Induction of early atherosclerosis in LDL-receptor-deficient mice immunized with beta2-glycoprotein I

BACKGROUND: Immunization with beta2-glycoprotein I (beta2GPI), the probable target of autoimmune anticardiolipin antibodies, results in experimental antiphospholipid syndrome in different mouse strains. The present study was undertaken to evaluate the effect of beta2GPI immunization on the progression of atherosclerosis. METHODS AND RESULTS: In the first experiment, 3 groups of LDL receptor-deficient (LDL-RD) mice (n=15 per group) were immunized with either beta2GPI or ovalbumin or were not immunized and were fed a chow diet for 12 weeks. In a second experiment, 3 groups of LDL-RD mice (n=10 per group) were immunized similarly and fed an atherogenic diet for 6 weeks. All beta2GPI-immunized mice developed high titers of anti-beta2GPI antibodies as well as a specific lymph node proliferation to beta2GPI. The average cholesterol levels did not differ between the mice fed similar diets, regardless of the immunization protocol. Atherosclerosis was enhanced in the beta2GPI-immunized mice (mean aortic lesion, 26 000+/-5700 microm2) in comparison with their ovalbumin-immunized (mean, 3000+/-1099 microm2; P<0.01) and nonimmunized (mean, 2250+/-700 microm2; P<0.01) littermates. The average lesion size in the beta2GPI-immunized mice fed an atherogenic diet (mean, 98 000+/-8305 microm2) was larger than the ovalbumin-immunized mice (mean, 81 250+/-12 933 microm2; P=NS) or the nonimmunized controls (mean, 75 625+/-7281 microm2; P=NS). The atherosclerotic plaques in the beta2GPI-immunized mice appeared to be more mature, and denser infiltration of CD4 lymphocytes was present in the subendothelium of the aortic sinuses from this group of mice. CONCLUSIONS: The results of the present study provide the first direct evidence for the proatherogenic effect of ss2GPI immunization and establish a new model for immune-mediated atherosclerosis.     

Towards a comprehensive methodology for KBS development

Abstract: The vitality of effective methods and processes for developing knowledge-based systems (KBS) is examined. The paper discusses what should be expected from a methodology. Have their advocates been getting it all wrong all the way? That is certainly a suggested view put forward. The criticism includes an articulation of the major schools of thought in developing KBS; their implicit assumptions and philosophies, especially the prototyping options, are presented in the light of this paper. After the criticism, the philosophical basis of a new comprehensive KBS development methodology is presented. This breeds the line model of development, which in turn creates what is suspected to be an essential concept of thought in the developer's mind.     

Issues affecting advanced passive light-water reactor safety analysis

Next generation commercial reactor designs emphasize enhanced safety by means of improved safety system reliability and performance. These objectives are achieved via safety system simplification and reliance on immutable natural forces for system operation. Simulating the performance of these safety systems will be central to analytical safety evaluation of advanced passive reactor designs. Yet, the characteristically small driving forces of these safety systems pose challenging computational problems to current thermal-hydraulic systems analysis codes. Additionally, the safety systems generally interact closely with one another, requiring accurate, integrated simulation of the nuclear steam supply system, engineered safeguards and containment. Furthermore, numerical safety analysis of these advanced passive reactor designs will necessitate simulation of long-duration, slowly-developing transients compared with current reactor designs. The composite effects of small computational inaccuracies on induced system interactions and perturbations over long periods may well lead to predicted results which are significantly different than would otherwise be expected or might actually occur. Comparisons between the engineered safety features of competing U.S. advanced light water reactor designs and analogous present day reactor designs are examined relative to the adequacy of existing thermal-hydraulic safety codes in predicting the mechanisms of passive safety. Areas where existing codes may require modification, extension or assessment relative to passive safety designs are identified. Conclusions concerning the applicability of these codes to advanced passive light water reactor safety analysis are presented.     

Caring for dying children: nurses' experiences

Interviews with 25 nurses in this grounded theory study show that when nurses recognized that a child's death was inevitable, they struggled with both grief distress and moral distress. Their distress occurred within the context of the nurse-patient relationship. Nurses employed a range of strategies to manage their distress. Several conditions facilitated or constrained nurses' strategies, and resulted in far-reaching implications both professionally and personally.     

