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Search Results: 1 - 10 of 12113 matches for " Nicholas Walter "
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Effects of Polyamines on Vibrio cholerae Virulence Properties
John Bradley Goforth, Nicholas Emmanuel Walter, Ece Karatan
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0060765
Abstract: Vibrio cholerae is the causative agent of the severe enteric disease cholera. To cause cholera the bacterium must be able to synthesize both cholera toxin (CT) and toxin-coregulated pilus (TCP) which mediates autoagglutination and is required for colonization of the small intestine. Only a few environmental signals have been shown to regulate V. cholerae virulence gene expression. Polyamines, which are ubiquitous in nature, and have been implicated in regulating virulence gene expression in other bacteria, have not been extensively studied for their effect on V. cholerae virulence properties. The objective of this study was to test the effect of several polyamines that are abundant in the human intestine on V. cholerae virulence properties. All of the polyamines tested inhibited autoagglutination of V. cholerae O1 classical strain in a concentration dependent manner. Putrescine and cadaverine decreased the synthesis of the major pilin subunit, TcpA, spermidine increased its production, and spermine had no effect. Putrescine and spermidine led to a decrease and increase, respectively, on the relative abundance of TCP found on the cell surface. Spermine led to a small reduction in cholera toxin synthesis whereas none of the other polyamines had an effect. The polyamines did not affect pili bundling morphology, but caused a small reduction in CTXφ transduction, indicating that the TCP present on the cell surface may not be fully functional. We hypothesize the inhibition of autoagglutination is likely to be caused by the positively charged amine groups on the polyamines electrostatically disrupting the pili-pili interactions which mediate autoagglutination. Our results implicate that polyamines may have a protective function against colonization of the small intestine by V. cholerae.
Measurement of the dynamic response of the CERN DC spark system and preliminary estimates of the breakdown turn-on time
Nicholas Shipman,Sergio Calatroni,Roger M. Jones,Walter Wuensch
Physics , 2012,
Abstract: The new High Repetition Rate (HRR) CERN DC Spark System has been used to investigate the current and voltage time structure of a breakdown. Simulations indicate that vacuum breakdowns develop on ns timescales or even less. An experimental benchmark for this timescale is critical for comparison to simulations. The fast rise time of breakdown may provide some explanation of the particularly high gradients achieved by low group velocity, and narrow bandwidth, accelerating structures such as the T18 and T24. Voltage and current measurements made with the previous system indicated that the transient responses measured were dominated by the inherent capacitances and inductances of the DC spark system itself. The bandwidth limitations of the HRR system are far less severe allowing rise times of approximately 12ns to be measured.
Wording effects in moral judgments
Ross E. O'Hara,Walter Sinnott-Armstrong,Nicholas A. Sinnott-Armstrong
Judgment and Decision Making , 2010,
Abstract: As the study of moral judgments grows, it becomes imperative to compare results across studies in order to create unified theories within the field. These efforts are potentially undermined, however, by variations in wording used by different researchers. The current study sought to determine whether, when, and how variations in wording influence moral judgments. Online participants responded to 15 different moral vignettes (e.g., the trolley problem) using 1 of 4 adjectives: ``wrong'', ``inappropriate'', ``forbidden'', or ``blameworthy''. For half of the sample, these adjectives were preceded by the adverb ``morally''. Results indicated that people were more apt to judge an act as wrong or inappropriate than forbidden or blameworthy, and that disgusting acts were rated as more acceptable when ``morally'' was included. Although some wording differences emerged, effects sizes were small and suggest that studies of moral judgment with different wordings can legitimately be compared.
A Transcriptional Signature for Active TB: Have We Found the Needle in the Haystack?
