Separated boundary layer transition under pressure gradient in the presence of free-stream turbulence

Large-eddy simulation (LES) has been carried out to investigate the transition process of a separated boundary layer on a flat plate. A streamwise pressure distribution is imposed to mimic the suction surface of a low-pressure turbine blade, and the free-stream turbulence intensity at the plate leading edge is 2.9%. A dynamic subgrid scale model is employed in the study, and the current LES results compare well with available experimental data and previous LES results. The transition process has been thoroughly analyzed, and streamwise streaky structures, known as the Klebanoff streaks, have been observed much further upstream of the separation. However, transition occurs in the separated shear layer and is caused by two mechanisms: streamwise streaks and the inviscid K-H instability. Analysis suggests that streamwise streaks play a dominant role in the transition process as those streaks severely disrupt and break up the K-H rolls once they are formed, leading to significant three-dimensional (3D) motions very rapidly. It is also demonstrated in the present study that the usual secondary instability stage under low free-stream turbulence intensity where coherent two-dimensional (2D) spanwise rolls get distorted gradually and eventually broken up into 3D structures has been bypassed.N/

Stereo-PIV measurements of spatio-temporal turbulence correlations in an axisymmetric jet

Stereoscopic three-component particle image velocimetry (3C-PIV) measurements have been made in a turbulent round jet to investigate the spatio-temporal correlations that are the origin of aerodynamic noise. Restricting attention to subsonic, isothermal jets, measurements were taken in a water flow experiment where, for the same Reynolds number and nozzle size, the shortest time scale of the dynamically important turbulent structures is more than an order of magnitude greater that in equivalent airflow experiments, greatly facilitating time-resolved PIV measurements. Results obtained (for a jet nozzle diameter and velocity of 40 mm and 1 m s\u1000001, giving Re D 4 104) show that, on the basis of both single-point statistics and two-point quantities (correlation functions, integral length scales) the present incompressible flow data are in excellent agreement with published compressible, subsonic airflow measurements. The 3C-PIV data are first compared to higher-spatial-resolution 2C-PIV data and observed to be in good agreement, although some deterioration in quality for higher-order correlations caused by high-frequency noise in the 3C-PIV data is noted. A filter method to correct for this is proposed, based on proper orthogonal decomposition (POD) of the 3C-PIV data. The corrected data are then used to construct correlation maps at the second- and fourth-order level for all velocity components. The present data are in accordance with existing hot-wire measurements, but provide significantly more detailed information on correlation components than has previously been available. The measured relative magnitudes of various components of the two-point fourth-order turbulence correlation coefficient (Rij;kl) – the fundamental building block for free shear flow aerodynamic noise sources – are presented and represent a valuable source of validation data for acoustic source modelling. The relationship between fourth-order and second-order velocity correlations is also examined, based on an assumption of a quasi-Gaussian nearly normal p.d.f. for the velocity fluctuations. The present results indicate that this approximation shows reasonable agreement for the measured relative magnitudes of several correlation components; however, areas of discrepancy are identified, indicating the need for work on alternative models such as the shell turbulence concept of Afsar (Eur. J. Mech. (B/Fluids), vol. 31, 2012, pp. 129–139)

Biallelic MLH1 SNP cDNA expression or constitutional promoter methylation can hide genomic rearrangements causing Lynch syndrome

A positive family history, germline mutations in DNA mismatch repair genes, tumours with high microsatellite instability, and loss of mismatch repair protein expression are the hallmarks of hereditary non-polyposis colorectal cancer (Lynch syndrome). However, in ~10-15% of cases of suspected Lynch syndrome, no disease-causing mechanism can be detected

Evidence for susceptibility genes to familial Wilms tumour in addition to WT1, FWT1 and FWT2

Three loci have been implicated in familial Wilms tumour: WT1 located on chromosome 11p13, FWT1 on 17q12-q21, and FWT2 on 19q13. Two out of 19 Wilms tumour families evaluated showed strong evidence against linkage at all three loci. Both of these families contained at least three cases of Wilms tumour indicating that they were highly likely to be due to genetic susceptibility and therefore that one or more additional familial Wilms tumour susceptibility genes remain to be found. © 2000 Cancer Research Campaig

Computational Study of Aero-acoustic Sources in Perforate Silencers

Reynolds Averaged Navier Stokes and Large Eddy Simulations of two perforate plates at a overall pressure ratio of 1.45 have been performed to allow analysis of the sensitivity of acoustic noise sources to porosity. Two geometries are presented: A 23% porosity and a 40% porosity 1mm plate with 2mm diameter holes. Results presented in this paper show the initial jetlet and fully merged jet flow-field to be sensitive to the porosity and the presence of partial holes around the circumference of the plate. The increase in porosity reduces the available entrainment flow, and increases the local jetlet interaction and resultant turbulence levels. This interaction fundamentally changes the flow structure from coherent vortex rings (found at low porosity) to a helical structure. The 2nd and 4th order spatio- temporal correlation Rij and Rij,kl are presented as suggested validation data for acoustic source modeling together with far-field noise spectra obtained via a Ffowcs-Williams & Hawkings surface integral method

