Biodegradable polymers for use in surgery — poly(glycolic)/poly(Iactic acid) homo and copolymers: 2. In vitro degradation

The degradation mechanism of a series of polyglycolic/polylactic acid, (PGA/PLA), homo and copolymers synthesized as in Part 1¹, has been studied _vitro. An in vitro test model similar to that described in a previous study⁹, was used. The effects of time, temperature and pH on the rate and mechanism of degradation were elucidated. The degree of degradation was monitored molecularly by gel permeation chromatography (g.p.c.), tensile strength determination and mass loss measurements. The mechanism of degradation is shown to be by hydrolysis. The copolymers of PGA and PLA are shown to have a wide range of degradation rates governed by the hydrophilic/hydrophobic balance and crystallinity of the respective copolymer. The effect of the glass transition temperature (T_g) of PGA on its sensitivity to degradation is also demonstrated.     

Application Development Productivity Tools: A Survey Of Importance and Popularity

Application development productivity is becoming an increasingly important issue in the MIS department. Unfortunately, dramatic improvements in hardware performance have not been matched with corresponding advances in software development, even though there have been significant investments in productivity tools. This article identifies a range of productivity tools and presents results from a survey of MIS managers that reveals which specific tools are being used and their relative importance to software development productivity.     

Cell-free apoptosis in Xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria

Apoptotic cell death involves a ritual series of morphological changes, presumably reflecting a conserved molecular pathway. We now report that the nuclear events typical of apoptosis can be reproduced in "apoptotic" Xenopus egg extracts. In this cell-free system, nuclear assembly and protein import are initially normal; after 2-4 hr, however, a process of nuclear destruction ensues involving chromatin condensation and the shrinkage and fragmentation of the nuclei. This apoptotic process, which also occurs in nuclei added exogenously, is blocked by the addition of baculovirus-expressed Bcl-2 protein. To block the disintegration of nuclei that are added later, Bcl-2 must be present during this latent period. "Apoptosis" in these extracts requires a dense organelle fraction enriched in mitochondria. The cell-free system described here provides a novel tool for understanding intracellular events in apoptosis and the inhibitory function of Bcl-2.     

Molecular structures and conformational studies of triarylcyclopropyl and related nonsteroidal antiestrogens

Molecular structures and conformational characteristics of a series of 1,1-dichloro-2,2,3-triarylcyclopropanes (DTACs), which were reported previously to be distinctly antiestrogenic and inhibitors of the estrogen-receptor-positive MCF-7 human breast cancer cells in culture, are reported. In addition, structural and conformational features of the DTACs were compared to the first-known nonsteroidal antiestrogen, MER25, and the clinically useful antiestrogen Tamoxifen. The molecular structures of four DTAC compounds were determined by X-ray diffraction. Crystallographic structures show that the DTAC molecules have nearly the same relative conformation for the three aryl rings which is designated as a "nonpropeller" conformation in contrast to the observed "propeller" conformation for the three rings in all known triarylethylenes. Systematic conformational searches were performed to find the conformational preferences of DTACs, MER25, and Tamoxifen using idealized model compounds built from their respective crystal structure. Energy-minimization and conformational-search studies demonstrated that all DTAC molecules have a common, single global minimum energy conformer for their central core containing the dichlorotriarylcyclopropyl system, which is similar to that found in their crystal structures. Conformational search of MER25 showed that the molecule can assume a number of low-energy conformers of which two, one anti (A1) and one gauche (G1A), have about the same energy. The anti conformation is similar to the one observed in its crystal structure and resembles the estrogenic E-isomer of Tamoxifen, while the lowest energy gauche conformer of MER25 resembles more closely the antiestrogenic Z-isomer of Tamoxifen. NMR spectroscopic analysis of MER25 showed that the molecule exists predominantly in the anti conformation in solution. A comparative review of the structural features and bioactivities of Tamoxifen, DTACs, and MER25 provides a possible explanation for their low estrogen receptor binding affinity which is common to these compounds together with their antiestrogenic activity.     

The necessity of conducting to the end the activities of vector control in the onchocerciasis control program in west Africa: recall of the stakes and proposal of a minimum budget for the period 1998-2002

After a brief presentation of the Onchocerciasis Control Programme in West Africa (OCP), the authors realize the health and socioeconomic consequences that could follow a cessation of larvicide treatment before 2002 in the south-eastern and western extensions of the Programme. Taking into account that OCP activities are theoretically supported until 1997, but aware of financial constraints that will probably increase from now to 2002, this paper proposes an a minima estimation of the residual vector control activities for a "phasing out" spread out for five years (1998-2002). These estimations essentially concern the larvicide coverage, the insecticides used, the entomological surveillance, the logistical support and their financial aspects. As far as 48 U.S. $ million amount for 5 years are concerned, the budget allocated for vector control activities should not exceed the third of the global amount allocated to OCP for the actual fourth financial phase of the Programme (1992-1997).     

