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Search Results: 1 - 10 of 151454 matches for " Douglas B. Murray "
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The Yin and Yang of Yeast Transcription: Elements of a Global Feedback System between Metabolism and Chromatin
Rainer Machné, Douglas B. Murray
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037906
Abstract: When grown in continuous culture, budding yeast cells tend to synchronize their respiratory activity to form a stable oscillation that percolates throughout cellular physiology and involves the majority of the protein-coding transcriptome. Oscillations in batch culture and at single cell level support the idea that these dynamics constitute a general growth principle. The precise molecular mechanisms and biological functions of the oscillation remain elusive. Fourier analysis of transcriptome time series datasets from two different oscillation periods (0.7 h and 5 h) reveals seven distinct co-expression clusters common to both systems (34% of all yeast ORF), which consolidate into two superclusters when correlated with a compilation of 1,327 unrelated transcriptome datasets. These superclusters encode for cell growth and anabolism during the phase of high, and mitochondrial growth, catabolism and stress response during the phase of low oxygen uptake. The promoters of each cluster are characterized by different nucleotide contents, promoter nucleosome configurations, and dependence on ATP-dependent nucleosome remodeling complexes. We show that the ATP:ADP ratio oscillates, compatible with alternating metabolic activity of the two superclusters and differential feedback on their transcription via activating (RSC) and repressive (Isw2) types of promoter structure remodeling. We propose a novel feedback mechanism, where the energetic state of the cell, reflected in the ATP:ADP ratio, gates the transcription of large, but functionally coherent groups of genes via differential effects of ATP-dependent nucleosome remodeling machineries. Besides providing a mechanistic hypothesis for the delayed negative feedback that results in the oscillatory phenotype, this mechanism may underpin the continuous adaptation of growth to environmental conditions.
Quantifying periodicity in omics data
Masaru Tomita,Douglas B. Murray
Frontiers in Cell and Developmental Biology , 2014, DOI: 10.3389/fcell.2014.00040
Abstract: Oscillations play a significant role in biological systems, with many examples in the fast, ultradian, circadian, circalunar, and yearly time domains. However, determining periodicity in such data can be problematic. There are a number of computational methods to identify the periodic components in large datasets, such as signal-to-noise based Fourier decomposition, Fisher's g-test and autocorrelation. However, the available methods assume a sinusoidal model and do not attempt to quantify the waveform shape and the presence of multiple periodicities, which provide vital clues in determining the underlying dynamics. Here, we developed a Fourier based measure that generates a de-noised waveform from multiple significant frequencies. This waveform is then correlated with the raw data from the respiratory oscillation found in yeast, to provide oscillation statistics including waveform metrics and multi-periods. The method is compared and contrasted to commonly used statistics. Moreover, we show the utility of the program in the analysis of noisy datasets and other high-throughput analyses, such as metabolomics and flow cytometry, respectively.
A Yeast Metabolite Extraction Protocol Optimised for Time-Series Analyses
Kalesh Sasidharan, Tomoyoshi Soga, Masaru Tomita, Douglas B. Murray
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0044283
Abstract: There is an increasing call for the absolute quantification of time-resolved metabolite data. However, a number of technical issues exist, such as metabolites being modified/degraded either chemically or enzymatically during the extraction process. Additionally, capillary electrophoresis mass spectrometry (CE-MS) is incompatible with high salt concentrations often used in extraction protocols. In microbial systems, metabolite yield is influenced by the extraction protocol used and the cell disruption rate. Here we present a method that rapidly quenches metabolism using dry-ice ethanol bath and methanol N-ethylmaleimide solution (thus stabilising thiols), disrupts cells efficiently using bead-beating and avoids artefacts created by live-cell pelleting. Rapid sample processing minimised metabolite leaching. Cell weight, number and size distribution was used to calculate metabolites to an attomol/cell level. We apply this method to samples obtained from the respiratory oscillation that occurs when yeast are grown continuously.
