393 research outputs found

    Optical quenching and recovery of photoconductivity in single-crystal diamond

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    We study the photocurrent induced by pulsed-light illumination (pulse duration is several nanoseconds) of single-crystal diamond containing nitrogen impurities. Application of additional continuous-wave light of the same wavelength quenches pulsed photocurrent. Characterization of the optically quenched photocurrent and its recovery is important for the development of diamond based electronics and sensing

    Emerging Pharmacotherapies for Adult Patients with Acute Lymphoblastic Leukemia

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    Acute lymphoblastic leukemia (ALL) treatment regimes are amongst the longest, most intensive and complex used in hematooncology. Despite this, while treatment of pediatric ALL is a success story, we are far from being able to ensure a durable response in adult ALL. This is not due to failure of induction therapy as a complete remission (CR) is achieved in over 90% of patients. However the challenge remains in ensuring a sustained remission. Furthermore in the face of relapsed disease, salvage therapies currently offer a poor chance of a good outcome. This article reviews the novel agents which show the most promise in the treatment of adult ALL

    Molecular characterization of TCF3::PBX1 chromosomal breakpoints in acute lymphoblastic leukemia and their use for measurable residual disease assessment

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    The translocation t(1;19)(q23;p13) with the resulting chimeric TCF3::PBX1 gene is the third most prevalent recurrent chromosomal translocation in acute lymphoblastic leukemia and accounts for 3-5% of cases. The molecular background of this translocation has been incompletely studied, especially in adult cases. We characterized the chromosomal breakpoints of 49 patients with TCF3::PBX1 and the corresponding reciprocal PBX1::TCF3 breakpoints in 15 cases at the molecular level, thus providing an extensive molecular overview of this translocation in a well-defined study patient population. Breakpoints were found to be remarkably clustered not only in TCF3 but also in PBX1. No association with DNA repeats or putative cryptic recombination signal sequence sites was observed. A simplified detection method for breakpoint identification was developed and the feasibility of patient-specific chromosomal break sites as molecular markers for detecting measurable residual disease (MRD) was explored. A highly sensitive generic real-time PCR for MRD assessment using these breakpoint sequences was established that could serve as a useful alternative to the classical method utilizing rearranged immune gene loci. This study provides the first extensive molecular data set on the chromosomal breakpoints of the t(1;19)/TCF3::PBX1 aberration in adult ALL. Based on the obtained data a generic MRD method was developed that has several theoretical advantages, including an on average higher sensitivity and a greater stability of the molecular marker in the course of disease

    FCRD Milestone Report: M21AF050901

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    The objective of this study was to perform mechanical testing on large scale heats of the advanced ODS 14YWT alloy to investigate the effects of processing parameters on mechanical properties. Mechanical properties tests were conducted on two heats of the advanced ODS 14YWT ferritic alloy: the 14YWT-SM11 was produced by extrusion at ORNL and OW4 was produced by HIP at UCSB. The 14YWT-SM11 showed very high tensile strength compared to OW4, but showed less ductility as a result. The fracture toughness transition temperature of 14YWT-SM11 was determined in two orientations and showed T{sub 0} = 48 C in the favorably strong L-T direction while shifting by 63 C to T{sub 0} = 111 C in the weaker T-L direction. The fracture toughness transition temperature for OW4 was not determined but appeared to be within the range observed for 14YWT-SM11. The fracture toughness of 14YWT-SM11 at room temperature was 86.8 MPa{radical}m and 93.1 MPa{radical}m, which was much higher than that of OW4 (27.4 MPa{radical}m). The strain rate jump tests conducted on OW4 indicated that the creep properties were similar to MA957 at 750 C

    Isolation-by-Distance and Outbreeding Depression Are Sufficient to Drive Parapatric Speciation in the Absence of Environmental Influences

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    A commonly held view in evolutionary biology is that speciation (the emergence of genetically distinct and reproductively incompatible subpopulations) is driven by external environmental constraints, such as localized barriers to dispersal or habitat-based variation in selection pressures. We have developed a spatially explicit model of a biological population to study the emergence of spatial and temporal patterns of genetic diversity in the absence of predetermined subpopulation boundaries. We propose a 2-D cellular automata model showing that an initially homogeneous population might spontaneously subdivide into reproductively incompatible species through sheer isolation-by-distance when the viability of offspring decreases as the genomes of parental gametes become increasingly different. This simple implementation of the Dobzhansky-Muller model provides the basis for assessing the process and completion of speciation, which is deemed to occur when there is complete postzygotic isolation between two subpopulations. The model shows an inherent tendency toward spatial self-organization, as has been the case with other spatially explicit models of evolution. A well-mixed version of the model exhibits a relatively stable and unimodal distribution of genetic differences as has been shown with previous models. A much more interesting pattern of temporal waves, however, emerges when the dispersal of individuals is limited to short distances. Each wave represents a subset of comparisons between members of emergent subpopulations diverging from one another, and a subset of these divergences proceeds to the point of speciation. The long-term persistence of diverging subpopulations is the essence of speciation in biological populations, so the rhythmic diversity waves that we have observed suggest an inherent disposition for a population experiencing isolation-by-distance to generate new species

    Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia

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    We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data
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