scispace - formally typeset
Search or ask a question

Showing papers by "Defence Science and Technology Laboratory published in 2009"


Journal ArticleDOI
TL;DR: It is reported that larvae of the wax moth (Galleria mellonella) are susceptible to infection with the human enteropathogen Yersinia pseudotuberculosis at 37 degrees C, and a superoxide dismutase C (sodC) mutant was constructed and tested, showing increased susceptibility to superoxide, a key mechanism of killing in insect haemocytes and mammalian phagocytes.
Abstract: We report that larvae of the wax moth (Galleria mellonella) are susceptible to infection with the human enteropathogen Yersinia pseudotuberculosis at 37 °C. Confocal microscopy demonstrated that in the initial stages of infection the bacteria were taken up into haemocytes. To evaluate the utility of this model for screening Y. pseudotuberculosis mutants we constructed and tested a superoxide dismutase C (sodC) mutant. This mutant showed increased susceptibility to superoxide, a key mechanism of killing in insect haemocytes and mammalian phagocytes. It showed reduced virulence in the murine yersiniosis infection model and in contrast to the wild-type strain IP32953 was unable to kill G. mellonella. The complemented mutant regained all phenotypic properties associated with SodC, confirming the important role of this metalloenzyme in two Y. pseudotuberculosis infection models.

105 citations


Journal ArticleDOI
TL;DR: Some of the work commissioned by the U.K. Ministry of Defence to assess the feasibility of using 60 GHz millimeter-wave smart antenna technology to provide covert communications capable of meeting these stringent networking needs is presented.
Abstract: Mobile ad hoc networking of dismounted combat personnel is expected to play an important role in the future of network-centric operations. High-speed, short-range, soldier-to-soldier wireless communications will be required to relay information on situational awareness, tactical instructions, and covert surveillance related data during special operations reconnaissance and other missions. This article presents some of the work commissioned by the U.K. Ministry of Defence to assess the feasibility of using 60 GHz millimeter-wave smart antenna technology to provide covert communications capable of meeting these stringent networking needs. Recent advances in RF front-end technology, alongside physical layer transmission schemes that could be employed in millimeter-wave soldier- mounted radio, are discussed. The introduction of covert communications between soldiers will require the development of a bespoke directive medium access layer. A number of adjustments to the IEEE 802.11 distribution coordination function that will enable directional communications are suggested. The successful implementation of future smart antenna technologies and direction of arrival-based protocols will be highly dependent on thorough knowledge of transmission channel characteristics prior to deployment. A novel approach to simulating dynamic soldier-to-soldier signal propagation using state-of-the-art animation-based technology developed for computer game design is described, and important channel metrics such as root mean square angle and delay spread for a team of four networked infantry soldiers over a range of indoor and outdoor environments is reported.

91 citations


Journal ArticleDOI
TL;DR: The crystal structure of the highly metastable beta- form of RDX shows that the molecules adopt different conformations compared to the alpha-form and that, contrary to previous reports, the beta-form obtained at ambient pressure is not the same form as that obtained at elevated temperatures and pressures.

89 citations


Proceedings Article
23 Mar 2009
TL;DR: In this paper, the authors present the development and assessment of wearable antennas which are integrated into clothing, considering antennas operating from 100MHz to 1GHz and measured radiation patterns and input impedances.
Abstract: There is an increasing interest in wearable antennas and electronics in both the civil and military domains. In the civil domain there is a move towards pervasive computing which utilises various electronic devices placed around the body. Electronic devices typically involve a communications element for transfer of entertainment media, information sources and social interaction. Communication may occur between devices through an on-body channel or to external devices. Flexible, conformal antennas are essential to provide an unobtrusive solution. In the military domain the current emphasis on network centric warfare and more complex body worn sensors contrasts with a desire to reduce the burden on the soldier. Flexible, conformal, wearable electronics and antennas provide technology to satisfy these conflicting requirements. This paper presents the development and assessment of wearable antennas which are integrated into clothing. This work considers antennas operating from 100MHz to 1GHz. Advantages and disadvantages of several construction methods and materials are discussed. Measured radiation patterns and input impedances are presented for the integrated antennas worn on the body.

