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51.
Formal verification has advanced to the point that developers can verify the correctness of small, critical modules. Unfortunately, despite considerable efforts, determining if a “verification” verifies what the author intends is still difficult. Previous approaches are difficult to understand and often limited in applicability. Developers need verification coverage in terms of the software they are verifying, not model checking diagnostics. We propose a methodology to allow developers to determine (and correct) what it is that they have verified, and tools to support that methodology. Our basic approach is based on a novel variation of mutation analysis and the idea of verification driven by falsification. We use the CBMC model checker to show that this approach is applicable not only to simple data structures and sorting routines, and verification of a routine in Mozilla’s JavaScript engine, but to understanding an ongoing effort to verify the Linux kernel read-copy-update mechanism. Moreover, we show that despite the probabilistic nature of random testing and the tendency to incompleteness of testing as opposed to verification, the same techniques, with suitable modifications, apply to automated test generation as well as to formal verification. In essence, it is the number of surviving mutants that drives the scalability of our methods, not the underlying method for detecting faults in a program. From the point of view of a Popperian analysis where an unkilled mutant is a weakness (in terms of its falsifiability) in a “scientific theory” of program behavior, it is only the number of weaknesses to be examined by a user that is important.  相似文献   
52.
International Journal on Software Tools for Technology Transfer - A test harness, in automated test generation, defines the set of valid tests for a system, as well as their correctness properties....  相似文献   
53.
54.
Endothelial cells and subendothelial matrix (ECM) are involved in the pathogenesis of vasculitis. Exposure of the ECM following vascular damage may promote further immune and inflammatory response. To investigate this, we studied the prevalence of antibodies against endothelial cells (AECA), ECM, and its major component collagen type IV in systemic vasculitis patients. Seventy-one percent of patients had AECA (binding index, means +/- SD: 64.8 +/- 48.1%; normal controls: 8.9 +/- 6.9%, P < 0.001). Anti-ECM and anti-collagen type IV antibodies were also significantly higher in patients compared to normals (anti-ECM: 28.6 +/- 29.6% vs 9.0 +/- 11.3%, P < 0.002; anti-collagen type IV: 23.5 +/- 20.3% vs 8.1 +/- 9.1%, P < 0.002). AECA correlated with anti-ECM (r = 0.75, P < 0.0001) but not with anti-collagen type IV. Anti-ECM correlated with anti-collagen type IV (r = 0.45, P < 0.01). Positivity of cytoplasmic anti-neutrophil cytoplasmic antibodies (cANCA) was significantly lower in patients positive for anti-ECM and/or anti-collagen type IV antibodies (58% vs 11%, P = 0.048). AECA binding was partially reduced with ECM incubation by 25.1%. The addition of heparin caused a dose-dependent inhibition of binding activity (19.2-30.6%) in the AECA ELISA. These results support the hypothesis that there is a humoral response against ECM components in addition to endothelial cells in systemic vasculitis patients which might have pathological significance in vascular damage.  相似文献   
55.
BACKGROUND: The clinical events surrounding acute HIV-1 infection have been well described, but little is known about whether the virologic course of acute HIV-1 infection influences the subsequent progression of disease. OBJECTIVE: To define the virologic natural history of acute and very early HIV infection. DESIGN: Prospective, longitudinal cohort study. SETTING: University of Washington Research Clinic PARTICIPANTS: 74 adults enrolled soon after acquisition of HIV (mean, 69 days). MEASUREMENTS: Plasma HIV-1 RNA levels; quantitative cell cultures; CD4 cell counts; and detailed clinical assessments done at study entry, biweekly for 1 month, monthly for 2 months, and quarterly thereafter. RESULTS: In the first 30 days after acquisition of HIV, HIV-1 RNA levels varied greatly among participants (range, 27,200 to 1.6 x 10(6) copies per mL of plasma). Levels of HIV-1 RNA decreased by a mean of 6.5% per week for the first 120 days and then increased by a mean of 0.15% per week. CD4 cell counts decreased by a mean of 5.2 cells/mm3 per week for the first 160 days and by a mean of 1.9 cells/mm3 per week thereafter (P < 0.01). Disease progressed faster in participants who sought medical care for their acute seroconversion syndrome (P = 0.01) and those who had high plasma HIV-1 RNA levels 120 to 365 days after acquisition (P < 0.01). Peak levels in the first 120 days were not predictive of disease progression. CONCLUSIONS: The variability in viral RNA levels associated with acute HIV-1 infection is greater than previously appreciated. Within 120 days of acquisition, plasma HIV RNA levels rapidly decrease to an inflection point, after which they gradually increase. Virus-host interactions soon after acquisition seem to have a major influence on the long-term outcome of HIV-1 disease.  相似文献   
56.
