Preferential exclusion of sucrose from recombinant interleukin-1 receptor antagonist: role in restricted conformational mobility and compaction of native state

Understanding the mechanism for sucrose-induced protein stabilization is important in many diverse fields, ranging from biochemistry and environmental physiology to pharmaceutical science. Timasheff and Lee [Lee, J. C. & Timasheff, S. N. (1981) J. Biol. Chem. 256, 7193-7201] have established that thermodynamic stabilization of proteins by sucrose is due to preferential exclusion of the sugar from the protein's surface, which increases protein chemical potential. The current study measures the preferential exclusion of 1 M sucrose from a protein drug, recombinant interleukin 1 receptor antagonist (rhIL-1ra). It is proposed that the degree of preferential exclusion and increase in chemical potential are directly proportional to the protein surface area and that, hence, the system will favor the protein state with the smallest surface area. This mechanism explains the observed sucrose-induced restriction of rhIL-1ra conformational fluctuations, which were studied by hydrogen-deuterium exchange and cysteine reactivity measurements. Furthermore, infrared spectroscopy of rhlL-1ra suggested that a more ordered native conformation is induced by sucrose. Electron paramagnetic resonance spectroscopy demonstrated that in the presence of sucrose, spin-labeled cysteine 116 becomes more buried in the protein's interior and that the hydrodynamic diameter of the protein is reduced. The preferential exclusion of sucrose from the protein and the resulting shift in the equilibrium between protein states toward the most compact conformation account for sucrose-induced effects on rhIL-1ra.     

Planar-flow spin-casting of molten metals: process behaviour

An experimental study of the planar-flow melt-spinning process was performed in order to gain a better understanding of the steady-state production of microcrystalline and amorphous ribbons. The dependence of the thickness of the ribbon product,T, on process parameters (wheel speed,U, nozzle/wheel gap,G, overpressure, ΔP, nozzle-slot breadth,R, and nozzle-slot width,W) was determined using an apparatus designed to deliver reproducible results. Thicknesses were reproducible to within 5%–8%. Guided by dimensional analysis, the non-dimensional thickness (T/G) was found to depend, within the experimental error, only on a non-dimensional pressure drop (ΔP/ρU ²) and slot breadth (R/G) for fixed thermal conditions. Data from the literature and our data, which considerably extend the range, correlate consistently on this basis. In contrast to the steady behaviour, the limits within which a uniform ribbon can be formed depend on a larger set of parameters; this dependence is sketched with the available data. Finally, a variety of observed ribbon surface textures (free meniscus side) is catalogued.     

A circuit approach to field computation

Many design objectives can be expressed more directly in terms of circuit parameters, such as capacitance and inductance, than in terms of the field vectors E and B. A simple, although radical, change is suggested to provide a closer link between the field and circuit views. The electric potential φ and magnetic vector A are defined, in energy terms, as the primary field quantities, and they are visualized as measures of the capacitance and inductance, respectively. E and B become auxiliary symbols denoting derivatives, so that the customary roles of the potentials and field vectors are reversed. Some of the practical advantages of the change are examined and are illustrated by example     

ART-EMAP: A neural network architecture for object recognition byevidence accumulation

A new neural network architecture is introduced for the recognition of pattern classes after supervised and unsupervised learning. Applications include spatio-temporal image understanding and prediction and 3D object recognition from a series of ambiguous 2D views. The architecture, called ART-EMAP, achieves a synthesis of adaptive resonance theory (ART) and spatial and temporal evidence integration for dynamic predictive mapping (EMAP). ART-EMAP extends the capabilities of fuzzy ARTMAP in four incremental stages. Stage 1 introduces distributed pattern representation at a view category field. Stage 2 adds a decision criterion to the mapping between view and object categories, delaying identification of ambiguous objects when faced with a low confidence prediction. Stage 3 augments the system with a field where evidence accumulates in medium-term memory. Stage 4 adds an unsupervised learning process to fine-tune performance after the limited initial period of supervised network training. Each ART-EMAP stage is illustrated with a benchmark simulation example, using both noisy and noise-free data.     

