Dramatically stabilized phosphotriesterase-polymers for nerve agent degradation

Phosphotriesterase (EC 3.1.8.1) was immobilized within a polyurethane foam matrix during polymer synthesis using a prepolymer synthesis strategy. In addition to retaining greater than 50% of the enzyme specific activity, numerous benefits were incurred upon immobilization. Orders of magnitude increases in storage and thermal stability (net stabilization energy = 12.5 kJ/mol) were observed without the need for enzyme premodification. The immobilized enzyme system was protease resistant and seemed to display no adverse effects from immobilization, such as an alteration of enzyme function. The organic solvent, dimethyl sulfoxide, also exhibited a stabilizing effect on phosphotriesterase enzyme systems over a range of intermediate concentrations. We attribute these effects in part to direct interaction between the aprotic solvent and metal containing residues present at the enzyme's active site. Our data demonstrate that just 2.5 kg of immobilized enzyme may be sufficient to degrade 30,000 tons of nerve agent in just 1 year. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 54: 105-114, 1997.     

Resistance to Bark Beetle Attack in Caribbean Pine: Potential Role of 4‐Allylanisole1

In the Neotropics, Caribbean pine is subject to epidemic attack by southern pine beetle. We found significantly higher levels (>2.5%) of 4‐allylanisole in the monoterpenoid fraction of the oleoresin of trees in stands with high beetle‐induced mortality, and a negative association between magnitude of attack and levels of 4‐allylanisole in individual trees. Results also suggest that individual trees with low 4‐allylanisole levels may escape attack if they occur in stands characterized by high levels of this compound.     

SULFISOMIDINE IN THE TREATMENT OF PERTUSSIS

Sulfisomidine and pertussis serum were used in the treatment of 21 patients with pertussis. Twenty of the patients were under six months of age and seven had bronchopneumonia.Therapeutic concentrations of the drug in the blood were obtained in 14 cases when it was given in dosage of 0.26 gm. per kilogram of body weight per 24 hours.The average stay in hospital was ten days. None of the patients died. Hematuria developed in one case but crystalluria was not concomitant and it abated promptly when fluid intake was increased.     

A Comparative Survey of Automated Parameter-Search Methods for Compartmental Neural Models

One of the most difficult and time-consuming aspects of building compartmental models of single neurons is assigning values to free parameters to make models match experimental data. Automated parameter-search methods potentially represent a more rapid and less labor-intensive alternative to choosing parameters manually. Here we compare the performance of four different parameter-search methods on several single-neuron models. The methods compared are conjugate-gradient descent, genetic algorithms, simulated annealing, and stochastic search. Each method has been tested on five different neuronal models ranging from simple models with between 3 and 15 parameters to a realistic pyramidal cell model with 23 parameters. The results demonstrate that genetic algorithms and simulated annealing are generally the most effective methods. Simulated annealing was overwhelmingly the most effective method for simple models with small numbers of parameters, but the genetic algorithm method was equally effective for more complex models with larger numbers of parameters. The discussion considers possible explanations for these results and makes several specific recommendations for the use of parameter searches on neuronal models.     

Isothiazolidinone inhibitors of PTP1B containing imidazoles and imidazolines

The structure-based design and synthesis of isothiazolidinone (IZD) inhibitors of PTP1B containing imidazoles and imidazolines and their modification to interact with the B site of PTP1B are described here. The X-ray crystal structures of 3I and 4I complexed with PTP1B were solved and revealed the inhibitors are interacting extensively with the B site of the enzyme.     

Setting standards based on patients' views on access and continuity: secondary analysis of data from the general practice assessment survey

ObjectivesTo examine patients'' views on access and continuity in general practice to derive quality standards.DesignSecondary analysis of data from general practice research studies and routine quality assessment activities undertaken by practices and primary care trusts.SettingGeneral practice.ParticipantsGeneral practice patients.ResultsSatisfactory standards of access were next day appointments with general practitioners and a 6-10 minute wait for consultations to begin. A satisfactory level of continuity was seeing the same general practitioner “a lot of the time.” Standards varied with the analytic method used and by sociodemographic group.ConclusionsStandards expected by patients in primary care can be derived from linked report-assessment pairs. Patients may have expectations of access that are in excess of government targets. Patients also have high expectations of continuity of care. It is unclear the degree to which such standards are reliable or valid, how conflicts between access and continuity should be resolved, or how these standards relate to other priorities of patients such as high quality interpersonal care.

What is already known on this topic

Standards are increasingly being set for the provision of health servicesSurveys and consultation exercises before the NHS plan helped set the standard for a maximum waiting time of 48 hours for appointments to see general practitionersThe optimal methods by which patients should be involved in setting standards and the utility of such standards are unclear

What this study adds

Satisfactory standards of access were next day appointments, a 6-10 minute wait for consultations to begin, and seeing the same general practitioner a lot of the timePatients may have expectations for access to primary care in excess of current government targets