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Search Results: 1 - 10 of 488369 matches for " Philip A. Lee "
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Millihertz Optical/UV Oscillations in 4U 1626-67: Evidence for a Warped Accretion Disk
Deepto Chakrabarty,Lee Homer,Philip A. Charles,Darragh O'Donoghue
Physics , 2001, DOI: 10.1086/323877
Abstract: We have detected large-amplitude 0.3-1.2 mHz quasi-periodic oscillations (QPOs) from the low-mass X-ray binary pulsar 4U 1626-67/KZ TrA, using UV photometry from HST and ground-based optical photometry. These 1 mHz QPOs, which have coherence (Nu/DeltaNu)=8, are entirely distinct from the 130 mHz pulsar spin frequency, a previously known 48 mHz QPO, and the 42 min binary period (independently confirmed here). Unlike the 48 mHz and 130 mHz oscillations which are present in both the optical/UV and the X-ray emission, the 1 mHz QPOs are not detected in simultaneous observations with RXTE. The rms amplitude of the mHz QPO decreases from 15% in the far UV to 3% in the optical, while the upper limit on a corresponding X-ray QPO is as low as 0.8%. We suggest that the mHz oscillations are due to warping of the inner accretion disk. We also report the detection of coherent upper and lower sidebands of the 130 mHz optical pulsations, with unequal amplitude and a spacing of 1.93 mHz around the main pulsation. The origin of these sidebands remains unclear.
Robust Expression and Secretion of Xylanase1 in Chlamydomonas reinhardtii by Fusion to a Selection Gene and Processing with the FMDV 2A Peptide
Beth A. Rasala, Philip A. Lee, Zhouxin Shen, Steven P. Briggs, Michael Mendez, Stephen P. Mayfield
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043349
Abstract: Microalgae have recently received attention as a potential low-cost host for the production of recombinant proteins and novel metabolites. However, a major obstacle to the development of algae as an industrial platform has been the poor expression of heterologous genes from the nuclear genome. Here we describe a nuclear expression strategy using the foot-and-mouth-disease-virus 2A self-cleavage peptide to transcriptionally fuse heterologous gene expression to antibiotic resistance in Chlamydomonas reinhardtii. We demonstrate that strains transformed with ble-2A-GFP are zeocin-resistant and accumulate high levels of GFP that is properly ‘cleaved’ at the FMDV 2A peptide resulting in monomeric, cytosolic GFP that is easily detectable by in-gel fluorescence analysis or fluorescent microscopy. Furthermore, we used our ble2A nuclear expression vector to engineer the heterologous expression of the industrial enzyme, xylanase. We demonstrate that linking xyn1 expression to ble2A expression on the same open reading frame led to a dramatic (~100-fold) increase in xylanase activity in cells lysates compared to the unlinked construct. Finally, by inserting an endogenous secretion signal between the ble2A and xyn1 coding regions, we were able to target monomeric xylanase for secretion. The novel microalgae nuclear expression strategy described here enables the selection of transgenic lines that are efficiently expressing the heterologous gene-of-interest and should prove valuable for basic research as well as algal biotechnology.
Rapamycin Response in Tumorigenic and Non-Tumorigenic Hepatic Cell Lines
Rosa H. Jimenez, Joan M. Boylan, Ju-Seog Lee, Mirko Francesconi, Gastone Castellani, Jennifer A. Sanders, Philip A. Gruppuso
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0007373
Abstract: Background The mTOR inhibitor rapamycin has anti-tumor activity across a variety of human cancers, including hepatocellular carcinoma. However, resistance to its growth inhibitory effects is common. We hypothesized that hepatic cell lines with varying rapamycin responsiveness would show common characteristics accounting for resistance to the drug. Methodology/Principal Findings We profiled a total of 13 cell lines for rapamycin-induced growth inhibition. The non-tumorigenic rat liver epithelial cell line WB-F344 was highly sensitive while the tumorigenic WB311 cell line, originally derived from the WB-F344 line, was highly resistant. The other 11 cell lines showed a wide range of sensitivities. Rapamycin induced inhibition of cyclin E–dependent kinase activity in some cell lines, but the ability to do so did not correlate with sensitivity. Inhibition of cyclin E–dependent kinase activity was related to incorporation of p27Kip1 into cyclin E–containing complexes in some but not all cell lines. Similarly, sensitivity of global protein synthesis to rapamycin did not correlate with its anti-proliferative effect. However, rapamycin potently inhibited phosphorylation of two key substrates, ribosomal protein S6 and 4E-BP1, in all cases, indicating that the locus of rapamycin resistance was downstream from inhibition of mTOR Complex 1. Microarray analysis did not disclose a unifying mechanism for rapamycin resistance, although the glycolytic pathway was downregulated in all four cell lines studied. Conclusions/Significance We conclude that the mechanisms of rapamycin resistance in hepatic cells involve alterations of signaling downstream from mTOR and that the mechanisms are highly heterogeneous, thus predicting that maintaining or promoting sensitivity will be highly challenging.
