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At least 469 records · Page 26Linked to original sources

arXiv2000

Laser Induced Heat Diffusion Limited Tissue Coagulation: Problem and General Properties

Previously we have developed a free boundary model for local thermal coagulation induced by laser light absorption when the tissue region affected directly by laser light is sufficiently small and heat diffusion into the surrounding tissue governs the necrosis growth. In the present paper surveying the obtained results we state the point of view on the necrosis formation under these conditions as the basis of an individual laser therapy mode exhibiting specific properties. In particular, roughly speaking, the size of the resulting necrosis domain is determined by the physical characteristics of the tissue and its response to local heating, and by the applicator form rather than the treatment duration and the irradiation power.

physics.med-ph↗

arXiv2001

Nonlinear Dynamics in the Binary DNA/RNA Coding Problem

The presence of low dimensional chaos in the protein secondary structures, using the binary coded $α$-helices and $β$-sheet motifs, has been investigated. In order to analyse symbolic DNA/RNA sequences the assignment, based on the purine/pyrimidine and strong/wea k H - bond classification sheme, of binary numbers to the nucleotides was made. We have found that this assignment leads to different averaged fractal dimensions for $α$-helices and $β$-sheets. When embedded in the two dimensional phase space the binary string structures show the attractor type behavior which depends on the value of the time lag parameter.

physics.bio-ph↗

arXiv2001

Elastic wave propagation along DNA

It is shown that information transmission inside a cell can occur by means of mechanical waves transmitted through DNA. The propagation of the waves is strongly dependent on the shape of the DNA thus proteins that change the shape of DNA can alter signal transmission. The overall effect is a method of signal processing by DNA binding proteins that creates a "cellular communications network". The propagation of small amplitude disturbances through DNA is treated according to the mechanical theory of elastic rods. According to the theory four types of mechanical waves affecting extension(compression), twist, bend or shear can propagate through DNA. Each type of wave has unique characteristic properties. Disturbances affecting all wave types can propagate independently of each other. Using a linear approximation to the theory of motion of elastic rods, the dispersion of these waves is investigated. The phase velocities of the waves lies in the range 5-8 angstroms/ps using constants suitable for a description of DNA. The dispersion of all wave types of arbitrary wave length is investigated for a straight, twisted rod. Based on these findings, we propose all-atom numerical simulations of DNA to investigate the propagation of these waves as an alternative measure of the wave velocity and dispersion analysis.

physics.bio-ph↗

arXiv2001

Mechanism of Anesthetic Action: Oxygen Pathway Perturbation Hypothesis

Although more than 150 years have past since the discovery of general anesthetics, how they precisely work remains a mystery. We propose a novel unitary mechanism of general anesthesia verifiable by experiments. In the proposed mechanism, general anesthetics perturb oxygen pathways in both membranes and oxygen-utilizing proteins such that the availabilities of oxygen to its sites of utilization are reduced which in turn triggers cascading cellular responses through oxygen-sensing mechanisms resulting in general anesthesia. Despite the general assumption that cell membranes are readily permeable to oxygen, exiting publications indicate that these membranes are plausible oxygen transport barriers. The present hypothesis provides a unified framework for explaining phenomena associated with general anesthesia and experimental results on the actions of general anesthetics. If verified by experiments, the proposed mechanism also has other significant medical and biological implications.

physics.med-ph↗

arXiv2001

Self-adaptive exploration in evolutionary search

We address a primary question of computational as well as biological research on evolution: How can an exploration strategy adapt in such a way as to exploit the information gained about the problem at hand? We first introduce an integrated formalism of evolutionary search which provides a unified view on different specific approaches. On this basis we discuss the implications of indirect modeling (via a ``genotype-phenotype mapping'') on the exploration strategy. Notions such as modularity, pleiotropy and functional phenotypic complex are discussed as implications. Then, rigorously reflecting the notion of self-adaptability, we introduce a new definition that captures self-adaptability of exploration: different genotypes that map to the same phenotype may represent (also topologically) different exploration strategies; self-adaptability requires a variation of exploration strategies along such a ``neutral space''. By this definition, the concept of neutrality becomes a central concern of this paper. Finally, we present examples of these concepts: For a specific grammar-type encoding, we observe a large variability of exploration strategies for a fixed phenotype, and a self-adaptive drift towards short representations with highly structured exploration strategy that matches the ``problem's structure''.

physics.bio-ph↗

arXiv2001

From features to expression: High-density oligonucleotide array analysis revisited

