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Search Results: 1 - 10 of 124236 matches for " Nicholas T. Lam "
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Nerve Growth Factor Stimulates Cardiac Regeneration via Cardiomyocyte Proliferation in Experimental Heart Failure
Nicholas T. Lam, Peter D. Currie, Graham J. Lieschke, Nadia A. Rosenthal, David M. Kaye
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0053210
Abstract: Although the adult heart likely retains some regenerative capacity, heart failure (HF) typically remains a progressive disorder. We hypothesise that alterations in the local environment contribute to the failure of regeneration in HF. Previously we showed that nerve growth factor (NGF) is deficient in the failing heart and here we hypothesise that diminished NGF limits the cardiac regenerative response in HF. The capacity of NGF to augment cardiac regeneration was tested in a zebrafish model of HF. Cardiac injury with a HF phenotype was induced in zebrafish larvae at 72 hours post fertilization (hpf) by exposure to aristolochic acid (AA, 2.5 μM, 72–75 hpf). By 168 hpf, AA induced HF and death in 37.5% and 20.8% of larvae respectively (p<0.001). NGF mRNA expression was reduced by 42% (p<0.05). The addition of NGF (50 ng/ml) after exposure to AA reduced the incidence of HF by 50% (p<0.01) and death by 65% (p<0.01). Mechanistically, AA mediated HF was characterised by reduced cardiomyocyte proliferation as reflected by a 6.4 fold decrease in BrdU+ cardiomyocytes (p<0.01) together with features of apoptosis and loss of cardiomyocytes. Following AA exposure, NGF increased the abundance of BrdU+ cardiomyocytes in the heart by 4.8 fold (p<0.05), and this was accompanied by a concomitant significant increase in cardiomyocyte numbers. The proliferative effect of NGF on cardiomyocytes was not associated with an anti-apoptotic effect. Taken together the study suggests that NGF stimulates a regenerative response in the failing zebrafish heart, mediated by stimulation of cardiomyocyte proliferation.
Effect of Oxygen on Cardiac Differentiation in Mouse iPS Cells: Role of Hypoxia Inducible Factor-1 and Wnt/Beta-Catenin Signaling
Tanya L. Medley, Milena Furtado, Nicholas T. Lam, Rejhan Idrizi, David Williams, Paul J. Verma, Mauro Costa, David M. Kaye
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080280
Abstract: Background Disturbances in oxygen levels have been found to impair cardiac organogenesis. It is known that stem cells and differentiating cells may respond variably to hypoxic conditions, whereby hypoxia may enhance stem cell pluripotency, while differentiation of multiple cell types can be restricted or enhanced under hypoxia. Here we examined whether HIF-1alpha modulated Wnt signaling affected differentiation of iPS cells into beating cardiomyocytes. Objective We investigated whether transient and sustained hypoxia affects differentiation of cardiomyocytes derived from murine induced pluripotent stem (iPS) cells, assessed the involvement of HIF-1alpha (hypoxia-inducible factor-1alpha) and the canonical Wnt pathway in this process. Methods Embryoid bodies (EBs) derived from iPS cells were differentiated into cardiomyocytes and were exposed either to 24 h normoxia or transient hypoxia followed by a further 13 days of normoxic culture. Results At 14 days of differentiation, 59±2% of normoxic EBs were beating, whilst transient hypoxia abolished beating at 14 days and EBs appeared immature. Hypoxia induced a significant increase in Brachyury and islet-1 mRNA expression, together with reduced troponin C expression. Collectively, these data suggest that transient and sustained hypoxia inhibits maturation of differentiating cardiomyocytes. Compared to normoxia, hypoxia increased HIF-1alpha, Wnt target and ligand genes in EBs, as well as accumulation of HIF-1alpha and beta-catenin in nuclear protein extracts, suggesting involvement of the Wnt/beta-catenin pathway. Conclusion Hypoxia impairs cardiomyocyte differentiation and activates Wnt signaling in undifferentiated iPS cells. Taken together the study suggests that oxygenation levels play a critical role in cardiomyocyte differentiation and suggest that hypoxia may play a role in early cardiogenesis.
On integral sum labeling of dense graphs
T. Nicholas
Tamkang Journal of Mathematics , 2010, DOI: 10.5556/j.tkjm.41.2010.317-324
Abstract: A graph is said to be a extit{sum graph} if there exists a set $S$ of positive integers as its vertex set with two vertices adjacent whenever their sum is in $S$. An integral sum graph is defined just as the sum graph, the difference being that the label set $S$ is a subset of $Z$ instead of set of positive integers. The sum number of a given graph $G$ is defined as the smallest number of isolated vertices which when added to $G$ results in a sum graph. The integral sum number of $G$ is analogous. In this paper, we mainly prove that any connected graph $G$ of order $n$ with at least three vertices of degree $(n-1)$ is not an integral sum graph. We characterise the integral sum graph $G$ of order $n$ having exactly two vertices of degree $(n-1)$ each and hence give an alternative proof for the existence theorem of sum graphs.
