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Rapid Variable-Number Tandem-Repeat Genotyping for Mycobacterium leprae Clinical Specimens
Kimura, M.,Sakamuri, R. M.,Groathouse, N. A.,Rivoire, B. L.,Gingrich, D.,Krueger-Koplin, S.,Cho, S.-N.,Brennan, P. J.,Vissa, V. American Society for Microbiology 2009 Journal of clinical microbiology Vol.47 No.6
<P>Mycobacterium leprae is the noncultivable pathogen of leprosy. Since the genome sequence of an isolate of M. leprae has become available, multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA) has been explored as a tool for strain typing and identification of chains of transmission of leprosy. In order to discover VNTRs and develop methods transferable to clinical samples, MLVA was applied to a global collection of M. leprae isolates derived from leprosy patients and propagated in armadillo hosts. PCR amplification, agarose gel electrophoresis, and sequencing methods were applied to DNA extracts from these infected armadillo tissues (n = 21). We identified polymorphisms in 15 out of 25 short-tandem-repeat (STR) loci previously selected by in silico analyses of the M. leprae genome. We then developed multiplex PCR for amplification of these 15 loci in four separate PCRs suitable for fluorescent fragment length analysis and demonstrated STR profiles highly concordant with those from the sequencing methods. Subsequently, we extended this method to DNA extracts from human clinical specimens, such as skin biopsy specimens (n = 30). With these techniques, mapping of multiple loci and differentiation of genotypes have been possible using total DNA extracts from limited amounts of clinical samples at a reduced cost and with less time. These practical methods are therefore available and applicable to answer focused epidemiological questions and to allow monitoring of the transmission of M. leprae in different countries where leprosy is endemic.</P>
Population-Based Molecular Epidemiology of Leprosy in Cebu, Philippines
Sakamuri, R. M.,Kimura, M.,Li, W.,Kim, H.-C.,Lee, H.,Kiran, M. D.,Black, W. C.,Balagon, M.,Gelber, R.,Cho, S.-N.,Brennan, P. J.,Vissa, V. American Society for Microbiology 2009 Journal of clinical microbiology Vol.47 No.9
<P>To address the persisting problem of leprosy in Cebu, Philippines, we compiled a database of more than 200 patients who attend an established referral skin clinic. We described the patient characteristics in conventional demographic parameters and also applied multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA) and single nucleotide polymorphism (SNP) typing for Mycobacterium leprae in biopsied skin lesion samples. These combined approaches revealed that transmission is ongoing, with the affected including the young Cebuano population under 40 years of age in both crowded cities and rural areas of the island. The emergence of multicase families (MCF) is indicative of infection unconstrained by standard care measures. For the SNPs, we designed a low-cost PCR-restriction fragment length polymorphism typing method. MLVA in M. leprae was highly discriminatory in this population yet could retain broad groups, as defined by the more stable SNPs, implying temporal marker stability suitable for interpreting population structures and evolution. The majority of isolates belong to an Asian lineage (SNP type 1), and the rest belong to a putative postcolonial lineage (SNP type 3). Specific alleles at two VNTR loci, (GGT)5 and 21-3, were highly associated with SNP type 3 in this population. MLVA identified M. leprae genotype associations for patients with known epidemiological links such as in MCFs and in some villages. These methods provide a molecular database and a rational framework for targeted approaches to search and confirm leprosy transmission in various scenarios.</P>
Cote, M.L.,Liu, M.,Bonassi, S.,Neri, M.,Schwartz, A.G.,Christiani, D.C.,Spitz, M.R.,Muscat, J.E.,Rennert, G.,Aben, K.K.,Andrew, A.S.,Bencko, V.,Bickeboller, H.,Boffetta, P.,Brennan, P.,Brenner, H.,Due Pergamon Press 2012 European journal of cancer Vol.48 No.13
Background and methods: Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analysed. Unconditional logistic regression models and generalised estimating equations were used to estimate odds ratios and 95% confidence intervals. Results: Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in the risk of lung cancer, after adjustment for smoking and other potential confounders (95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (odds ratios (OR)=1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR=1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR=1.44, 95% CI: 1.07, 1.93), after adjustment. Conclusions: The occurrence of lung cancer among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those risks associated with cigarette smoking. While the role of genetic variation in the aetiology of lung cancer remains to be fully characterised, family history assessment is immediately available and those with a positive history represent a higher risk group.
