483 research outputs found

    Testing object-oriented industrial software without precise oracles or results

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    Software testing such as object-oriented software Testing At the Class and Cluster LEvels, or TACCLE, can be achieved by defining the test objectives, selecting and executing test cases, and checking results. The software specifications are extracted from technical drawings of mechanical and electronic hardware designed by process engineers using an in-house technique. TACCLE enables software engineers to test each individual class independently, then test the interaction among classes. The TACCLE methodology is described in three sections that include class-level testing, cluster-level testing, and test case generation and test script translation. The notion of testing observational equivalence and bypassing the need for oracles is important in test automation for industrial projects where it is impractical to define a precise relationship between specification and the software under test.postprin

    Diagnosing Sporadic Creutzfeldt-Jakob Disease by the Detection of Abnormal Prion Protein in Patient Urine

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    IMPORTANCE: Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder associated with the accumulation of infectious abnormal prion protein through a mechanism of templated misfolding. A recent report has described the detection of abnormal prion protein in the urine of patients with variant CJD (vCJD) using protein misfolding by cyclic amplification, which was apparently absent in the more common sporadic form of CJD (sCJD). A noninvasive diagnostic test could improve early diagnosis of sCJD and, by screening donations, mitigate the potential risks of prion transmission through human urine–derived pharmaceuticals. Here, we describe the adaptation of the direct detection assay, developed originally as a blood test for vCJD, for the detection of disease-associated prion protein in urine samples from patients with sCJD. OBJECTIVE: To determine the feasibility of sCJD diagnosis by adaptation of an established vCJD diagnostic blood test to urine. DESIGN, SETTINGS AND PARTICIPANTS: This retrospective, cross-sectional study included anonymized urine samples from healthy nonneurological control individuals (n = 91), patients with non-prion neurodegenerative diseases (n = 34), and patients with prion disease (n = 37) of which 20 had sCJD. Urine samples obtained during the Medical Research Council PRION-1 Trial, the National Prion Monitoring Cohort Study, and/or referred to the National Prion Clinic or Dementia Research Centre at the National Hospital for Neurology and Neurosurgery in the United Kingdom. MAIN OUTCOMES AND MEASURES: Presence of sCJD infection determined by an assay that captures, enriches, and detects disease-associated prion protein isoforms. RESULTS: A total of 162 samples were analyzed, composed of 91 normal control individuals (51 male, 33 female, and 7 not recorded), 34 neurological disease control individuals (19 male and 15 female), and 37 with prion disease (22 male and 15 female). The assay’s specificity for prion disease was 100% (95% CI, 97%-100%), with no false-positive reactions from 125 control individuals, including 34 from a range of neurodegenerative diseases. In contrast to a previous study, which used a different method, sensitivity to vCJD infection was low (7.7%; 95% CI, 0.2%-36%), with only 1 of 13 patients with positive test results, while sensitivity to sCJD was unexpectedly high at 40% (95% CI, 19%-64%). CONCLUSIONS AND RELEVANCE: We determined 40% of sCJD urine sample results as positive. To our knowledge, this is the first demonstration of an assay that can detect sCJD infection in urine or any target analyte outside of the central nervous system. Urine detection could allow the development of rapid, molecular diagnostics for sCJD and has implications for other neurodegenerative diseases where disease-related assemblies of misfolded proteins might also be present in urine

    Bank vole prion protein extends the use of RT-QuIC assays to detect prions in a range of inherited prion diseases

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    The cerebrospinal fluid (CSF) real-time quaking-induced conversion assay (RT-QuIC) is an ultrasensitive prion amyloid seeding assay for diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) but several prion strains remain unexplored or resistant to conversion with commonly used recombinant prion protein (rPrP) substrates. Here, bank vole (BV) rPrP was used to study seeding by a wide range of archived post-mortem human CSF samples from cases of sporadic, acquired and various inherited prion diseases in high throughput 384-well format. BV rPrP substrate yielded positive reactions in 70/79 cases of sporadic CJD [Sensitivity 88.6% (95% CI 79.5-94.7%)], 1/2 variant CJD samples, and 9/20 samples from various inherited prion diseases; 5/57 non-prion disease control CSFs had positive reactions, yielding an overall specificity of 91.2% (95% CI 80.1-97.1%). Despite limitations of using post-mortem samples and our results' discrepancy with other studies, we demonstrated for the first time that BV rPrP is susceptible to conversion by human CSF samples containing certain prion strains not previously responsive in conventional rPrPs, thus justifying further optimisation for wider diagnostic and prognostic use

    Two-Channel Kondo Lattice: An Incoherent Metal

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    The two-channel Kondo lattice model is examined with a Quantum Monte Carlo simulation in the limit of infinite dimensions. We find non-fermi-liquid behavior at low temperatures including a finite low-temperature single-particle scattering rate, the lack of a fermi edge and Drude weight. However, the low-energy density of electronic states is finite. Thus, we identify this system as an incoherent metal. We discuss the relevance of our results for concentrated heavy fermion metals with non-Fermi-Liquid behavior.Comment: LaTex, 5 pages, 3 Postscript files. Revision - in reference 5 and 6(a

    Phase Diagram of the Two-Channel Kondo Lattice

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    The phase diagram of the two-channel Kondo lattice model is examined with a Quantum Monte Carlo simulation in the limit of infinite dimensions. Commensurate (and incommensurate) antiferromagnetic and superconducting states are found. The antiferromagnetic transition is very weak and continuous; whereas the superconducting transition is discontinuous to an odd-frequency channel-singlet and spin-singlet pairing state.Comment: 5 pages, LaTeX and 4 PS figures (see also cond-mat/9609146 and cond-mat/9605109

    Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome

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    Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18-60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.published_or_final_versio
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