87 citations


Journal ArticleDOI
TL;DR: It is proposed that antibiotic selection acts to maintain resistance genes on the plasmid, but there is also competition between plasmids encoding the same resistance phenotype.
Abstract: A global collection of plasmids of the IncHI1 incompatibility group from Salmonella enterica serovar Typhi were analyzed by using a combination of DNA sequencing, DNA sequence analysis, PCR, and microarrays. The IncHI1 resistance plasmids of serovar Typhi display a backbone of conserved gene content and arrangement, within which are embedded preferred acquisition sites for horizontal DNA transfer events. The variable regions appear to be preferred acquisition sites for DNA, most likely through composite transposition, which is presumably driven by the acquisition of resistance genes. Plasmid multilocus sequence typing, a molecular typing method for IncHI1 plasmids, was developed using variation in six conserved loci to trace the spread of these plasmids and to elucidate their evolutionary relationships. The application of this method to a collection of 36 IncHI1 plasmids revealed a chronological clustering of plasmids despite their difference in geographical origins. Our findings suggest that the predominant plasmid types present after 1993 have not evolved directly from the earlier predominant plasmid type but have displaced them. We propose that antibiotic selection acts to maintain resistance genes on the plasmid, but there is also competition between plasmids encoding the same resistance phenotype.

82 citations


Journal ArticleDOI
TL;DR: It is suggested that most TIR domains in bacteria have nothing to do with subverting eukaryotic cells and function simply as general purpose protein-protein interaction domains put to diverse uses.

56 citations


Journal ArticleDOI
16 Jul 2009-Vaccine
TL;DR: The protective efficacy of heat-inactivated Burkholderia thailandensis, B. mallei or B. pseudomallei cells as vaccines against murine melioidosis and glanders is reported.

53 citations


Journal ArticleDOI
TL;DR: The ability to detect T cell responses to defined B. pseudomallei proteins in large numbers of individuals now provides the opportunity to screen candidate antigens for inclusion in protein or polysaccharide–conjugate subunit vaccines against this important but neglected disease.
Abstract: Background: Infection with the Gram-negative bacterium Burkholderia pseudomallei is an important cause of community-acquired lethal sepsis in endemic regions in southeast Asia and northern Australia and is increasingly reported in other tropical areas. In animal models, production of interferon-gamma (IFN-gamma) is critical for resistance, but in humans the characteristics of IFN-gamma production and the bacterial antigens that are recognized by the cell-mediated immune response have not been defined. Methods: Peripheral blood from 133 healthy individuals who lived in the endemic area and had no history of melioidosis, 60 patients who had recovered from melioidosis, and 31 other patient control subjects were stimulated by whole bacteria or purified bacterial proteins in vitro, and IFN-gamma responses were analyzed by ELISPOT and flow cytometry. Findings: B. pseudomallei was a potent activator of human peripheral blood NK cells for innate production of IFN-gamma. In addition, healthy individuals with serological evidence of exposure to B. pseudomallei and patients recovered from active melioidosis developed CD4(+) (and CD8(+)) T cells that recognized whole bacteria and purified proteins LolC, OppA, and PotF, members of the B. pseudomallei ABC transporter family. This response was primarily mediated by terminally differentiated T cells of the effector-memory (T(EMRA)) phenotype and correlated with the titer of anti-B. pseudomallei antibodies in the serum. Conclusions: Individuals living in a melioidosis-endemic region show clear evidence of T cell priming for the ability to make IFN-gamma that correlates with their serological status. The ability to detect T cell responses to defined B. pseudomallei proteins in large numbers of individuals now provides the opportunity to screen candidate antigens for inclusion in protein or polysaccharide-conjugate subunit vaccines against this important but neglected disease.