One of the most popular tools for large scale gene expression studies are high-density oligonucleotide (GeneChip(R)) arrays. These currently have 16-20 small probe cells (``features'') for evaluating the transcript abundance of each gene. In addition, each probe is accompanied by a mismatched probe designed as a control for non-specificity. An algorithm is presented to compute comparative expression levels from the intensities of the individual features, based on a statistical study of their distribution. Interestingly, MM probes need not be included in the analysis. We show that our algorithm improves significantly upon the current standard and leads to a substantially larger number of genes brought above the noise floor for further analysis.

physics.bio-ph↗

arXiv2001

Statistical Approach to Gene Evolution

The evolution in coding DNA sequences brings new flexibility and freedom to the codon words, even as the underlying nucleotides get significantly ordered. These curious contra-rules of gene organisation are observed from the distribution of words and the second moments of the nucleotide letters. These statistical data give us the physics behind the classification of bacteria.

physics.bio-ph↗

arXiv2001

Optimality of the genetic code with respect to protein stability and amino acid frequencies

How robust is the natural genetic code with respect to mistranslation errors? It has long been known that the genetic code is very efficient in limiting the effect of point mutation. A misread codon will commonly code either for the same amino acid or for a similar one in terms of its biochemical properties, so the structure and function of the coded protein remain relatively unaltered. Previous studies have attempted to address this question more quantitatively, namely by statistically estimating the fraction of randomly generated codes that do better than the genetic code regarding its overall robustness. In this paper, we extend these results by investigating the role of amino acid frequencies in the optimality of the genetic code. When measuring the relative fitness of the natural code with respect to a random code, it is indeed natural to assume that a translation error affecting a frequent amino acid is less favorable than that of a rare one, at equal mutation cost. We find that taking the amino acid frequency into account accordingly decreases the fraction of random codes that beat the natural code, making the latter comparatively even more robust. This effect is particularly pronounced when more refined measures of the amino acid substitution cost are used than hydrophobicity. To show this, we devise a new cost function by evaluating with computer experiments the change in folding free energy caused by all possible single-site mutations in a set of known protein structures. With this cost function, we estimate that of the order of one random code out of 100 millions is more fit than the natural code when taking amino acid frequencies into account. The genetic code seems therefore structured so as to minimize the consequences of translation errors on the 3D structure and stability of proteins.

physics.bio-ph↗

arXiv2002

Errors drive the evolution of biological signalling to costly codes

Reduction of costs in biological signalling seems an evolutionary advantage, but recent experiments have shown signalling codes shifted to signals of high cost with a underutilisation of low cost signals. Here I show that errors in the efficient translation of biological states into signals shift codes to higher costs, effectively performing a quality control. The statistical structure of signal usage is predicted to be of a generalised Boltzmann form that penalises signals that are costly and sensitive to errors. This predicted distribution of signal usage against signal cost has two main features: an exponential tail required for cost efficiency and an underutilisation of the low cost signals required to protect the signalling quality from the errors. These predictions are shown to correspond quantitatively to the experiments in which gathering signal statistics is feasible as in visual cortex neurons.

physics.bio-ph↗

arXiv2001

Compositional representation of protein sequences and the number of Eulerian loops

An amino acid sequence of a protein may be decomposed into consecutive overlapping strings of length K. How unique is the converse, i.e., reconstruction of amino acid sequences using the set of K-strings obtained in the decomposition? This problem may be transformed into the problem of counting the number of Eulerian loops in an Euler graph, though the well-known formula must be modified. By exhaustive enumeration and by using the modified formula we show that the reconstruction is unique at K equal or greater than 5 for an overwhelming majority of the proteins in the PDB.seq database. The corresponding Euler graphs provide a means to study the structure of repeated segments in protein sequences.

physics.bio-ph↗

arXiv2001

From Discrete Protein Kinetics to Continuous Brownian Dynamics: A New Perspective

An analysis on the discrete versus continuous views of kinetics of macromolecules is presented. It is shown that the discrete approach traditional to biochemistry is insufficient for understanding the dynamics of protein molecules in aqueous solution. A continous view based on the Brownian dynamics in energy landscape offers a more comprehensive description of the biological macromolecules. Two examples, one on protein folding and one on channel gating, are discussed.

physics.bio-ph↗

arXiv2001

On the Doublet Formation in the Flocculation Process of the Yeast Cells

The combination of single cells to form doublets is regarded as the rate-limiting step of flocculation and requires the presence of surface proteins in active form. The process of activation of the flocculation proteins of yeast cells is described in the frame of the autocrine interaction regime (Cantrell, D. A. and Smith, K. A., 1984, Science 224, 1312-1316). The influence of several effectors (the cell efficiency to use sugars, the calcium content in the external medium and the probability that free cells collide each other under thermal motion conditions) on the initial rate of flocculation and on the fraction of remaining free cells in the steady state is briefly discussed in the paper. The present model offers an useful tool for further quantitative investigations in this topic. Also, it indicates qualitatively a way in which the regulation of flocculation might be controlled at the level of the expression of cell-surface activation abilities. Keywords: flocculation; yeast; autocrine binding; lectin hypothesis

