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Search Results: 1 - 10 of 183259 matches for " Mark E Wickham "
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Crossing the Line: Selection and Evolution of Virulence Traits
Nat F Brown equal contributor,Mark E Wickham equal contributor,Brian K Coombes,B. Brett Finlay
PLOS Pathogens , 2006, DOI: 10.1371/journal.ppat.0020042
Abstract: The evolution of pathogens presents a paradox. Pathogenic species are often absolutely dependent on their host species for their propagation through evolutionary time, yet the pathogenic lifestyle requires that the host be damaged during this dependence. It is clear that pathogenic strategies are successful in evolutionary terms because a diverse array of pathogens exists in nature. Pathogens also evolve using a broad range of molecular mechanisms to acquire and modulate existing virulence traits in order to achieve this success. Detailing the benefit of enhanced selection derived through virulence and understanding the mechanisms through which virulence evolves are important to understanding the natural world and both have implications for human health.
Oral infection of mice with Salmonella enterica serovar Typhimurium causes meningitis and infection of the brain
Mark E Wickham, Nat F Brown, John Provias, B Brett Finlay, Brian K Coombes
BMC Infectious Diseases , 2007, DOI: 10.1186/1471-2334-7-65
Abstract: Five mouse lines including C57BL/6, Balb/c, 129S6-Slc11a1tm1Mcg, 129S1/SvImJ, B6.129-Inpp5dtm1Rkh were used in the murine typhoid model to examine the dissemination of systemic Salmonella enterica serovar Typhimurium following oral infection.We report data on spontaneous meningitis and brain infection following oral infection of mice with Salmonella enterica serovar Typhimurium.This model may provide a system in which dissemination of bacteria through the central nervous system and the influence of host and bacterial genetics can be queried.Salmonella species are Gram-negative, facultative intracellular bacteria that are distributed globally. Two recognized species of Salmonella include S. enterica and S. bongori, with S. enterica serovars Typhimurium, Typhi and Enteriditis causing the vast majority of human infections worldwide. Humans are infected with S. enterica though contaminated food and water and present with a range of acute symptoms including gastroenteritis, fever, and headache. Although systemic infections with S. Typhi are uncommon in developed countries, typhoid remains a significant public health problem in the developing world [1]. Infections with non-typhoidal strains of Salmonella are a global burden, with an estimated 1.4 million cases in the United States alone [2].Salmonella meningitis is an uncommon complication of salmonellosis, occurring more frequently in neonates and infants [3,4], although adult cases are reported. While considered rare in the developed world, Salmonella is a common cause of enterobacterial meningitis in Africa, Brazil and Thailand [4,5]. Cases in adults of Salmonella infection report colonization of the cerebrospinal fluid, fatal brain abscesses caused by intracranial colonization of S. enterica serotype Typhimurium [6], adult Salmonella meningitis [7] and CSF pleocytosis [7]. Mortality rates are typically high, especially in infants where rates have been 60% [8]. Other major issues concerning Salmonella meningitis is a h
Crossing the line: selection and evolution of virulence traits.
Brown Nat F,Wickham Mark E,Coombes Brian K,Finlay B Brett
PLOS Pathogens , 2006,
Abstract: The evolution of pathogens presents a paradox. Pathogenic species are often absolutely dependent on their host species for their propagation through evolutionary time, yet the pathogenic lifestyle requires that the host be damaged during this dependence. It is clear that pathogenic strategies are successful in evolutionary terms because a diverse array of pathogens exists in nature. Pathogens also evolve using a broad range of molecular mechanisms to acquire and modulate existing virulence traits in order to achieve this success. Detailing the benefit of enhanced selection derived through virulence and understanding the mechanisms through which virulence evolves are important to understanding the natural world and both have implications for human health.
Salmonella Phage ST64B Encodes a Member of the SseK/NleB Effector Family
Nat F. Brown,Brian K. Coombes,Jenna L. Bishop,Mark E. Wickham,Michael J. Lowden,Ohad Gal-Mor,David L. Goode,Erin C. Boyle,Kristy L. Sanderson,B. Brett Finlay
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0017824
Abstract: Salmonella enterica is a species of bacteria that is a major cause of enteritis across the globe, while certain serovars cause typhoid, a more serious disease associated with a significant mortality rate. Type III secreted effectors are major contributors to the pathogenesis of Salmonella infections. Genes encoding effectors are acquired via horizontal gene transfer, and a subset are encoded within active phage lysogens. Because the acquisition of effectors is in flux, the complement of effectors possessed by various Salmonella strains frequently differs. By comparing the genome sequences of S. enterica serovar Typhimurium strain SL1344 with LT2, we identified a gene with significant similarity to SseK/NleB type III secreted effector proteins within a phage ST64B lysogen that is absent from LT2. We have named this gene sseK3. SseK3 was co-regulated with the SPI-2 type III secretion system in vitro and inside host cells, and was also injected into infected host cells. While no role for SseK3 in virulence could be identified, a role for the other family members in murine typhoid was found. SseK3 and other phage-encoded effectors were found to have a significant but sparse distribution in the available Salmonella genome sequences, indicating the potential for more uncharacterised effectors to be present in less studied serovars. These phage-encoded effectors may be principle subjects of contemporary selective processes shaping Salmonella-host interactions.
