81 research outputs found
Integrated genome-wide genotyping and gene expression profiling reveals BCL11B as a putative oncogene in acute myeloid leukemia with 14q32 aberrations
Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia
Wide shear zones and the spot model: Implications from the split-bottom geometry
The spot model has been developed by Bazant and co-workers to describe
quasistatic granular flows. It assumes that granular flow is caused by the
opposing flow of so-called spots of excess free volume, with spots moving along
the slip lines of Mohr-Coulomb plasticity. The model is two-dimensional and has
been successfully applied to a number of different geometries. In this paper we
investigate whether the spot model in its simplest form can describe the wide
shear zones observed in experiments and simulations of a Couette cell with
split bottom. We give a general argument that is independent of the particular
description of the stresses, but which shows that the present formulation of
the spot model in which diffusion and drift terms are postulated to balance on
length scales of order of the spot diameter, i.e. of order 3-5 grain diameters,
is difficult to reconcile with the observed wide shear zones. We also discuss
the implications for the spot model of co-axiality of the stress and strain
rate tensors found in these wide shear flows, and point to possible extensions
of the model that might allow one to account for the existence of wide shear
zones.Comment: 6 pages, 6 figures, to be published in EPJ
Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia
ACO2 homozygous missense mutation associated with complicated Hereditary spastic paraplegia
Objective: To identify the clinical characteristics and genetic etiology of a family affected with hereditary spastic paraplegia (HSP). Methods: Clinical, genetic, and functional analyses involving genome-wide linkage coupled to whole-exome sequencing in a consanguineous family with complicated HSP. Results: A homozygous missense mutation was identified in the ACO2 gene (c.1240T>G p.Phe414Val) that segregated with HSP complicated by intellectual disability and microcephaly. Lymphoblastoid cell lines of homozygous carrier patients revealed significantly decreased activity of the mitochondrial aconitase enzyme and defective mitochondrial respiration. ACO2 encodes mitochondrial aconitase, an essential enzyme in the Krebs cycle. Recessive mutations in this gene have been previously associated with cerebellar ataxia. Conclusions: Our findings nominate ACO2 as a disease-causing gene for autosomal recessive complicated HSP and provide further support for the central role of mitochondrial defects in the pathogenesis of HSP
Lanthanide-based time-resolved luminescence immunoassays
The sensitive and specific detection of analytes such as proteins in biological samples is critical for a variety of applications, for example disease diagnosis. In immunoassays a signal in response to the concentration of analyte present is generated by use of antibodies labeled with radioisotopes, luminophores, or enzymes. All immunoassays suffer to some extent from the problem of the background signal observed in the absence of analyte, which limits the sensitivity and dynamic range that can be achieved. This is especially the case for homogeneous immunoassays and surface measurements on tissue sections and membranes, which typically have a high background because of sample autofluorescence. One way of minimizing background in immunoassays involves the use of lanthanide chelate labels. Luminescent lanthanide complexes have exceedingly long-lived luminescence in comparison with conventional fluorophores, enabling the short-lived background interferences to be removed via time-gated acquisition and delivering greater assay sensitivity and a broader dynamic range. This review highlights the potential of using lanthanide luminescence to design sensitive and specific immunoassays. Techniques for labeling biomolecules with lanthanide chelate tags are discussed, with aspects of chelate design. Microtitre plate-based heterogeneous and homogeneous assays are reviewed and compared in terms of sensitivity, dynamic range, and convenience. The great potential of surface-based time-resolved imaging techniques for biomolecules on gels, membranes, and tissue sections using lanthanide tracers in proteomics applications is also emphasized
Granular Flow in Silo Discharge: Discrete Element Method Simulations and Model Assessment
CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer
The functional roles of SNPs within the 8q24 gene desert in the cancer phenotype are not yet well understood. Here, we report that CCAT2, a novel long noncoding RNA transcript (lncRNA) encompassing the rs6983267 SNP, is highly overexpressed in microsatellite-stable colorectal cancer and promotes tumor growth, metastasis, and chromosomal instability. We demonstrate that MYC, miR-17-5p, and miR-20a are up-regulated by CCAT2 through TCF7L2-mediated transcriptional regulation. We further identify the physical interaction between CCAT2 and TCF7L2 resulting in an enhancement of WNT signaling activity. We show that CCAT2 is itself a WNT downstream target, which suggests the existence of a feedback loop. Finally, we demonstrate that the SNP status affects CCAT2 expression and the risk allele G produces more CCAT2 transcript. Our results support a new mechanism of MYC and WNT regulation by the novel lncRNA CCAT2 in colorectal cancer pathogenesis, and provide an alternative explanation of the SNP-conferred cancer risk
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