Ribonucleotide reductase inhibitors (RRIs) have been recently shown to inhibit retroviral replication. We examined a new series of RRIs, 3,4-dihydroxybenzohydroxamic acid (Didox) and 3,4,5-trihydroxybenzohydroxamidoxime (Trimidox) for their ability to alter disease progression in murine acquired immunodeficiency syndrome (MAIDS), both alone and in combination with 2',3'-dideoxyinosine (ddI). MAIDS disease was induced by inoculation of female C57BL/6 mice with the LP-BM5 murine leukemia virus (MuLV) and disease progression characterized by extensive peripheral lymphadenopathy and splenomegaly. Efficacy of treatment with these drugs was based upon their ability to influence survival and disease pathophysiology by monitoring the development of splenomegaly. Toxicity was determined by changes in body weight, total peripheral white blood cell count and hematocrit. Didox or trimidox monotherapy was associated with increased survival and decreased disease pathophysiology, with no apparent toxicity. Combined with ddI, their ability to reduce development of viral induced splenomegaly was enhanced compared to trimidox, didox or ddI alone. These results demonstrate RRIs have potent activity in reversing the disease manifestations characteristic of MAIDS. Further studies are warranted to determine human clinical efficacy.  相似文献   
57.
The percentage of long-term survivors after intensive chemotherapy and the outcome of MDS patients who achieve partial remission (PR) with intensive chemotherapy (IC) are not known. Between 1981 and 1996 we treated 99 patients with de novo MDS who had high-risk MDS or progression to AML, with IC. 41 (41%) achieved CR, 16 (16%) achieved partial remission (PR), 26 (26%) had failure, and 16 (16%) died in aplasia. Eight of the patients who achieved CR were autografted, three were allografted and the remaining cases received moderate consolidation chemotherapy. After IC, the 16 PR patients fulfilled the criteria for RA in 15 cases and CMML in one case. Median PR duration was 17 months, and three PR were > 3 years (39, 50+, 82+ months). Median actuarial survival of patients who achieved PR and CR was 18 months and 20 months from the onset of IC, respectively (difference not significant). Of the 71 patients treated before 1993, with sufficient follow-up, 10 (14%) had survived > 4 years (long-term survivors). Four of them were alive in first CR after 49+ to 110+ months and probably cured, two were alive in PR after 50+ and 82+ months and four had died after 49-78 months. Long-term survivors were characterized by a significantly higher incidence of RAEB-T at diagnosis, and with normal or favourable cytogenetic findings. In patients with RAEB-T at diagnosis included before 1993, 8/23 (35%) cases who had no unfavourable karyotype had survived > 4 years. Our findings suggest that MDS patients who achieve PR with IC, and not only those who achieve CR, can benefit from this type of treatment. The percentage of long-term survivors remains low, however, and is almost restricted to patients with RAEB-T at diagnosis and no unfavourable karyotype.  相似文献   
58.
A retrospective case reference study examining the use of alcohol and tobacco in 303 women aged 40 or over suffering from oral or oropharyngeal cancer was conducted in the south-west Netherlands. Both alcohol and tobacco consumption are important in the development of oral and oropharyngeal cancer with increased consumption of both markedly increasing the risks of cancer, but alcohol having the greater effect.  相似文献   
59.
60.
The in-line development of crystalline morphology and orientation during melt extrusion of low density polyethylene (LDPE) tape at nil and low haul-off speeds has been investigated using Small-Angle X-Ray Scattering (SAXS). The processing parameters, namely haul-off speed and distance down the tape-line have been varied and the resulting crystalline morphology is described from detailed analysis of the SAXS data. Increasing haul-off speed increased orientation in the polymer tape and the resulting morphology could be described in terms of regular lamellar stacking perpendicular to the elongation direction. In contrast, under nil haul-off conditions the tape still showed some orientation down the tape-line, but a shish-kebab structure prevails. The final lamellae thickness ( ∼50 Å) and bulk crystallinity (∼20%), were low at, for all processing conditions investigated, which is attributed to the significant short-chain branching in the polymer acting as point defects limiting lamellae crystal growth.  相似文献   
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