Uncertainty of discrete stochastic systems: general theory andstatistical inference

Uncertainty is defined in a new manner, as a function of discrete probability distributions satisfying a simple and intuitively appealing weak monotonicity condition. It is shown that every uncertainty is Schur-concave and conversely, every Schur-concave function of distributions is an uncertainty. General properties of uncertainties are systematically studied. Many characteristics of distributions introduced previously in statistical physics, mathematical statistics, econometrics and information theory are shown to be particular examples of uncertainties. New examples are introduced, and traditional as well as some new methods for obtaining uncertainties are discussed. The information defined by decrease of uncertainty resulting from an observation is investigated and related to previous concepts of information. Further, statistical inference about uncertainties is investigated, based on independent observations of system states. In particular, asymptotic distributions of maximum likelihood estimates of uncertainties and uncertainty-related functions are derived, and asymptotically α-level Neyman-Pearson tests of hypotheses about these system characteristics are presented     

Comparison of computational results obtained with different programs for radiation transfer

Main Science Center of the Russian Federation — Institute of High-Energy Physics. Translated from Atomnaya énergiya, Vol. 79, No. 4, pp. 269–279, October, 1995.     

Stochastic modelling of temperatures for a full-scale occupied building zone subject to natural random influences

Buildings are usually subject to a variety of stochastic influences. Though the deterministic approach to building thermal modelling is widespread, it cannot easily model the effects of such influences, and a different approach might be better. In this study, stochastic models are derived which describe the thermal behaviour of a full-scale room exposed to the naturally occurring disturbances of climate (temperature, solar irradiance, infiltration), occupancy and appliance usage. A Box-Jenkins time series analysis technique is employed, and univariate stochastic models are fitted to the internal and external air temperature series. The models are validated by comparing the observed temperature with values forecasted ahead (in steps of 1 h) by the models, over a 36-h period; agreement was found to be good. It is concluded that the stochastic modelling approach can be applied successfully to the thermal analysis of a building's behaviour, thereby affording a method which accounts for random influences in a compact model format. The technique has particular relevance to advanced model-based control implemented via ‘intelligent’ digital controllers and building energy management systems, and its application in this respect is discussed.     

Energy consumption modeling and optimization for SRAM's

The recent trends in portable computing technologies have established the need for energy efficient design strategies. To achieve minimum energy design goals, system designers need a technique to accurately model the energy consumption of their design alternatives without performing a full physical design and full-circuit simulation. This paper presents and compares five approaches for modeling the energy consumption of CMOS circuits. These five modeling approaches have been chosen to represent the various levels of model complexity and accuracy found in the current literature. These modeling approaches are applied to the energy consumption of SRAM's to provide examples of their use and to allow for the comparison of their modeling qualities. It was found that a mixed characterization model-using a CV² prediction for digital subsections and fitted simulation results for the analog subsections-is satisfactory (within ±1 process variation) for predicting the absolute energy consumed per cycle. This same model is also very good (within 2%) for predicting an optimum organization for the internal structures of the SRAM. Several common architectures and circuit designs for SRAM's are analyzed with these models. This analysis shows that global, rather than local improvements, produce the largest energy savings     

Failure of Ixodes ticks to inherit Borrelia afzelii infection

To define conditions promoting inherited infection by Lyme disease spirochetes in Ixodes ticks, we variously infected ticks with Borrelia afzelii and examined their progenies by dark-field microscopy, immunofluorescence, PCR, and serial passage. No episode of inherited infection was evident, regardless of instar or gender infected or frequency of exposure. We suggest that these spirochetes rarely, if ever, are inherited by vector ticks.     

Transcytosis of alpha1-acidic glycoprotein in the continuous microvascular endothelium

By using perfusions and bolus administration, coupled with postembedding immunocytochemical procedures, we have identified the structures involved in the transport of derivatized orosomucoid (alpha1-acidic glycoprotein) across the continuous microvascular endothelium of the murine myocardium. Our findings indicate that: (i) monomeric orosomucoid binds to the luminal surface of the endothelium; (ii) it is restricted to caveolae during its transport across the endothelium; (iii) it is detected in the perivascular spaces at early time points (by 1 min) and in larger quantities at later time points (>5 min) from the beginning of its perfusion or its intravascular administration; (iv) no orosomucoid molecules are found in the intercellular junctions or at the abluminal exits of interendothelial spaces; and (v) the vesicular transport of orosomucoid is strongly inhibited by N-ethylmaleimide (>80%). Because, by size and shape, the orosomucoid qualifies as a preferential probe for the postulated small pore system, our results are discussed in relation to the pore theory of capillary permeability.