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.     

Identification of novel exons 3'' to the human SNRPN gene

This paper examines the relationship between self-efficacy and social power (expert and referent) and how the application of this relationship, leads to client adherence and compliance. Referent power is defined, including methods that health care professionals may use to develop and apply referent power. Expert power is defined and addressed in the context of referent power, self-esteem and self-efficacy as a means of promoting adherence. Self-efficacy as a concept is defined and explored in the context of social power. The relationships between self-efficacy and social power (expert and referent) are shown as important determinants of adherence and compliance. The theory of the application of referent and expert power in relationship with self-efficacy has been compared with an effective programme, yielding high compliance, at Western Psychiatric Institute and Clinic, showing the theory's relevance and applicability in determining compliance. Explored are the reasons for non-compliance in the elderly population and how the theory model can remedy these detriments for compliance. The empowerment of elderly patients through the application of this theory to medication compliance is examined. The determination of adherence and compliance is shown by the application of the relationship between self-efficacy and both expert and referent power.     

Differential divalent cation requirements uncouple the assembly and catalytic reactions of human immunodeficiency virus type 1 integrase

Previous in vitro analyses have shown that the human immunodeficiency virus type 1 (HIV-1) integrase uses either manganese or magnesium to assemble as a stable complex on the donor substrate and to catalyze strand transfer. We now demonstrate that subsequent to assembly, catalysis of both 3' end processing and strand transfer requires a divalent cation cofactor and that the divalent cation requirements for assembly and catalysis can be functionally distinguished based on the ability to utilize calcium and cobalt, respectively. The different divalent cation requirements manifest by these processes are exploited to uncouple assembly and catalysis, thus staging the reaction. Staged 3' end processing and strand transfer assays are then used in conjunction with exonuclease III protection analysis to investigate the effects of integrase inhibitors on each step in the reaction. Analysis of a series of related inhibitors demonstrates that these types of compounds affect assembly and not either catalytic process, therefore reconciling the apparent disparate results obtained for such inhibitors in assays using isolated preintegration complexes. These studies provide evidence for a distinct role of the divalent cation cofactor in assembly and catalysis and have implications for both the identification and characterization of integrase inhibitors.     

One or two incisions for nephroureterectomy in transitional cell renal pelvis tumours

A retrospective study comprising 18 patients with transitional cell renal pelvis tumours (TCPT) was carried out to evaluate the results after two different surgical procedures for nephroureterectomy. The kidney was removed by a flank incision and the lower part of the ureter by either an incision in the lower part of the abdomen or intussusception of the ureter followed by transurethral resection of the ureteral orifice. Eight patients were subjected to nephroureterectomy by means of two incisions and another eight patients underwent a simple nephrectomy followed by ureteral intus-susception and transurethral resection. Two patients received other treatments. After nephroureterectomy with a separate incision for ureterectomy, the average hospital stay was 12 days, compared with 7.5 days in patients operated upon with only one abdominal incision. Recurrence of tumour or survival was not significantly different in the two groups.     

A biased percolation model for the analysis of electronic-device degradation

The biased percolation model is proposed for investigating device degradation and failure associated with the generation of defects due to local Joule heating. The degradation processes of a thin conducting or semiconducting film is monitored by a set of relevant indicators, such as: the evolution of damage pattern, the current distribution, the film resistance and its fluctuations, the defect concentration, the film lifetime, etc. The conductor-insulator (CI) and conductor-superconductor (CS) like degradation processes are considered. The results can be used to propose non-destructive indicators to test the reliability of samples and to interpret the corresponding experiments.     

Error in the UNITY substitution rule for subscripted operators

UNITY, introduced by Chandy and Misra [ChM88], is a programming logic intended to reason about temporal properties of distributed programs. Despite the fact that UNITY does not have the full power of, for example, linear temporal logic, it enjoys popularity due to its simplicity.There was however a serious problem with the Substitution Rule. The logic is incomplete without the rule, and with the rule it is inconsistent.     

Performance evaluation of rule grouping on a real-time expertsystem architecture

Uses a Markov process to model a real-time expert system architecture characterized by message passing and event-driven scheduling. The model is applied to the performance evaluation of rule grouping for real-time expert systems running on this architecture. An optimizing algorithm based on Kernighan-Lin heuristic graph partitioning for the real-time architecture is developed and a demonstration system based on the model and algorithm has been developed and tested on a portion of the advanced GPS receiver (AGR) and manned manoeuvring unit (MMU) knowledge bases     

The performance of cache-based error recovery in multiprocessors

Several variations of cache-based checkpointing for rollback error recovery from transient errors in shared-memory multiprocessors have been recently developed. By modifying the cache replacement policy, these techniques use the inherent redundancy in the memory hierarchy to periodically checkpoint the computation state. Three schemes, different in the manner in which they avoid rollback propagation, are evaluated in this paper. By simulation with address traces from parallel applications running on an Encore Multimax shared-memory multiprocessor, we evaluate the performance effect of integrating the recovery schemes in the cache coherence protocol. Our results indicate that the cache-based schemes can provide checkpointing capability with low performance overhead, but with uncontrollable high variability in the checkpoint interval     

Quantization effects in digitally behaving circuit implementationsof Kohonen networks

Implementing a neural network on a digital or mixed analog and digital chip yields the quantization of the synaptic weights dynamics. This paper addresses this topic in the case of Kohonen's self-organizing maps. We first study qualitatively how the quantization affects the convergence and the properties, and deduce from this analysis the way to choose the parameters of the network (adaptation gain and neighborhood). We show that a spatially decreasing neighborhood function is far more preferable than the usually rectangular neighborhood function, because of the weight quantization. Based on these results, an analog nonlinear network, integrated in a standard CMOS technology, and implementing this spatially decreasing neighborhood function is then presented. It can be used in a mixed analog and digital circuit implementation.     

A model for evaluation and administration of security inobject-oriented databases

The integration of object-oriented programming concepts with databases is one of the most significant advances in the evolution of database systems. Many aspects of such a combination have been studied, but there are few models to provide security for this richly structured information. We develop an authorization model for object-oriented databases. This model consists of a set of policies, a structure for authorization rules, and algorithms to evaluate access requests against the authorization rules. User access policies are based on the concept of inherited authorization applied along the class structure hierarchy. We propose also a set of administrative policies that allow the control of user access and its decentralization. Finally, we study the effect of class structuring changes on authorization