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

Ten Years of the Real World Design Challenge

Preparing students to be successful in STEM careers is important to foster continued growth in the US and the world. The Real World Design Challenge is a high school design competition focused on the area of aviation. Students work in teams to solve a real world problem using professional tools. The 2018 challenge marks the tenth anniversary of this program. The first students to compete in this competition are now in the work force. This paper describes the background of RWDC, the different challenges that have been used throughout its ten years, the current precision agriculture challenges using UAS, and the judging system used in the competition. Finally, the impact of the program on the students is discussed

Fast and Accurate Computation of Orbital Collision Probability for Short-Term Encounters

International audienceThis article provides a new method for computing the probability of collision between two spherical space objects involved in a short-term encounter under Gaussian-distributed uncertainty. In this model of conjunction, classical assumptions reduce the probability of collision to the integral of a two-dimensional Gaussian probability density function over a disk. The computational method presented here is based on an analytic expression for the integral, derived by use of Laplace transform and D-finite functions properties. The formula has the form of a product between an exponential term and a convergent power series with positive coefficients. Analytic bounds on the truncation error are also derived and are used to obtain a very accurate algorithm. Another contribution is the derivation of analytic bounds on the probability of collision itself, allowing for a very fast and - in most cases - very precise evaluation of the risk. The only other analytical method of the literature - based on an approximation - is shown to be a special case of the new formula. A numerical study illustrates the efficiency of the proposed algorithms on a broad variety of examples and favorably compares the approach to the other methods of the literature

Electronic States in Diffused Quantum Wells

In the present study we calculate the energy values and the spatial distributions of the bound electronic states in some diffused quantum wells. The calculations are performed within the virtual crystal approximation, $sp^3 s^*$ spin dependent empirical tight-binding model and the surface Green function matching method. A good agreement is found between our results and experimental data obtained for AlGaAs/GaAs quantum wells with thermally induced changes in the profile at the interfaces. Our calculations show that for diffusion lengths $L_{D}=20\div100$ {\AA} the transition (C3-HH3) is not sensitive to the diffusion length, but the transitions (C1-HH1), (C1-LH1), (C2-HH2) and (C2-LH2) display large "blue shifts" as L_{D} increases. For diffusion lengths $L_{D}=0\div20$ {\AA} the transitions (C1-HH1) and (C1-LH1) are less sensitive to the L_{D} changes than the (C3-HH3) transition. The observed dependence is explained in terms of the bound states spatial distributions.Comment: ReVTeX file, 7pp., no macros, 4 figures available on the reques

Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy.

Retinal nerve fibre layer (RNFL) thickness is related to the axonal anterior visual pathway and is considered a marker of overall white matter 'integrity'. We hypothesised that RNFL changes would occur in people with epilepsy, independently of vigabatrin exposure, and be related to clinical characteristics of epilepsy

Baseline characteristics and treatment-emergent risk factors associated with cerebrovascular event and death with risperidone in dementia patients

BACKGROUND: Use of antipsychotics to treat behavioural symptoms of dementia has been associated with increased risks of mortality and stroke. Little is known about individual patient characteristics that might be associated with bad or good outcomes. AIMS: We examined the risperidone clinical trial data to look for individual patient characteristics associated with these adverse outcomes. METHOD: Data from all double-blind randomised controlled trials of risperidone in dementia patients (risperidone n = 1009, placebo n = 712) were included. Associations between characteristics and outcome were analysed based on crude incidences and exposure-adjusted incidence rates, and by time-to-event analyses using Cox proportional hazards regression. Interactions between treatment (risperidone or placebo) and characteristic were analysed with a Cox proportional hazards regression model with main effects for treatment and characteristic in addition to the interaction term. RESULTS: Baseline complications of depression (treatment by risk factor interaction on cerebrovascular adverse event (CVAE) hazard ratio (HR): P = 0.025) and delusions (P = 0.043) were associated with a lower relative risk of CVAE in risperidone-treated patients (HR = 1.47 and 0.54, respectively) compared to not having the complication (HR = 5.88 and 4.16). For mortality, the only significant baseline predictor in patients treated with risperidone was depression, which was associated with a lower relative risk (P<0.001). The relative risk of mortality was increased in risperidone patients treated with anti-inflammatory medications (P = 0.021). CONCLUSIONS: Only anti-inflammatory medications increased mortality risk with risperidone. The reduced risks of CVAE in patients with comorbid depression and delusions, and of mortality with depression, may have clinical implications when weighing the benefits and risks of treatment with risperidone in patients with dementia