physics.bio-ph↗

arXiv2001

Phase-Transitions in a model for the formation of herpes simplex ulcers

The critical properties of a cellular automaton model describing the spreading of infection of the Herpes Simplex Virus in corneal tissue are investigated through the dynamic Monte Carlo method. The model takes into account different cell susceptibilities to the viral infection, as suggested by experimental findings. In a two-dimensional square lattice, the sites are associated to two distinct types of cells, namely, permissive and resistant to the infection. While a permissive cell becomes infected in the presence of a single infected cell in its neighborhood, a resistant cell needs to be surrounded by at least R>1 infected or dead cells in order to become infected. The infection is followed by the death of the cells resulting in ulcers whose forms may be dendritic (self-limited clusters) or amoeboid (percolating clusters) depending on the degree of resistance R of the resistant cells as well as on the density of permissive cells in the healthy tissue. We show that a phase transition between these two regimes occurs only for R>=5 and, in addition, that the phase-transition is in the universality class of the ordinary percolation.

physics.bio-ph↗

arXiv2001

Mechanical oscillations at the cellular scale

Active phenomena which involve force generation and motion play a key role in a number of phenomena in living cells such as cell motility, muscle contraction and the active transport of material and organelles. Here we discuss mechanical oscillations generated by active systems in cells. Examples are oscillatory regimes in muscles, the periodic beating of axonemal cilia and flagella and spontaneous oscillations of auditory hair cells which play a role in active amplification of weak sounds in hearing. As a prototype system for oscillation generation by proteins, we discuss a general mechanism by which many coupled active elements such as motor molecules can generate oscillations.

physics.bio-ph↗

arXiv2001

Folding DNA into nucleosome and chromatin: dynamics

A theoretical framework for evaluating the approximate energy and dynamic properties associated with the folding of DNA into nucleosomes and chromatin is presented. For this purpose experimentally determined elastic constants of linear DNA and a simple fold geometry are assumed to derive constants for the higher order folding. The model predicts the correct order of magnitude for the experimentally determined Young's and shear modulus of condensed chromatin. Thus we have demonstrated that the elastic properties of DNA are the primary determinant of the elastic properties of each folded state. The derived elastic constants are then used to predict the speed of propagation of small amplitude waves. It is shown that extension/compression, twist, bend or shear waves can be excite in each folded state.

physics.bio-ph↗

arXiv2001

Algorithm for Finding Optimal Gene Sets in Microarray Prediction

Motivation: Microarray data has been recently been shown to be efficacious in distinguishing closely related cell types that often appear in the diagnosis of cancer. It is useful to determine the minimum number of genes needed to do such a diagnosis both for clinical use and to determine the importance of specific genes for cancer. Here a replication algorithm is used for this purpose. It evolves an ensemble of predictors, all using different combinations of genes to generate a set of optimal predictors. Results: We apply this method to the leukemia data of the Whitehead/MIT group that attempts to differentially diagnose two kinds of leukemia, and also to data of Khan et. al. to distinguish four different kinds of childhood cancers. In the latter case we were able to reduce the number of genes needed from 96 down to 15, while at the same time being able to perfectly classify all of their test data. Availability: http://stravinsky.ucsc.edu/josh/gesses/ Contact: josh@physics.ucsc.edu

physics.bio-ph↗

arXiv2001

Species Orthogonalization

We discuss general formation of complementary behaviors, functions and forms in biological species competing for resources. We call orthogonalization the related processes on macro and micro-level of a self-organized formation of correlations in the species properties. Orthogonalization processes could be, for example, easily observed in sympatric speciation, as we show in numerical studies carried with a new population equation. As a practical result, we find that the number of species is proportional to the effective richness of resources and depends on their history.

physics.bio-ph↗

arXiv2001

Finite genome size can halt Muller's ratchet

We study the accumulation of deleterious mutations in a haploid, asexually reproducing population, using analytical models and computer simulations. We find that Muller's ratchet can come to a halt in small populations as a consequence of a finite genome size only, in the complete absence of backward or compensatory mutations, epistasis, or recombination. The origin of this effect lies in the fact that the number of loci at which mutations can create considerable damage decreases with every turn of the ratchet, while the total number of mutations per genome and generation remains constant. Whether the ratchet will come to a halt eventually depends on the ratio of the per-locus deleterious mutation rate $u$ and the selection strength $s$. For sufficiently small $u/s$, the ratchet halts after only a few clicks. We discuss the implications of our results for bacterial and virus evolution.

physics.bio-ph↗