53 citations


Journal ArticleDOI
TL;DR: The results suggest that the BALB/c mouse is highly susceptible to B. pseudomallei by the aerosol route and represents a relevant model system of acute human melioidosis.
Abstract: Burkholderia pseudomallei, the aetiological agent of melioidosis, is widely distributed throughout the tropical countries of the world, where it exists as a free-living bacterium in soil and water (Pitt 1990). Melioidosis in humans has a wide clinical presentation. Acute disease includes pneumonia and septicaemia, may be rapidly progressive and has a high mortality rate. Subacute and chronic forms of melioidosis also exist and re-activation following sometimes lengthy latent periods is common. Natural infection in humans occurs either via contamination of skin abrasions or by the inhalation of aerosols containing the bacterium (Leelarasamee & Bovornkitti 1989). B. pseudomallei is also considered a candidate organism for use in biological warfare or for deliberate release, most likely as an aerosol and respiratory disease would probably predominate. Current recommended treatment for acute melioidosis is high-dose intravenous ceftazidime, or a carbapenem, for at least 10–14 days, followed by prolonged oral eradication therapy (Chaowagul 2000; Dance 2002; Health Protection Agency, 2003; Cheng et al. 2004). To date, no licensed vaccine for human use exists, although several candidates have been studied. Acute and chronic models of B. pseudomallei infection in mice have been described previously (Veljanov et al. 1996; Leakey et al. 1998; Hoppe et al. 1999; Santanirand et al. 1999; Gauthier et al. 2001; Liu et al. 2002; Jeddeloh et al. 2003) and with one exception (Jeddeloh et al. 2003), these studies delivered organisms via either the intraperitoneal, intravenous or intranasal routes of infection. The clinical manifestations of disease have been shown, in part, to be dependent on the route of infection (Liu et al. 2002) and although any organ system may be involved during human B. pseudomallei infection, the lungs, liver and spleen are the primary targets of pathological involvement (Piggot & Hochholzer 1970; Wong et al. 1995; White 2003). The aim of this study therefore, was to establish and further characterize an acute aerosol-challenge model of respiratory B. pseudomallei infection in the mouse. Such a model is needed for studies of pathogenesis of B. pseudomallei and for evaluation of antimicrobials and vaccine candidates.

43 citations


Journal ArticleDOI
TL;DR: This work shows how a statistical inference technique can be used to successfully predict the existence of links that are missed during network sampling, and is demonstrated using network data obtained from open source publications.
Abstract: Determining the pattern of links within a large social network is often problematic due to the labour-intensive nature of the data collection and analysis process With constrained data collection capabilities it is often only possible to either make detailed observations of a limited number of individuals in the network, or to make fewer observations of a larger number of people Previously we have shown how detailed observation of a small network can be used, which infer where in the network previously unconnected individuals are likely to fit, thereby attempting to predict network growth as new people are considered for inclusion Here, by contrast, we show how social network topology can be inferred following a limited observation of a large network Essentially the issue is one of inferring the presence of links that are missed during a constrained data collection campaign on the network It is particularly difficult to infer network structures for those organizations that actively seek to remain covert and undetected However, it is often very useful to know if two given individuals are likely to be connected even though limited surveillance effort yields no evidence of a link Specifically, we show how a statistical inference technique can be used to successfully predict the existence of links that are missed during network sampling The procedure is demonstrated using network data obtained from open source publications

39 citations


Journal ArticleDOI
TL;DR: Tularaemia disease progression in the common marmoset appears to be consistent with the disease seen in humans and other animal models, and may be considered a suitable model for further studies of inhalational tular aemia.
Abstract: Susceptibility and lethality studies of inhalational tularaemia were undertaken using the common marmoset (Callithrix jacchus) to determine its suitability as a non-human primate model. Pairs of marmosets were exposed to varying challenge doses of Francisella tularensis by the airborne route and monitored for up to 14 days postchallenge (p.c.). Lethal infection was achieved following a retained dose of less than 10 bacterial colony-forming units (CFU). However, precise LD(50) determination was not possible. The model was characterized using a target challenge dose of approximately 100 CFU. Increased core body temperature was the first indicator of disease, at approximately 2.5 days p.c. Overt clinical signs were first observed 12-18 h after the temperature increase. Significantly decreased activity was observed after approximately 3 days. All animals succumbed to infection between 4.5 and 7 days p.c. At postmortem examination, gross pathology was evident in the liver, spleen and lungs of all animals and high bacterial numbers were detected in all the organs assessed. Bacteraemia was demonstrated in all animals postmortem. Histopathological observations included severe suppurative bronchopneumonia, severe multifocal pyogranulomatous hepatitis, splenitis and lymphadenitis. Tularaemia disease progression in the common marmoset therefore appears to be consistent with the disease seen in humans and other animal models. The common marmoset may therefore be considered a suitable model for further studies of inhalational tularaemia.