Overview of results from the National Spherical Torus Experiment (NSTX)
Gates, D.A.,Ahn, J.,Allain, J.,Andre, R.,Bastasz, R.,Bell, M.,Bell, R.,Belova, E.,Berkery, J.,Betti, R.,Bialek, J.,Biewer, T.,Bigelow, T.,Bitter, M.,Boedo, J.,Bonoli, P.,Boozer, A.,Brennan, D.,Breslau IOP Publishing 2009 Nuclear fusion Vol.49 No.10
Optimization of a Quasi-Zero-Stiffness Isolator
Carrella A,Brennan M. J,Waters T. P 대한기계학회 2007 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.21 No.6
The frequency range over which a mount can isolate a mass from a vibrating base (or vice versa) is often limited by the mount stiffness required to support the weight of the mass. This compromise can be made more favourable by employing non-linear mounts with a softening spring characteristic such that small excursions about the static equilibrium position result in small dynamic spring forces and a correspondingly low natural frequency. This paper concerns the force-displacement characteristic of a so-called quasi-zero-stiffness (QZS) mechanism which is characterised by an appreciable static stiffness but very small (theoretically zero) dynamic stiffness. The mechanism studied comprises a vertical spring acting in parallel with two further springs which, when inclined at an appropriate angle to the vertical, produce a cancelling negative stiffness effect. Analysis of the system shows that a QZS characteristic can be obtained if the system's parameters (angle of inclination and ratio of spring stiffnesses) are opportunely chosen. By introducing the additional criterion that the displacement of the system be largest without exceeding a desired (low) value of stiffness an optimal set of parameter values is derived. Under sufficiently large displacements the stiffness of the QZS mechanism can eventually exceed that of the simple mass-spring system and criteria for this detrimental scenario to arise are presented.
Shin, K.,Brennan, M.J.,Joe, Y.G.,Oh, J.E. The Korean Society of Automotive Engineers 2004 International journal of automotive technology Vol.5 No.1
This paper suggests two simple two-degree-of-freedom models to describe the dynamical interaction between the pad and the disc of a disc brake system. Separate models for in-plane and out -of-plane vibration are described. Although a brake pad and disc have many modes of vibration, the interaction between a single mode of each component is considered as this is thought to be crucial for brake noise. For both models, the pad and the disc are connected by a sliding friction interface having a velocity dependent friction coefficient. In this paper, it is shown that this friction model acts as negative damping in the system that describes the in-plane vibration, and as negative stiffness in system that describes the out-of-plane vibration. Stability analysis is performed to investigate the conditions under which the systems become unstable. The results of the stability analysis show that the damping is the most important parameter for in-plane vibration, whereas the stiffness is the most important parameter for the out-of-plane vibration.
Current practices and recent advances in condition assessment of aged ships
Rizzo, C. M.,Paik, J. K.,Brennan, F.,Carlsen, C. A.,Daley, C.,Garbatov, Y.,Ivanov, L.,Simonsen, B. C.,Yamamoto, N.,Zhuang, H. Z. Taylor Francis 2007 SHIPS AND OFFSHORE STRUCTURES Vol.2 No.3
<P> Ship structures are likely to be subject to age-related deterioration such as corrosion wastage, cracking or mechanical damage. It has reportedly been recognised that such age-related deterioration is almost always involved in the catastrophic failures of ship structures including total losses. While such accidents typically cause concern to the public, maintenance and repair of aged structures is quite costly and complex. It is thus of great importance to develop advanced technologies allowing for proper management and control of such age-related deterioration. This paper summarises the report of the ISSC 2006 Committee V.6 presenting current practices, recent advances and future trends on condition assessment of aged ships. This includes assessment of the structural condition in view of the serviceability and safety, methods for repair, quantification of strength of deteriorated and repaired ships (as well as criteria for acceptable damage), with due account of the uncertainties involved. Consideration is also given to cost-benefit and risk-based decision procedures for remedial actions.</P>
K. SHIN,M. J. BRENNAN,Y-G. JOE,J-E. OH 한국자동차공학회 2004 International journal of automotive technology Vol.5 No.1
This paper suggests two simple two-degree-of-freedom models to describe the dynamical interaction between the pad and the disc of a disc brake system. Separate models for in-plane and out-of-plane vibration are described. Although a brake pad and disc have many modes of vibration, the interaction between a single mode of each component is considered as this is thought to be crucial for brake noise. For both models. the pad and the disc are connected by a sliding friction interface having a velocity dependent friction coefficient. In this paper, it is shown that this friction model acts as negative damping in the system that describes the in-plane vibration, and as negative stiffness in system that describes the out-of-plane vibration. Stability analysis is performed to investigate the conditions under which the systems become unstable. The results of the stability analysis show that the damping is the most important parameter for in-plane vibration, whereas the stiffness is the most important parameter for the out-of-plane vibration.