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Search Results: 1 - 10 of 349 matches for " Serguei Lejnine "
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Clinical validation of a genetic model to estimate the risk of developing choroidal neovascular age-related macular degeneration
Gregory S Hageman, Karen Gehrs, Serguei Lejnine, Aruna T Bansal, Margaret M DeAngelis, Robyn H Guymer, Paul N Baird, Rando Allikmets, Cosmin Deciu, Paul Oeth, Lorah T Perlee
Human Genomics , 2011, DOI: 10.1186/1479-7364-5-5-420
Abstract: Many diseases of ageing characterised by complex inheritance patterns are progressive; the individual may be asymptomatic in the early stages. One of these diseases, age-related macular degeneration (AMD), is the most common cause of visual impairment and the leading cause of blindness in the elderly population in the developed world. The prevalence of AMD increases with advancing age in all populations studied. Thus, in developed nations such as the USA, UK, Canada and Australia, with increasingly aged populations, the condition affects a progressively larger segment of the population and has become a major public health issue. Early- or late-stage AMD is present in 15 per cent of individuals over the age of 60 years [1]. It is estimated that there are currently 9.1 million patients in the USA with AMD, of which 1.7 million suffer with the vision-threatening late-stage complications of choroidal neovascularisation (CNV) or geographic atrophy [1]. Moreover, it is predicted that the number of cases of early AMD will increase to 17.8 million by 2050 and, if untreated, cases of late-stage blinding AMD will increase to 3.8 million [1]. It has been determined that vision loss from AMD decreases quality of life by 60 per cent, similar to the experience of dealing with a stroke that requires intensive nursing care [2].The clinical presentation and natural course of AMD are highly variable. The disease may present as early as the fifth decade of life or as late as the ninth decade. The clinical symptoms of AMD range from no visual disturbances in early disease to profound loss of central vision in the advanced late stages of the disease. Some patients never progress beyond early AMD; however, in 10-15 per cent of Caucasian patients with early-stage disease, the condition progresses to an exudative neovascular (or 'wet' form) or geographic atrophic (or 'dry' form) AMD, which threatens vision. The phenotype is characterised by development of subretinal choroidal neovascular c
Development of a microarray platform for FFPET profiling: application to the classification of human tumors
Sven Duenwald, Mingjie Zhou, Yanqun Wang, Serguei Lejnine, Amit Kulkarni, Jaime Graves, Ryan Smith, John Castle, George Tokiwa, Bernard Fine, Hongyue Dai, Thomas Fare, Matthew Marton
Journal of Translational Medicine , 2009, DOI: 10.1186/1479-5876-7-65
Abstract: We developed a two-color microarray-based profiling platform by optimizing target amplification, experimental design, quality control, and microarray content and applied it to the profiling of FFPET samples. We profiled a set of 50 fresh frozen (FF) breast cancer samples and assigned class labels according to the signature and method by van 't Veer et al [1] and then profiled 50 matched FFPET samples to test how well the FFPET data predicted the class labels. We also compared the sorting power of classifiers derived from FFPET sample data with classifiers derived from data from matched FF samples.When a classifier developed with matched FF samples was applied to FFPET data to assign samples to either "good" or "poor" outcome class labels, the classifier was able to assign the FFPET samples to the correct class label with an average error rate = 12% to 16%, respectively, with an Odds Ratio = 36.4 to 60.4, respectively. A classifier derived from FFPET data was able to predict the class label in FFPET samples (leave-one-out cross validation) with an error rate of ~14% (p-value = 3.7 × 10-7). When applied to the matched FF samples, the FFPET-derived classifier was able to assign FF samples to the correct class labels with 96% accuracy. The single misclassification was attributed to poor sample quality, as measured by qPCR on total RNA, which emphasizes the need for sample quality control before profiling.We have optimized a platform for expression analyses and have shown that our profiling platform is able to accurately sort FFPET samples into class labels derived from FF classifiers. Furthermore, using this platform, a classifier derived from FFPET samples can reliably provide the same sorting power as a classifier derived from matched FF samples. We anticipate that these techniques could be used to generate hypotheses from archives of FFPET samples, and thus may lead to prognostic and predictive classifiers that could be used, for example, to segregate patients for cl
cDNA targets improve whole blood gene expression profiling and enhance detection of pharmocodynamic biomarkers: a quantitative platform analysis
Mark L Parrish, Chris Wright, Yarek Rivers, David Argilla, Heather Collins, Brendan Leeson, Andrey Loboda, Michael Nebozhyn, Matthew J Marton, Serguei Lejnine
Journal of Translational Medicine , 2010, DOI: 10.1186/1479-5876-8-87