Journal ArticleDOI
TL;DR: Adenovirus-delivered IFN-alpha protected mice from VEEV disease when administered 24 h prior to challenge, but not when administered 6 h post-challenge, suggesting that up to 24 h is required for the development of the IFn-mediated antiviral response.
Abstract: There are no widely available vaccines or antiviral drugs capable of protecting against infection with Venezuelan equine encephalitis virus (VEEV), although an adenovirus vector expressing VEEV structural proteins protects mice from challenge with VEEV and is potentially a vaccine suitable for human use. This work examines whether alpha interferon (IFN-alpha) could act as an adjuvant for the adenovirus-based vaccine. IFN-alpha was either expressed by a plasmid linked to the adenovirus vaccine or encoded by a separate adenovirus vector administered as a mixture with the vaccine. In contrast to previous reports with other vaccines, the presence of IFN-alpha reduced the antibody response to VEEV. When IFN-alpha was encoded by adenovirus, the lack of a VEEV-specific response was accompanied by an increase in the immune response to the adenovirus vector. IFN-alpha also plays a direct role in defence against virus infection, inducing the expression of a large number of antiviral proteins. Adenovirus-delivered IFN-alpha protected mice from VEEV disease when administered 24 h prior to challenge, but not when administered 6 h post-challenge, suggesting that up to 24 h is required for the development of the IFN-mediated antiviral response.

Journal ArticleDOI
11 May 2009-Vaccine
TL;DR: The smallest protective fragment of V antigen identified comprised amino acids 135-262 and the ability of this fragment to confer protection when given in the context of a DNA vaccine was confirmed.

Journal ArticleDOI
TL;DR: In this article, the authors developed mouse models of infection with aerosolized Brucella melitensis and Brucela suis and demonstrated their utility for the evaluation of vaccines using the model live B. melitense vaccine strain Rev.1.
Abstract: There is a need to identify vaccines that can protect against Brucella, a potential bioterrorism agent. We have developed mouse models of infection with aerosolized Brucella melitensis and Brucella suis and demonstrated their utility for the evaluation of vaccines using the model live B. melitensis vaccine strain Rev.1.

Journal ArticleDOI
TL;DR: In this paper, the authors explored the phenomenology behind the LEV, the reasons for its stability, and the effects of changing Reynolds number or angle-of-attack are studied.
Abstract: The aerodynamics of insect-like flapping are dominated by the production of a large, stable, and lift-enhancing leading-edge vortex (LEV) above the wing. In this paper the phenomenology behind the LEV is explored, the reasons for its stability are investigated, and the effects on the LEV of changing Reynolds number or angle-of-attack are studied. A predominantly-computational method has been used, validated against both existing and new experimental data. It is concluded that the LEV is stable over the entire range of Reynolds numbers investigated here and that changes in angle-of-attack do not affect the LEV’s stability. The primary motivation of the current work is to ascertain whether insect-like flapping can be successfully ‘scaled up’ to produce a flapping-wing micro air vehicle (FMAV) and the results presented here suggest that this should be the case.

Journal ArticleDOI
23 Nov 2009-Vaccine
TL;DR: It is suggested that Mab7.3 protects by binding to LcrV(Ype) and interfering with protein-protein interactions necessary for type three secretion and protecting J774A.1 macrophages in vitro from killing by a Yersinia pseudotuberculosis strain expressing LCrV (Ype).

Journal ArticleDOI
TL;DR: The results show no change in mortality, lung edema, or shunt fraction; however, some beneficial effects on cardiac parameters e.g., stroke volume, left ventricular stroke work, were noted.
Abstract: Toxic industrial chemicals e.g., phosgene, are widely used as reactive intermediates in industrial processes. Inhalation exposure to these chemicals can result in life-threatening acute lung injury (ALI), to which no specific antidote exists. This study aimed to assess the potential benefit of steroids in treating phosgene induced ALI. Anesthetized pigs were instrumented, exposed to phosgene Ct 2000 mg.min.m-3 (Ct is the product of concentration [mg·m−3] × time [min]), and ventilated with intermittent positive pressure ventilation before being randomized to study part 1: treatment with intravenous glucose saline (20 mL) or methylprednisolone (12.5 mg·kg−1 in 20 mL) 6 h postexposure or study part 2: treatment with inhaled glucose saline (2 mL) or budesonide (2 mL of 0.5 mg·mL−1 solution) at 1, 6, 12, and 18 h postexposure. Biochemical parameters and animal physiology were monitored to 24 h postexposure. The results show no change in mortality, lung edema, or shunt fraction; however, some beneficial...

