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Search Results: 1 - 10 of 144765 matches for " Ludmil B. Alexandrov "
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Computer Modeling Describes Gravity-Related Adaptation in Cell Cultures
Ludmil B. Alexandrov,Stoyana Alexandrova,Anny Usheva
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008332
Abstract: Questions about the changes of biological systems in response to hostile environmental factors are important but not easy to answer. Often, the traditional description with differential equations is difficult due to the overwhelming complexity of the living systems. Another way to describe complex systems is by simulating them with phenomenological models such as the well-known evolutionary agent-based model (EABM). Here we developed an EABM to simulate cell colonies as a multi-agent system that adapts to hyper-gravity in starvation conditions. In the model, the cell's heritable characteristics are generated and transferred randomly to offspring cells. After a qualitative validation of the model at normal gravity, we simulate cellular growth in hyper-gravity conditions. The obtained data are consistent with previously confirmed theoretical and experimental findings for bacterial behavior in environmental changes, including the experimental data from the microgravity Atlantis and the Hypergravity 3000 experiments. Our results demonstrate that it is possible to utilize an EABM with realistic qualitative description to examine the effects of hypergravity and starvation on complex cellular entities.
DNA Dynamics Is Likely to Be a Factor in the Genomic Nucleotide Repeats Expansions Related to Diseases
Boian S. Alexandrov,Vlad I. Valtchinov,Ludmil B. Alexandrov,Vladimir Gelev,Yossi Dagon,Jonathan Bock,Isaac S. Kohane,Kim ?. Rasmussen,Alan R. Bishop,Anny Usheva
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019800
Abstract: Trinucleotiderepeats sequences (TRS) represent a common type of genomic DNA motif whose expansion is associated with a large number of human diseases. The driving molecular mechanisms of the TRS ongoing dynamic expansion across generations and within tissues and its influence on genomic DNA functions are not well understood. Here we report results for a novel and notable collective breathing behavior of genomic DNA of tandem TRS, leading to propensity for large local DNA transient openings at physiological temperature. Our Langevin molecular dynamics (LMD) and Markov Chain Monte Carlo (MCMC) simulations demonstrate that the patterns of openings of various TRSs depend specifically on their length. The collective propensity for DNA strand separation of repeated sequences serves as a precursor for outsized intermediate bubble states independently of the G/C-content. We report that repeats have the potential to interfere with the binding of transcription factors to their consensus sequence by altered DNA breathing dynamics in proximity of the binding sites. These observations might influence ongoing attempts to use LMD and MCMC simulations for TRS–related modeling of genomic DNA functionality in elucidating the common denominators of the dynamic TRS expansion mutation with potential therapeutic applications.
Mammalian Stem Cells Reprogramming in Response to Terahertz Radiation
Jonathan Bock,Yayoi Fukuyo,Sona Kang,M. Lisa Phipps,Ludmil B. Alexandrov,Kim ?. Rasmussen,Alan R. Bishop,Evan D. Rosen,Jennifer S. Martinez,Hou-Tong Chen,George Rodriguez,Boian S. Alexandrov,Anny Usheva
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015806
Abstract: We report that extended exposure to broad-spectrum terahertz radiation results in specific changes in cellular functions that are closely related to DNA-directed gene transcription. Our gene chip survey of gene expression shows that whereas 89% of the protein coding genes in mouse stem cells do not respond to the applied terahertz radiation, certain genes are activated, while other are repressed. RT-PCR experiments with selected gene probes corresponding to transcripts in the three groups of genes detail the gene specific effect. The response was not only gene specific but also irradiation conditions dependent. Our findings suggest that the applied terahertz irradiation accelerates cell differentiation toward adipose phenotype by activating the transcription factor peroxisome proliferator-activated receptor gamma (PPARG). Finally, our molecular dynamics computer simulations indicate that the local breathing dynamics of the PPARG promoter DNA coincides with the gene specific response to the THz radiation. We propose that THz radiation is a potential tool for cellular reprogramming.