Leptospirosis in American Samoa – Estimating and Mapping Risk Using Environmental Data
Colleen L. Lau ,Archie C. A. Clements,Chris Skelly,Annette J. Dobson,Lee D. Smythe,Philip Weinstein
PLOS Neglected Tropical Diseases , 2012, DOI: 10.1371/journal.pntd.0001669
Abstract: Background The recent emergence of leptospirosis has been linked to many environmental drivers of disease transmission. Accurate epidemiological data are lacking because of under-diagnosis, poor laboratory capacity, and inadequate surveillance. Predictive risk maps have been produced for many diseases to identify high-risk areas for infection and guide allocation of public health resources, and are particularly useful where disease surveillance is poor. To date, no predictive risk maps have been produced for leptospirosis. The objectives of this study were to estimate leptospirosis seroprevalence at geographic locations based on environmental factors, produce a predictive disease risk map for American Samoa, and assess the accuracy of the maps in predicting infection risk. Methodology and Principal Findings Data on seroprevalence and risk factors were obtained from a recent study of leptospirosis in American Samoa. Data on environmental variables were obtained from local sources, and included rainfall, altitude, vegetation, soil type, and location of backyard piggeries. Multivariable logistic regression was performed to investigate associations between seropositivity and risk factors. Using the multivariable models, seroprevalence at geographic locations was predicted based on environmental variables. Goodness of fit of models was measured using area under the curve of the receiver operating characteristic, and the percentage of cases correctly classified as seropositive. Environmental predictors of seroprevalence included living below median altitude of a village, in agricultural areas, on clay soil, and higher density of piggeries above the house. Models had acceptable goodness of fit, and correctly classified ~84% of cases. Conclusions and Significance Environmental variables could be used to identify high-risk areas for leptospirosis. Environmental monitoring could potentially be a valuable strategy for leptospirosis control, and allow us to move from disease surveillance to environmental health hazard surveillance as a more cost-effective tool for directing public health interventions.
Characterization of Amoeboaphelidium protococcarum, an Algal Parasite New to the Cryptomycota Isolated from an Outdoor Algal Pond Used for the Production of Biofuel
Peter M. Letcher, Salvador Lopez, Robert Schmieder, Philip A. Lee, Craig Behnke, Martha J. Powell, Robert C. McBride
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0056232
Abstract: Mass culture of algae for the production of biofuels is a developing technology designed to offset the depletion of fossil fuel reserves. However, large scale culture of algae in open ponds can be challenging because of incidences of infestation with algal parasites. Without knowledge of the identity of the specific parasite and how to control these pests, algal-based biofuel production will be limited. We have characterized a eukaryotic parasite of Scenedesmus dimorphus growing in outdoor ponds used for biofuel production. We demonstrated that as the genomic DNA of parasite FD01 increases, the concentration of S. dimorphus cells decreases; consequently, this is a highly destructive pathogen. Techniques for culture of the parasite and host were developed, and the endoparasite was identified as the Aphelidea, Amoeboaphelidium protococcarum. Phylogenetic analysis of ribosomal sequences revealed that parasite FD01 placed within the recently described Cryptomycota, a poorly known phylum based on two species of Rozella and environmental samples. Transmission electron microscopy demonstrated that aplanospores of the parasite produced filose pseudopodia, which contained fine fibers the diameter of actin microfilaments. Multiple lipid globules clustered and were associated with microbodies, mitochondria and a membrane cisternae, an arrangement characteristic of the microbody-lipid globule complex of chytrid zoospores. After encystment and attachment to the host cells, the parasite injected its protoplast into the host between the host cell wall and plasma membrane. At maturity the unwalled parasite occupied the entire host cell. After cleavage of the protoplast into aplanospores, a vacuole and lipids remained in the host cell. Amoeboaphelidium protococcarum isolate FD01 is characteristic of the original description of this species and is different from strain X-5 recently characterized. Our results help put a face on the Cryptomycota, revealing that the phylum is more diverse than previously understood and include some of the Aphelidea as well as Rozella species and potentially Microsporidia.
