Computer evaluation of network dynamics models with application to cell cycle control in budding yeast.

Cellular processes are governed by complex networks of interacting genes and proteins. Theoretical molecular biologists attempt to describe these processes via mathematical models by writing biochemical reaction equations. Modellers are building increasingly larger and complex mathematical models to describe these cellular processes, making model evaluation a time consuming and difficult task. The authors describe an automatable process for model evaluation and a software system that implements this process. The software is adaptable to many types of models and is freely available along with all needed data files. The cell cycle control system for budding yeast is known in fine detail and constrained by more than 100 phenotypic observations in mutant strains. As an example, the authors apply their process to a model of cell cycle control in budding yeast containing dozens of regulatory equations and explaining nearly all of the known mutant phenotypes.

Building collaborative capacity in community coalitions: a review and integrative framework.

This article presents the results of a qualitative analysis of 80 articles, chapters, and practitoners' guides focused on collaboration and coalition functioning. The purpose of this review was to develop an integrative framework that captures the core competencies and processes needed within collaborative bodies to facilitate their success. The resulting framework for building collaborative capacity is presented. Four critical levels of collaborative capacity--member capacity, relational capacity, organizational capacity, and programmatic capacity--are described and strategies for building each type are provided. The implications of this model for practitioners and scholars are discussed.

Facilitating interorganizational collaboration: the contributions of interorganizational alliances.

In an attempt to promote service delivery integration and improve interorganizational collaboration, many recent human service delivery initiatives have included the development of interorganizational alliances such as coalitions and coordinating councils. Despite their popularity, little is known about how these alliances influence interorganizational collaboration, specifically the extent to which they alter the interactions among human service delivery organizations. The present study examined the interorganizational interactions, specifically the exchange relationships, within one county that was implementing two interorganizational alliances--a countywide coordinating council and interagency service delivery teams. Membership on both alliances was associated with broader interorganizational exchange networks. Organizations involved in a coordinating council were more likely to be included in client, information, and resource exchanges, and participate in joint ventures with a broader range of organizations. Providers involved in interagency teams also exchanged clients and information with a broader sector of service delivery organizations than nonparticipating providers. Observational data suggested that both alliances created structures and processes intended to facilitate interorganizational exchanges. Together, these results suggest that the development of opportunities for and encouragement of staff and leader involvement in these types of alliances may be an important part of our attempt to create a more integrated social service delivery system. The implications of these findings for researchers and practitioners are discussed.

Practical guidelines for responding to an outbreak of meningococcal disease among university students based on experience in Southampton.

Six students at the University of Southampton developed meningococcal disease in October 1997, five of them with confirmed serogroup C infections, and three died. The outbreak had major organisational and financial implications for the agencies involved. Detailed planning and good working relationships with the management of higher educational institutions can prove invaluable in such situations. This paper summarises the management of the outbreak in Southampton and presents recommendations based on our experience.

Cytogenetic characterization of the ionizing radiation-sensitive Chinese hamster mutant irs1.

The X-ray-sensitive mutant V79 cell line irs1 was characterized with respect to chromosomal aberrations induced by 137Cs, mitomycin C (MMC), and decarbamoyl mitomycin C (DCMMC). To measure chromosome damage induced at different cell cycle stages, irs1 and the parental V79-4 cell lines were pulse-labeled with bromodeoxyuridine (BrdUrd) at the time of exposure and harvested at various intervals corresponding to exposure in G1, S, and G2 phases of the cell cycle. Metaphase spreads were stained with an anti-BrdUrd antibody, followed by a fluorescein-conjugated second antibody. With propidium iodide as a counter stain, cells were scored for aberrations. Compared to the parental V79 cells, irs1 cells had: (1) greatly increased sensitivity to all 3 agents; (2) a high frequency of chromatid exchanges after exposure in each phase of the cell cycle; and (3) more sensitivity to the agent causing crosslinks (MMC) than its monofunctional analog (DCMMC). The finding of chromatid-type damage in cells exposed to ionizing radiation during G1 is atypical of normal cells, but is similar to observations made in several mutant rodent cell lines and in ataxia telangiectasia cells. Our results suggest that the defect in irs1 cells can manifest itself as misrepair or misreplication during all phases of the cell cycle and leads to a high incidence of chromatid exchanges and deletions.

