Showing papers by "Defence Science and Technology Laboratory published in 2002"

Cloning, sequencing, and characterization of the hexahydro-1,3,5-Trinitro-1,3,5-triazine degradation gene cluster from Rhodococcus rhodochrous.

Abstract: Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is a high explosive which presents an environmental hazard as a major land and groundwater contaminant. Rhodococcus rhodochrous strain 11Y was isolated from explosive contaminated land and is capable of degrading RDX when provided as the sole source of nitrogen for growth. Products of RDX degradation in resting-cell incubations were analyzed and found to include nitrite, formaldehyde, and formate. No ammonium was excreted into the medium, and no dead-end metabolites were observed. The gene responsible for the degradation of RDX in strain 11Y is a constitutively expressed cytochrome P450-like gene, xplA, which is found in a gene cluster with an adrenodoxin reductase homologue, xplB. The cytochrome P450 also has a flavodoxin domain at the N terminus. This study is the first to present a gene which has been identified as being responsible for RDX biodegradation. The mechanism of action of XplA on RDX is thought to involve initial denitration followed by spontaneous ring cleavage and mineralization.

A Mutant of Burkholderia pseudomallei, Auxotrophic in the Branched Chain Amino Acid Biosynthetic Pathway, Is Attenuated and Protective in a Murine Model of Melioidosis

Abstract: Using a transposon mutagenesis approach, we have identified a mutant of Burkholderia pseudomallei that is auxotrophic for branched chain amino acids. The transposon was shown to have interrupted the ilvI gene encoding the large subunit of the acetolactate synthase enzyme. Compared to the wild type, this mutant was significantly attenuated in a murine model of disease. Mice inoculated intraperitoneally with the auxotrophic mutant, 35 days prior to challenge, were protected against a challenge dose of 6,000 median lethal doses of wild-type B. pseudomallei.

Characterisation of an acapsular mutant of Burkholderia pseudomallei identified by signature tagged mutagenesis.

Abstract: A Burkholderia pseudomallei mutant which was attenuated in a mouse model of melioidosis was identified by a signature tagged mutagenesis approach. The transposon was shown to be inserted into a gene within the capsular biosynthetic operon. Compared with the wild-type bacteria this mutant demonstrated a 10(5)-fold increase in the median lethal dose in a mouse model and it did not react with a monoclonal antibody against high mol. wt polysaccharide of B. pseudomallei. To determine the kinetics of infection, mice were dosed intraperitoneally (i.p.) and intravenously (i.v.) with mutant and wild-type bacteria. After i.p challenge, the number of mutant bacteria in the peritoneal cavity declined, whereas wild-type bacteria proliferated. When administered by the i.v. route, the mutant was able to cause disease but the time to death was increased compared with the wild type. Mice were dosed with the mutant and subsequently challenged with wild-type B. pseudomallei, but the mutant failed to induce a protective immune response.

Pathophysiological responses following phosgene exposure in the anaesthetized pig.