The Effect of the LISA Response Function on Observations of Monochromatic Sources
A. Vecchio,E. D. L. Wickham
Physics , 2004, DOI: 10.1103/PhysRevD.70.082002
Abstract: The Laser Interferometer Space Antenna (LISA) is expected to provide the largest observational sample of binary systems of faint sub-solar mass compact objects, in particular white-dwarfs, whose radiation is monochromatic over most of the LISA observational window. Current astrophysical estimates suggest that the instrument will be able to resolve about 10000 such systems, with a large fraction of them at frequencies above 3 mHz, where the wavelength of gravitational waves becomes comparable to or shorter than the LISA arm-length. This affects the structure of the so-called LISA transfer function which cannot be treated as constant in this frequency range: it introduces characteristic phase and amplitude modulations that depend on the source location in the sky and the emission frequency. Here we investigate the effect of the LISA transfer function on detection and parameter estimation for monochromatic sources. For signal detection we show that filters constructed by approximating the transfer function as a constant (long wavelength approximation) introduce a negligible loss of signal-to-noise ratio -- the fitting factor always exceeds 0.97 -- for f below 10mHz, therefore in a frequency range where one would actually expect the approximation to fail. For parameter estimation, we conclude that in the range 3mHz to 30mHz the errors associated with parameter measurements differ from about 5% up to a factor of 10 (depending on the actual source parameters and emission frequency) with respect to those computed using the long wavelength approximation.
A Markov Chain Monte Carlo approach to the study of massive black hole binary systems with LISA
E. D. L. Wickham,A. Stroeer,A. Vecchio
Physics , 2006, DOI: 10.1088/0264-9381/23/19/S20
Abstract: The Laser Interferometer Space Antenna (LISA) will produce a data stream containing a vast number of overlapping sources: from strong signals generated by the coalescence of massive black hole binary systems to much weaker radiation form sub-stellar mass compact binaries and extreme-mass ratio inspirals. It has been argued that the observation of weak signals could be hampered by the presence of loud ones and that they first need to be removed to allow such observations. Here we consider a different approach in which sources are studied simultaneously within the framework of Bayesian inference. We investigate the simplified case in which the LISA data stream contains radiation from a massive black hole binary system superimposed over a (weaker) quasi-monochromatic waveform generated by a white dwarf binary. We derive the posterior probability density function of the model parameters using an automatic Reversible Jump Markov Chain Monte Carlo algorithm (RJMCMC). We show that the information about the sources and noise are retrieved at the expected level of accuracy without the need of removing the stronger signal. Our analysis suggests that this approach is worth pursuing further and should be considered for the actual analysis of the LISA data.
Reshaping Data with the reshape Package
Hadley Wickham
Journal of Statistical Software , 2007,
Abstract: This paper presents the reshape package for R, which provides a common framework for many types of data reshaping and aggregation. It uses a paradigm of 'melting' and 'casting', where the data are 'melted' into a form which distinguishes measured and identifying variables, and then 'cast' into a new shape, whether it be a data frame, list, or high dimensional array. The paper includes an introduction to the conceptual framework, practical advice for melting and casting, and a case study.
The Split-Apply-Combine Strategy for Data Analysis
Hadley Wickham
Journal of Statistical Software , 2011,
Abstract: Many data analysis problems involve the application of a split-apply-combine strategy, where you break up a big problem into manageable pieces, operate on each piece independently and then put all the pieces back together. This insight gives rise to a new R package that allows you to smoothly apply this strategy, without having to worry about the type of structure in which your data is stored.The paper includes two case studies showing how these insights make it easier to work with batting records for veteran baseball players and a large 3d array of spatio-temporal ozone measurements.
Understanding the individual with Alzheimer’s disease: Can socioemotional selectivity theory guide us?  [PDF]
Ruth E. Mark
Advances in Alzheimer's Disease (AAD) , 2012, DOI: 10.4236/aad.2012.13010
Abstract: Individuals often get lost behind the diagnosis of Alzheimer’s disease (AD) while widespread differences between these patients are morecommon than similarities. Socioemotional Selectivity Theory (SST) suggests that as we age our goals change from future-oriented (acquiringnew information) to present-oriented (enhancing the emotional, especially positive, meaning of encounters). The goal of the current article is to examine whether the principles of SST might also apply for people with AD. Some aspects of SST are found especially in the early stages of AD when awareness is often intact and cognitive impairment is relatively limited. This review has clinical significance for the treatment of AD because it focuses on what is important to the individual rather than treating patients as a homogenous group. It also highlights the importance of social networks and emphasizes the role of the proxy in AD care. Lastly, it suggests that if those with AD (like the healthy elderly) have a positivity bias then positive emotional stimuli/wording/instructions could usefully be employed in their daily treatment. I suggest that SST may be a useful starting point when attempting to address what matters to individuals with AD and conclude by providing a few suggestions for future studies.
What Is “African Bioethics” as Used by Sub-Saharan African Authors: An Argumentative Literature Review of Articles on African Bioethics  [PDF]
Albert Mark E. Coleman
Open Journal of Philosophy (OJPP) , 2017, DOI: 10.4236/ojpp.2017.71003
Abstract:
The term “African bioethics” is more often used by some Sub-Saharan African (SSA) authors to denote an African framework of resolving pertinent moral dilemmas arising in the interface of human persons with biomedical sciences, as juxtaposed against what is deemed “Western bioethics paradigms/theories, considered otherwise as a form of “moral/ethical imperialism”; and considered foreign to SSA tradition(s). This article is a literature review of articles on African bioethics to clarify what actually is meant epistemologically by African bioethics vis a vis, Western bioethics, as well as ascertain whether African bioethics as used by SSA authors is wishful thinking, yet to be realised in actuality.
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