Journal ArticleDOI
TL;DR: A custom microarray platform directed towards immune and inflammatory markers was used to investigate the temporal expression profiles of genes in a Balb/c mouse model of inhalational ricin exposure to establish a rational basis for the identification of more generic medical countermeasures.

Journal ArticleDOI
TL;DR: Results have shown overall improvements for both within- and inter-laboratory reproducibility with respect to delta13C and delta15N measurements and highlighted the importance of sample preparation procedures and the need to standardise both these procedures and calibration against Standard Reference Materials.

Journal ArticleDOI
TL;DR: Since B. ovis is not known to cause human brucellosis, functional ABC systems absent in the B. Ovis genome may represent virulence factors in human Brucellosis.
Abstract: Brucellosis is a prevalent zoonotic disease and is endemic in the Middle East, South America, and other areas of the world. In this study, complete inventories of putative functional ABC systems of five Brucella species have been compiled and compared. ABC systems of Brucella melitensis 16M, Brucella abortus 9-941, Brucella canis RM6/66, Brucella suis 1330, and Brucella ovis 63/290 were identified and aligned. High numbers of ABC systems, particularly nutrient importers, were found in all Brucella species. However, differences in the total numbers of ABC systems were identified (B. melitensis, 79; B. suis, 72; B. abortus 64; B. canis, 74; B. ovis, 59) as well as specific differences in the functional ABC systems of the Brucella species. Since B. ovis is not known to cause human brucellosis, functional ABC systems absent in the B. ovis genome may represent virulence factors in human brucellosis.

Journal ArticleDOI
TL;DR: Nebulised salbutamol treatment following phosgene induced acute lung injury does not improve survival, and worsens various physiological parameters including arterial oxygen partial pressure and shunt fraction.
Abstract: Objectives To examine the effectiveness of nebulised salbutamol in the treatment of phosgene induced acute lung injury. Method Using previously validated methods, 12 anaesthetised large white pigs were exposed to phosgene (Ct 1978 ± 8 mg min m-3), established on mechanical ventilation and randomised to treatment with either nebulised salbutamol (2.5mg per dose) or saline control. Treatments were given 1, 5, 9, 13, 17 and 21 hours following phosgene exposure. The animals were followed to 24 hours following phosgene exposure. Results Salbutamol treatment had no effect on mortality and had a deleterious effect on arterial oxygenation, shunt fraction and heart rate. There was a reduction in the number of neutrophils from 24.0% ± 4.4 to 12.17% ± 2.1 (p Conclusion Nebulised salbutamol treatment following phosgene induced acute lung injury does not improve survival, and worsens various physiological parameters including arterial oxygen partial pressure and shunt fraction. Salbutamol treatment reduces neutrophil influx into the lung. Its sole use following phosgene exposure is not recommended.

Journal ArticleDOI
TL;DR: The utility of optimising genes encoding the structural proteins of VEEV is demonstrated for the first time and informs us that including optimised genes in gene-based vaccines for VEEv is essential to obtain maximum immunogenicity and protective efficacy.
Abstract: Optimisation of genes has been shown to be beneficial for expression of proteins in a range of applications. Optimisation has increased protein expression levels through improved codon usage of the genes and an increase in levels of messenger RNA. We have applied this to an adenovirus (ad)-based vaccine encoding structural proteins (E3-E2-6K) of Venezuelan equine encephalitis virus (VEEV). Following administration of this vaccine to Balb/c mice, an approximately ten-fold increase in antibody response was elicited and increased protective efficacy compared to an ad-based vaccine containing non-optimised genes was observed after challenge. This study, in which the utility of optimising genes encoding the structural proteins of VEEV is demonstrated for the first time, informs us that including optimised genes in gene-based vaccines for VEEV is essential to obtain maximum immunogenicity and protective efficacy.

