Molecular follow-up of disease progression and interferon therapy in chronic myelocytic leukemia

We previously reported that the abl promoter (Pa) undergoes de novo DNA methylation in the course of chronic myelocytic leukemia (CML). The clinical implications of this finding are the subject of the present study in which samples of CML patients, including a group treated with interferon alpha (IFNalpha) were surveyed. The methylation status of the abl promoter was monitored by polymerase chain reaction (PCR) amplification of the Pa region after digestion with several site-methylation sensitive restriction enzymes. Some 74% of the DNA samples from blood and marrow drawn in the chronic phase were nonmethylated, similar to control samples from non-CML patients. The remaining 26% were partially methylated in the abl Pa region. The latter samples were derived from patients who were indistinguishable from the others on the basis of clinical presentation. Methylated samples were mostly derived from patients known to have a disease of longer duration (26 months v 7.5 months, P = .01). Samples of 30 IFNalpha-treated patients were sequentially analyzed in the course of treatment. Fifteen patients with no evidence of Pa methylation before treatment remained methylation-free. The remainder, who displayed Pa methylation before treatment, reverted to the methylation-free status. The outcome is attributed to IFNalpha therapy, as the Pa methylation status was not reversed in any of the patients treated with hydroxyurea. Methylation of the abl promoter indicates a disease of long-standing, most likely associated with a higher probability of imminent blastic transformation. It appears to predict the outcome of IFNalpha therapy far better than the cytogenetic response.     

Large reference displacement analysis of composite plates. Part II: Computer implementation

This investigation concerns itself with the computer implementation of the dynamic formulation of thin laminated composite plates consisting of layers of orthotropic laminae that undergo large arbitrary rigid body displacements and small elastic deformations. A finite element preprocessor computer program is developed to automatically generate the invariants of the laminae, which may have arbitrary orientations. The laminae invariants are then used to obtain the invariants of the elements and the composite laminated plate. The consistent and lumped mass formulations of the invariants of motion of composite plates are compared and it is concluded that the two methods are comparable, if a fine enough finite element mesh is used. The structure of the dynamic equations of motion, based on the formulation presented in Part I of this paper, is examined. Non-linear centrifugal and Coriolis forces arising as the result of the finite rotations of the laminae are defined, and the solution schemes of the resulting non-linear differential equations of motion are discussed. Numerical examples illustrating the differences between homogeneous isotropic and laminated composite plates are presented. An RSSR (Revolute-Spherical-Spherical-Revolute) mechanism is used in the numerical examples, with the coupler modelled as a laminated plate flexible body. It is found that the inertia of the plate contributed greatly to the transverse deformation. The effects of laminae orientation is also investigated.     

Parallel, self-organizing, hierarchical neural networks. II

For pt.I see IEEE Trans. Neural Networks, vol.1, p.167-78 (1990). Parallel, self-organizing, hierarchical neural networks (PSHNNs) involve a number of stages with error detection at the end of each stage, i.e., rejection of error-causing vectors, which are then fed into the next stage after a nonlinear transformation. The stages operate in parallel during testing. Statistical properties and the mechanisms of vector rejection of the PSHNN are discussed in comparison to the maximum likelihood method and the backpropagation network. The PSHNN is highly fault tolerant and robust against errors in the weight values due to the adjustment of the error detection bounds to compensate errors in the weight values. These properties are exploited to develop architectures for programmable implementations in which the programmable parts are reduced to on-off or bipolar switching operations for bulk computations and attenuators for pointwise operations     

Representing context, cognition, and crew performance in a shutdown risk assessment

This paper presents a potentially practical treatment of dynamic operator-system interactions. The approach employs a dynamic event tree framework to explicitly address plant dynamics, system indications, crew-plant interactions, time available, crew cognition, errors of commission (mistakes), and multiple planning and diagnosis possibilities. The approach is applied in an analysis of a hypothesize medium break loss of coolant accident for a test reactor that occurs during plant shutdown. This transient was selected on the basis of: a significant cognitive component being present, high consequences being associated with operator actions, and the importance of event timing to scenario progression. The results presented show how quantitative risk predictions are affected by the treatment of dynamics, and demonstrate how non-proceduralized recovery actions and a number of performance shaping factors (e.g., crew experience, stress, and confidence) can be explicitly treated. Insights and lessons learned regarding the performance of a dynamic assessment are also presented.     

False aneurysm of the left ventricle and coronary aneurysms in Beh?et disease

A false left ventricular aneurysm and coronary artery aneurysm were discovered in a 29 year old patient with Beh?et's syndrome. The operation under cardiopulmonary bypass consisted of closing the neck of the false aneurysm by an endo-aneurysmal approach with a Gore-Tex patch. The coronary artery aneurysms were respected. There were no postoperative complications. Cardiac involvement is rare in Beh?et's syndrome (6%). The originality of this case is the association of two aneurysmal pathologies: the coronary and ventricular aneurysms due to the angiitis and the myocardial fragility induced by ischaemia.     

A major isoform of the maize plasma membrane H(+)-ATPase: characterization and induction by auxin in coleoptiles

The plasma membrane (PM) H(+)-ATPase has been proposed to play important transport and regulatory roles in plant physiology, including its participation in auxin-induced acidification in coleoptile segments. This enzyme is encoded by a family of genes differing in tissue distribution, regulation, and expression level. A major expressed isoform of the maize PM H(+)-ATPase (MHA2) has been characterized. RNA gel blot analysis indicated that MHA2 is expressed in all maize organs, with highest levels being in the roots. In situ hybridization of sections from maize seedlings indicated enriched expression of MHA2 in stomatal guard cells, phloem cells, and root epidermal cells. MHA2 mRNA was induced threefold when nonvascular parts of the coleoptile segments were treated with auxin. This induction correlates with auxin-triggered proton extrusion by the same part of the segments. The PM H(+)-ATPase in the vascular bundies does not contribute significantly to auxin-induced acidification, is not regulated by auxin, and masks the auxin effect in extracts of whole coleoptile segments. We conclude that auxin-induced acidification in coleoptile segments most often occurs in the nonvascular tissue and is mediated, at least in part, by increased levels of MHA2.