HOX-mediated LMO2 expression in embryonic mesoderm is recapitulated in acute leukaemias

The Lim Domain Only 2 (LMO2) leukaemia oncogene encodes an LIM domain transcriptional cofactor required for early haematopoiesis. During embryogenesis, LMO2 is also expressed in developing tail and limb buds, an expression pattern we now show to be recapitulated in transgenic mice by an enhancer in LMO2 intron 4. Limb bud expression depended on a cluster of HOX binding sites, while posterior tail expression required the HOX sites and two E-boxes. Given the importance of both LMO2 and HOX genes in acute leukaemias, we further demonstrated that the regulatory hierarchy of HOX control of LMO2 is activated in leukaemia mouse models as well as in patient samples. Moreover, Lmo2 knock-down impaired the growth of leukaemic cells, and high LMO2 expression at diagnosis correlated with poor survival in cytogenetically normal AML patients. Taken together, these results establish a regulatory hierarchy of HOX control of LMO2 in normal development, which can be resurrected during leukaemia development. Redeployment of embryonic regulatory hierarchies in an aberrant context is likely to be relevant in human pathologies beyond the specific example of ectopic activation of LMO2

NPM1 Deletion Is Associated with Gross Chromosomal Rearrangements in Leukemia

BACKGROUND: NPM1 gene at chromosome 5q35 is involved in recurrent translocations in leukemia and lymphoma. It also undergoes mutations in 60% of adult acute myeloid leukemia (AML) cases with normal karyotype. The incidence and significance of NPM1 deletion in human leukemia have not been elucidated. METHODOLOGY AND PRINCIPAL FINDINGS: Bone marrow samples from 145 patients with myelodysplastic syndromes (MDS) and AML were included in this study. Cytogenetically 43 cases had isolated 5q-, 84 cases had 5q- plus other changes and 18 cases had complex karyotype without 5q deletion. FISH and direct sequencing investigated the NPM1 gene. NPM1 deletion was an uncommon event in the "5q- syndrome" but occurred in over 40% of cases with high risk MDS/AML with complex karyotypes and 5q loss. It originated from large 5q chromosome deletions. Simultaneous exon 12 mutations were never found. NPM1 gene status was related to the pattern of complex cytogenetic aberrations. NPM1 haploinsufficiency was significantly associated with monosomies (p<0.001) and gross chromosomal rearrangements, i.e., markers, rings, and double minutes (p<0.001), while NPM1 disomy was associated with structural changes (p=0.013). Interestingly, in complex karyotypes with 5q- TP53 deletion and/or mutations are not specifically associated with NPM1 deletion. CONCLUSIONS AND SIGNIFICANCE: NPM1/5q35 deletion is a consistent event in MDS/AML with a 5q-/-5 in complex karyotypes. NPM1 deletion and NPM1 exon 12 mutations appear to be mutually exclusive and are associated with two distinct cytogenetic subsets of MDS and AML

Crystal Structure of EHEC Intimin: Insights into the Complementarity between EPEC and EHEC

Enterohaemorrhagic E. coli (EHEC) O157:H7 is a primary food-borne bacterial pathogen capable of causing life-threatening human infections which poses a serious challenge to public health worldwide. Intimin, the bacterial outer-membrane protein, plays a key role in the initiating process of EHEC infection. This activity is dependent upon translocation of the intimin receptor (Tir), the intimin binding partner of the bacteria-encoded host cell surface protein. Intimin has attracted considerable attention due to its potential function as an antibacterial drug target. Here, we report the crystal structure of the Tir-binding domain of intimin (Int188) from E. coli O157:H7 at 2.8 Å resolution, together with a mutant (IntN916Y) at 2.6 Å. We also built the structural model of EHEC intimin-Tir complex and analyzed the key binding residues. It suggested that the binding pattern of intimin and Tir between EHEC and Enteropathogenic E. coli (EPEC) adopt a similar mode and they can complement with each other. Detailed structural comparison indicates that there are four major points of structural variations between EHEC and EPEC intimins: one in Domain I (Ig-like domain), the other three located in Domain II (C-type lectin-like domain). These variations result in different binding affinities. These findings provide structural insight into the binding pattern of intimin to Tir and the molecular mechanism of EHEC O157: H7