Book ChapterDOI
01 Jan 2009
TL;DR: In this paper, the authors describe the fundamentals of explosive technology and the properties of some common explosives, and their availability, performance, and any feature that might lead a terrorist to choose one over another.
Abstract: Publisher Summary This chapter describes the fundamentals of explosive technology and the properties of some common explosives. The detection-related aspects and their availability, performance, and any feature that might lead a terrorist to choose one over another are also discussed in this chapter. Chemical explosives, with proper initiation, undergo violent decomposition to produce heat, gas, and rapid expansion of matter and its practical effect depends on the speed at which the decomposition takes place as well as on the amount of gas and heat released. A chemical reaction which proceeds through the material at a rate less than or equal to the speed of sound in the unreacted material is known as a deflagration. A chemical reaction that proceeds through the material at a rate greater than the speed of sound in the unreacted material is known as a detonation. Explosives are classed as primary or secondary, and typically a small quantity of a primary explosive is used in a detonator, whereas larger quantities of secondary explosives are used in the booster and the main charge of a device. Plastic explosives are widely used in terrorist bombs and they contain one or more explosives, molded in an inert, flexible binder. As powders do not readily hold a shape and TNT is the only common melt-castable explosive, most of the explosive powders are plasticized to make a moldable material. To date, the terrorists have used FO (the commercial fuel), icing sugar (little associated odor), or aluminum (added heat release) and when these combustibles are added to AN, a more powerful material is obtained.

Journal ArticleDOI
TL;DR: The hydrophobicity of a range of Bacillus species was determined to evaluate the correlation between bacterial hydrophobia and pathogenicity and the results confirmed the importance of knowing the phytochemical properties of these organisms.
Abstract: Aims: The genus Bacillus encompasses a wide range of species which display varying pathogenic abilities. The hydrophobicity of a range of Bacillus species was determined to evaluate the correlation between bacterial hydrophobicity and pathogenicity. Methods and Results: Bacterial adhesion to hydrocarbon assays were used to determine the hydrophobicity of various Bacillus species. Significant differences in the hydrophobicity of vegetative Bacilli were found. Specifically, vegetative Bacillus anthracis or Bacillus thuringiensis cells were highly hydrophobic whereas Bacillus cereus or Bacillus subtilis were only slightly hydrophobic using this test. Cell adhesion assays using A549 or J774 cells were used to demonstrate a correlation between the bacterial hydrophobicity profiles with the ability to adhere to the mammalian cell lines. Conclusions: The ability of Bacillus species to adhere to mammalian cell lines correlates with the hydrophobicity of the bacteria and also correlates with the relative pathogenicity of some of the Bacillus species tested. Significance and Impact of the Study: This work suggests that study of the physical-chemical properties of vegetative cells could inform future approaches for the rapid identification and discrimination of potentially pathogenic Bacilli.

Journal ArticleDOI
TL;DR: A monoclonal antibody possessing reactivity to a wide range of VEEV strains may be of benefit as a generic antiviral therapy, however, humanisation of the murine antibody will be required before it can be tested in humans.
Abstract: There is currently a requirement for antiviral therapies capable of protecting against infection with Venezuelan equine encephalitis virus (VEEV), as a licensed vaccine is not available for general human use. Monoclonal antibodies are increasingly being developed as therapeutics and are potential treatments for VEEV as they have been shown to be protective in the mouse model of disease. However, to be truly effective, the antibody should recognise multiple strains of VEEV and broadly reactive monoclonal antibodies are rarely and only coincidentally isolated using classical hybridoma technology. In this work, methods were developed to reliably derive broadly reactive murine antibodies. A phage library was created that expressed single chain variable fragments (scFv) isolated from mice immunised with multiple strains of VEEV. A broadly reactive scFv was identified and incorporated into a murine IgG2a framework. This novel antibody retained the broad reactivity exhibited by the scFv but did not possess virus neutralising activity. However, the antibody was still able to protect mice against VEEV disease induced by strain TrD when administered 24 h prior to challenge. A monoclonal antibody possessing reactivity to a wide range of VEEV strains may be of benefit as a generic antiviral therapy. However, humanisation of the murine antibody will be required before it can be tested in humans. Crown Copyright © 2009

