Reranking candidate gene models with cross-species comparison for improved gene prediction

Background: Most gene finders score candidate gene models with state-based methods, typically HMMs, by combining local properties (coding potential, splice donor and acceptor patterns, etc). Competing models with similar state-based scores may be distinguishable with additional information. In particular, functional and comparative genomics datasets may help to select among competing models of comparable probability by exploiting features likely to be associated with the correct gene models, such as conserved exon/intron structure or protein sequence features. Results: We have investigated the utility of a simple post-processing step for selecting among a set of alternative gene models, using global scoring rules to rerank competing models for more accurate prediction. For each gene locus, we first generate the K best candidate gene models using the gene finder Evigan, and then rerank these models using comparisons with putative orthologous genes from closely-related species. Candidate gene models with lower scores in the original gene finder may be selected if they exhibit strong similarity to probable orthologs in coding sequence, splice site location, or signal peptide occurrence. Experiments on Drosophila melanogaster demonstrate that reranking based on cross-species comparison outperforms the best gene models identified by Evigan alone, and also outperforms the comparative gene finders GeneWise and Augustus+. Conclusion: Reranking gene models with cross-species comparison improves gene prediction accuracy. This straightforward method can be readily adapted to incorporate additional lines of evidence, as it requires only a ranked source of candidate gene models

Cholesterol cholelithiasis in pregnant women: pathogenesis, prevention and treatment

Epidemiological and clinical studies have found that gallstone prevalence is twice as high in women as in men at all ages in every population studied. Hormonal changes occurring during pregnancy put women at higher risk. The incidence rates of biliary sludge (a precursor to gallstones) and gallstones are up to 30 and 12%, respectively, during pregnancy and postpartum, and 1-3% of pregnant women undergo cholecystectomy due to clinical symptoms or complications within the first year postpartum. Increased estrogen levels during pregnancy induce significant metabolic changes in the hepatobiliary system, including the formation of cholesterol-supersaturated bile and sluggish gallbladder motility, two factors enhancing cholelithogenesis. The therapeutic approaches are conservative during pregnancy because of the controversial frequency of biliary disorders. In the majority of pregnant women, biliary sludge and gallstones tend to dissolve spontaneously after parturition. In some situations, however, the conditions persist and require costly therapeutic interventions. When necessary, invasive procedures such as laparoscopic cholecystectomy are relatively well tolerated, preferably during the second trimester of pregnancy or postpartum. Although laparoscopic operation is recommended for its safety, the use of drugs such as ursodeoxycholic acid (UDCA) and the novel lipid-lowering compound, ezetimibe would also be considered. In this paper, we systematically review the incidence and natural history of pregnancy-related biliary sludge and gallstone formation and carefully discuss the molecular mechanisms underlying the lithogenic effect of estrogen on gallstone formation during pregnancy. We also summarize recent progress in the necessary strategies recommended for the prevention and the treatment of gallstones in pregnant women

Demonstration of Machine Learning-Based Model-Independent Stabilization of Source Properties in Synchrotron Light Sources.

Synchrotron light sources, arguably among the most powerful tools of modern scientific discovery, are presently undergoing a major transformation to provide orders of magnitude higher brightness and transverse coherence enabling the most demanding experiments. In these experiments, overall source stability will soon be limited by achievable levels of electron beam size stability, presently on the order of several microns, which is still 1-2 orders of magnitude larger than already demonstrated stability of source position and current. Until now source size stabilization has been achieved through corrections based on a combination of static predetermined physics models and lengthy calibration measurements, periodically repeated to counteract drift in the accelerator and instrumentation. We now demonstrate for the first time how the application of machine learning allows for a physics- and model-independent stabilization of source size relying only on previously existing instrumentation. Such feed-forward correction based on a neural network that can be continuously online retrained achieves source size stability as low as 0.2  μm (0.4%) rms, which results in overall source stability approaching the subpercent noise floor of the most sensitive experiments

A crossover study comparing in-plane and out-of-plane approaches for simulated ultrasound-guided central venous cannulation on phantom models by anaesthesiology trainees

This prospective crossover study compared the incidence of posterior vessel wall puncture between two approaches during ultrasound-guided simulated central venous cannulation by anaesthesiology trainees. Each phantom model, simulating a central vein and artery, was cannulated by 37 anaesthesiology trainees under ultrasound-guidance using the in-plane approach (IPA) and out-of-plane approach (OPA). Total procedural time and the time taken from starting image scanning until commencing puncture, was recorded. The number of attempts required to achieve successful venous cannulation was noted. Finally, the models were examined for posterior venous wall and arterial puncture. Total procedural time was shorter with the OPA (26.5 vs 50.3 seconds, p=0.001). The time taken from starting image scanning until commencing puncture was shorter for the OPA (2.2 vs 12.3 seconds, p<0.0001). The IPA resulted in significantly more attempts for cannulation. Twenty and eleven participants were successful within the first pass using the OPA and IPA, respectively (p=0.034). There was no difference in the incidence of posterior vessel wall puncture between these two techniques. The OPA resulted in less arterial puncture compared to the IPA (2 vs 9, p=0.022). The incidence of posterior vessel wall puncture between the IPA and OPA during ultrasound-guided simulated central venous cannulation by anaesthesiology trainees was comparable

Magnetism and high magnetic-field-induced stability of alloy carbides in Fe-based materials.