The Scale-Free Dynamics of Eukaryotic Cells
Miguel A. Aon, Marc R. Roussel, Sonia Cortassa, Brian O'Rourke, Douglas B. Murray, Manfred Beckmann, David Lloyd
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003624
Abstract: Temporal organization of biological processes requires massively parallel processing on a synchronized time-base. We analyzed time-series data obtained from the bioenergetic oscillatory outputs of Saccharomyces cerevisiae and isolated cardiomyocytes utilizing Relative Dispersional (RDA) and Power Spectral (PSA) analyses. These analyses revealed broad frequency distributions and evidence for long-term memory in the observed dynamics. Moreover RDA and PSA showed that the bioenergetic dynamics in both systems show fractal scaling over at least 3 orders of magnitude, and that this scaling obeys an inverse power law. Therefore we conclude that in S. cerevisiae and cardiomyocytes the dynamics are scale-free in vivo. Applying RDA and PSA to data generated from an in silico model of mitochondrial function indicated that in yeast and cardiomyocytes the underlying mechanisms regulating the scale-free behavior are similar. We validated this finding in vivo using single cells, and attenuating the activity of the mitochondrial inner membrane anion channel with 4-chlorodiazepam to show that the oscillation of NAD(P)H and reactive oxygen species (ROS) can be abated in these two evolutionarily distant species. Taken together these data strongly support our hypothesis that the generation of ROS, coupled to redox cycling, driven by cytoplasmic and mitochondrial processes, are at the core of the observed rhythmicity and scale-free dynamics. We argue that the operation of scale-free bioenergetic dynamics plays a fundamental role to integrate cellular function, while providing a framework for robust, yet flexible, responses to the environment.
An exploratory study of food safety and food handling: Examining ready-to-eat foods in independent delicatessen operations  [PDF]
Douglas Murray, Charles Feldman, Lee Lee, Casey Schuckers
Advances in Bioscience and Biotechnology (ABB) , 2013, DOI: 10.4236/abb.2013.43A057

The US Center for Disease Control and Prevention (CDC, 2009) reports that each year 76 million cases of foodborne illness occur with over 300,000 people hospitalized and 5000 deaths. This study, phase I of a continuing study, identifies key areas for food safety improvement. This study is designed as an exploratory evaluation of independently owned and operated delicatessen operations, using Escherichia coli and Staphylococcus aureus as indicators to assess food handling and the public’s risk for pathogenic contamination from commonly served ready-to-eat/take-away foods. The analysis consisted of a comprehensive strategy of laboratory testing of samples for pathogenic contamination, informal field observation of food handling procedures, and the examination of the most recent health inspection reports for each of the 18 operations visited. The deli turkey, cream cheese and lettuce were tested using bacteria indicator plates. The results showed widespread levels of contamination. Of the 54 samples tested for Escherichia coli, 26 showed positive results which are ~45% for E. coli contamination. Of the 54 samples tested for Staphy-lococcus aureus, 31 showed positive results which are ~57% for S. aureus contamination. One issue discovered while conducting the study was the lack of consistent uniform international standards of contamination tolerance levels. The informal field observations and health report analyses revealed widespread temperature violations and numerous instances of poor food handling. The study offers independent practitioners a strategy designed to improve their health inspections scores, food handling, and mitigation of operator liability. Independent operators traditionally do not enjoy the resources of centralized supervision and expert on-staff training;

Douglas R. Givens,Tim Murray
Bulletin of the History of Archaeology , 2002, DOI: 10.5334/bha.12201
The simple non-Lie Malcev algebra as a Lie-Yamaguti algebra
Murray R. Bremner,Andrew Douglas
Mathematics , 2011,
Abstract: The simple 7-dimensional Malcev algebra $M$ is isomorphic to the irreducible $\mathfrak{sl}(2,\mathbb{C})$-module V(6) with binary product $[x,y] = \alpha(x \wedge y)$ defined by the $\mathfrak{sl}(2,\mathbb{C})$-module morphism $\alpha\colon \Lambda^2 V(6) \to V(6)$. Combining this with the ternary product $(x,y,z) = \beta(x \wedge y) \cdot z$ defined by the $\mathfrak{sl}(2,\mathbb{C})$-module morphism $\beta\colon \Lambda^2 V(6) \to V(2) \approx \s$ gives $M$ the structure of a generalized Lie triple system, or Lie-Yamaguti algebra. We use computer algebra to determine the polynomial identities of low degree satisfied by this binary-ternary structure.
