955 resultados para Genomic Instability


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The effect of surface tension on global stability of co-flow jets and wakes at a moderate Reynolds number is studied. The linear temporal two-dimensional global modes are computed without approximations. All but one of the flow cases under study are globally stable without surface tension. It is found that surface tension can cause the flow to be globally unstable if the inlet shear (or equivalently, the inlet velocity ratio) is strong enough. For even stronger surface tension, the flow is re-stabilized. As long as there is no change of the most unstable mode, increasing surface tension decreases the oscillation frequency. Short waves appear in the high-shear region close to the nozzle, and their wavelength increases with increasing surface tension. The critical shear (the weakest inlet shear at which a global instability is found) gives rise to antisymmetric disturbances for the wakes and symmetric disturbances for the jets. However, at stronger shear, the opposite symmetry can be the most unstable one, in particular for wakes at high surface tension. The results show strong effects of surface tension that should be possible to reproduce experimentally as well as numerically.

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Motivated by applications such as gecko-inspired adhesives and microdevices featuring slender rod-like bodies, there has been an increase in interest in the deformed shapes of elastic rods adhering to rigid surfaces. A central issue in analyses of the rod-based models for these systems is the stability of the predicted equilibrium configurations. Such analyses can be complicated by the presence of intrinsic curvatures induced by fabrication processes. The results in the present paper are used to show how this curvature can lead to shear-induced bifurcations and instabilities. To characterize potential instabilities, a new set of necessary conditions for stability are employed which cater to the possible combinations of buckling and delaminating instabilities. © 2013 Elsevier Ltd. All rights reserved.

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We present a nonparametric Bayesian method for disease subtype discovery in multi-dimensional cancer data. Our method can simultaneously analyse a wide range of data types, allowing for both agreement and disagreement between their underlying clustering structure. It includes feature selection and infers the most likely number of disease subtypes, given the data. We apply the method to 277 glioblastoma samples from The Cancer Genome Atlas, for which there are gene expression, copy number variation, methylation and microRNA data. We identify 8 distinct consensus subtypes and study their prognostic value for death, new tumour events, progression and recurrence. The consensus subtypes are prognostic of tumour recurrence (log-rank p-value of $3.6 \times 10^{-4}$ after correction for multiple hypothesis tests). This is driven principally by the methylation data (log-rank p-value of $2.0 \times 10^{-3}$) but the effect is strengthened by the other 3 data types, demonstrating the value of integrating multiple data types. Of particular note is a subtype of 47 patients characterised by very low levels of methylation. This subtype has very low rates of tumour recurrence and no new events in 10 years of follow up. We also identify a small gene expression subtype of 6 patients that shows particularly poor survival outcomes. Additionally, we note a consensus subtype that showly a highly distinctive data signature and suggest that it is therefore a biologically distinct subtype of glioblastoma. The code is available from https://sites.google.com/site/multipledatafusion/

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Hydrodynamic instabilities in gas turbine fuel injectors help to mix the fuel and air but can sometimes lock into acoustic oscillations and contribute to thermoacoustic instability. This paper describes a linear stability analysis that predicts the frequencies and strengths of hydrodynamic instabilities and identifies the regions of the flow that cause them. It distinguishes between convective instabilities, which grow in time but are convected away by the flow, and absolute instabilities, which grow in time without being convected away. Convectively unstable flows amplify external perturbations, while absolutely unstable flows also oscillate at intrinsic frequencies. As an input, this analysis requires velocity and density fields, either from a steady but unstable solution to the Navier-Stokes equations, or from time-averaged numerical simulations. In the former case, the analysis is a predictive tool. In the latter case, it is a diagnostic tool. This technique is applied to three flows: a swirling wake at Re = 400, a single stream swirling fuel injector at Re - 106, and a lean premixed gas turbine injector with five swirling streams at Re - 106. Its application to the swirling wake demonstrates that this technique can correctly predict the frequency, growth rate and dominant wavemaker region of the flow. It also shows that the zone of absolute instability found from the spatio-temporal analysis is a good approximation to the wavemaker region, which is found by overlapping the direct and adjoint global modes. This approximation is used in the other two flows because it is difficult to calculate their adjoint global modes. Its application to the single stream fuel injector demonstrates that it can identify the regions of the flow that are responsible for generating the hydrodynamic oscillations seen in LES and experimental data. The frequencies predicted by this technique are within a few percent of the measured frequencies. The technique also explains why these oscillations become weaker when a central jet is injected along the centreline. This is because the absolutely unstable region that causes the oscillations becomes convectively unstable. Its application to the lean premixed gas turbine injector reveals that several regions of the flow are hydrodynamically unstable, each with a different frequency and a different strength. For example, it reveals that the central region of confined swirling flow is strongly absolutely unstable and sets up a precessing vortex core, which is likely to aid mixing throughout the injector. It also reveals that the region between the second and third streams is slightly absolutely unstable at a frequency that is likely to coincide with acoustic modes within the combustion chamber. This technique, coupled with knowledge of the acoustic modes in a combustion chamber, is likely to be a useful design tool for the passive control of mixing and combustion instability. Copyright © 2012 by ASME.

