A CFD study of two-phase frozen flow of air/water through a safety relief valve

The air-water two phase critical flows through a safety relief valve commonly used in the refrigeration industry is examined with particular emphasis on the prediction of the critical mass flowrates using CFD based approaches. The expansion of the gas through the valve and the associated acceleration is coupled to the liquid phase and results in changes to the velocity slip with the possibility of influencing the choking conditions and the magnitude of the critical mass flows. These conditions are poorly reported in the literature for safety valves. This paper presents a study where the ability of established two phase multi-dimensional modelling approaches to predict such conditions are investigated. Comparison with the simplified mixture model will show that this model tends to underestimate mass flowrates for medium to high liquid mass fraction. However, the two fluid model can adequately account for the thermal and mechanical non equilibrium for these complex flow conditions with the use of simplified droplet sizing rules

CFD study of Jet Impingement Test erosion using Ansys Fluent® and OpenFOAM®

The initial aim of this study was to compare OpenFoam and Ansys Fluent in order to verify OpenFoam’s Lagrangian Library and erosion capabilities. However, it was found that previous versions of Fluent have been providing wrong results for the discrete phase and the differences with the latest version (Ansys Fluent 15) are shown. A Submerged Jet Impingement Test is an effective method for studying erosion created by solid particles entrained in a liquid. When considering low particle concentrations a Lagrangian modeling of the particulate phase is a reasonable approach. Proper linkage between OpenFOAM’s Lagrangian library and the solver pimpleFoam for incompressible transient flows allows two-phase simulations to be undertaken for comparison with Ansys Fluent with the aim of verifying OpenFoam’s accuracy. Steady state convergence for the fluid flow is first accomplished and the results are compared, confirming a good agreement between the two packages. A transient simulation was then set up and spherical particles incorporated into the fluid flow. An assessment of the two codes’ discrete phase models was carried out, focusing on the differences between impact angles and velocities yielded at the impingement plate’s surface employing a similar strategy to that outlined first by Hattori et al. (2008) and later by Gnanavelu et al. (2009, 2011). In the comparison of OpenFoam with the latest version of Fluent, the main differences between the injection models are highlighted and the coupling possibilities between phases are taken into consideration. Agreement between trends for both impact angles and velocities is satisfactory when the last version of the commercial package is considered and the average discrepancy between numerical values is very low, verifying OpenFoam’s Lagrangian library. Two different Jet Impingement Test configurations are also compared and the differences highlighted

The Latent Class Structure of ADHD is stable across informants

Previous studies have looked at the structure of attention-deficit/ hyperactivity disorder (ADHD) using latent class analysis (LCA) of Child Behavior Checklist (CBCL) or Diagnostic and Statistical Manual of Mental Disorders (DSM) symptom structure. These studies have identified distinct classes of children with inattentive, hyperactive, or combined subtypes and have used these classes to refine genetic analyses. The objective of the current report is to determine if the latent class structure of ADHD subtypes is consistent across informant using the Conners' Rating Scales (CRS). LCA was applied to CRS forms from mother, father, and teacher reports of 1837, 1329 and 1048 latency aged Dutch twins, respectively. The optimal solution for boys was a 5-class solution for mothers, a 3-class solution for fathers, and a 4-class solution for teachers. For girls, a 4-class solution for mothers and a 3-class for fathers and teachers was optimal. Children placed into a class by one informant had markedly increased odds ratio of being placed into the same or similar class by the other informants. Results from LCA using Dutch twins with the CRS show stability across informants suggesting that more stable phenotypes may be accessible for genotyping using a multi-informant approach

Discovery and characterization of a specific inhibitor of serine-threonine kinase cyclin dependent kinase-like 5 (CDKL5) demonstrates role in hippocampal CA1 physiology

Pathological loss-of-function mutations in cyclin-dependent kinase-like 5 (CDKL5) cause CDKL5 deficiency disorder (CDD), a rare and severe neurodevelopmental disorder associated with severe and medically refractory early-life epilepsy, motor, cognitive, visual, and autonomic disturbances in the absence of any structural brain pathology. Analysis of genetic variants in CDD has indicated that CDKL5 kinase function is central to disease pathology. CDKL5 encodes a serine-threonine kinase with significant homology to GSK3β, which has also been linked to synaptic function. Further, Cdkl5 knock-out rodents have increased GSK3β activity and often increased long-term potentiation (LTP). Thus, development of a specific CDKL5 inhibitor must be careful to exclude cross-talk with GSK3β activity. We synthesized and characterized specific, high-affinity inhibitors of CDKL5 that do not have detectable activity for GSK3β. These compounds are very soluble in water but blood–brain barrier penetration is low. In rat hippocampal brain slices, acute inhibition of CDKL5 selectively reduces postsynaptic function of AMPA-type glutamate receptors in a dose-dependent manner. Acute inhibition of CDKL5 reduces hippocampal LTP. These studies provide new tools and insights into the role of CDKL5 as a newly appreciated key kinase necessary for synaptic plasticity. Comparisons to rodent knock-out studies suggest that compensatory changes have limited the understanding of the roles of CDKL5 in synaptic physiology, plasticity, and human neuropathology

Agreement between two large pan-cancer CRISPR-Cas9 gene dependency data sets.

