Monomers of human beta 1 beta 1 alcohol dehydrogenase exhibit activity that differs from the dimer

A previously unreported enzymatic activity is described for monomers of the beta 1 beta 1 isoenzyme of human alcohol dehydrogenase that were prepared from dimeric enzyme by freeze-thaw in liquid nitrogen. Whereas the dimeric enzyme has optimal activity at low substrate concentrations (2.5 mM ethanol, 50 microM NAD+; "low Km" activity), the monomer has its highest activity at high substrate concentrations (1.5 M ethanol, 2.5 mM NAD+; "high Km" activity). While the activity of the monomer does not appear to be saturated at 1.5 M ethanol, its maximal activity at this high ethanol concentration exceeds the Vmax of the dimer by about 3-fold. The apparent Km of NAD+ with monomers is 270 microM, and no activity could be detected with nicotinamide mononucleotide as cofactor. During gel filtration the high Km activity elutes at a lower apparent molecular weight position than the dimer. The kinetics of monomer-to-dimer reassociation are consistent with a second-order process with a rate constant of 240 M-1 s-1. The reassociation rate is markedly enhanced by the presence of NAD+. During refolding of beta 1 beta 1 following denaturation in 6 M guanidine hydrochloride, an enzyme species with high Km activity and spectral properties similar to the freeze-thaw monomer is observed, indicating that a catalytically active monomer is an intermediate in the refolding pathway. The enzymatic activity of the monomer implies that the intersubunit contacts of beta 1 beta 1 are not crucial in establishing a catalytically competent enzyme. However, the differences in specific activity and Km between monomer and dimer suggest that dimerization may serve to modulate the catalytic properties.     

Autogenous shrinkage in high-performance cement paste: An evaluation of basic mechanisms

In this paper, various mechanisms suggested to cause autogenous shrinkage are presented. The mechanisms are evaluated from the point of view of their soundness and applicability to quantitative modeling of autogenous shrinkage. The capillary tension approach is advantageous, because it has a sound mechanical and thermodynamical basis. Furthermore, this mechanism is easily applicable in a numerical model when dealing with a continuously changing microstructure. In order to test the numerical model, autogenous deformation and internal relative humidity (RH) of a Portland cement paste were measured during the first week of hardening. The isothermal heat evolution was also recorded to monitor the progress of hydration and the elastic modulus in compression was measured. RH change, degree of hydration and elastic modulus were used as input data for the calculation of autogenous deformation based on the capillary tension approach. Because a part of the RH drop in the cement paste is due to dissolved salts in the pore solution, a method is suggested to separate this effect from self-desiccation and to calculate the actual stress in the pore fluid associated with menisci formation.     

Chromosome studies in "preleukemia". III. Myelofibrosis

Cytogenetic studies were done on 18 patients with myelofibrosis or the closely related syndrome, undifferentiated myeloproliferative disorder (MPD). Clones of cells with chromosome abnormalities were demonstrated in the blood of eight individuals, including two with a history of radiation therapy and two with "acute myelofibrosis". Trisomy 8 was present in the latter two patients, but otherwise, there was no consistent cytogenetic pattern or correlation with specific hematologic findings. Sixteen of these patients have been followed for more than 1 year or until death; none has progressed to leukemia. The results indicate that chromosome abnormalities are relatively common in this disorder, but as with polycythemia vera, and unlike some other "preleukemic" states, the aberrant clones in myelofibrosis do not appear to indicate that clinical leukemia is imminent.     

Structural optimization of non-linear systems under stochastic excitation

This work concentrates on the structural optimization of a class of non-linear systems with deterministic structural parameters subject to stochastic excitation. The optimization problem is formulated as the minimization of an objective function subject to constraints on the response level. The stochastic response is characterized by its first two statistical moments, which are computed by a statistical equivalent linearization technique. The implicit structural optimization problem is replaced by a sequence of explicit sub-optimization problems. The sub-problems are constructed by using a conservative first-order approximation of the objective and constraint functions. The applicability of the proposed design process is demonstrated in three numerical examples where the methodology is applied to systems with nonlinearity of hardening and hysteretic type. The effects of the nonlinearity on the general performance of the final designs are discussed. At the same time, some engineering implications of the results obtained in this work are addressed.     

Migration of DCE applications into CORBA and SOAP environments

Legacy applications based on the Distributed Computing Environment (DCE) are subject to several significant limitations. As the development and support of DCE wanes, object‐oriented development becomes more desirable, and transmission over HTTP is established as the preferred protocol over the Internet, DCE application managers and developers are pressed to find extensions and alternatives to DCE. This paper briefly discusses several alternative targets for migration of DCE systems, then proceeds to detail, compare, and contrast two preferred candidates: CORBA and SOAP. Although we have found that developing a general migration solution for legacy DCE applications to CORBA or SOAP to be a non‐trivial, long‐term project, developing specific solutions that are based on a general architecture is feasible. Given a short list of reasonable premises, many DCE applications may be ported to technologies such as CORBA and SOAP. Copyright © 2002 John Wiley & Sons, Ltd.     

Generating robust and flexible job shop schedules using genetic algorithms

The problem of finding robust or flexible solutions for scheduling problems is of utmost importance for real-world applications as they operate in dynamic environments. In such environments, it is often necessary to reschedule an existing plan due to failures (e.g., machine breakdowns, sickness of employees, deliveries getting delayed, etc.). Thus, a robust or flexible solution may be more valuable than an optimal solution that does not allow easy modifications. This paper considers the issue of robust and flexible solutions for job shop scheduling problems. A robustness measure is defined and its properties are investigated. Through experiments, it is shown that using a genetic algorithm it is possible to find robust and flexible schedules with a low makespan. These schedules are demonstrated to perform significantly better in rescheduling after a breakdown than ordinary schedules. The rescheduling performance of the schedules generated by minimizing the robustness measure is compared with the performance of another robust scheduling method taken from literature, and found to outperform this method in many cases.     

Thermal distribution during destructive pulses in ESD protection devices using a single-shot two-dimensional interferometric method

Thermal distribution during single destructive electrostatic discharge (ESD) events is investigated in smart power ESD protection devices using a two-dimensional holographic interferometry technique. The hot spot dynamics and the position of destructive current filaments is correlated with the thermal distribution under the nondestructive conditions and with the failure analysis results.     

Rendering Caustics on Non-Lambertian Surfaces

This paper presents a new technique for rendering caustics on non-Lambertian surfaces. The method is based on an extension of the photon map which removes previous restrictions limiting the usage to Lambertian surfaces. We add information about the incoming direction to the photons and this allows us to combine the photon map with arbitrary reflectance functions. By using a cone-filter we improve the quality of the radiance estimate in particular at discontinuities. Furthermore we introduce balancing of the photon map which not only reduces the memory requirements but also significantly reduces the rendering time. We have used the method to render caustics on surfaces with reflectance functions varying from Lambertian to glossy specular.