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The turbulent drag reduction due to riblets is a function of their size and, for different configurations, collapses well with a length scale l+g=(A+g)1/2, based in the groove cross-section Ag. The initially linear drag reduction breaks down for l+g≈11, which agrees in our DNS with the previously reported appearance of quasi-two-dimensional spanwise rollers immediately above the riblets. They are similar to those found over porous surfaces and plant canopies, and can be traced to a Kelvin-Helmholtz-like instability associated with the relaxation of the impermeability condition for the wall-normal velocity. The extra Reynolds stress associated with them accounts quantitatively for the drag degradation. An inviscid model for the instability confirms its nature, agreeing well with the observed perturbation wavelengths and shapes. The onset of the instability is determined by a length scale L+w that, for conventional riblet geometries, is proportional to l+g. The instability onset, L+w≥4, corresponds to the empirical breakdown point l+g≈11.

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The laser-diode parameters at which the steady-state regime of generation becomes unstable are analyzed within the framework of the mode-locking model. The crucial role of the transverse inhomogeneity of the field, pumping intensity, and spectrum width in developing the instabilities of the steady-state regime of generation is demonstrated. The calculated values of the instability threshold are shown to be consistent with the experimental results. © 2008 Springer Science+Business Media, Inc.

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The self-excited global instability mechanisms existing in flat-plate laminar separation bubbles are studied here, in order to shed light on the causes of unsteadiness and three- dimensionality of unforced, nominally two-dimensional separated flows. The presence of two known linear global mechanisms, namely an oscillator behavior driven by local regions of absolute inflectional instability and a centrifugal instability giving rise to a steady three- dimensionalization of the bubble, is studied in a series of model separation bubbles. Present results indicate that absolute instability, and consequently a global oscillator behavior, does not exist for two-dimensional bubbles with a peak reversed-flow velocity below 12% of the free-stream velocity. However, the three-dimensional instability becomes active for recirculation levels as low as urev ≈ 7%. These findings suggest a route to the three-dimensionality and unsteadiness observed in experiments and simulations substantially different from that usually found in the literature, in which two-dimensional vortex shedding is followed by three-dimensionalization.

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To investigate germline development and germ cell specification, we identified a Dazl homolog (CagDazl) from gynogenetic gibel carp (Carassius auratus gibelio). Its cDNA sequence and BAC clone sequence analyses revealed the genomic organization conservation and conserved synteny of the Dazl family members and their neighborhood genes among vertebrates, especially in fish. Moreover, a polyclonal antibody specific to CagDazl was produced and used to examine its expression and distribution throughout germline development at protein level. Firstly, ovary-specific expression pattern of CagDazl was confirmed in adult tissues by RT-PCR and Western blot. In addition, in situ hybridization and immunofluorescence localization demonstrated its specific expression in germ cells, and both its transcript and protein were localized to germ plasm. Then, co-localization of CagDazl and mitochondrial cloud was found, confirming that CagDazl transcript and its protein are germ plasm component and move via METRO pathway during oogenesis. Furthermore, the CagDazl is abundant and continuous throughout germline development and germ cell specification including primordial germ cell (PGC) formation, oogonium differentiation, oocyte development, and embryogenesis, and the dynamic distribution occurs at different development stages. The data suggest that maternal CagDazl might play an important role in gibel carp PGC formation. Therefore, CagDazl is a useful and specific marker for tracing germ plasm and germ cell development in the gynogenetic gibel carp. In addition, in comparison with previous studies in sexual reproduction species, the continuous and dynamic distribution of CagDazl protein in the germ plasm throughout the life cycle seems to have significant implication in sex evolution of vertebrates. J. Exp. Zool. (Mol. Deu. Euol.) 312B:855-871, 2009. (C) 2009 Wiley-Liss, Inc.

