Virulence of Aspergillus fumigatus double mutants lacking restriction and an alkaline protease in a low-dose model of invasive pulmonary aspergillosis

To investigate the pathogenicity of Aspergillus fumigatus mutants lacking putative virulence factors, we have developed a new murine model of invasive pulmonary aspergillosis based on neutropenia, the major factor predisposing patients to this infection. Mice were treated with cyclophosphamide and inoculated by the intranasal route with 5 x 10(3) conidia, a significant reduction from inoculum levels used in previous models. Evidence for the production of the extracellular alkaline protease (Alp) in lung tissue was obtained by using a fungal transformant harboring an alp::lacZ reporter gene fusion. The pathogenicities of single mutant strains lacking either Alp or the ribotoxin restrictocin and of a double mutant strain lacking both proteins were assessed in this infection model. There were no significant differences between the mutant and the wild-type strains in terms of mortality or histological-features. Inoculations with mixtures of conidia showed that the double mutant strain is slightly less virulent than the wild-type strain. We conclude that Alp and restrictocin are not important virulence determinants in pulmonary infection.     

Dynamic thermographic imaging for estimation of regional perfusion in the tuberculin reaction in healthy adults

A sensitive method for measurement of the volume of blood flow through the skin, based on the kinetics of reheating after localised cooling, is described in this paper. This method has been used to study the tuberculin reaction as a model of cutaneous delayed-type hypersensitivity (DHS) in man. Over the positive reaction there is accelerated reheating similar in kinetics and extent to that seen after maximal hyperaemia induced by intradermal injection of histamine or prostaglandin E2. The earlier phase of reheating (10-100 s) is more dependent on blood flow, whereas the later phase (100-300 s) is apparently more dependent on non-perfusion heat exchange mechanisms, including conduction. The reheat kinetic method is largely dependent on blood flow in the deep dermal vessels (diameter > 50 microns), whereas the alternative approach of measurement of the velocity of flow of erythrocytes in the microcirculation by laser Doppler (LD) flowmetry gives results biased towards the most superficial dermal circulation. Previous studies with LD flowmetry have shown that the blood velocity is greatest at the centre of weak and strong reactions, while in the most intense reactions it is raised at the centre but maximal at the periphery (central relative slowing, CRS) raising the possibility of central ischaemia. The reheat kinetics approach has now indicated that the deep dermal circulation is not impaired in CRS reactions. It is concluded that there must be partial obstruction of the parts of the microcirculation communicating between the deep and superficial dermal plexuses, presumably from the accumulation of exudate oedema in the most intense tuberculin reactions.     

Performance characteristics of a composite multivariate quality control system.

We present the results of an evaluation of the performance characteristics of a composite multivariate quality control (CMQC) system that incorporates quality control rules for univariate, multivariate, and correlation conditions. The CMQC system evaluated is designed to help analysts detect unacceptable trends and systematic error in one or more variables, unacceptable random error in one or more variables, and unacceptable changes in the correlation structure of any pair of variables. It is also designed to be tolerant of missing data, to allow analysts to reject as few as one or as many as all variables in a run, and to provide analysts with control statistics and graphics that logically relate to sources of analytical error. We show that the various components of the CMQC system have adequate statistical power to detect systematic errors, random errors, and correlation changes under the conditions likely to be encountered with multivariate analytical measurement systems: (1) a single variable with increased systematic or random error; (2) all variables or a subgroup of variables affected by a common problem that increases systematic or random error; and (3) missing data for one or more variables in a run. We also show that the power of the multivariate component of the CMQC system to detect systematic and random errors is higher than the power of an alternative multivariate test criterion.     

Accelerated aging of extruded dielectric power cables. I. Controland monitoring methodology

An improved accelerated cable life test is described. Through the use of programmable logic controllers (PLCs), very precise and consistent control of the accelerated aging process has been achieved. A computer has been utilized to make continuous real-time acquisition and storage of key operating parameters possible. This precise control and monitoring methodology has permitted the study of the synergistic effects of voltage and temperature on the accelerated aging of full-sized cables in the laboratory     

A STUDY OF SUPERIMPOSED FRACTURE MODES I, II AND III ON PMMA

A test apparatus has been developed to study the fracture behaviour of engineering materials subjected to superimposed tensile and shear (Mode I and II) loads using a single edge notch specimen. Stress intensity factors were calculated using finite element analysis. Test results for PMMA are reported. Results from circumferentially notched round bar specimens, subjected to combined tension and torsion (Mode I and III) loading are also reported. The Mode I/II results are consistent with the mixed mode fracture response of a wide range of brittle materials, although there is some evidence of non-linear behaviour. The fracture behaviour for superimposed Modes I and III indicates the strong influence of non-linear deformation which causes the mixed mode toughness to be dependent on the sequence and type of loading.     

Potential contribution of therapy to cancer mortality reduction

Reductions in cancer mortality may come about for a number of reasons, including improvements in treatment. The impact will vary from cancer to cancer. For some, expert curative surgery is crucial, whereas for others, the use of appropriate chemotherapy is a key factor. Examples of the latter, in which there are already discernible reductions in national cancer mortality data resulting from chemotherapy, include testicular cancer and Hodgkin's disease. For more common diseases, such as ovarian cancer, reductions also are being seen. For others, such as breast and colorectal cancer, the current more widespread use of adjuvant chemotherapy may lead to overall mortality reduction in the future. It should be recognized that chemotherapy should be given only by those experienced in its use, and that this facility should form part of a larger provision for health care in relation to cancer, ranging from public education to population screening and from better oncology training for clinicians to greater encouragement to participation in clinical trials. New drug development is clearly a priority, but further advances can be made in many countries already using available forms of chemotherapy if treatment facilities are organized appropriately.     

Synthesis and properties of 2,2,6,6-tetramethyl-1-(1-phenethyloxy)piperidine,an initiator for living free radical styrene polymerization

Summary An initiator for living free radical polymerization may be prepared by trapping the benzylic ethylbenzene radical with the stable 2,2,6,6-tetramethylpiperidinyl-1-oxy (TEMPO) radical. The adduct, 2,2,6,6-tetramethyl-1-(1-phenethyloxy)piperidine (TMPEP), smoothly undergoes thermal fragmentation at temperatures approaching 140° C to afford an active carbon radical capable of initiating polymerization and a passive mediating nitroxyl radical to reversibly cap and preserve the propagating polymer chain.