Given genomic variation data from multiple individuals, computing the likelihood of complex population genetic models is often infeasible. To circumvent this problem, we introduce a novel ...likelihood-free inference framework by applying deep learning, a powerful modern technique in machine learning. Deep learning makes use of multilayer neural networks to learn a feature-based function from the input (e.g., hundreds of correlated summary statistics of data) to the output (e.g., population genetic parameters of interest). We demonstrate that deep learning can be effectively employed for population genetic inference and learning informative features of data. As a concrete application, we focus on the challenging problem of jointly inferring natural selection and demography (in the form of a population size change history). Our method is able to separate the global nature of demography from the local nature of selection, without sequential steps for these two factors. Studying demography and selection jointly is motivated by Drosophila, where pervasive selection confounds demographic analysis. We apply our method to 197 African Drosophila melanogaster genomes from Zambia to infer both their overall demography, and regions of their genome under selection. We find many regions of the genome that have experienced hard sweeps, and fewer under selection on standing variation (soft sweep) or balancing selection. Interestingly, we find that soft sweeps and balancing selection occur more frequently closer to the centromere of each chromosome. In addition, our demographic inference suggests that previously estimated bottlenecks for African Drosophila melanogaster are too extreme.
Mesoporous SBA-15 materials were functionalized with amine groups through postsynthesis and one-pot synthesis, and the resulting functionalized materials were investigated as matrixes for controlled ...drug delivery. The materials were characterized by FTIR, N(2) adsorption/desorption analysis, zeta potential measurement, XRD, XPS, and TEM. Ibuprofen (IBU) and bovine serum albumin (BSA) were selected as model drugs and loaded onto the unmodified and functionalized SBA-15. It was revealed that the adsorption capacities and release behaviors of these model drugs were highly dependent on the different surface properties of SBA-15 materials. The release rate of IBU from SBA-15 functionalized by postsynthesis is found to be effectively controlled as compared to that from pure SBA-15 and SBA-15 functionalized by one-pot synthesis due to the ionic interaction between carboxyl groups in IBU and amine groups on the surface of SBA-15. However, SBA-15 functionalized by one-pot synthesis is found to be more favorable for the adsorption and release of BSA due to the balance of electrostatic interaction and hydrophilic interaction between BSA and the functionalized SBA-15 matrix.
It has recently been demonstrated that inference methods based on genealogical processes with recombination can uncover past population history in unprecedented detail. However, these methods scale ...poorly with sample size, limiting resolution in the recent past, and they require phased genomes, which contain switch errors that can catastrophically distort the inferred history. Here we present SMC++, a new statistical tool capable of analyzing orders of magnitude more samples than existing methods while requiring only unphased genomes (its results are independent of phasing). SMC++ can jointly infer population size histories and split times in diverged populations, and it employs a novel spline regularization scheme that greatly reduces estimation error. We apply SMC++ to analyze sequence data from over a thousand human genomes in Africa and Eurasia, hundreds of genomes from a Drosophila melanogaster population in Africa, and tens of genomes from zebra finch and long-tailed finch populations in Australia.
Previous studies have shown that translation elongation is regulated by multiple factors, but the observed heterogeneity remains only partially explained. To dissect quantitatively the different ...determinants of elongation speed, we use probabilistic modeling to estimate initiation and local elongation rates from ribosome profiling data. This model-based approach allows us to quantify the extent of interference between ribosomes on the same transcript. We show that neither interference nor the distribution of slow codons is sufficient to explain the observed heterogeneity. Instead, we find that electrostatic interactions between the ribosomal exit tunnel and specific parts of the nascent polypeptide govern the elongation rate variation as the polypeptide makes its initial pass through the tunnel. Once the N-terminus has escaped the tunnel, the hydropathy of the nascent polypeptide within the ribosome plays a major role in modulating the speed. We show that our results are consistent with the biophysical properties of the tunnel.
The hot ductility of a 1Cr–0.5Mo low alloy steel is investigated over a temperature range of 700–1050°C using a Gleeble thermomechanical simulator in conjunction with various characterization ...techniques. The steel samples undoped and doped with cerium are heated at 1300°C for 3min and then cooled with a rate of 5Ks−1 down to different test temperatures, followed by tensile deformation until fracture. The results show that the hot ductility of the steel, evaluated by the reduction in area, can be substantially enhanced by a minor addition of cerium, especially in the range 800–1000°C. In the austenite–ferrite dual-phase region, cerium may delay the formation of proeutectoid ferrite layers along austenite grain boundaries, thereby increasing the hot ductility of the steel. In the single austenite region, grain boundary segregation of cerium may increase the grain boundary cohesion, toughening the steel and thus raising the resistance to grain boundary sliding as well as promoting dynamic recrystallization. Consequently, the hot ductility of the steel is enhanced.
Meaningful analysis of next-generation sequencing (NGS) data, which are produced extensively by genetics and genomics studies, relies crucially on the accurate calling of SNPs and genotypes. Recently ...developed statistical methods both improve and quantify the considerable uncertainty associated with genotype calling, and will especially benefit the growing number of studies using low- to medium-coverage data. We review these methods and provide a guide for their use in NGS studies.
Probiotics administration in aquafeed is known to increase feed consumption and absorption due to their capacity to release a wide range of digestive enzymes and nutrients which can participate in ...digestion process and feed utilization, along with the absorption of diet components led to an increase in host’s health and well‐being. Furthermore, probiotics improve gut maturation, prevention of intestinal disorders, predigestion of antinutrient factors found in the feed ingredients, gut microbiota, disease resistance against pathogens and metabolism. The beneficial immune effects of probiotics are well established in finfish. However, in comparison, similar studies are less abundant in the shellfish. In this review, the discussions will mainly focus on studies reported the last 2 years. In recent studies, native probiotic bacteria were isolated and fed back to their hosts. Although beneficial effects were demonstrated, some studies showed adverse effects when treated with a high concentration. This adverse effect may be due to the imbalance of the gut microbiota caused by the replenished commensal probiotics. Probiotics revealed greatest effect on the shrimp digestive system particularly in the larval and early post‐larval stages, and stimulate the production of endogenous enzymes in shrimp and contribute with improved the enzyme activities in the gut, as well as disease resistance.
Neuromyelitis optica (NMO) is associated with destructive inflammatory lesions, resulting in necrosis and axonal injury. Disability from multiple sclerosis (MS) is due to a combination of ...demyelination and varying axonal involvement. Optical coherence tomography (OCT), by measuring retinal nerve fiber layer (RNFL) as a surrogate of axonal injury, has potential to discriminate between these two conditions.
Included were 22 subjects with NMO or NMO spectrum disorders and 47 with MS. Seventeen subjects with NMO and all with MS had a remote history of optic neuritis (ON) in at least one eye, at least 6 months before OCT. Linear mixed modeling was used to compare the two diagnoses for a given level of vision loss, while controlling for age, disease duration, and number of episodes of ON.
After ON, NMO was associated with a thinner mean RNFL compared to MS. This was found when controlling for visual acuity (56.7 vs 66.6 microm, p = 0.01) or for contrast sensitivity (61.2 vs 70.3 microm, p = 0.02). The superior and inferior quadrants were more severely affected in NMO than MS.
Optic neuritis (ON) within neuromyelitis optica (NMO) is associated with a thinner overall average retinal nerve fiber layer compared to multiple sclerosis, with particular involvement of the superior and inferior quadrants. This suggests that NMO is associated with more widespread axonal injury in the affected optic nerves. Optical coherence tomography can help distinguish the etiology of these two causes of ON, and may be useful as a surrogate marker of axonal involvement in demyelinating disease.
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