Many-body localization in a quantum simulator with programmable random disorder
Jacob Smith,Aaron Lee,Philip Richerme,Brian Neyenhuis,Paul W. Hess,Philipp Hauke,Markus Heyl,David A. Huse,Christopher Monroe
Physics , 2015,
Abstract: When a system thermalizes it loses all local memory of its initial conditions. This is a general feature of open systems and is well described by equilibrium statistical mechanics. Even within a closed (or reversible) quantum system, where unitary time evolution retains all information about its initial state, subsystems can still thermalize using the rest of the system as an effective heat bath. Exceptions to quantum thermalization have been predicted and observed, but typically require inherent symmetries or noninteracting particles in the presence of static disorder. The prediction of many-body localization (MBL), in which disordered quantum systems can fail to thermalize in spite of strong interactions and high excitation energy, was therefore surprising and has attracted considerable theoretical attention. Here we experimentally generate MBL states by applying an Ising Hamiltonian with long-range interactions and programmably random disorder to ten spins initialized far from equilibrium. We observe the essential signatures of MBL: memory retention of the initial state, a Poissonian distribution of energy level spacings, and entanglement growth in the system at long times. Our platform can be scaled to higher numbers of spins, where detailed modeling of MBL becomes impossible due to the complexity of representing such entangled quantum states. Moreover, the high degree of control in our experiment may guide the use of MBL states as potential quantum memories in naturally disordered quantum systems.
FGFR2 protein expression in breast cancer: nuclear localisation and correlation with patient genotype
Amy J Martin, Andrew Grant, Alison M Ashfield, Colin N Palmer, Lee Baker, Philip R Quinlan, Colin A Purdie, Alastair M Thompson, Lee B Jordan, Jonathan N Berg
BMC Research Notes , 2011, DOI: 10.1186/1756-0500-4-72
Abstract: FGFR2 immunohistochemistry demonstrated variable nuclear staining in normal tissue and tumour tissue, as well as consistent cytoplasmic staining. We did not find an association between nuclear staining for FGFR2 and genotype, and there was no association between FGFR2 staining and estrogen or progestogen receptor status. There was an association between presence of nuclear staining for FGFR2 in normal tissue and presence of nuclear staining in the adjacent tumour (Fishers exact test, p = 0.002).Variable nuclear staining for FGFR2 in breast cancer, but an absence of correlation with rs2981582 genotype suggests that the mechanism of action of polymorphisms at the FGFR2 locus may be more complex than a direct effect on mRNA expression levels in the final cancer. The effect may relate to FGFR2 function or localisation during breast development or tumourigenesis. Nuclear localisation of FGFR2 suggests an important additional role for this protein in breast development and breast cancer, in addition to its function as a classical cell surface receptor.Fibroblast growth factor receptor type 2 (FGFR2) is a receptor tyrosine kinase involved in a number of cell signalling pathways that contribute to cell growth and differentiation [1]. FGFR2 is important in development of a number of tissues including breast and kidney [2,3]. Mutations in FGFR2 can also cause rare monogenic diseases such as lacrimo-auriculo-dento-digital (LADD) syndrome and syndromic craniosynostosis [4]. However, recent interest has focussed on Single Nucleotide Polymorphisms (SNPs) in intron 2 of FGFR2 , including rs2981582, which form a high risk haplotype that is associated with an increased risk of breast cancer [5,6]. The risk haplotype in FGFR2 is associated with both oestrogen receptor positive (ER+ve) and ER-ve tumours, although the association with ER+ve tumours is stronger.Although principally considered a cell surface receptor, FGFR2 is also found to have nuclear localisation in a number of differ
The Fundamentally Different Dynamics of Dust and Gas in Molecular Clouds
Philip F. Hopkins,Hyunseok Lee
Physics , 2015,