Understanding the nature of the magnetic-field-induced precipitation behaviors represents a major step forward towards unravelling the real nature of interesting phenomena in Fe-based alloys and especially towards solving the key materials problem for the development of fusion energy. Experimental results indicate that the applied high magnetic field effectively promotes the precipitation of M23C6 carbides. We build an integrated method, which breaks through the limitations of zero temperature and zero external field, to concentrate on the dependence of the stability induced by the magnetic effect, excluding the thermal effect. We investigate the intimate relationship between the external field and the origins of various magnetics structural characteristics, which are derived from the interactions among the various Wyckoff sites of iron atoms, antiparallel spin of chromium and Fe-C bond distances. The high-magnetic-field-induced exchange coupling increases with the strength of the external field, which then causes an increase in the parallel magnetic moment. The stability of the alloy carbide M23C6 is more dependent on external field effects than thermal effects, whereas that of M2C, M3C and M7C3 is mainly determined by thermal effects

Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies

<p>Abstract</p> <p>Background</p> <p>Human insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone insensitivity syndrome and diabetes mellitus. In the present study, an efficient plant expression system was developed to produce biologically active recombinant hIGF-I (rhIGF-I) in transgenic rice grains.</p> <p>Results</p> <p>The plant-codon-optimized hIGF-I was introduced into rice via <it>Agrobacterium</it>-mediated transformation. To enhance the stability and yield of rhIGF-I, the endoplasmic reticulum-retention signal and glutelin signal peptide were used to deliver rhIGF-I to endoplasmic reticulum for stable accumulation. We found that only glutelin signal peptide could lead to successful expression of hIGF-I and one gram of hIGF-I rice grain possessed the maximum activity level equivalent to 3.2 micro molar of commercial rhIGF-I. <it>In vitro </it>functional analysis showed that the rice-derived rhIGF-I was effective in inducing membrane ruffling and glucose uptake on rat skeletal muscle cells. Oral meal test with rice-containing rhIGF-I acutely reduced blood glucose levels in streptozotocin-induced and Zucker diabetic rats, whereas it had no effect in normal rats.</p> <p>Conclusion</p> <p>Our findings provided an alternative expression system to produce large quantities of biologically active rhIGF-I. The provision of large quantity of recombinant proteins will promote further research on the therapeutic potential of rhIGF-I.</p

Effect of martensitic phase transformation on the behavior of 304 austenitic stainless steel under tension

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Glycine receptor in rat hippocampal and spinal cord neurons as a molecular target for rapid actions of 17-β-estradiol

Glycine receptors (GlyRs) play important roles in regulating hippocampal neural network activity and spinal nociception. Here we show that, in cultured rat hippocampal (HIP) and spinal dorsal horn (SDH) neurons, 17-β-estradiol (E2) rapidly and reversibly reduced the peak amplitude of whole-cell glycine-activated currents (IGly). In outside-out membrane patches from HIP neurons devoid of nuclei, E2 similarly inhibited IGly, suggesting a non-genomic characteristic. Moreover, the E2 effect on IGly persisted in the presence of the calcium chelator BAPTA, the protein kinase inhibitor staurosporine, the classical ER (i.e. ERα and ERβ) antagonist tamoxifen, or the G-protein modulators, favoring a direct action of E2 on GlyRs. In HEK293 cells expressing various combinations of GlyR subunits, E2 only affected the IGly in cells expressing α2, α2β or α3β subunits, suggesting that either α2-containing or α3β-GlyRs mediate the E2 effect observed in neurons. Furthermore, E2 inhibited the GlyR-mediated tonic current in pyramidal neurons of HIP CA1 region, where abundant GlyR α2 subunit is expressed. We suggest that the neuronal GlyR is a novel molecular target of E2 which directly inhibits the function of GlyRs in the HIP and SDH regions. This finding may shed new light on premenstrual dysphoric disorder and the gender differences in pain sensation at the CNS level

Black holes in D=4 higher-derivative gravity

Extensions of Einstein gravity with higher-order derivative terms are natural generalizations of Einstein’s theory of gravity. They may arise in string theory and other effective theories, as well as being of interest in their own right. In this paper we study static black-hole solutions in the example of Einstein gravity with additional quadratic curvature terms in four dimensions. A Lichnerowicz-type theorem simplifies the analysis by establishing that they must have vanishing Ricci scalar curvature. By numerical methods we then demonstrate the existence of further black-hole solutions over and above the Schwarzschild solution. We discuss some of their thermodynamic properties, and show that they obey the first law of thermodynamics

Topological semimetal in a fermionic optical lattice

Optical lattices play a versatile role in advancing our understanding of correlated quantum matter. The recent implementation of orbital degrees of freedom in chequerboard and hexagonal optical lattices opens up a new thrust towards discovering novel quantum states of matter, which have no prior analogs in solid state electronic materials. Here, we demonstrate that an exotic topological semimetal emerges as a parity-protected gapless state in the orbital bands of a two-dimensional fermionic optical lattice. The new quantum state is characterized by a parabolic band-degeneracy point with Berry flux $2\pi$, in sharp contrast to the $\pi$ flux of Dirac points as in graphene. We prove that the appearance of this topological liquid is universal for all lattices with D$_4$ point group symmetry as long as orbitals with opposite parities hybridize strongly with each other and the band degeneracy is protected by odd parity. Turning on inter-particle repulsive interactions, the system undergoes a phase transition to a topological insulator whose experimental signature includes chiral gapless domain-wall modes, reminiscent of quantum Hall edge states.Comment: 6 pages, 3 figures and Supplementary Informatio