3,232 research outputs found

    An Experimental Investigation Into the Performance of a Flush Water-Jet Inlet

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    An experimental investigation of the flow within a generic flush type water-jet inlet has been carried out to identify the principal flow features and provide a basis for development of computational fluid dynamics (CFD) models. Tests were performed in a cavitation tunnel with the model inlet fitted to the test section ceiling, and effects of thickening the ingested tunnel wall boundary layer were investigated. The model was fitted with a range of instrumentation to investigate the ramp pressure distribution and boundary layer development, lip incidence, and pump face flow properties. Observations of lip and duct cavitation inception and behavior were also made. The results showed the inlet performance to be generally improved with the ingestion of a thicker boundary layer. The thickened boundary layer significantly reduced ramp boundary layer separation and distortion of flow at the notional pump face. However, a greater range of lip incidence occurred with the thickened boundary layer with consequent greater likelihood of lip separation and cavitation occurrence. Ideal lip incidence and pump face flow uniformity occurred at flow parameters significantly different from those for ideal pump face pressure recovery. Large developed cavities on the inlet lip were observed for a range of conditions typical of conventional high-speed vessel operation

    Xist and Tsix transcription dynamics is regulated by the X-to-autosome ratio and semistable transcriptional states

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    In female mammals, X chromosome inactivation (XCI) is a key process in the control of gene dosage compensation between Xlinked genes and autosomes. Xist and Tsix, two overlapping antisense-transcribed noncoding genes, are central elements of the X inactivation center (Xic) regulating XCI. Xist upregulation results in the coating of the entire X chromosome by Xist RNA in cis, whereas Tsix transcription acts as a negative regulator of Xist. Here, we generated Xist and Tsix reporter mouse embryonic stem (ES) cell lines to study the genetic and dynamic regulation of these genes upon differentiation. Our results revealed mutually antagonistic roles for Tsix on Xist and vice versa and indicate the presence of semistable transcriptional states of the Xic locus predicting the outcome of XCI. These transcriptional states are instructed by the X-t

    Wnt3a protein reduces growth factor-driven expansion of human hematopoietic stem and progenitor cells in serum-free cultures

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    Abstract Ex vivo expansion of hematopoietic stem and progenitor cells (HSPC) is a promising approach to improve insufficient engraftment after umbilical cord blood stem cell transplantation (UCB-SCT). Although culturing HSPC with hematopoietic cytokines results in robust proliferation, it is accompanied with extensive differentiation and loss of self-renewal capacity. Wnt signaling has been implicated in regulating HSPC fate decisions in vivo and in promoting HSPC self-renewal by inhibition of differentiation, but the effects of Wnt on the ex vivo expansion of HSPC are controversial. Here, we demonstrate that exogenous Wnt3a protein suppresses rather than promotes the expansion of UCB-derived CD34+ cells in serum free expansion cultures. The reduced expansion was also observed in cultures initiated with LinCD34+ CD38lowCD45RACD90+ cells which are highly enriched in HSC and was also observed in response to activation of beta-catenin signaling by GSK3 inhibition. The presence of Wnt3a protein during the culture reduced the frequency of multilineage CFU-GEMM and the long-term repopulation ability of the expanded HSPC. These data suggest that Wnt signaling reduces expansion of human HSPC in growth factor-driven expansion cultures by promoting differentiation of HSPC

    Sparsest factor analysis for clustering variables: a matrix decomposition approach

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    We propose a new procedure for sparse factor analysis (FA) such that each variable loads only one common factor. Thus, the loading matrix has a single nonzero element in each row and zeros elsewhere. Such a loading matrix is the sparsest possible for certain number of variables and common factors. For this reason, the proposed method is named sparsest FA (SSFA). It may also be called FA-based variable clustering, since the variables loading the same common factor can be classified into a cluster. In SSFA, all model parts of FA (common factors, their correlations, loadings, unique factors, and unique variances) are treated as fixed unknown parameter matrices and their least squares function is minimized through specific data matrix decomposition. A useful feature of the algorithm is that the matrix of common factor scores is re-parameterized using QR decomposition in order to efficiently estimate factor correlations. A simulation study shows that the proposed procedure can exactly identify the true sparsest models. Real data examples demonstrate the usefulness of the variable clustering performed by SSFA

    Riding the techwave in an era of change

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    Learn how innovation is finding its way within the healthcare sector and get a grip on the latest technological developments. Based on insights from 77 stakeholders within the Dutch healthcare system, including healthcare professionals, entrepreneurs, researchers, consultants, policy makers, and input from 80 healthcare consumers this book helps you to understand: • the technologies with the highest implementation potential in the healthcare

    Prx1 and Prx2 in skeletogenesis: Roles in the craniofacial region, inner ear and limbs

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    Lipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells

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    Wnt signalling proteins are essential for culture of human organ stem cells in organoids, but most Wnt protein formulations are poorly active in serum-free media. Here we show that purified Wnt3a protein is ineffective because it rapidly loses activity in culture media due to its hydrophobic nature, and its solubilization requires a detergent, CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate), that interferes with stem cell self-renewal. By stabilizing the Wnt3a protein using phospholipids and cholesterol as carriers, we address both problems: Wnt activity remains stable in serum-free media, while non-toxic carriers allow the use of high Wnt concentrations. Stabilized Wnt3a supports strongly increased self-renewal of organ and embryonic stem cells and the serum-free establishment of human organoids from healthy and diseased intestine and liver. Moreover, the lipophilicity of Wnt3a protein greatly facilitates its purification. Our findings remove a major obstacle impeding clinical applications of adult stem cells and offer advantages for all cell culture uses of Wnt3a protein

    Insights from Amphioxus into the Evolution of Vertebrate Cartilage

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    Central to the story of vertebrate evolution is the origin of the vertebrate head, a problem difficult to approach using paleontology and comparative morphology due to a lack of unambiguous intermediate forms. Embryologically, much of the vertebrate head is derived from two ectodermal tissues, the neural crest and cranial placodes. Recent work in protochordates suggests the first chordates possessed migratory neural tube cells with some features of neural crest cells. However, it is unclear how and when these cells acquired the ability to form cellular cartilage, a cell type unique to vertebrates. It has been variously proposed that the neural crest acquired chondrogenic ability by recruiting proto-chondrogenic gene programs deployed in the neural tube, pharynx, and notochord. To test these hypotheses we examined the expression of 11 amphioxus orthologs of genes involved in neural crest chondrogenesis. Consistent with cellular cartilage as a vertebrate novelty, we find that no single amphioxus tissue co-expresses all or most of these genes. However, most are variously co-expressed in mesodermal derivatives. Our results suggest that neural crest-derived cartilage evolved by serial cooption of genes which functioned primitively in mesoderm
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