Abstract: This study aimed to develop a reproducible model of phosgene-induced lung injury in the pig to facilitate the future development of therapeutic strategies. Ten female young adult large white pigs were used. Following induction of anaesthesia using a halothane/oxygen/nitrous oxide mixture, arterial and venous catheters were inserted together with a pulmonary artery thermodilution catheter, and a suprapubic urinary catheter by laparotomy. Anaesthesia was maintained throughout the experiment by intravenous infusion of ketamine, midazolam and alfentanil. On completion of surgery the animals were allowed to equilibrate for 1 h and then were divided into two groups. Group 1 (n = 5) was exposed to phosgene for 10 min (mean Ct = 2443 +/- 35 mg min m(-3)) while spontaneously breathing, whereas control animals (Group 2 n = 5) were exposed to air. At 30 min post-exposure, anaesthesia was deepened in order to allow the initiation of intermittent positive pressure ventilation and the animals were monitored for up to 24 h. Cardiovascular and respiratory parameters were monitored every 30 min and blood samples were taken for arterial and mixed venous blood gas analysis and clinical chemistry. A detailed post-mortem and histopathology was carried out on all animals following death or euthanasia at the end of the 24-h monitoring period. Control animals (Group 2) all survived until the end of the 24-h monitoring period with normal pathophysiological parameters. Histopathology showed only minimal passive congestion of the lung. Following exposure to phosgene (Group 1) there was one survivor to 24 h, with the remainder dying between 16.5 and 23 h (mean = 20 h). Histopathology from these animals showed areas of widespread pulmonary oedema, petechial haemorrhage and bronchial epithelial necrosis. There was also a significant increase in lung wet weight/body weight ratio (P < 0.001). During and immediately following exposure, a transient decrease in oxygen saturation and stroke volume index was observed. From 6 h there were significant decreases in arterial pH (P < 0.01), P(a)O(2) (P < 0.01) and lung compliance (P < 0.01), whereas oxygen delivery and consumption was reduced from 15 h onwards in phosgene-exposed animals. Mean pulmonary artery pressure of phosgene-exposed animals was increased from 15 h post-exposure, with periods of increased pulmonary vascular resistance index being recorded from 9 h onwards. We have developed a reproducible model of phosgene-induced lung injury in the anaesthetized pig. We have followed changes in cardiovascular and pulmonary dynamics for up to 24 h after exposure in order to demonstrate evidence of primary acute lung injury from 16 h post-exposure. Histopathology showed evidence of widespread damage to the lung and there was also a significant increase in lung wet weight/body weight ratio (P < 0.001).

Novel load cell for measuring axial force, shear force, and bending movement in large-scale structural experiments

Abstract: This paper describes the design, construction and testing of a load cell to measure the axial force, shear force, and bending moment at the end of a structural beam. The capacities of the load cell are 780 kN in axial load, 350 kN in shear, and 200 kNm in bending. These magnitudes, together with the requirement that the load cell should be kept as slim as possible, necessitated a novel design comprising three steel double-spring elements machined with semicircular channels to provide localized strain amplification. The load cell was designed with the aid of detailed finite element analysis and was machined from grade 55 steel. After strain gaging, it was subjected to an extensive series of calibration tests. Results from these tests are reported, together with those from some early experiments in which two load cells were used to measure the behavior of structural steel knee elements.

Application of central composite design in the optimisation of thermal desorption parameters for the trace level determination of the chemical warfare agent chloropicrin

Abstract: A quantitative trace-level thermal desorption gas chromatography mass spectrometry method was developed for chloropicrin CCl3NO2 using central composite design. Factors influencing the thermal decomposition were elucidated and optimum conditions for maximum response deduced. Four factors were investigated: desorption time, desorption temperature, valve temperature and line temperature. Only valve and line temperature influenced the response. The storage stability of chloropicrin on Tenax TA™ was investigated. Only the storage conditions affected recovery: no significant loss of chloropicrin was observed for spiked tubes stored in a refrigerator for up to 30 days. The application of central composite design to study thermal degradation of chloropicrin has not been described in the literature. The benefits in adopting this approach are reflected in the limit of detection, 22 ng on the sorbent tube (equivalent to 3.2 ppbv), the lowest atmospheric detection limit reported to date.

Bayesian decision making and military command and control

Abstract: We discuss firstly the problem of military decision, in the context of the more general development of ideas in the representation of decision making. Within this context, we have considered a mathematical model—Bayesian Decision—of decision making and military command. Previous work has been extended, and applied to this problem. A distribution of belief in outcome, given that a decision is made, and a Loss function—a measure of the effect of this outcome relative to a goal—are formed. The Bayes' Decision is the decision which globally minimises the resultant bimodal (or worse) Expected Loss function. The set of all minimising decisions corresponds to the surface of an elementary Catastrophe. This allows smooth parameter changes to lead to a discontinuous change in the Bayes' decision. In future work this approach will be used to help develop a number of hypotheses concerning command processes and military headquarters structure. It will also be used to help capture such command and control processes in simulation modelling of future defence capability and force structure.

