Interpretation of the reversible inhibition of adenosine deaminase by small cosolutes in terms of molecular crowding

Published results on the inhibitory effects of small cosolutes on adenosine deamination by adenosine deaminase [Kurz. L. C.. Weitkamp, E., and Frieden, C. (1987) Biochemistry 26, 3027-3032; Dzingeleski, G., and Wolfenden, R. (1993) Biochemistry 32, 9143 -9147] have been reexamined. Results for sucrose, dioxane, methanol, and ethanol are shown to be qualitatively consistent with thermodynamic interpretation in terms of molecular crowding effects arising from the occurrence of a minor increase in enzyme volume and/or asymmetry during the kinetic reaction-a conformational transition that could be either preexisting or ligand induced. Direct evidence for the existence of the putative isomeric transition is provided by active enzyme gel chromatography on Sephadex G-100, which demonstrates a negative dependence of enzyme elution volume upon substrate concentration and is therefore consistent with substrate-mediated conformational changes that favor a larger (or more asymmetric) isomeric state of the enzyme. There are thus experimental grounds for adopting the present description of the inhibitory effects of unrelated cosolutes on the kinetics of adenosine deamination by adenosine deaminase in terms of thermodynamic nonideality.

Analysis of thermodynamic non-ideality in terms of protein solvation

The effects of thermodynamic non-ideality on the forms of sedimentation equilibrium distributions for several isoelectric proteins have been analysed on the statistical-mechanical basis of excluded volume to obtain an estimate of the extent of protein solvation. Values of the effective solvation. parameter delta are reported for ellipsoidal as well as spherical models of the proteins, taken to be rigid, impenetrable macromolecular structures. The dependence of the effective solvated radius upon protein molecular mass exhibits reasonable agreement with the relationship calculated for a model in which the unsolvated protein molecule is surrounded by a 0.52-nm solvation shell. Although the observation that this shell thickness corresponds to a double layer of water molecules may be of questionable relevance to mechanistic interpretation of protein hydration, it augurs well for the assignment of magnitudes to the second virial coefficients of putative complexes in the quantitative characterization of protein-protein interactions under conditions where effects of thermodynamic non-ideality cannot justifiably be neglected. (C) 2001 Elsevier Science B.V. All rights reserved.

It's all in the contract: Rethinking feminist critiques of contract

This article examines contemporary feminist arguments about contract. It does not aim to advance new arguments for or against contract but to call into question the dominant feminist position which is that contract has to be cast aside and/or that alternative approaches to contract have to be developed in order to advance the position of women. In a reworking of Elizabeth Kingdom's anti-essentialist approach to rights, Sullivan argues that a feminist but non-essentialist approach to contract is both possible and desirable. Sullivan explores a number of concrete situations in the Australian context where contract approaches have been deployed in law and public policy and demonstrates that contract may be detrimental or advantageous to the position of women. Sullivan argues, therefore, for a strategic and critical feminist approach to the utilisation of the language and practice of contract.

Comparative study of symmetric and asymmetric cylindrical MRI gradient Y-coils in terms of induced eddy currents

We have recently introduced the concept of whole-body asymmetric MRI systems [1]. In this theoretical study, we investigate the PNS characteristics of whole-body asymmetric gradient systems as compared to conventional symmetric systems. Recent experimental evidence [2] supports the hypothesis of transverse gradients being the largest contributor of PNS due to induced electric currents. Asymmetric head gradient coils have demonstrated benefits in the past [3]. The numerical results are based on an anatomically-accurate 2mm-human voxel-phantom NORMAN [4]. The results of this study can facilitate the optimization of whole-body asymmetric gradients in terms of patient comfort/safety (less PNS), while prospering the use of asymmetric MRI systems for in-vivo medical interventions.

On compliance of business processes with business contracts

This paper addresses the problem of ensuring compliance of business processes, implemented within and across organisational boundaries, with the constraints stated in related business contracts. In order to deal with the complexity of this problem we propose two solutions that allow for a systematic and increasingly automated support for addressing two specific compliance issues. One solution provides a set of guidelines for progressively transforming contract conditions into business processes that are consistent with contract conditions thus avoiding violation of the rules in contract. Another solution compares rules in business contracts and rules in business processes to check for possible inconsistencies. Both approaches rely on a computer interpretable representation of contract conditions that embodies contract semantics. This semantics is described in terms of a logic based formalism allowing for the description of obligations, prohibitions, permissions and violations conditions in contracts. This semantics was based on an analysis of typical building blocks of many commercial, financial and government contracts. The study proved that our contract formalism provides a good foundation for describing key types of conditions in contracts, and has also given several insights into valuable transformation techniques and formalisms needed to establish better alignment between these two, traditionally separate areas of research and endeavour. The study also revealed a number of new areas of research, some of which we intend to address in near future.