Binding of Nucleoid-Associated Protein Fis to DNA Is Regulated by DNA Breathing Dynamics
Kristy Nowak-Lovato,Ludmil B. Alexandrov,Afsheen Banisadr,Amy L. Bauer,Alan R. Bishop,Anny Usheva,Fangping Mu,Elizabeth Hong-Geller,Kim ?. Rasmussen,William S. Hlavacek ,Boian S. Alexandrov
PLOS Computational Biology , 2013, DOI: 10.1371/journal.pcbi.1002881
Abstract: Physicochemical properties of DNA, such as shape, affect protein-DNA recognition. However, the properties of DNA that are most relevant for predicting the binding sites of particular transcription factors (TFs) or classes of TFs have yet to be fully understood. Here, using a model that accurately captures the melting behavior and breathing dynamics (spontaneous local openings of the double helix) of double-stranded DNA, we simulated the dynamics of known binding sites of the TF and nucleoid-associated protein Fis in Escherichia coli. Our study involves simulations of breathing dynamics, analysis of large published in vitro and genomic datasets, and targeted experimental tests of our predictions. Our simulation results and available in vitro binding data indicate a strong correlation between DNA breathing dynamics and Fis binding. Indeed, we can define an average DNA breathing profile that is characteristic of Fis binding sites. This profile is significantly enriched among the identified in vivo E. coli Fis binding sites. To test our understanding of how Fis binding is influenced by DNA breathing dynamics, we designed base-pair substitutions, mismatch, and methylation modifications of DNA regions that are known to interact (or not interact) with Fis. The goal in each case was to make the local DNA breathing dynamics either closer to or farther from the breathing profile characteristic of a strong Fis binding site. For the modified DNA segments, we found that Fis-DNA binding, as assessed by gel-shift assay, changed in accordance with our expectations. We conclude that Fis binding is associated with DNA breathing dynamics, which in turn may be regulated by various nucleotide modifications.
Stored light and released fiction
E. B. Alexandrov,V. S. Zapasskii
Physics , 2003,
Abstract: It is shown that the interpretation of the experimental results reported in the publication Storage of Light in Atomic Vapor" by D.F.Phillips et al., Phys. Rev.Lett. 86, 783 (2001) is incorrect. The experimental observation of this paper can be consistently explained in the framework of standard concepts of the physics of optical pumping and have nothing to do with "storage of light'', or "dynamic reduction of the group velocity'', or "light pulse compression''.
Small adiabatic polaron with a long-range electron-phonon interaction
A. S. Alexandrov,B. Ya. Yavidov
Physics , 2003, DOI: 10.1103/PhysRevB.69.073101
Abstract: Two-site single electron system interacting with many vibrating ions of a lattice via a long-range (Fr\"{o}hlich) electron-phonon interaction is studied in the adiabatic regime. The renormalised hopping integral of small adiabatic Fr\"{o}hlich polarons is calculated and compared with the hopping integral of small adiabatic Holstein polarons.
Fourier Synthesization of Optical Pulses and "Polar'' Light
V. S. Zapasskii,E. B. Alexandrov
Physics , 2002, DOI: 10.1134/1.1481139
Abstract: It is shown that the direct Fourier synthesization of light beams allows one to create polarity-asymmetric waves, which are able, in the process of nonlinear interaction with a medium, to break its inversion symmetry. As a result, these "polar" waves may show the effect of optical rectification in nonlinear centrosymmetric media by generating light-induced dc electric polarization. At the same time, the waves of this type, due to their unusual symmetry properties, can be used for detecting the direction and sign of a dc electric field applied to the medium. The prospects of application of polar waves to data recording and processing are discussed.
Polynomial splines interpolating prime series
Lumomir Alexandrov,D. B. Baranov,Plamen Yotov
Mathematics , 2002,
Abstract: Differentiable real function reproducing primes up to a given number and having a differentiable inverse function is constructed. This inverse function is compared with the Riemann-Von Mangoldt exact expression for the number of primes not exceeding a given value. Software for computation of the direct and inverse functions and their derivatives is developed. Examples of approximate solution of Diophantine equations on the primes are given.
Factorization theorems for the representations of the fundamental groups of quasiprojective varieties and some applications
Ludmil Katzarkov
Mathematics , 1994,
Abstract: In this paper, using Gromov-Jost-Korevaar-Schoen technique of harmonic maps to nonpositively curved targets, we study the representations of the fundamental groups of quasiprojective varieties. As an application of the above considerations we give a proof of a weak version of the Shafarevich Conjecture.
Nilpotent groups and universal coverings of smooth projective varieties
Ludmil Katzarkov
Mathematics , 1995,
Abstract: In this paper we prove that the universal cover of a smooth projective variety with nilpotent fundamental group is holomorphically convex.
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