Adithya Cattamanchi ,Nicholas D. Walter,John Z. Metcalfe,J. Lucian Davis
PLOS Medicine , 2013, DOI: 10.1371/journal.pmed.1001539
Population-Level Impact of Same-Day Microscopy and Xpert MTB/RIF for Tuberculosis Diagnosis in Africa
David W. Dowdy, J. Lucian Davis, Saskia den Boon, Nicholas D. Walter, Achilles Katamba, Adithya Cattamanchi
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070485
Abstract: Objective To compare the population-level impact of two World Health Organization-endorsed strategies for improving the diagnosis of tuberculosis (TB): same-day microscopy and Xpert MTB/RIF (Cepheid, USA). Methods We created a compartmental transmission model of TB in a representative African community, fit to the regional incidence and mortality of TB and HIV. We compared the population-level reduction in TB burden over ten years achievable with implementation over two years of same-day microscopy, Xpert MTB/RIF testing, and the combination of both approaches. Findings Same-day microscopy averted an estimated 11.0% of TB incidence over ten years (95% uncertainty range, UR: 3.3%–22.5%), and prevented 11.8% of all TB deaths (95% UR: 7.7%–27.1%). Scaling up Xpert MTB/RIF to all centralized laboratories to achieve 75% population coverage had similar impact on incidence (9.3% reduction, 95% UR: 1.9%–21.5%) and greater effect on mortality (23.8% reduction, 95% UR: 8.6%–33.4%). Combining the two strategies (i.e., same-day microscopy plus Xpert MTB/RIF) generated synergistic effects: an 18.7% reduction in incidence (95% UR: 5.6%–39.2%) and 33.1% reduction in TB mortality (95% UR: 18.1%–50.2%). By the end of year ten, combining same-day microscopy and Xpert MTB/RIF could reduce annual TB mortality by 44% relative to the current standard of care. Conclusion Scaling up novel diagnostic tests for TB and optimizing existing ones are complementary strategies that, when combined, may have substantial impact on TB epidemics in Africa.
Macroscopic effects of the spectral structure in turbulent flows
Tuan Tran,Pinaki Chakraborty,Nicholas Guttenberg,Alisia Prescott,Hamid Kellay,Walter Goldburg,Nigel Goldenfeld,Gustavo Gioia
Physics , 2009, DOI: 10.1038/nphys1674
Abstract: Two aspects of turbulent flows have been the subject of extensive, split research efforts: macroscopic properties, such as the frictional drag experienced by a flow past a wall, and the turbulent spectrum. The turbulent spectrum may be said to represent the fabric of a turbulent state; in practice it is a power law of exponent \alpha (the "spectral exponent") that gives the revolving velocity of a turbulent fluctuation (or "eddy") of size s as a function of s. The link, if any, between macroscopic properties and the turbulent spectrum remains missing. Might it be found by contrasting the frictional drag in flows with differing types of spectra? Here we perform unprecedented measurements of the frictional drag in soap-film flows, where the spectral exponent \alpha = 3 and compare the results with the frictional drag in pipe flows, where the spectral exponent \alpha = 5/3. For moderate values of the Reynolds number Re (a measure of the strength of the turbulence), we find that in soap-film flows the frictional drag scales as Re^{-1/2}, whereas in pipe flows the frictional drag scales as Re^{-1/4} . Each of these scalings may be predicted from the attendant value of \alpha by using a new theory, in which the frictional drag is explicitly linked to the turbulent spectrum. Our work indicates that in turbulence, as in continuous phase transitions, macroscopic properties are governed by the spectral structure of the fluctuations.
Maximum-Entropy Inference with a Programmable Annealer
Nicholas Chancellor,Szilard Szoke,Walter Vinci,Gabriel Aeppli,Paul A. Warburton
Physics , 2015,
Abstract: Optimisation problems in science and engineering typically involve finding the ground state (i.e. the minimum energy configuration) of a cost function with respect to many variables. If the variables are corrupted by noise then this approach maximises the likelihood that the solution found is correct. An alternative approach is to make use of prior statistical information about the noise in conjunction with Bayes's theorem. The maximum entropy solution to the problem then takes the form of a Boltzmann distribution over the ground and excited states of the cost function. Here we use a programmable Josephson junction array for the information decoding problem which we simulate as a random Ising model in a field. We show experimentally that maximum entropy decoding at finite temperature can in certain cases give competitive and even slightly better bit-error-rates than the maximum likelihood approach at zero temperature, confirming that useful information can be extracted from the excited states of the annealing device. Furthermore we introduce a microscopic bit-by-bit analytical method which is agnostic to the specific application and use it to show that the annealing device samples from a highly Boltzmann-like distribution. Machines of this kind are therefore candidates for use in a wide variety of machine learning applications which exploit maximum entropy inference, including natural language processing and image recognition. We further show that the limiting factor for performance in our experiments is likely to be control errors rather than failure to reach equilibrium. Our work also provides a method for determining if a system is in equilibrium which can be easily generalized. We discuss possible applications of this method to spin glasses and probing the performance of the quantum annealing algorithm.
