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Search Results: 1 - 10 of 320497 matches for " Paul J. Johnson "
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Pharmacodynamics, Population Dynamics, and the Evolution of Persistence in Staphylococcus aureus
Paul J. T. Johnson,Bruce R. Levin
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003123
Abstract: When growing populations of bacteria are confronted with bactericidal antibiotics, the vast majority of cells are killed, but subpopulations of genetically susceptible but phenotypically resistant bacteria survive. In accord with the prevailing view, these “persisters” are non- or slowly dividing cells randomly generated from the dominant population. Antibiotics enrich populations for pre-existing persisters but play no role in their generation. The results of recent studies with Escherichia coli suggest that at least one antibiotic, ciprofloxacin, can contribute to the generation of persisters. To more generally elucidate the role of antibiotics in the generation of and selection for persisters and the nature of persistence in general, we use mathematical models and experiments with Staphylococcus aureus (Newman) and the antibiotics ciprofloxacin, gentamicin, vancomycin, and oxacillin. Our results indicate that the level of persistence varies among these drugs and their concentrations, and there is considerable variation in this level among independent cultures and mixtures of independent cultures. A model that assumes that the rate of production of persisters is low and persisters grow slowly in the presence of antibiotics can account for these observations. As predicted by this model, pre-treatment with sub-MIC concentrations of antibiotics substantially increases the level of persistence to drugs other than those with which the population is pre-treated. Collectively, the results of this jointly theoretical and experimental study along with other observations support the hypothesis that persistence is the product of many different kinds of errors in cell replication that result in transient periods of non-replication and/or slowed metabolism by individual cells in growing populations. This Persistence as Stuff Happens (PaSH) hypothesis can account for the ubiquity of this phenomenon. Like mutation, persistence is inevitable rather than an evolved character. What evolved and have been identified are genes and processes that affect the frequency of persisters.
Genetic Variation for Biomass and Related Morphological Traits in Cup Plant (Silphium perfoliatum L.)  [PDF]
Teshale Assefa, Jixiang Wu, Kenneth A. Albrecht, Paul J. Johnson, Arvid Boe
American Journal of Plant Sciences (AJPS) , 2015, DOI: 10.4236/ajps.2015.68114
Abstract: Cup plant (Silphium perfoliatum L.) has demonstrated potential for bioenergy production in North America, South America, and Europe. Our objectives were to: 1) determine genetic variation and narrow-sense heritability for biomass and related morphological traits, and 2) identify half-sib families with superior biomass yield and potential for use in cultivar development in cup plant. Thirty three half-sib families and a check were evaluated at two locations in 2011, 2012, and 2013. Annual biomass yield at Brookings ranged from 2183 kg·ha-1 in 2012 to 8053 kg·ha-1 in 2013; whereas, yields at Arlington were similar among years. Mean individual half-sib family biomass yield ranged from 3912 to 6784 kg·ha-1 at Brookings and from 5682 to 11,269 kg·ha-1 at Arlington. Heritability estimates for five biomass-related morphological traits ranged from 0.52 to 0.72. This cup plant population had potential for biomass production in the north central USA and contained sufficient additive genetic variation to expect progress from among-and-within-family selection for biomass yield and related traits.
Groupthink and the blunder of the gauges
Paul J Cote,Mark A Johnson
Physics , 2009,
Abstract: We address the issue of the fallacy of the gauge concept in electromagnetism. The role of groupthink in the perpetuation of this concept in the physics literature is also discussed. Brief, elementary arguments suffice to demonstrate the fallacy. The simplicity of the proofs indicates that the norms of the scientific method have been neglected on this topic.
On the peculiarity of the Coulomb gauge
Paul J Cote,Mark A Johnson
Physics , 2009,
Abstract: In an earlier paper we provided an alternative to the standard gauge concept for deriving the classical electromagnetic wave equations. This alternative involves recognition of two previously overlooked basic equations and represents a simplification of the formalism and a clarification of some basic physics that is obscured in the standard method. It also removes inconsistencies inherent in the gauge approach. The present paper relates to the Coulomb gauge and addresses another example of a major inconsistency that derives directly from the gauge concept
Comments on "What the Electromagnetic Vector Potential Describes" by E. J. Konopinski
Paul J Cote,Mark A. Johnson
Physics , 2010,
Abstract: The seminal paper on the meaning of the vector potential by E. J. Konopinski is revisited. The full significance of this work has not been generally recognized to date. We first briefly review Konopinski's findings and show that many of his key results can be obtained from a simpler and more familiar approach. We then discuss the additional implications of his analyses, which were overlooked by Konopinski himself.
Mesoporous Silicate Materials in Sensing
Brian J. Melde,Brandy J. Johnson,Paul T. Charles
Sensors , 2008, DOI: 10.3390/s8085202
Abstract: Mesoporous silicas, especially those exhibiting ordered pore systems and uniform pore diameters, have shown great potential for sensing applications in recent years. Morphological control grants them versatility in the method of deployment whether as bulk powders, monoliths, thin films, or embedded in coatings. High surface areas and pore sizes greater than 2 nm make them effective as adsorbent coatings for humidity sensors. The pore networks also provide the potential for immobilization of enzymes within the materials. Functionalization of materials by silane grafting or through cocondensation of silicate precursors can be used to provide mesoporous materials with a variety of fluorescent probes as well as surface properties that aid in selective detection of specific analytes. This review will illustrate how mesoporous silicas have been applied to sensing changes in relative humidity, changes in pH, metal cations, toxic industrial compounds, volatile organic compounds, small molecules and ions, nitroenergetic compounds, and biologically relevant molecules.