Abstract: We study the behavior of large dust grains in turbulent molecular clouds (MCs). In primarily neutral regions, dust grains move as aerodynamic particles, not necessarily with the gas. We therefore directly simulate, for the first time, the behavior of aerodynamic grains in highly supersonic, magnetohydrodynamic turbulence typical of MCs. We show that, under these conditions, grains with sizes a >0.01 micron exhibit dramatic (exceeding factor ~1000) fluctuations in the local dust-to-gas ratio (implying large small-scale variations in abundances, dust cooling rates, and dynamics). The dust can form highly filamentary structures (which would be observed in both dust emission and extinction), which can be much thinner than the characteristic width of gas filaments. Sometimes, the dust and gas filaments are not even in the same location. The 'clumping factor' of the dust (critical for dust growth/coagulation/shattering) can reach ~100, for grains in the ideal size range. The dust clustering is maximized around scales ~0.2pc*(a/micron)*(100 cm^-3/n_gas), and is 'averaged out' on larger scales. However, because the density varies widely in supersonic turbulence, the dynamic range of scales (and interesting grain sizes) for these fluctuations is much broader than in the subsonic case. Our results are applicable to MCs of essentially all sizes and densities, but we note how Lorentz forces and other physics (neglected here) may change them in some regimes. We discuss the potentially dramatic consequences for star formation, dust growth and destruction, and dust-based observations of MCs.
Asymptotic Properties of an Estimator of the Drift Coefficients of Multidimensional Ornstein-Uhlenbeck Processes that are not Necessarily Stable
Gopal K. Basak,Philip Lee
Mathematics , 2008, DOI: 10.1214/08-EJS290
Abstract: In this paper, we investigate the consistency and asymptotic efficiency of an estimator of the drift matrix, $F$, of Ornstein-Uhlenbeck processes that are not necessarily stable. We consider all the cases. (1) The eigenvalues of $F$ are in the right half space (i.e., eigenvalues with positive real parts). In this case the process grows exponentially fast. (2) The eigenvalues of $F$ are on the left half space (i.e., the eigenvalues with negative or zero real parts). The process where all eigenvalues of $F$ have negative real parts is called a stable process and has a unique invariant (i.e., stationary) distribution. In this case the process does not grow. When the eigenvalues of $F$ have zero real parts (i.e., the case of zero eigenvalues and purely imaginary eigenvalues) the process grows polynomially fast. Considering (1) and (2) separately, we first show that an estimator, $\hat{F}$, of $F$ is consistent. We then combine them to present results for the general Ornstein-Uhlenbeck processes. We adopt similar procedure to show the asymptotic efficiency of the estimator.
Scalable Matting: A Sub-linear Approach
Philip G. Lee,Ying Wu
Computer Science , 2014,
Abstract: Natural image matting, which separates foreground from background, is a very important intermediate step in recent computer vision algorithms. However, it is severely underconstrained and difficult to solve. State-of-the-art approaches include matting by graph Laplacian, which significantly improves the underconstrained nature by reducing the solution space. However, matting by graph Laplacian is still very difficult to solve and gets much harder as the image size grows: current iterative methods slow down as $\mathcal{O}\left(n^2 \right)$ in the resolution $n$. This creates uncomfortable practical limits on the resolution of images that we can matte. Current literature mitigates the problem, but they all remain super-linear in complexity. We expose properties of the problem that remain heretofore unexploited, demonstrating that an optimization technique originally intended to solve PDEs can be adapted to take advantage of this knowledge to solve the matting problem, not heuristically, but exactly and with sub-linear complexity. This makes ours the most efficient matting solver currently known by a very wide margin and allows matting finally to be practical and scalable in the future as consumer photos exceed many dozens of megapixels, and also relieves matting from being a bottleneck for vision algorithms that depend on it.
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