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Toll-like receptor 3 (TLR3) participates in the innate immune response by recognizing viral pathogens. To investigate grass carp immune system responding to GCRV (grass carp reovirus) infection, the full-length cDNA sequence and genomic organization of grass carp TLR3 (CiTLR3) was identified and characterized. The full-length genome sequence of CiTLR3 is composed of 5668 nucleotides, including five exons and four introns. The full-length of CiTLR3 cDNA is 3681 bp in length and encodes a polypeptide of 904 amino acids with an estimated molecular mass of 102,765 Da and a predicted isoelectric point of 8.35. Analysis of the deduced amino acid sequence indicated that CiTLR3 has four main structural domains, including a signal peptide sequence, 14 LRR (leucine-rich repeat) motifs, a transmembrane region and a TIR (Toll/interleukin-1 receptor) domain. It is most similar to the crucian carp (Carassius auratus) TLR3 amino acid sequence with an identity of 99%. Quantitative RT-PCR analysis showed that CiTLR3 transcripts were significantly up-regulated starting at day 1 and continued through day 7 following GCRV infection (P < 0.05). These data implied that CiTLR3 is involved in antiviral defense, provide molecular and functional information for grass carp TLR3, and implicate their role in mediating immune protection against grass carp viral diseases. (C) 2009 Elsevier Ltd. All rights reserved.

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A new amino silica monolithic column was developed for DNA extraction in a miniaturized format. The monolithic column was prepared in situ by polymerization of tetraethoxysilane (TEOS) and N-(beta-aminoethyl)-gamma-aminopropylmethyldimethoxysilane (AEAPMDMS). DNA was loaded in 50 mM tris(hydroxylmethyl)aminomethane-EDTA buffer at pH 7.0 and eluted with 300 mM potassium phosphate solution at pH 10.0. Under optimal condition, a 6.0-cm monolithic column provided a capacity of 56 ng DNA with an extraction efficiency of 71 +/- 5.2% (X +/- RSD). When the amino silica monolithic column was applied to extract genomic DNA from the whole blood of crucian carp, an extraction efficiency of 52 +/- 5.6% (X +/- SD) was obtained by three extractions. Since the chaotropic-based sample loading and organic solvent wash steps were avoided in this procedure, the purified DNA was suitable for downstream processes such as PCR. This amino silica monolithic column was demonstrated to allow rapid and efficient DNA purification in microscale.

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The complete genome of mandarin fish Siniperca chuatsi rhabdovirus (SCRV) was cloned and sequenced. It comprises 11,545 nucleotides and contains five genes encoding the nucleoprotein N, the phosphoprotein P, the matrix protein M, the glycoprotein G, and the RNA-dependent RNA polymerase protein L. At the 3' and 5' termini of SCRV genome, leader and trailer sequences show inverse complementarity. The N, P, M and G proteins share the highest sequence identities (ranging from 14.8 to 41.5%) with the respective proteins of rhabdovirus 903/87, the L protein has the highest identity with those of vesiculoviruses, especially with Chandipura virus (44.7%). Phylogenetic analysis of L proteins showed that SCRV clustered with spring vireamia of carp virus (SVCV) and was most closely related to viruses in the genus Vesiculovirus. In addition, an overlapping open reading frame (ORF) predicted to encode a protein similar to vesicular stomatitis virus C protein is present within the P gene of SCRV. Furthermore, an unoverlapping small ORF downstream of M ORF within M gene is predicted (tentatively called orf4). Therefore, the genomic organization of SCRV can be proposed as 3' leader-N-P/C-M-(orf4)-G-L-trailer 5'. Orf4 transcription or translation products could not be detected by northern or Western blot, respectively, though one similar mRNA band to M mRNA was found. This is the first report on one small unoverlapping ORF in M gene of a fish rhabdovirus. (c) 2007 Elsevier B.V. All rights reserved.