Comparison of the eye's wave-front aberration measured psychophysically and with the Shack-Hartmann wave-front sensor

The Shack-Hartmann wave-front sensor offers many theoretical advantages over other methods for measuring aberrations of the eye; therefore it is essential that its accuracy be thoroughly tested. We assessed the accuracy of a Shack-Hartmann sensor by directly comparing its measured wave-front aberration function with that obtained by the Smirnov psychophysical method for the same eyes. Wave-front profiles measured by the two methods agreed closely in terms of shape and magnitude with rms differences of approximately lambda/2 and approximately lambda/6 (5.6-mm pupil) for two eyes. Primary spherical aberration was dominant in these profiles, and, in one subject, secondary coma was opposite in sign to primary coma, thereby canceling its effect. Discovery of an unusual, subtle wave-front anomaly in one individual further demonstrated the accuracy and sensitivity of the Shack-Hartmann wave-front sensor for measuring the optical quality of the human eye.     

Quality of care problems among Medicare and Medicaid patients

The purpose of this study was to characterize quality of care problems among Medicare and Medicaid inpatients in New York State. The patients selected for this study comprised 1991 and 1992 Medicare and all 1992 Medicaid inpatients in whom quality of care problems with actual or potential adverse effects were found. The patients in this study were drawn from public, proprietary, voluntary and teaching hospitals. A total of 1000 quality of care problems with either actual or potential adverse effects were found in 706 Medicare patients. Two hundred and seventy-five (275) quality of care problems with actual or potential adverse effects were found in 154 Medicaid patients. Premature death occurred in 53 (7.4%) of the 706 Medicare and in 42 (27.2%) of the 154 Medicaid patients. Treatment problems and monitoring failures accounted for the majority of quality of care problems with actual or potential adverse effects for both Medicare (63.0%) and Medicaid (75.7%) patients. Among Medicare patients, the treatment of infections and antibiotic use, fluid and electrolyte management, and inappropriate drug use were among the leading causes of quality of care problems. Attending physicians were associated with the majority of Medicare quality of care problems while house staff and attending physicians were associated with the majority of those among Medicaid patients. The results of this study indicate that there are several leading causes of quality of care problems among Medicare and Medicaid patients. Treatment problems and monitoring failures together comprise the majority of such problems. Among Medicare patients, it was found that most quality of care problems were associated with the treatment of infections and antibiotic use, fluid and electrolyte management, and inappropriate drug use. Most quality of care problems among Medicaid patients were associated with these categories as well as with labor and delivery problems, and poor discharge planning. The results of this study reflect the peer-review process in which providers are given an opportunity to respond to physician-reviewer decisions about the presence of actual or potential adverse effects. Such a process, which permits the presentation of additional data and information by providers, produces fewer final adverse outcome determinations than a process uniquely based on chart review. The quality of care problems observed in this study are amenable to focused educational interventions. Such remedial interventions could yield significant improvements in the quality of care for all patients.     

Transient conduction in a slab with chemical reaction

The heat-balance integral technique is used to analyse a one-dimensional transient conduction process. Heat is transferred by convection to the surface of a slab and when the surface temperature reaches a certain value, an endothermic reaction is triggered which propagates as an isothermal front in the same direction as the conduction front. Two possible routes to the fully developed heat transfer condition are treated in a way which allows the approximate temperature distribution in the slab to be predicted as a function of the main process variables.     

Full expression of the exaggerated salt appetite of the spontaneously hypertensive rat requires a prenatal factor

1. The spontaneously hypertensive rat (SHR) exhibits a lower bodyweight in utero and an exaggerated salt appetite post partum. To determine whether salt appetite is affected by the perinatal environment, we measured the salt appetite of embryo-cross-transferred SHR and Wistar Kyoto (WKY) rats at maturity. 2. One-cell embryos were collected from the oviducts of donor rats and transferred into the oviducts of recipients through the infundibulum. The salt appetite of the resultant female offspring for 0.10 and 0.15 mol/L saline was measured at 20-30 weeks of age. 3. Salt intake of SHR gestated in WKY rats was significantly lower than that of SHR gestated in SHR, while that of WKY rats gestated in SHR was higher than that of WKY rats gestated in WKY rats. 4. Therefore, some maternal factor plays a role in the development of the exaggerated salt appetite of the SHR. This factor is also able to affect the later salt appetite of WKY rat offspring born to SHR surrogates.