Genome-scale CRISPR-Cas9 viability screens performed in cancer cell lines provide a systematic approach to identify cancer dependencies and new therapeutic targets. As multiple large-scale screens become available, a formal assessment of the reproducibility of these experiments becomes necessary. We analyze data from recently published pan-cancer CRISPR-Cas9 screens performed at the Broad and Sanger Institutes. Despite significant differences in experimental protocols and reagents, we find that the screen results are highly concordant across multiple metrics with both common and specific dependencies jointly identified across the two studies. Furthermore, robust biomarkers of gene dependency found in one data set are recovered in the other. Through further analysis and replication experiments at each institute, we show that batch effects are driven principally by two key experimental parameters: the reagent library and the assay length. These results indicate that the Broad and Sanger CRISPR-Cas9 viability screens yield robust and reproducible findings

Dysmorphometrics: the modelling of morphological abnormalities

<p>Abstract</p> <p>Background</p> <p>The study of typical morphological variations using quantitative, morphometric descriptors has always interested biologists in general. However, unusual examples of form, such as abnormalities are often encountered in biomedical sciences. Despite the long history of morphometrics, the means to identify and quantify such unusual form differences remains limited.</p> <p>Methods</p> <p>A theoretical concept, called dysmorphometrics, is introduced augmenting current geometric morphometrics with a focus on identifying and modelling form abnormalities. Dysmorphometrics applies the paradigm of detecting form differences as outliers compared to an appropriate norm. To achieve this, the likelihood formulation of landmark superimpositions is extended with outlier processes explicitly introducing a latent variable coding for abnormalities. A tractable solution to this augmented superimposition problem is obtained using Expectation-Maximization. The topography of detected abnormalities is encoded in a dysmorphogram.</p> <p>Results</p> <p>We demonstrate the use of dysmorphometrics to measure abrupt changes in time, asymmetry and discordancy in a set of human faces presenting with facial abnormalities.</p> <p>Conclusion</p> <p>The results clearly illustrate the unique power to reveal unusual form differences given only normative data with clear applications in both biomedical practice & research.</p

CFD study of fluid flow changes with erosion

For the first time, a three dimensional mesh deformation algorithm is used to assess fluid flow changes with erosion. The validation case chosen is the Jet Impingement Test, which was thoroughly analysed in previous works by Hattori et al. (Kenichi Sugiyama and Harada, 2008), Gnanavelu et al. in (Gnanavelu et al., 2009, 2011), Lopez et al. in (Lopez et al., 2015) and Mackenzie et al. in (Mackenzie et al., 2015). Nguyen et al. (2014) showed the formation of a new stagnation area when the wear scar is deep enough by performing a three-dimensional scan of the wear scar after 30 min of jet impingement test. However, in the work developed here, this stagnation area was obtained solely by computational means. The procedure consisted of applying an erosion model in order to obtain a deformed geometry, which, due to the changes in the flow pattern lead to the formation of a new stagnation area. The results as well as the wear scar were compared to the results by Nguyen et al. (2014) showing the same trend. OpenFOAM⃝R was the software chosen for the implementation of the deforming mesh algorithm as well as remeshing of the computational domain after deformation. Different techniques for mesh deformation and approaches to erosion modelling are discussed and a new methodology for erosion calculation including mesh deformation is developed. This new approach is independent of the erosion modelling approach, being applicable to both Eulerian and Lagrangian based equations for erosion calculation. Its different applications such as performance decay in machinery subjected to erosion as well as modelling of natural erosion processes are discussed here

Unsupervised assessment of microarray data quality using a Gaussian mixture model

<p>Abstract</p> <p>Background</p> <p>Quality assessment of microarray data is an important and often challenging aspect of gene expression analysis. This task frequently involves the examination of a variety of summary statistics and diagnostic plots. The interpretation of these diagnostics is often subjective, and generally requires careful expert scrutiny.</p> <p>Results</p> <p>We show how an unsupervised classification technique based on the Expectation-Maximization (EM) algorithm and the naïve Bayes model can be used to automate microarray quality assessment. The method is flexible and can be easily adapted to accommodate alternate quality statistics and platforms. We evaluate our approach using Affymetrix 3' gene expression and exon arrays and compare the performance of this method to a similar supervised approach.</p> <p>Conclusion</p> <p>This research illustrates the efficacy of an unsupervised classification approach for the purpose of automated microarray data quality assessment. Since our approach requires only unannotated training data, it is easy to customize and to keep up-to-date as technology evolves. In contrast to other "black box" classification systems, this method also allows for intuitive explanations.</p

BAF complex maintains glioma stem cells in pediatric H3K27M glioma

Diffuse midline gliomas are uniformly fatal pediatric central nervous system cancers that are refractory to standard-of-care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape. To interrogate for epigenetic dependencies, we performed a CRISPR screen and show that patient-derived H3K27M-glioma neurospheres are dependent on core components of the mammalian BAF (SWI/SNF) chromatin remodeling complex. The BAF complex maintains glioma stem cells in a cycling, oligodendrocyte precursor cell–like state, in which genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacologic suppression, opposes proliferation, promotes progression of differentiation along the astrocytic lineage, and improves overall survival of patient-derived xenograft models. In summary, we demonstrate that therapeutic inhibition of the BAF complex has translational potential for children with H3K27M gliomas. Significance: Epigenetic dysregulation is at the core of H3K27M-glioma tumorigenesis. Here, we identify the BRG1–BAF complex as a critical regulator of enhancer and transcription factor landscapes, which maintain H3K27M glioma in their progenitor state, precluding glial differentiation, and establish pharmacologic targeting of the BAF complex as a novel treatment strategy for pediatric H3K27M glioma