Journal ArticleDOI
TL;DR: Although there were major differences in pathogenesis, the recombinant F1 and V antigen vaccine and ciprofloxacin protected against plague infections caused by small- and large-particle aerosols.
Abstract: Presently there is a significant effort to develop and evaluate vaccines and antibiotics against the potential bioterrorism agent Yersinia pestis. The animal models used to test these countermeasures involve the deposition of small particles within the lung. However, deliberate aerosol release of Y. pestis will generate both small and large inhalable particles. We report in this study that the pathogenesis patterns of plague infections caused by the deposition of 1- and 12-μm-particle aerosols of Y. pestis in the lower and upper respiratory tracts (URTs) of mice are different. The median lethal dose for 12-μm particles was 4.9-fold greater than that for 1-μm particles. The 12-μm-particle infection resulted in the degradation of the nasal mucosa and nasal-associated lymphoid tissue (NALT) plus cervical lymphadenopathy prior to bacteremic dissemination. Lung involvement was limited to secondary pneumonia. In contrast, the 1-μm-particle infection resulted in primary pneumonia; in 40% of mice, the involvement of NALT and cervical lymphadenopathy were observed, indicating entry via both URT lymphoid tissues and lungs. Despite bacterial deposition in the gastrointestinal tract, the involvement of Peyer's patches was not observed in either infection. Although there were major differences in pathogenesis, the recombinant F1 and V antigen vaccine and ciprofloxacin protected against plague infections caused by small- and large-particle aerosols.

Book ChapterDOI
01 Jan 2009
TL;DR: In this article, a North Atlantic Trade Organization (NATO) study is based on a Task Group 023 on Team Effectiveness and report (HFM-087 TP/59) written by the authors.
Abstract: This chapter is based on a North Atlantic Trade Organization (NATO) study (NATO/RTO/HFM Task Group 023 on Team Effectiveness) and report (HFM-087 TP/59) written by the authors (published by NATO RTO, April, 2005)

Journal ArticleDOI
TL;DR: In this paper, a methodology for making inference about parameters of a possible covert chemical or biological atmospheric release from sensor readings is presented, which uses some of the components in a sequential Monte Carlo algorithm.
Abstract: Summary. A methodology is developed for making inference about parameters of a possible covert chemical or biological atmospheric release from sensor readings. The key difficulty in performing this inference is that the results must be obtained in a very short timescale (5 min) to make use of the inference for protection. The methodology that is developed uses some of the components in a sequential Monte Carlo algorithm. However, this inference problem is different from many other sequential Monte Carlo problems, in that there are no state evolution equations, the forward model is highly non-linear and the likelihoods are non-Gaussian. The algorithm that is developed can use stored output from complex physics models for more rapid update of the posterior from new data without having to rerun the models. The use of differential evolution Markov chain sampling allows new samples to diverge rapidly from degenerate sample sets. Results for inferences made of atmospheric releases (both real and simulated) of material are presented, demonstrating that the sampling scheme performs adequately despite constraints of a short time span for calculations.

Journal ArticleDOI
TL;DR: A series of command decision-making games which were analysed using a probit-based statistical approach gives strong support to the way in which rapid planning captures such decision- making in algorithmic form.

Journal ArticleDOI
TL;DR: In vitro studies indicated that magainin II protected a human bronchial epithelial cell line (BEAS-2B) from killing by Bcc and suggest that this peptide may have therapeutic potential against these organisms.
Abstract: This study was undertaken to determine the antibacterial activity of eight cationic antimicrobial peptides towards strains of genomovars I-V of the Burkholderia cepacia complex (Bcc) in time-kill assays. All but one of the peptides failed to show activity against the panel of test strains. The exception was magainin II, a 23 aa peptide isolated from the epidermis of the African clawed frog, Xenopus laevis, which exhibited significant bactericidal activity for Bcc genomovars most frequently associated with lung infection of patients with cystic fibrosis. In vitro studies indicated that magainin II protected a human bronchial epithelial cell line (BEAS-2B) from killing by Bcc and suggest that this peptide may have therapeutic potential against these organisms.