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.     

Laparoscopic operation of a Morgagni hernia

Morgagni hernias are the least common form of diaphragmatic hernias. Although they are congenital, most of them are not diagnosed until later in life. The indication for surgery is based on the patient's symptoms or on the radiological evidence of incarcerated tissue, and until quite recently involved a laparotomy or thoracotomy. Laparoscopy not only permits the suspected diagnosis to be confirmed--which is otherwise often difficult--but also makes it possible to close the hernia site by suturing. For improved security, the hernia site is augmented by fixing in place a non-absorbable mesh. The operative technique employed is described.     

Expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases in adenocarcinoma cell lines

The levels of mRNA expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases (GalNAc-transferases) were quantified for human adenocarcinoma cell lines from pancreas, colon, stomach, and breast. Two of the GalNAc-transferases, GalNAc-T1 and GalNAc-T2, were expressed constitutively and at low levels in most or all cell lines examined. A third GalNAc-transferase, GalNAc-T3, was differentially expressed. Well-differentiated adenocarcinoma cell lines expressed high levels and moderately differentiated cell lines expressed lower levels of GalNAc-T3. Cell lines classified as poorly differentiated failed to express GalNAc-T3 mRNA at levels that could be detected by Northern blot analysis. Differential expression of the GalNAc-T3 protein was confirmed in these cell lines by Western blotting. We propose that glycosylation in tumor cell lines may be regulated in part by differential expression of GalNAc-transferases, and we suggest that GalNAc-T3 gene expression may be a molecular indicator of differentiated adenocarcinoma.     

An algebraic theory of object-oriented systems

The paper presents an algebraic specification of net objects. By net objects we mean those that are defined in object-oriented paradigms and those defined with nested relations in complex database models. An algebraic specification is set up that involves structures of net objects, accesses of net objects, and some features of object-oriented programming, such as multiple inheritance and polymorphism. Objects and their relationships are then characterized formally in the modeling, which utilizes the hierarchical approach in the algebraic theory of abstract data types, and is further developed by adding mechanisms from existing object systems. Categories of net objects are presented with the properties of accesses among them     

On loop transformations for generalized cycle shrinking

This paper describes several loop transformation techniques for extracting parallelism from nested loop structures. Nested loops can then be scheduled to run in parallel so that execution time is minimized. One technique is called selective cycle shrinking, and the other is called true dependence cycle shrinking. It is shown how selective shrinking is related to linear scheduling of nested loops and how true dependence shrinking is related to conflict-free mappings of higher dimensional algorithms into lower dimensional processor arrays. Methods are proposed in this paper to find the selective and true dependence shrinkings with minimum total execution time by applying the techniques of finding optimal linear schedules and optimal and conflict-free mappings proposed by W. Shang and A.B. Fortes     

Neural network control of communications systems

Neural networks appear well suited to applications in the control of communications systems for two reasons: adaptivity and high speed. This paper describes application of neural networks to two problems, admission control and switch control, which exploit the adaptivity and speed property, respectively. The admission control problem is the selective admission of a set of calls from a number of inhomogeneous call classes, which may have widely differing characteristics as to their rate and variability of traffic, onto a network. It is usually unknown in advance which combinations of calls can be simultaneously accepted so as to ensure satisfactory performance. The approach adopted is that key network performance parameters are observed while carrying various combinations of calls, and their relationship is learned by a neural network structure. The network model chosen has the ability to interpolate or extrapolate from the past results and the ability to adapt to new and changing conditions. The switch control problem is the service policy used by a switch controller in transmitting packets. In a crossbar switch with input queueing, significant loss of throughput can occur when head-of-line service order is employed. A solution can be based on an algorithm which maximizes throughput. However since this solution is typically required in less than one microsecond, software implementation policy is infeasible. We will carry out an analysis of the benefits of such a policy, describe some existing proposed schemes for its implementation, and propose a further scheme that provides this submicrosecond optimization.     

A semantic modeling approach for image retrieval by content

We introduce a semantic data model to capture the hierarchical, spatial, temporal, and evolutionary semantics of images in pictorial databases. This model mimics the user's conceptual view of the image content, providing the framework and guidelines for preprocessing to extract image features. Based on the model constructs, a spatial evolutionary query language (SEQL), which provides direct image object manipulation capabilities, is presented. With semantic information captured in the model, spatial evolutionary queries are answered efficiently. Using an object-oriented platform, a prototype medical-image management system was implemented at UCLA to demonstrate the feasibility of the proposed approach.     

Cholesterol and vascular disease. Study of pravastatin

Variations in lipid profile and incidence of vascular events were evaluated. Group 1 had a 29.3% reduction of total and a 38.3% reduction of LDL cholesterol as against reductions of 9% and 9.6% respectively in group 2. No significant difference was observed between the two groups as far as the vascular events considered were concerned. Pravastatin is an effective and safe drug. The lack of influence on the evolution of vascular disease would appear to be correlated to the small number of subjects studied and the short follow-up.