Statistical-mechanical lattice models for protein-DNA binding in chromatin

Statistical-mechanical lattice models for protein-DNA binding are well established as a method to describe complex ligand binding equilibriums measured in vitro with purified DNA and protein components. Recently, a new field of applications has opened up for this approach since it has become possible to experimentally quantify genome-wide protein occupancies in relation to the DNA sequence. In particular, the organization of the eukaryotic genome by histone proteins into a nucleoprotein complex termed chromatin has been recognized as a key parameter that controls the access of transcription factors to the DNA sequence. New approaches have to be developed to derive statistical mechanical lattice descriptions of chromatin-associated protein-DNA interactions. Here, we present the theoretical framework for lattice models of histone-DNA interactions in chromatin and investigate the (competitive) DNA binding of other chromosomal proteins and transcription factors. The results have a number of applications for quantitative models for the regulation of gene expression.Comment: 19 pages, 7 figures, accepted author manuscript, to appear in J. Phys.: Cond. Mat

Strings, Matrix Models, and Meanders

I briefly review the present status of bosonic strings and discretized random surfaces in D>1 which seem to be in a polymer rather than stringy phase. As an explicit example of what happens, I consider the Kazakov-Migdal model with a logarithmic potential which is exactly solvable for any D (at large D for an arbitrary potential). I discuss also the meander problem and report some new results on its representation via matrix models and the relation to the Kazakov-Migdal model. A supersymmetric matrix model is especially useful for describing the principal meanders.Comment: 12 pages, 4 Latex figures, uses espcrc2.sty Talk at the 29th Ahrenshoop Symp., Buckow, Germany, Aug.29 - Sep.2, 199

Universal geometrical factor of protein conformations as a consequence of energy minimization

The biological activity and functional specificity of proteins depend on their native three-dimensional structures determined by inter- and intra-molecular interactions. In this paper, we investigate the geometrical factor of protein conformation as a consequence of energy minimization in protein folding. Folding simulations of 10 polypeptides with chain length ranging from 183 to 548 residues manifest that the dimensionless ratio (V/(A)) of the van der Waals volume V to the surface area A and average atomic radius of the folded structures, calculated with atomic radii setting used in SMMP [Eisenmenger F., et. al., Comput. Phys. Commun., 138 (2001) 192], approach 0.49 quickly during the course of energy minimization. A large scale analysis of protein structures show that the ratio for real and well-designed proteins is universal and equal to 0.491\pm0.005. The fractional composition of hydrophobic and hydrophilic residues does not affect the ratio substantially. The ratio also holds for intrinsically disordered proteins, while it ceases to be universal for polypeptides with bad folding properties.Comment: 6 pages, 1 table, 4 figure

Performance of Grain Cleaner APB-M1 in Cleaning of Maize Grain

The research to evaluate perfornlance of grain cleaner APB-MI was conducted in the Research Institute for Maize and Other Cereals tit the beginning of 1998. Five engine circles were tested: 1200, 1350, 1500, I650 and 1800 rpm with three replications. Bisma variety was used us maize grrrin with 13% moisture content (wet basis) and for each replication the amount was 25 kg. The results showed that power transmission efficiency was at the average of 95.0% on the strainer and 94.2% on the blower. Fuel conszrtnptionwas at the rate of 0,81 //hour with average cleaning capacity of 598 kg/hour

Scope for Credit Risk Diversification

This paper considers a simple model of credit risk and derives the limit distribution of losses under different assumptions regarding the structure of systematic risk and the nature of exposure or firm heterogeneity. We derive fat-tailed correlated loss distributions arising from Gaussian risk factors and explore the potential for risk diversification. Where possible the results are generalised to non-Gaussian distributions. The theoretical results indicate that if the firm parameters are heterogeneous but come from a common distribution, for sufficiently large portfolios there is no scope for further risk reduction through active portfolio management. However, if the firm parameters come from different distributions, then further risk reduction is possible by changing the portfolio weights. In either case, neglecting parameter heterogeneity can lead to underestimation of expected losses. But, once expected losses are controlled for, neglecting parameter heterogeneity can lead to overestimation of risk, whether measured by unexpected loss or value-at-risk

Genome-Wide Studies of Histone Demethylation Catalysed by the Fission Yeast Homologues of Mammalian LSD1

In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1+ gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1¿ strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression

Modal Ω-Logic: Automata, Neo-Logicism, and Set-Theoretic Realism

This essay examines the philosophical significance of $\Omega$-logic in Zermelo-Fraenkel set theory with choice (ZFC). The duality between coalgebra and algebra permits Boolean-valued algebraic models of ZFC to be interpreted as coalgebras. The modal profile of $\Omega$-logical validity can then be countenanced within a coalgebraic logic, and $\Omega$-logical validity can be defined via deterministic automata. I argue that the philosophical significance of the foregoing is two-fold. First, because the epistemic and modal profiles of $\Omega$-logical validity correspond to those of second-order logical consequence, $\Omega$-logical validity is genuinely logical, and thus vindicates a neo-logicist conception of mathematical truth in the set-theoretic multiverse. Second, the foregoing provides a modal-computational account of the interpretation of mathematical vocabulary, adducing in favor of a realist conception of the cumulative hierarchy of sets