Winter Survival and Resource Use of Translocated Northern Bobwhite in the Mid-Atlantic United States

Northern bobwhite (Colinus virginianus; hereafter, bobwhite) in the Mid-Atlantic United States have been experiencing precipitous population declines due to a combination of habitat deterioration, urban and suburban sprawl, change in forest management regimes, and farming practices. In recent years, restocking of bobwhite through translocation efforts has gained interest to rebuild local populations. However, empirical studies are warranted to understand the limitations of translocation as it relates to its potential use for long-term population recovery and persistence in this region. Further, few studies nation-wide have evaluated resource use and survival during the non-breeding season on translocated sites. As such, we translocated 360 bobwhites from source populations from southern latitudes during March–April 2015–2017 into 2 different landscape types similar to the source population vegetative communities (agricultural cropland dominated in Maryland, USA versus pine forest dominated in New Jersey, USA) and tested the effects of habitat fragmentation on survival and habitat use during the subsequent non-breeding season. We found habitat fragmentation negatively affecting survival and resource use among translocated bobwhite on fragmented cropland-dominated sites as compared to larger unfragmented forested sites. Survival was lower on cropland sites compared to forested sites such that bobwhite in cropland-dominated landscapes were \u3e125 times less likely to survive the winter than those on forested sites. In our examination of resource use, bobwhite in structurally complex forested sites used cut pine, early-successional woody, early-successional herbaceous, and thinned pine more than what was available on the landscape. On the cropland sites bobwhite used food plots, early-successional woody, and mixed woods more than what was available on the landscape and only food plots at the home range scale. While larger unfragmented forested bobwhite habitat ultimately provided a more successful translocation landscape, birds still had large home ranges and relatively low survival. Therefore, proper pine management may be necessary to optimize habitat availability during the non-breeding season. Our findings provide rare information on demographic resiliency and resource use for translocated bobwhite during the non-breeding season. Further, this research provides valuable information to improve future translocation efforts in the Mid-Atlantic

Porting Decision Tree Algorithms to Multicore using FastFlow

The whole computer hardware industry embraced multicores. For these machines, the extreme optimisation of sequential algorithms is no longer sufficient to squeeze the real machine power, which can be only exploited via thread-level parallelism. Decision tree algorithms exhibit natural concurrency that makes them suitable to be parallelised. This paper presents an approach for easy-yet-efficient porting of an implementation of the C4.5 algorithm on multicores. The parallel porting requires minimal changes to the original sequential code, and it is able to exploit up to 7X speedup on an Intel dual-quad core machine.Comment: 18 pages + cove

Going with the µFlow: Reinterpreting Energy Input in Organic Synthesis

The popularity of microflow chemistry has skyrocketed in the last 20 years, more and more chemists are switching from macro-batch reactors to miniaturized flow devices. As a result, microfluidics is paving its way into the future by consolidating its position in organic chemistry not only as a trend but as a new, effective, and sustainable way of conducting chemistry, that clearly will continue to grow and evolve. This perspective highlights the most relevant examples of innovative enhancing technologies applied to microflow reactors aimed to improve and intensify chemical processes. The extensive applicability of microflow chemistry is further illustrated by briefly discussing examples of complex integrated microsystems and scale-up technologies, demonstrating ultimately that microflow chemistry has the potential to become the ideal technology for the future