Localization of the coagulation processHistorically, the blood coagulation system is divided into two initiating pathways: the tissue factor (extrinsic) pathway and the contact factor (intrinsic) pathway which meet at a ®nal, common pathway, whereby factor Xa converts prothrombin to thrombin which then acts on ®brinogen. These pathways were identi®ed and categorized during experiments to examine the effects of suf®ciency and de®ciency of the various circulating factors on assays of plasma coagulation. At present the immediate clinical investigation of haemostatic disorders still requires this compartmentalized, cascade-type model as the laboratorybased tests of coagulation focus on each of these separate aspects. The prothrombin time (PT) is a plasma and test-REVIEW ARTICLE

BACKGROUNDGWAS of schizophrenia demonstrated that variations in the non-coding regions are responsible for most of common variation heritability of the disease. It is hypothesized that these risk variants alter gene expression. Thus, studying alterations in gene expression in schizophrenia may provide a direct approach to understanding the etiology of the disease. In this study we use Cultured Neural progenitor cells derived from Olfactory Neuroepithelium (CNON) as a genetically unaltered cellular model to elucidate the neurodevelopmental aspects of schizophrenia.METHODSWe performed a gene expression study using RNA-Seq of CNON from 111 controls and 144 individuals with schizophrenia. Differentially expressed (DEX) genes were identified with DESeq2, using covariates to correct for sex, age, library batches and one surrogate variable component.RESULTS80 genes were DEX (FDR<10%), showing enrichment in cell migration, cell adhesion, developmental process, synapse assembly, cell proliferation and related gene ontology categories. Cadherin and Wnt signaling pathways were positive in overrepresentation test, and, in addition, many genes are specifically involved in Wnt5A signaling. The DEX genes were significantly, enriched in the genes overlapping SNPs with genome-wide significant association from the PGC GWAS of schizophrenia (PGC SCZ2). We also found substantial overlap with genes associated with other psychiatric disorders or brain development, enrichment in the same GO categories as genes with mutations de novo in schizophrenia, and studies of iPSC-derived neural progenitor cells.CONCLUSIONSCNON cells are a good model of the neurodevelopmental aspects of schizophrenia and can be used to elucidate the etiology of the disorder.

BackgroundRecently, measurement of RNA at single cell resolution has yielded surprising insights. Methods for single-cell RNA sequencing (scRNA-seq) have received considerable attention, but the broad reliability of single cell methods and the factors governing their performance are still poorly known.ResultsHere, we conducted a large-scale control experiment to assess the transfer function of three scRNA-seq methods and factors modulating the function. All three methods detected greater than 70% of the expected number of genes and had a 50% probability of detecting genes with abundance greater than 2 to 4 molecules. Despite the small number of molecules, sequencing depth significantly affected gene detection. While biases in detection and quantification were qualitatively similar across methods, the degree of bias differed, consistent with differences in molecular protocol. Measurement reliability increased with expression level for all methods and we conservatively estimate measurements to be quantitative at an expression level greater than ~5–10 molecules.ConclusionsBased on these extensive control studies, we propose that RNA-seq of single cells has come of age, yielding quantitative biological information.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3300-3) contains supplementary material, which is available to authorized users.

This paper details a practical method for the direct reconstruction of high dose rate (192)Ir source dwell positions in ring applicators using gafchromic film in the treatment planning of brachytherapy cervix patients. It also details the uncertainties associated with such a process. Eight Nucletron interstitial ring applicators-Ø26 mm (×4), Ø30 mm (×3) and Ø34 mm (×1), and one 60 mm intrauterine tube were used in this study. RTQA2 and XRQA2 gafchromic films were irradiated at pre-programmed dwell positions with three successive (192)Ir sources and used to derive the coordinates of the source dwell positions. The source was observed to deviate significantly from its expected position by up to 6.1 mm in all ring sizes. Significant inter applicator differences of up to 2.6 mm were observed between a subset of ring applicators. Also, the measured data were observed to differ significantly from commercially available source path models provided by Nucletron with differences of up to 3.7 mm across all ring applicator sizes. The total expanded uncertainty (k = 2) averaged over all measured dwell positions in the rings was observed to be 1.1 ± 0.1 mm (Ø26 mm and Ø30 mm rings) and 1.0 ± 0.3 mm (Ø34 mm ring) respectively, and when transferred to the treatment planning system, equated to maximum %dose changes of 1.9%, 13.2% and 1.5% at regions representative of the parametrium, lateral fornix and organs at risk respectively.

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