Characterization of mutated transforming growth factor-beta s which possess unique biological properties

Transforming growth factor-beta (TGF-beta) is a potent regulator of cell growth and differentiation. On the basis of the crystal structure of TGF-beta 2, we have designed and synthesized two mutant TGF-beta s, TGF-beta 1 (71 Trp) and TGF-beta 1 (delta 69-73). Although both of these molecules inhibited the growth of Mv1Lu mink lung epithelial cells and LS1034 colorectal cancer cells, which are affected equally by TGF-beta 1 and TGF-beta 2, TGF-beta 1 (delta 69-73) was much less potent than TGF-beta 1 or TGF-beta 1 (71 Trp) at inhibiting the growth of LS513 colorectal cancer cells which are growth-inhibited by TGF-beta 1 but not TGF-beta 2. Both TGF-beta 1 (71 Trp) and TGF-beta 1 (delta 69-73) increased levels of mRNAs for fibronectin and plasminogen activator inhibitor with Mv1Lu cells, whereas only TGF-beta 1 (71 Trp) and not TGF-beta 1 (delta 69-73) up-regulated the mRNA level of carcinoembryonic antigen in LS513 cells. The expression level of carcinoembryonic antigen mRNA in LS1034 cells was not altered by either wild-type or mutant TGF-beta s. Receptor labeling experiments demonstrated that TGF-beta 1 (71 Trp) bound with high affinity to the cell-surface receptors of Mv1Lu, LS1034, and LS513 cells while TGF-beta 1 (delta 69-73) bound effectively to the receptors of Mv1Lu and LS1034 cells but much less to the receptors on LS513 cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hidden Implementation Dependencies in High Assurance and Critical Computing Systems

Critical and catastrophic failures in high assurance and critical computing systems can arise from unfounded assumptions of independence between system components, requirements, and constraints (work product sections), which can stem from misunderstandings and miscommunication between system engineers, managers, and operators and from inadequate or incomplete traceability between system work products. In this article, we propose a formal framework for the effective implementation of traceability between work product sections along with a technique for discovering potential causes of critical failures in high assurance and critical computing system models. We introduce a new abstraction of interrelated work product sections called implementation meta-work product and describe how our technique finds these meta-work products. We also demonstrate how this technique can be used to help analysts discover potential causes of safety-related errors in high assurance and critical computing systems by applying it to one case study of a known critical error and to one case study where we anticipate potential safety hazards     

Complete transformer model for electromagnetic transients

A complete, three phase transformer model for the calculation of electromagnetic transients is presented. The model consists of a set of state equations solved with the trapezoidal rule of integration in order to obtain an equivalent Norton circuit at the transformer terminals. Thus the transformer model can be easily interfaced with an electromagnetic transients program. Its main features are: (a) the basic elements for the winding model are the turns; (b) the complete model includes the losses due to eddy currents in the windings and in the iron core; and (c) the solution of the state equations is obtained in decoupled iterations. For validation, the frequency response of the model is compared with tests on several transformers. Applications to the calculation of transients are given for illustration     

Photoelectrical properties of In/n-CuIn5Se8 Schottky barriers

CuIn₅Se₈ homogeneous crystals of n-type conductivity have been grown. Donor centers activation energy has been estimated. In/n-CuIn₅Se₈ Schottky barriers have been created and the first spectral dependencies of quantum efficiency of photoconversion of these structures have been derived. The nature of interband optical transitions has been interpreted and the band gap values for direct and indirect transitions in CuIn₅Se₈ crystals have been determined on the results of analysis of the Schottky barriers photoactive edge absorption. A possibility of utilization of CuIn₅Se₈ crystals in wide-band photoconverters of the optical radiation has been established.     

Principal axes and surface fitting methods for three-dimensional image registration

We evaluated the effect of the image acquisition parameters on the accuracy of the principal axes and surface-fitting techniques for three-dimensional image registration. Using two types of phantom objects, MR brain image and a mathematically defined ellipsoid, we simulated pairs of scans with known acquisition parameters, including longitudinal coverage, magnitude of mis-registration, number of sections and section thickness. Both methods are sensitive to the systematic deformation of contours. The principal axes method is also sensitive to incomplete scan coverage and to the x-axis and y-axis misangulation. Both methods are insensitive to the number of sections, section thickness and the number of points per section. Surface fitting performed well without user supervision. There is no need for routine inclusion of the scaling factors as search parameters. The results confirm the feasibility of three-dimensional multimodality registration of brain scans with accuracy 1-2 mm, with surface fitting being the method of choice.     

Attenuation of ischemic liver injury by prostaglandin E1 analogue, misoprostol, and prostaglandin I2 analogue, OP-41483

Workplace AIDS training is a recent addition to many corporations' occupational health agenda. However, little is known about the objectives, content, and practices of AIDS training programs. A survey of 126 workplace AIDS trainers was conducted to determine the impact of the trainer's organizational affiliation (in-house, consultant, union, etc.) and personal motives on training program objectives, content, and practices. Results indicate that the organizational affiliation of trainers is significantly related to training objectives, topics, and practices, whereas strong personal motives for becoming an AIDS trainer is significantly associated with an emphasis on more controversial content areas and training practices. Findings are discussed in terms of applicability to other values-oriented training topics, applications to practice, and future research needs.     

Activity of the plasma membrane H(+)-ATPase and optimal glycolytic flux are required for rapid adaptation and growth of Saccharomyces cerevisiae in the presence of the weak-acid preservative sorbic acid

The weak acid sorbic acid transiently inhibited the growth of Saccharomyces cerevisiae in media at low pH. During a lag period, the length of which depended on the severity of this weak-acid stress, yeast cells appeared to adapt to this stress, eventually recovering and growing normally. This adaptation to weak-acid stress was not due to metabolism and removal of the sorbic acid. A pma1-205 mutant, with about half the normal membrane H+-ATPase activity, was shown to be more sensitive to sorbic acid than its parent. Sorbic acid appeared to stimulate plasma membrane H+-ATPase activity in both PMA1 and pma1-205. Consistent with this, cellular ATP levels showed drastic reductions, the extent of which depended on the severity of weak-acid stress. The weak acid did not appear to affect the synthesis of ATP because CO2 production and O2 consumption were not affected significantly in PMA1 and pma1-205 cells. However, a glycolytic mutant, with about one-third the normal pyruvate kinase and phosphofructokinase activity and hence a reduced capacity to generate ATP, was more sensitive to sorbic acid than its isogenic parent. These data are consistent with the idea that adaptation by yeast cells to sorbic acid is dependent on (i) the restoration of internal pH via the export of protons by the membrane H+-ATPase in an energy-demanding process and (ii) the generation of sufficient ATP to drive this process and still allow growth.