitazone was reduced in TSHR* and abolished in gsp* expressing 3T3L1 cells. TSHR* and gsp* did not inactivate PPARĪ³ (PPARG as listed in the HUGO database) by phosphorylation but expression of PPARĪ³1 was reduced and PPARĪ³2 undetectable in gsp*. FOXO1 phosphorylation (required to inactivate this repressor of adipogenesis) was lowest in gsp* despite the activation of AKT by phosphorylation. PROF is a mediator that facilitates FOXO1 phosphorylation by phospho-Akt. Its transcript levels remained constantly low in the gsp* population. In most measurements, the TSHR* cells were between the gsp* and control 3T3L1 preadipocytes. The enhanced down-regulation of PREF1 (adipogenesis inhibitor) permits retention of some adipogenic potential in the TSHR* population. We conclude that GsĪ± signalling impedes FOXO1 phosphorylation and thus inhibits PPARĪ³ transcription and the alternative promoter usage required to generate PPARĪ³2, the fat-specific transcription factor necessary for adipogenesis
Climatic and tectonic drivers shaped the tropical distribution of coral reefs
Today, warm-water coral reefs are limited to tropical-to-subtropical latitudes. These diverse ecosystems extended further poleward in the geological past, but the mechanisms driving these past distributions remain uncertain. Here, we test the role of climate and palaeogeography in shaping the distribution of coral reefs over geological timescales. To do so, we combine habitat suitability modelling, Earth System modelling and the ~247-million-year geological record of scleractinian coral reefs. A broader latitudinal distribution of climatically suitable habitat persisted throughout much of the Mesozoicāearly Paleogene due to an expanded tropical belt and more equable distribution of shallow marine substrate. The earliest Cretaceous might be an exception, with reduced shallow marine substrate during a ācold-snapā interval. Climatically suitable habitat area became increasingly skewed towards the tropics from the late Paleogene, likely steepening the latitudinal biodiversity gradient of reef-associated taxa. This was driven by global cooling and increases in tropical shallow marine substrate resulting from the tectonic evolution of the Indo-Australian Archipelago. Although our results suggest global warming might permit long-term poleward range expansions, coral reef ecosystems are unlikely to keep pace with the rapid rate of anthropogenic climate change
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