Who's really hypertensive? - Quality control issues in the assessment of blood pressure for randomized trials

The characterization of blood pressure in treatment trials assessing the benefits of blood pressure lowering regimens is a critical factor for the appropriate interpretation of study results. With numerous operators involved in the measurement of blood pressure in many thousands of patients being screened for entry into clinical trials, it is essential that operators follow pre-defined measurement protocols involving multiple measurements and standardized techniques. Blood pressure measurement protocols have been developed by international societies and emphasize the importance of appropriate choice of cuff size, identification of Korotkoff sounds, and digit preference. Training of operators and auditing of blood pressure measurement may assist in reducing the operator-related errors in measurement. This paper describes the quality control activities adopted for the screening stage of the 2nd Australian National Blood Pressure Study (ANBP2). ANBP2 is cardiovascular outcome trial of the treatment of hypertension in the elderly that was conducted entirely in general practices in Australia. A total of 54 288 subjects were screened; 3688 previously untreated subjects were identified as having blood pressure >140/90 mmHg at the initial screening visit, 898 (24%) were not eligible for study entry after two further visits due to the elevated reading not being sustained. For both systolic and diastolic blood pressure recording, observed digit preference fell within 7 percentage points of the expected frequency. Protocol adherence, in terms of the required minimum blood pressure difference between the last two successive recordings, was 99.8%. These data suggest that adherence to blood pressure recording protocols and elimination of digit preferences can be achieved through appropriate training programs and quality control activities in large multi-centre community-based trials in general practice. Repeated blood pressure measurement prior to initial diagnosis and study entry is essential to appropriately characterize hypertension in these elderly patients.

Extending choreography with business contract constraints

Business contracts play a central role in governing commercial interactions between organizations. It is increasingly recognized that business contract conditions need to be closely linked to internal and external business processes, both to reduce the risk of contract violations and to ensure compliance with legislative regimes. Recent research has proposed contract languages allowing the specification of obligations, permissions and prohibitions in business contracts. Business processes that cross-organizational boundaries can be specified in choreography and coordination languages but these do not provide appropriate abstractions for contract constraints. In this paper, we examine the transformation of contract constraints in a business contract language into expressions in a choreography language. An example cross-organizational process is presented, along with a specification of the process in a choreography language and a specification of a set of contract conditions for the process in a business contract language. The contract terms are then translated into choreography expressions that govern the process to ensure compliance. Subsequent discussion explores a number of business and technology issues related to the results. We conclude that cross-organizational business processes can be monitored and enforced according to business contract specifications through the transformation of a contract definition to constraints on process behavior.

Inter- and intralaboratory variation of in vitro diffusion cell measurements: An international multicenter study using quasi-standardized methods and materials

In vitro measurements of skin absorption are an increasingly important aspect of regulatory studies, product support claims, and formulation screening. However, such measurements are significantly affected by skin variability. The purpose of this study was to determine inter- and intralaboratory variation in diffusion cell measurements caused by factors other than skin. This was attained through the use of an artificial (silicone rubber) rate-limiting membrane and the provision of materials including a standard penetrant, methyl paraben (MP), and a minimally prescriptive protocol to each of the 18 participating laboratories. Standardized calculations of MP flux were determined from the data submitted by each laboratory by applying a predefined mathematical model. This was deemed necessary to eliminate any interlaboratory variation caused by different methods of flux calculations. Average fluxes of MP calculated and reported by each laboratory (60 +/- 27 mug cm(-2) h(-1), n = 25, range 27-101) were in agreement with the standardized calculations of MP flux (60 +/- 21 mug cm(-2) h(-1), range 19-120). The coefficient of variation between laboratories was approximately 35% and was manifest as a fourfold difference between the lowest and highest average flux values and a sixfold difference between the lowest and highest individual flux values. Intra-laboratory variation was lower, averaging 10% for five individuals using the same equipment within a single laboratory. Further studies should be performed to clarify the exact components responsible for nonskin-related variability in diffusion cell measurements. It is clear that further developments of in vitro methodologies for measuring skin absorption are required. (C) 2005 Wiley-Liss, Inc.

Effects of psychological contract breach on performance of IT employees: The mediating role of affective commitment

In this study, we investigated the relationships between psychological contract breach, affective commitment, and two types of employee performance (i.e. civic virtue behaviour and in-role performance). It was predicted that an experience of contract breach can severely hurt the affective commitment of the employees and this, in turn, results in poor in-role performance and less civic virtue behaviours. Results revealed that affective commitment had differential mediating effects on the two types of employee performance. That is, affective commitment mediated the relationship between breach and self-reported and supervisor-rated civic virtue, but not the relationship between breach and in-role performance.