Abstract: To compare and quantify the impact of different mitigation technologies, we used a globin transcript spike-in strategy to synthetically generate a globin-induced signature and then mitigate it with the three different technologies. Biological differences, in globin transcript spiked samples, were modeled by supplementing with either 1% of liver or 1% brain total RNA. In order to demonstrate the biological utility of a robust globin artifact mitigation strategy in biomarker discovery, we treated whole blood ex vivo with suberoylanilide hydroxamic acid (SAHA) and compared the overlap between the obtained signatures and signatures of a known biomarker derived from SAHA-treated cell lines and PBMCs of SAHA-treated patients.We found cDNA hybridization targets detect at least 20 times more specific differentially expressed signatures (2597) between 1% liver and 1% brain in globin-supplemented samples than the PNA (117) or no treatment (97) method at FDR = 10% and p-value < 3x10-3. In addition, we found that the ex vivo derived gene expression profile was highly concordant with that of the previously identified SAHA pharmacodynamic biomarkers.We conclude that an amplification method for gene expression profiling employing cDNA targets effectively mitigates the negative impact on data of abundant globin transcripts and greatly improves the ability to identify relevant gene expression based pharmacodynamic biomarkers from whole blood.Whole blood is a complex mixture of cell types that are exquisitely acute sensors of the body's physiological state [1-8]. It has long been the source tissue used in numerous tests for the identification of disease and the monitoring of disease progression. Peripheral blood is easily accessed and the available analytical techniques are well-established with a focus on the quantification of various chemical analytes (proteins, lipids, etc). Yet, gene expression profiling of peripheral whole blood has yet to be employed broadly. With the prolifera
The Underwater Historical Cultural Heritage of Russia Research and Preservation
Serguei Fazlullin
Journal of Cultural Research , 2012,
Abstract: he author analyses the current state of affairs in the study and preservation of the underwater historical and cultural heritage in the Russian Federation and proposes recommendations for harmonising attitudes of the society and the State towards objects of the underwater historical and cultural heritage and rising public awareness.
An Approach to Balancing the Positive and Negative Effects of Elevated Nitrogen Oxides in the Lower Atmosphere on Terrestrial Plants
Serguei Semenov
The Scientific World Journal , 2001, DOI: 10.1100/tsw.2001.87
The Impact of Discoveries of Ferroelectricity and Charge Disproportionation in Organic Conductors
Serguei Brazovskii
Physics , 2003,
Abstract: Discoveries of the Ferroelectric anomaly (Nad, Monceau, et al) and of the related charge disproportionation (Brown et al) call for a revaluation of the phase diagram of the (TMTTF)2X compounds and return the attention to the interplay of electronic and structural properties. We shall describe a concept of the Combined Mott-Hubbard state as the source for the ferroelectricity. We shall demonstrate the existence of two types of spinless solitons: pi- solitons, the holons, are observed via the activated conductivity; the noninteger alpha- solitons are responsible for the depolarization of the FE order. We propose that the (anti) ferroelectricity does exists hiddenly even in the Se subfamily, giving rise to the unexplained yet optical peak. We remind then the abandoned theory by the author and Yakovenko for the universal phase diagram which we contrast with the recent one.
Inclusive Search for the SM Higgs Boson in the H->gammagamma channel at the LHC
Serguei Ganjour
Physics , 2008, DOI: 10.1063/1.3051903
Abstract: A prospective for the inclusive search of the Standard Model Higgs boson in the decay channel H->gammagamm is presented with the CMS experiment at the LHC. The analysis relies on a strategy to determine the background characteristics and systematics from data. The strategy is applied to a Monte Model of the QCD background, with full simulation of the detector response. The discrimination between signal and background exploits information on photon isolation and kinematics. The resolution for the reconstructed Higgs boson mass profits from the excellent energy resolution of the CMS crystal calorimeter. A discovery significance above 5 sigma is expected at integrated LHC luminosities below 30 inverse femtobarn for Higgs boson masses below 140 GeV/c^2.
Fractal vortex structure in the lattice model of superconductors
Serguei Ktitorov
Physics , 2002,
Abstract: The problem of the vortex structure in the lattice modele of superconductors has been reduced to the nonlinear map problem characteristic for the fractal theory.
The description of an arbitrary configuration evolution in the Conway's Game Life in terms of the elementary configurations evolution in the first generation
Serguei Vorojtsov
Physics , 2001,
Abstract: The connection between the evolution of an arbitrary configuration and the evolution of its parts in the first generation is established. The equivalence of Conway's evolution rules to the elementary configurations' (containing one, two, three, and four pieces) evolution laws in the first generation has been proved.
Coulomb Blockade Oscillations of Conductance at Finite Energy Level Spacing in a Quantum Dot
Serguei Vorojtsov
Physics , 2002, DOI: 10.1142/S0217979204026706
Abstract: We find an analytical expression for the conductance of a single electron transistor in the regime when temperature, level spacing, and charging energy of a grain are all of the same order. We consider the model of equidistant energy levels in a grain in the sequential tunneling approximation. In the case of spinless electrons our theory describes transport through a dot in the quantum Hall regime. In the case of spin-1/2 electrons we analyze the line shape of a peak, shift in the position of the peak's maximum as a function of temperature, and the values of the conductance in the odd and even valleys.
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