Learning Models for Following Natural Language Directions in Unknown Environments
Sachithra Hemachandra,Felix Duvallet,Thomas M. Howard,Nicholas Roy,Anthony Stentz,Matthew R. Walter
Computer Science , 2015,
Abstract: Natural language offers an intuitive and flexible means for humans to communicate with the robots that we will increasingly work alongside in our homes and workplaces. Recent advancements have given rise to robots that are able to interpret natural language manipulation and navigation commands, but these methods require a prior map of the robot's environment. In this paper, we propose a novel learning framework that enables robots to successfully follow natural language route directions without any previous knowledge of the environment. The algorithm utilizes spatial and semantic information that the human conveys through the command to learn a distribution over the metric and semantic properties of spatially extended environments. Our method uses this distribution in place of the latent world model and interprets the natural language instruction as a distribution over the intended behavior. A novel belief space planner reasons directly over the map and behavior distributions to solve for a policy using imitation learning. We evaluate our framework on a voice-commandable wheelchair. The results demonstrate that by learning and performing inference over a latent environment model, the algorithm is able to successfully follow natural language route directions within novel, extended environments.
Three Philosophical Problems about Consciousness and their Possible Resolution  [PDF]
Nicholas Maxwell
Open Journal of Philosophy (OJPP) , 2011, DOI: 10.4236/ojpp.2011.11001
Abstract: Three big philosophical problems about consciousness are: Why does it exist? How do we explain and understand it? How can we explain brain-consciousness correlations? If functionalism were true, all three problems would be solved. But it is false, and that means all three problems remain unsolved (in that there is no other obvious candidate for a solution). Here, it is argued that the first problem cannot have a solution; this is inherent in the nature of explanation. The second problem is solved by recognizing that (a) there is an explanation as to why science cannot explain consciousness, and (b) consciousness can be explained by a different kind of explanation, empathic or “personalistic” explanation, compatible with, but not reducible to, scientific explanation. The third problem is solved by exploiting David Chalmers“principle of structural coherence”, and involves postulating that sensations experienced by us–visual, auditory, tactile, and so on–amount to minute scattered regions in a vast, multi dimensional “space” of all possible sensations, which vary smoothly, and in a linear way, throughout the space. There is also the space of all possible sentient brain processes. There is just one, unique one-one mapping between these two spaces that preserves continuity and linearity. It is this which provides the explanation as to why brain processes and sensations are correlated as they are. I consider objections to this unique-matching theory, and consider how the theory might be empirically confirmed.
Origins and Mechanisms in the Development of Major Mental Disorders: A Clinical Approach  [PDF]
Nicholas Pediaditakis
Journal of Behavioral and Brain Science (JBBS) , 2012, DOI: 10.4236/jbbs.2012.22030
Abstract: This paper considers the following collective significance of the shared, clinical characteristics of the major mental disorders (MMDs), their co-morbidities, overlaps and pharmacological responses with the following conclusions: 1) These disorders have a common, initial, neurodevelopmental origin. 2) They can occur probabilistically on susceptible individuals, on account of pre-existing, extreme, temperamental variances-signifying underlying structural variance. 3) Each of these syndromes can be considered the expression of disturbances in the overall, common, operating mode of brain function which normally ensures the synchrony, coordination, elegance and subtlety in the expression of all the brain’s higher faculties. 4) Lastly, this function is a complex, emergent phenomenon based on the individual’s temperamental/structural underlying makeup, switching intermittently from a normal phase to a pathologically, ordered one-the latter phase expressing itself with symptoms made up of expressing either/or, antithetical substitutes for each of the MMDs-similar to the fluctuations found in patient’s with Parkinson’s disease.
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