Search results for "Breakpoint"
showing 10 items of 70 documents
Quality assurance in RT-PCR-based BCR/ABL diagnostics--results of an interlaboratory test and a standardization approach.
2000
Here we describe the results of an interlaboratory test for RT-PCR-based BCR/ABL analysis. The test was organized in two parts. The number of participating laboratories in the first and second part was 27 and 20, respectively. In the first part samples containing various concentrations of plasmids with the ela2, b2a2 or b3a2 BCR/ABL transcripts were analyzed by PCR. In the second part of the test, cell samples containing various concentrations of BCR/ABL-positive cells were analyzed by RT-PCR. Overall PCR sensitivity was sufficient in approximately 90% of the tests, but a significant number of false positive results were obtained. There were significant differences in sensitivity in the cel…
Comparative cytogenetics of human chromosome 3q21.3 reveals a hot spot for ectopic recombination in hominoid evolution
2004
Fluorescence in situ hybridization mapping of fully integrated human BAC clones to primate chromosomes, combined with precise breakpoint localization by PCR analysis of flow-sorted chromosomes, was used to analyze the evolutionary rearrangements of the human 3q21.3-syntenic region in orangutan, siamang gibbon, and silvered-leaf monkey. Three independent evolutionary breakpoints were localized within a 230-kb segment contained in BACs RP11-93K22 and RP11-77P16. Approximately 200 kb of the human 3q21.3 sequence was not present on the homologous orangutan, siamang, and Old World monkey chromosomes, suggesting a genomic DNA insertion into the breakpoint region in the lineage leading to humans a…
Quantifying treatment effects when flexibly modeling individual change in a nonlinear mixed effects model
2021
A core task in analyzing randomized clinical trials based on longitudinal data is to find the best way to describe the change over time for each treatment arm. We review the implementation and estimation of a flexible piecewise Hierarchical Linear Model (HLM) to model change over time. The flexible piecewise HLM consists of two phases with differing rates of change. The breakpoints between these two phases, as well as the rates of change per phase are allowed to vary between treatment groups as well as individuals. While this approach may provide better model fit, how to quantify treatment diff erences over the longitudinal period is not clear. In this paper, we develop a procedure for summ…
Interval estimation for the breakpoint in segmented regression: a smoothed score-based approach
2017
Summary This paper is concerned with interval estimation for the breakpoint parameter in segmented regression. We present score-type confidence intervals derived from the score statistic itself and from the recently proposed gradient statistic. Due to lack of regularity conditions of the score, non-smoothness and non-monotonicity, naive application of the score-based statistics is unfeasible and we propose to exploit the smoothed score obtained via induced smoothing. We compare our proposals with the traditional methods based on the Wald and the likelihood ratio statistics via simulations and an analysis of a real dataset: results show that the smoothed score-like statistics perform in prac…
Testing with a nuisance parameter present only under the alternative: a score-based approach with application to segmented modelling
2016
ABSTRACTWe introduce a score-type statistic to test for a non-zero regression coefficient when the relevant term involves a nuisance parameter present only under the alternative. Despite the non-regularity and complexity of the problem and unlike the previous approaches, the proposed test statistic does not require the nuisance to be estimated. It is simple to implement by relying on the conventional distributions, such as Normal or t, and it justified in the setting of probabilistic coherence. We focus on testing for the existence of a breakpoint in segmented regression, and illustrate the methodology with an analysis on data of DNA copy number aberrations and gene expression profiles from…
Segmented relationships to model erosion of regression effect in Cox regression
2010
In this article we propose a parsimonious parameterisation to model the so-called erosion of the covariate effect in the Cox model, namely a covariate effect approaching to zero as the follow-up time increases. The proposed parameterisation is based on the segmented relationship where proper constraints are set to accomodate for the erosion. Relevant hypothesis testing is discussed. The approach is illustrated on two historical datasets in the survival analysis literature, and some simulation studies are presented to show how the proposed framework leads to a test for a global effect with good power as compared with alternative procedures. Finally, possible generalisations are also present…
NFATc1 Is Transcriptionally Activated in Chronic Lymphocytic Leukemia (CLL) By Promotor DNA-Hypomethylation Which Correlates with in-Vitro Vulnerabil…
2014
Abstract Chronic lymphocytic leukemia (CLL), the most frequent adult leukemia in Western countries, is characterized by progressive accumulation of mature, monoclonal B lymphocytes in blood, bone marrow, and lymphoid tissues. In the pathogenesis and treatment of CLL, B cell receptor (BCR) signaling plays a crucial role, and aberrations in downstream pathways that become activated in CLL need to be better defined. One downstream target of BCR signaling is NFATc1, a transcription factor with a high oncogenic and transforming potential. Employing a genome-wide comparative DNA methylation analysis the NFATc1 5’ region was identified to be DNA hypomethylated in CLL patient samples. The pilot ser…
The determination of maturity stages in male elasmobranchs (Chondrichthyes) using a segmented regression of clasper length on total length
2013
A novel statistical method for estimating the stages of maturity in male sharks and skates based on a segmented regression (SRM) is proposed. We hypothesize that this method is able to find the transition points in the three-phase relationship between total length (TL) and clasper length (CL). We applied an SRM to TL–CL data of nine species, from large pelagic sharks (e.g., Carcharhinus falciformis) to small coastal skates (e.g., Rioraja agassizi), captured in the southwestern Atlantic and northeastern Pacific. As expected, SRM detected two breakpoints, defining three maturity stages (immature, maturing, and mature), in six out of nine species. For three species, it was not possible to fin…
Variabilité de la température entre 1951 et 2014 en Allemagne associée à l’évolution de la floraison des pommiers.
2018
Apple tree bloom onset in Germany has advanced by 2 days/decade in 1951-2014 and by 3 days/decade in 1988-2014, behaving similarly in respect to its evolution since 1951 and its sensitivity to temperature to other species’ phenological spring phases. The evolution however was not linear; by conducting a split moving-window dissimilarity analysis (SMWDA) we were able to detect the “break-period” 1987-1989 which coincides with a breakpoint that has been identified in the phases of the North Atlantic Oscillation (NAO). We observed distinct spatial patterns with apple bloom advancing from southwest to northeast and, most interestingly, a longitudinal gradient in the trend of apple bloom onset r…
Cationic lipide mediated transfer of c-abl and bcr antisense oligonucleotides to immature normal myeloid cells: Uptake, biological effects and modula…
1996
Uptake and biochemical and biological effects of antisense oligodeoxynucleotides (ODN) specific for c-abl and bcr genes were studied in normal immature myeloid cells. CD34-positive cells were purified by positive and negative selection and cultured in liquid culture for 7 days. These cells were then incubated with ODNs, either alone or in combination with cationic lipids. The uptake of ODNs was enhanced by the use of cationic lipids. In addition, very low concentrations of ODNs in combination with cationic lipids were capable of specifically inhibiting the expression of the c-abl gene. In contrast, no effects were seen on the expression of bcr. However, despite the effective blocking of c-a…