A survey of general anaesthesia and sedation in dental practice in two cities.

Using a postal questionnaire, the use of general anaesthesia and sedation in general dental practice in two cities over a 4-week period was investigated. Questionnaires were sent to a random sample of one in five dental practitioners in Bristol and Sheffield, and an 82% response rate was attained. More practices in Sheffield administered general anaesthesia than those in Bristol. The differences between the facilities provided are discussed. Equipment and facilities have improved since a larger survey was described in 1976, but the use and availability of monitoring equipment has changed little since then. The results reflect the decline in the use of general anaesthesia in dental practice seen nationally. The survey provides an insight into the current anaesthetic services provided in general dental practice in two cities, both of which contain dental hospitals, and provides a basis for the design of a protocol for a further national survey.

In vivo cytogenetic effects of cooked food mutagens.

Using a variety of in vivo cytogenetic endpoints, we have investigated the effects of several compounds formed during the cooking of meat. C57Bl/6 mice were used to test for an increase in the frequency of sister-chromatid exchanges (SCEs), chromosomal aberrations, and micronucleated erythrocytes by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). MeIQx and DiMeIQx did not induce SCEs in mouse bone marrow cells. PhIP induced sister-chromatid exchanges, but not chromosomal aberrations in bone marrow. In peripheral blood lymphocytes, PhIP did induce aberrations at 100 mg/kg, the highest dose tested. PhIP induced a low but significantly increased frequency of micronuclei in normochromatic but not polychromatic erythrocytes in bone marrow and peripheral blood. However, dose responses were not observed. With the exception of the SCEs induced by PhIP, these results contrast with observations made in vitro, where these compounds were found to have significant genotoxicity in mammalian cells and a very high mutation frequency in prokaryotic systems.

Hypoxaemia during outpatient dental anaesthesia.

Eighty children, ASA grade 1, who had outpatient general anaesthesia for tooth extraction were studied. An inhalational induction was performed, with patients receiving halothane, nitrous oxide and either 33% or 50% oxygen. Oxygen saturation was measured throughout the procedure using the Ohmeda Biox 3700 pulse oximeter. No significant difference in the incidence of hypoxaemia was found between the two groups. There was no association between the grade of surgeon or anaesthetist and the incidence of hypoxaemia.

Variation in the human lymphocyte sister-chromatid exchange frequency: results of a long-term longitudinal study.

The variation in lymphocyte sister-chromatid exchange (SCE) frequency as a function of time was investigated in nonsmokers and smokers. The smokers were divided into 3 groups depending on their smoking status. The group termed 'smokers' participated in a program to stop smoking but did not reduce or eliminate their use of tobacco; 'smoke enders' successfully completed the smokending program and remained free of tobacco for the duration of the study, while the 'variable' group stopped smoking for a limited time but then resumed smoking. 8 or more blood samples per person were obtained over a period of at least 12 months. The SCE frequencies for each of these groups were compared with each other and with those of two previous longitudinal study groups from our laboratory. The proportion of high-frequency cells (HFCs) was also determined for each sample. The results confirm our previous finding that SCE frequencies and the proportion of HFCs observed in separate samples from the same individual are more likely to be different as the time between samples increases. We also show that smokers have significantly more SCEs and HFCs than do nonsmokers, that SCE frequencies in smokers do not decline for at least 12 months when smoking is stopped, and that among smokers, significant seasonal variation in the SCE frequency occurs. These results provide useful information concerning the effects of smoking upon SCE frequencies, and will be helpful in designing and interpreting the results of long-term human population cytogenetic studies.