SATCHMORE: SATCHMO with RElevancy

We introduce a relevancy detection algorithm to be used in conjunction with the SATCHMO prover. The version of SATCHMO considered here is essentially a bidirectional prover, utilizing Prolog (back chaining) on Horn clauses and forward chaining on non-Horn clauses. Our extension, SATCHMORE (SATCHMO with RElevancy), addresses the major weakness of SATCHMO: the uncontrolled use of forward chaining. By marking potentially relevant clause head literals, and then requiring that all the head literals be marked relevant (be totally relevant) before a clause is used for forward chaining, SATCHMORE is able to guide the use of these rules. Furthermore, the relevancy testing is performed without extending the proof search beyond what is done in SATCHMO. A simple implementation of the extended SATCHMO can be written in Prolog. We describe our relevancy testing approach, present the implementation, prove soundness and completeness, and provide examples that demonstrate the power of relevancy testing.This research was partially supported by NSF Grants IRI-8805696 and CCR-9116203. This paper is a major revision of Wilson and Loveland (1989).     

Low cycle fatigue life prediction in shot‐peened components of different geometries—part I: residual stress relaxation

In this study, the residual stress relaxation behaviour occurring during low‐cycle fatigue in shot‐peened specimens with either a flat or a notched geometry has been studied. A representative low‐pressure steam turbine material, FV448, was used. The residual stress and strain hardening profiles caused by shot peening were measured experimentally and were then incorporated into a finite element model. By allowing for both effects of shot peening, the residual stress relaxation behaviour was successfully simulated using this model and correlated well with the experimental data. Although more modelling work may be required to simulate the interaction between shot peening effects and external loads in a range of notched geometries, the model predictions are consistent with the specimens tested in the current study. The novelty of this study lies in the development of such a modelling approach which can be used to effectively simulate the complex interaction between shot peening effects and external loads in notched regions. Compared with the un‐notched geometry, the notched geometry was found to be more effective in retaining the improvement in fatigue life resulting from shot peening, by restricting the compressive residual stress relaxation during fatigue loading.     

'98 Escherichia coli SWISS-2DPAGE database update

The combination of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), computer image analysis and several protein identification techniques allowed the Escherichia coli SWISS-2DPAGE database to be established. This is part of the ExPASy molecular biology server accessible through the WWW at the URL address http://www.expasy.ch/ch2d/ch2d-top.html . Here we report recent progress in the development of the E. coli SWISS-2DPAGE database. Proteins were separated with immobilized pH gradients in the first dimension and sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the second dimension. To increase the resolution of the separation and thus the number of identified proteins, a variety of wide and narrow range immobilized pH gradients were used in the first dimension. Micropreparative gels were electroblotted onto polyvinylidene difluoride membranes and spots were visualized by amido black staining. Protein identification techniques such as amino acid composition analysis, gel comparison and microsequencing were used, as well as a recently described Edman "sequence tag" approach. Some of the above identification techniques were coupled with database searching tools. Currently 231 polypeptides are identified on the E. coli SWISS-2DPAGE map: 64 have been identified by N-terminal microsequencing, 39 by amino acid composition, and 82 by sequence tag. Of 153 proteins putatively identified by gel comparison, 65 have been confirmed. Many proteins have been identified using more than one technique. Faster progress in the E. coli proteome project will now be possible with advances in biochemical methodology and with the completion of the entire E. coli genome.     

Electrophysiological evidence for a postperceptual locus of suppression during the attentional blink

When an observer detects a target in a rapid stream of visual stimuli, there is a brief period of time during which the detection of subsequent targets is impaired. In this study, event-related potentials (ERPs) were recorded from normal adult observers to determine whether this "attentional blink" reflects a suppression of perceptual processes or an impairment in postperceptual processes. No suppression was observed during the attentional blink interval for ERP components corresponding to sensory processing (the P1 and N1 components) or semantic analysis (the N400 component). However, complete suppression was observed for an ERP component that has been hypothesized to reflect the updating of working memory (the P3 component). Results indicate that the attentional blink reflects an impairment in a postperceptual stage of processing.     

The incidence of drug-related problems as a cause of hospital admissions in children

OBJECTIVES: To determine the incidence of hospital admissions for drug-related problems (DRPs) among children, and to examine cases for causality, preventability and clinical severity. DESIGN: Prospective assessment involving review of case notes and parent interview to determine if an admission was associated with a DRP. PATIENTS AND SETTING: All patients admitted to a large university-affiliated paediatric hospital in Melbourne, Victoria, for medical reasons (i.e., not surgical, trauma or oncology patients) during 56 consecutive days from 24 June to 19 August 1996 for which a DRP could be identified. Patients whose parents or guardians could not communicate adequately in English were excluded. MAIN OUTCOME MEASURES: The incidence, type, causality, preventability and clinical severity of DRPs associated with admission. RESULTS: Of 1682 eligible patients admitted to the Royal Children's Hospital during the study period, 58 admissions (3.4%) were associated with DRPs. Non-compliance was implicated in 50%. Causality was ranked as "definite" (34.5%), "possible" (56.9%) and "doubtful" (8.6). Two-thirds of admissions associated with DRPs were deemed preventable. Although no patients died from DRPs, four were admitted to the intensive care unit. CONCLUSIONS: The incidence of DRPs as a cause of hospital admission in this study falls within the range of incidences published for the Australian adult population (range, 2.4%-22%). In contrast to findings among Australian adults, a high proportion of admissions for DRPs in this study were associated with non-compliance. The high percentage of preventable admissions indicates that further study is necessary to characterise risk factors within this population and to test prevention strategies.