Mesoporous Silicate Materials in Sensing
Brian J. Melde,Brandy J. Johnson,Paul T. Charles
Sensors , 2008,
Abstract: Mesoporous silicas, especially those exhibiting ordered pore systems and uniform pore diameters, have shown great potential for sensing applications in recent years. Morphological control grants them versatility in the method of deployment whether as bulk powders, monoliths, thin films, or embedded in coatings. High surface areas and pore sizes greater than 2 nm make them effective as adsorbent coatings for humidity sensors. The pore networks also provide the potential for immobilization of enzymes within the materials. Functionalization of materials by silane grafting or through cocondensation of silicate precursors can be used to provide mesoporous materials with a variety of fluorescent probes as well as surface properties that aid in selective detection of specific analytes. This review will illustrate how mesoporous silicas have been applied to sensing changes in relative humidity, changes in pH, metal cations, toxic industrial compounds, volatile organic compounds, small molecules and ions, nitroenergetic compounds, and biologically relevant molecules.
Is host-schistosome coevolution going anywhere?
Joanne P Webster, Jaya Shrivastava, Paul J Johnson, Lynsey Blair
BMC Evolutionary Biology , 2007, DOI: 10.1186/1471-2148-7-91
Abstract: We demonstrated variation in, and a reciprocal impact on, the fitness of both host and pathogen phenotype and genotype, an outcome dependent on the combinations of genotypes involved, and evidence of change over time. Most apparent was the observation that parasites appeared to rapidly adapt to those intermediate hosts previously selected for resistance.Our results illustrate the potential for host-schistosome coevolution and, in particular, suggest that host resistance may be a temporary phenomenon in nature due, in part, to rapid counter-adaptations by parasites.Host-parasite coevolution is driven by the reciprocal evolution of host resistance [1] and parasite infectivity and/or virulence [2] (see Appendix for definitions). Coevolution maintains polymorphisms at relevant loci [3,4] and has important repercussions for traits such as host-parasite compatibility, range and virulence [5]. Understanding how pathogens respond to evolved changes in host characteristics may also provide a good model for their all too apparent potential to respond to other kinds of selective pressures, such as the use of new drugs or vaccines to combat disease [6,7]. A substantial body of theory has been developed to explore the likelihood and consequences of coevolution. Classic theories, such as that of the Red Queen Hypothesis [8-11], provide a conceptual underpinning to discussions of biological evolutionary arms races or reciprocal change. However, direct tests of coevolution remain elusive and empirical evidence of host-parasite coevolution is rarely available, particularly for vertebrate host-parasite populations [12]. Some have taken this to suggest that either host-pathogen coevolution does not occur or that it is not important [13,14]. Others, in contrast, have suggested that in order to detect coevolution we must improve our techniques for how to look for it [12].Host-parasite coevolution requires additive genetic variation in the relevant host and parasite traits, reciprocal ef
In vitro propagation of Solidago virgaurea L. through nodal culture
John Peter Paul J,Revathy I,Johnson, M
Research in Plant Biology , 2012,
Abstract:
The Pharmaco –, Population and Evolutionary Dynamics of Multi-drug Therapy: Experiments with S. aureus and E. coli and Computer Simulations
Peter Ankomah,Paul J. T. Johnson,Bruce R. Levin
PLOS Pathogens , 2013, DOI: 10.1371/journal.ppat.1003300
Abstract: There are both pharmacodynamic and evolutionary reasons to use multiple rather than single antibiotics to treat bacterial infections; in combination antibiotics can be more effective in killing target bacteria as well as in preventing the emergence of resistance. Nevertheless, with few exceptions like tuberculosis, combination therapy is rarely used for bacterial infections. One reason for this is a relative dearth of the pharmaco-, population- and evolutionary dynamic information needed for the rational design of multi-drug treatment protocols. Here, we use in vitro pharmacodynamic experiments, mathematical models and computer simulations to explore the relative efficacies of different two-drug regimens in clearing bacterial infections and the conditions under which multi-drug therapy will prevent the ascent of resistance. We estimate the parameters and explore the fit of Hill functions to compare the pharmacodynamics of antibiotics of four different classes individually and in pairs during cidal experiments with pathogenic strains of Staphylococcus aureus and Escherichia coli. We also consider the relative efficacy of these antibiotics and antibiotic pairs in reducing the level of phenotypically resistant but genetically susceptible, persister, subpopulations. Our results provide compelling support for the proposition that the nature and form of the interactions between drugs of different classes, synergy, antagonism, suppression and additivity, has to be determined empirically and cannot be inferred from what is known about the pharmacodynamics or mode of action of these drugs individually. Monte Carlo simulations of within-host treatment incorporating these pharmacodynamic results and clinically relevant refuge subpopulations of bacteria indicate that: (i) the form of drug-drug interactions can profoundly affect the rate at which infections are cleared, (ii) two-drug therapy can prevent treatment failure even when bacteria resistant to single drugs are present at the onset of therapy, and (iii) this evolutionary virtue of two-drug therapy is manifest even when the antibiotics suppress each other's activity.
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