The Synthesis and Properties of Some Fluorinated Dialkyl Phosphoramidates

Abstract: The synthesis and physical properties of the first fluorinated dialkyl phosphoramidates of structure (RCH 2 O) 2 P(O)NHCH 2 R F , where R = CH 3 , CF 3 or CCl 3 and R F = CF 3 or C 2 F 5 , are described. They were obtained by treatment of the respective dialkyl phosphorochloridates with trifluoroethylamine or pentafluoropropylamine in ether in the presence of triethylamine.

Synthesis of soluble halogenated aryloxy substituted indium phthalocyanines

Abstract: Phthalocyanines solubilised by either 8 or 16 aryloxy or haloaryloxy groups are described. A series of phthalocyanine derivatives were prepared containing indium. 1,2-Dinitriles and the corresponding diiminoisoindolines were used as precursors. A naphthalocyanine metallated with indium and solubilised with four tert-butyl groups is reported.

Aeromedical evacuation following abdominal surgery.

Abstract: It is generally accepted that there are no absolute contraindications to the movement of patients by air (1, 2). However, there are special physical and physiological factors that must be considered before subjecting a patient to the potentially hostile flight environment. The major considerations are altitude and airframe whilst minor considerations include space, noise, vibration, turbulence, G forces, temperature, humidity, fatigue, anxiety, time zone changes and airsickness. The purpose of this review is to consider when, following abdominal surgery, a patient can be considered for aeromedical evacuation. This review will consider only fixed wing aeromedical evacuation (AE) in pressurised aircraft capable of maintaining a cabin altitude of 8000 feet or better, which depends primarily on the airframe and secondarily on the altitude flown but includes all fixed wing aircraft deployed on aeromedical evacuation missions in the RAF. Furthermore, this review will concentrate on patients following abdominal surgery. Each aeromedical evacuation must be judged on its merits and in each case the anticipated benefits must outweigh the associated risks. In order to achieve this, the destination medical facility should be of a higher standard of medical care than the originating facility and the standard of care during aeromedical transfer should be at least equal to that of the originating facility.

A role for recombinant activated factor VII in trauma

Abstract: It is possible that recombinant activated factor VII (rFVIIa) could revolutionize the medical and surgical management of haemorrhage following trauma due to its ease of administration and mechanism of action. This article reviews the evidence for the use of rFVIIa as a procoagulant, its mechanism of action and its potential role in blunt and penetrating trauma. The role of rFVIIa in the emergency room or operating theatre and in the pre-hospital environment is discussed. Administration of rFVIIa `at the roadside’ may have signifi cant potential implications, especially for the trauma surgeon and even for strategic planners. Finally, the areas where further research is needed to provide objective evidence of its effi cacy are elaborated.

Knowledge systems for coalition operations

Abstract: Most major military, peacekeeping, and humanitarian operations are now coalition-based and require agility and effective use of limited resources to achieve complex and multiple objectives. This raises many challenges given technical incompatibilities, rules and regulations, as well as cultural norms. This special issue examines the contributions of intelligent systems to help address this important problem domain.

Campaign analysis: representation of historical events in a military campaign simulation model

Abstract: Dstl has sponsored the development and use of several campaign level models of military operations. The models are required to provide insight into force assessment, procurement decisions of future concepts and for investigations into potential doctrinal developments. COMAND is a theatre level representation of the naval-air (maritime) campaign. COMAND also contains a simple representation of the joint force influence on the land campaign. COMAND is a stochastic model, and runs on a desktop PC under Windows NT. The key to COMAND is the representation of command and control aspects of the campaign, with representation of sensor and communication systems, information flows, command decision making, combat and perception of the battlefield. As part of the process to establish the validation status of COMAND, an attempt was made to replicate the 1982 Falkland Islands Campaign. This attempt was largely successful, and provided much information on the strengths and weaknesses of the model.

A New Synthetic Route to Donor—Acceptor Porphyrins.

Abstract: Some new donor–acceptor porphyrins have been prepared based on a metallated bis(ethynyl) porphyrin core. 4-(Dimethylamino)phenyl was used as the donor group and 4-nitrophenyl, 4-cyanophenyl and 5-nitrothiazoyl as the acceptor groups. Dipyrrylmethane was used for large scale porphyrin ring synthesis because the absence of methylene substituents reduces the difficulty of substituent scrambling that occurs during porphyrin synthesis.