Nonlinear Complexity Analysis of Brain fMRI Signals in Schizophrenia
Moses O. Sokunbi, Victoria B. Gradin, Gordon D. Waiter, George G. Cameron, Trevor S. Ahearn, Alison D. Murray, Douglas J. Steele, Roger T. Staff
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095146
Abstract: We investigated the differences in brain fMRI signal complexity in patients with schizophrenia while performing the Cyberball social exclusion task, using measures of Sample entropy and Hurst exponent (H). 13 patients meeting diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM IV) criteria for schizophrenia and 16 healthy controls underwent fMRI scanning at 1.5 T. The fMRI data of both groups of participants were pre-processed, the entropy characterized and the Hurst exponent extracted. Whole brain entropy and H maps of the groups were generated and analysed. The results after adjusting for age and sex differences together show that patients with schizophrenia exhibited higher complexity than healthy controls, at mean whole brain and regional levels. Also, both Sample entropy and Hurst exponent agree that patients with schizophrenia have more complex fMRI signals than healthy controls. These results suggest that schizophrenia is associated with more complex signal patterns when compared to healthy controls, supporting the increase in complexity hypothesis, where system complexity increases with age or disease, and also consistent with the notion that schizophrenia is characterised by a dysregulation of the nonlinear dynamics of underlying neuronal systems.
Torsion in Groups of Integral Triangles  [PDF]
Will Murray
Advances in Pure Mathematics (APM) , 2013, DOI: 10.4236/apm.2013.31015

Let 0γ<π be a fixed pythagorean angle. We study the abelian group Hr of primitive integral triangles (a,b,c) for which the angle opposite side c is γ. Addition in Hr is defined by adding the angles β opposite side b and modding out by π-γ. The only Hr for which the structure is known is Hπ/2, which is free abelian. We prove that for generalγ, Hr has an element of order two iff 2(1-

Prolonged Opioid-Sparing Pain Control after Hemorrhoidectomy with Liposome Bupivacaine: Results from a Cohort of 95 Patients  [PDF]
Allen B. Jetmore, Douglas Hagen
Pain Studies and Treatment (PST) , 2016, DOI: 10.4236/pst.2016.41002
Abstract: The objective of this retrospective study was to examine the effects of an intraoperative injection of liposome bupivacaine on the quality and duration of postsurgical pain control, patient satisfaction, and opioid use in a cohort of patients undergoing hemorrhoidectomy in an outpatient setting. Patients underwent ambulatory hemorrhoidectomy conducted by a single surgeon. Liposome bupivacaine 266 mg/20 mL was administered via infiltration at the end of surgery. After discharge, pain-related outcomes were assessed via telephone interviews. Outcomes of interest included first onset of pain after surgery, patient-reported pain intensity (0 = no pain; 10 = worst pain imaginable), time to first use of orally administered opioids after surgery, number of opioid tablets consumed postsurgery, and patient’s satisfaction with postsurgical pain control. A total of 95 patients were included; the average number of hemorrhoids excised was 3.0 (median, 2.7) per patient. Mean time to first onset of pain after surgery was 36 hours; mean time to first consumption of postsurgical opioids was 38 hours. Mean pain intensity scores remained <5 through 72 hours after surgery. The average number of opioid analgesic tablets consumed after surgery was 12.4; 13% (12/95) of patients required no postsurgical opioids. Seventy-five percent of patients reported being “very satisfied” or “perfectly satisfied” with their overall pain control. No liposome bupivacaine-related adverse events were observed. A single intraoperative injection of liposome bupivacaine safely facilitated ambulatory hemorrhoidectomy, eliminated the need for intravenous opioids, minimized opioid use, and was associated with high levels of patient satisfaction.
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