Optical Fiber Sensing Based on Reflection Laser Spectroscopy
Gianluca Gagliardi,Mario Salza,Pietro Ferraro,Edmond Chehura,Ralph P. Tatam,Tarun K. Gangopadhyay,Nicholas Ballard,Daniel Paz-Soldan,Jack A. Barnes,Hans-Peter Loock,Timothy T.-Y. Lam,Jong H. Chow,Paolo De Natale
Sensors , 2010, DOI: 10.3390/s100301823
Abstract: An overview on high-resolution and fast interrogation of optical-fiber sensors relying on laser reflection spectroscopy is given. Fiber Bragg-gratings (FBGs) and FBG resonators built in fibers of different types are used for strain, temperature and acceleration measurements using heterodyne-detection and optical frequency-locking techniques. Silica fiber-ring cavities are used for chemical sensing based on evanescent-wave spectroscopy. Various arrangements for signal recovery and noise reduction, as an extension of most typical spectroscopic techniques, are illustrated and results on detection performances are presented.
Bass's Work in Ring Theory and Projective Modules
T. Y. Lam
Mathematics , 2000,
Abstract: The early papers of Hyman Bass in the late 50s and the early 60s leading up to his pioneering work in algebraic K-theory have played an important and very special role in ring theory and the theory of projective (and injective) modules. In this article, we give a general survey of Bass's fundamental contributions in this early period of his work, and explain how much this work has influenced and shaped the thinking of subsequent researchers in the area.
Unit regular elements in corner rings
T. Y. Lam,Will Murray
Mathematics , 2014,
Abstract: For any ring \(R\), some characterizations are obtained for unit regular elements in a corner ring \(eRe\) in terms of unit regular elements in \(R\). \noindent {\bf Key Words}: von Neumann regular rings, unit regular rings, corner rings, idempotents \noindent {\bf AMS Classification}: 16A30
Do Auditory Temporal Discrimination Tasks Measure Temporal Resolution of the CNS?  [PDF]
Ian T. Zajac, Nicholas R. Burns
Psychology (PSYCH) , 2011, DOI: 10.4236/psych.2011.27114
Abstract: Rammsayer & Brandler (2002) have proposed that auditory temporal discrimination tasks provide a measure of temporal resolution of the CNS which is argued to be partly responsible for higher order cognitive functioning. We report on two studies designed to elicit the nature of the functions underpinning these auditory tasks. Study 1 assessed whether temporal generalisation (TG) might be better considered as a measure of working memory rather than of temporal resolution of the CNS. In N = 66 undergraduates TG did not predict speed of processing tasks; however, there was evidence of a relationship between TG and working memory. Study 2 reanalyzed pre- viously published data on temporal discrimination tasks and showed that the relationship between auditory tem- poral tasks and intelligence reflects memory functions and processing speed. Auditory temporal discrimination tasks are confounded by speed and memory and should not be considered as measures of temporal resolution of the CNS.
Heisenberg Groups as Platform for the AAG key-exchange protocol
Delaram Kahrobaei,Ha T. Lam
Mathematics , 2014,
Abstract: Garber, Kahrobaei, and Lam studied polycyclic groups generated by number field as platform for the AAG key-exchange protocol. In this paper, we discuss the use of a different kind of polycyclic groups, Heisenberg groups, as a platform group for AAG by submitting Heisenberg groups to one of AAG's major attacks, the length-based attack.
A maximum volume density estimator generalized over a proper motion-limited sample
Marco C. Lam,Nicholas Rowell,Nigel C. Hambly
Physics , 2015, DOI: 10.1093/mnras/stv876
Abstract: The traditional Schmidt density estimator has been proven to be unbiased and effective in a magnitude-limited sample. Previously, efforts have been made to generalize it for populations with non-uniform density and proper motion-limited cases. This work shows that the then-good assumptions for a proper motion-limited sample are no longer sufficient to cope with modern data. Populations with larger differences in the kinematics as compared to the local standard of rest are most severely affected. We show that this systematic bias can be removed by treating the discovery fraction inseparable from the generalized maximum volume integrand. The treatment can be applied to any proper motion-limited sample with good knowledge of the kinematics. This work demonstrates the method through application to a mock catalogue of a white dwarf-only solar neighbourhood for various scenarios and compared against the traditional treatment using a survey with Pan-STARRS-like characteristics.
Topology and Robustness in the Drosophila Segment Polarity Network
Nicholas T. Ingolia
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0020123
Abstract: A complex hierarchy of genetic interactions converts a single-celled Drosophila melanogaster egg into a multicellular embryo with 14 segments. Previously, von Dassow et al. reported that a mathematical model of the genetic interactions that defined the polarity of segments (the segment polarity network) was robust (von Dassow et al. 2000). As quantitative information about the system was unavailable, parameters were sampled randomly. A surprisingly large fraction of these parameter sets allowed the model to maintain and elaborate on the segment polarity pattern. This robustness is due to the positive feedback of gene products on their own expression, which induces individual cells in a model segment to adopt different stable expression states (bistability) corresponding to different cell types in the segment polarity pattern. A positive feedback loop will only yield multiple stable states when the parameters that describe it satisfy a particular inequality. By testing which random parameter sets satisfy these inequalities, I show that bistability is necessary to form the segment polarity pattern and serves as a strong predictor of which parameter sets will succeed in forming the pattern. Although the original model was robust to parameter variation, it could not reproduce the observed effects of cell division on the pattern of gene expression. I present a modified version that incorporates recent experimental evidence and does successfully mimic the consequences of cell division. The behavior of this modified model can also be understood in terms of bistability in positive feedback of gene expression. I discuss how this topological property of networks provides robust pattern formation and how large changes in parameters can change the specific pattern produced by a network.
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