Semi-algebraic methods for symbolic analysis of complex reaction networks

The identification of chemical mechanism that can exhibit oscillatory phenomena in reaction networks are currently of intense interest. In particular, the parametric question of the existence of Hopf bifurcations has gained increasing popularity due to its relation to the oscillatory behavior around the fixed points. However, the detection of oscillations in high-dimensional systems and systems with constraints by the available symbolic methods has proven to be difficult. The development of new efficient methods are therefore required to tackle the complexity caused by the high-dimensionality and non-linearity of these systems. In this thesis, we mainly present efficient algorithmic methods to detect Hopf bifurcation fixed points in (bio)-chemical reaction networks with symbolic rate constants, thereby yielding information about their oscillatory behavior of the networks. The methods use the representations of the systems on convex coordinates that arise from stoichiometric network analysis. One of the methods called HoCoQ reduces the problem of determining the existence of Hopf bifurcation fixed points to a first-order formula over the ordered field of the reals that can then be solved using computational-logic packages. The second method called HoCaT uses ideas from tropical geometry to formulate a more efficient method that is incomplete in theory but worked very well for the attempted high-dimensional models involving more than 20 chemical species. The instability of reaction networks may lead to the oscillatory behaviour. Therefore, we investigate some criterions for their stability using convex coordinates and quantifier elimination techniques. We also study Muldowney's extension of the classical Bendixson-Dulac criterion for excluding periodic orbits to higher dimensions for polynomial vector fields and we discuss the use of simple conservation constraints and the use of parametric constraints for describing simple convex polytopes on which periodic orbits can be excluded by Muldowney's criteria. All developed algorithms have been integrated into a common software framework called PoCaB (platform to explore bio- chemical reaction networks by algebraic methods) allowing for automated computation workflows from the problem descriptions. PoCaB also contains a database for the algebraic entities computed from the models of chemical reaction networks.

On Vessiot's Theory of Partial Differential Equations

The object of research presented here is Vessiot's theory of partial differential equations: for a given differential equation one constructs a distribution both tangential to the differential equation and contained within the contact distribution of the jet bundle. Then within it, one seeks n-dimensional subdistributions which are transversal to the base manifold, the integral distributions. These consist of integral elements, and these again shall be adapted so that they make a subdistribution which closes under the Lie-bracket. This then is called a flat Vessiot connection. Solutions to the differential equation may be regarded as integral manifolds of these distributions. In the first part of the thesis, I give a survey of the present state of the formal theory of partial differential equations: one regards differential equations as fibred submanifolds in a suitable jet bundle and considers formal integrability and the stronger notion of involutivity of differential equations for analyzing their solvability. An arbitrary system may (locally) be represented in reduced Cartan normal form. This leads to a natural description of its geometric symbol. The Vessiot distribution now can be split into the direct sum of the symbol and a horizontal complement (which is not unique). The n-dimensional subdistributions which close under the Lie bracket and are transversal to the base manifold are the sought tangential approximations for the solutions of the differential equation. It is now possible to show their existence by analyzing the structure equations. Vessiot's theory is now based on a rigorous foundation. Furthermore, the relation between Vessiot's approach and the crucial notions of the formal theory (like formal integrability and involutivity of differential equations) is clarified. The possible obstructions to involution of a differential equation are deduced explicitly. In the second part of the thesis it is shown that Vessiot's approach for the construction of the wanted distributions step by step succeeds if, and only if, the given system is involutive. Firstly, an existence theorem for integral distributions is proven. Then an existence theorem for flat Vessiot connections is shown. The differential-geometric structure of the basic systems is analyzed and simplified, as compared to those of other approaches, in particular the structure equations which are considered for the proofs of the existence theorems: here, they are a set of linear equations and an involutive system of differential equations. The definition of integral elements given here links Vessiot theory and the dual Cartan-Kähler theory of exterior systems. The analysis of the structure equations not only yields theoretical insight but also produces an algorithm which can be used to derive the coefficients of the vector fields, which span the integral distributions, explicitly. Therefore implementing the algorithm in the computer algebra system MuPAD now is possible.

Non-Born-Oppenheimer Dynamics of Hydrogen Molecules in Strong Laser-Fields

Die Arbeit behandelt die numerische Untersuchung von Wasserstoff-Moleküldynamik in starken Laserfeldern. Im Speziellen wird die Struktur von Ionisationsspektren bei Einfach-Photoionisation betrachtet. Korrelationen zwischen Elektron- und Kernbewegung werden identifiziert und mit Effekten in den Energiespektren in Verbindung gebracht. Dabei wird stets auf die Integration der zeitabhängigen Schrödingergleichung zurückgegriffen.

First-principles electronic theory of non-collinear magnetic order in transition-metal nanowires

The structural, electronic and magnetic properties of one-dimensional 3d transition-metal (TM) monoatomic chains having linear, zigzag and ladder geometries are investigated in the frame-work of first-principles density-functional theory. The stability of long-range magnetic order along the nanowires is determined by computing the corresponding frozen-magnon dispersion relations as a function of the 'spin-wave' vector q. First, we show that the ground-state magnetic orders of V, Mn and Fe linear chains at the equilibrium interatomic distances are non-collinear (NC) spin-density waves (SDWs) with characteristic equilibrium wave vectors q that depend on the composition and interatomic distance. The electronic and magnetic properties of these novel spin-spiral structures are discussed from a local perspective by analyzing the spin-polarized electronic densities of states, the local magnetic moments and the spin-density distributions for representative values q. Second, we investigate the stability of NC spin arrangements in Fe zigzag chains and ladders. We find that the non-collinear SDWs are remarkably stable in the biatomic chains (square ladder), whereas ferromagnetic order (q =0) dominates in zigzag chains (triangular ladders). The different magnetic structures are interpreted in terms of the corresponding effective exchange interactions J(ij) between the local magnetic moments μ(i) and μ(j) at atoms i and j. The effective couplings are derived by fitting a classical Heisenberg model to the ab initio magnon dispersion relations. In addition they are analyzed in the framework of general magnetic phase diagrams having arbitrary first, second, and third nearest-neighbor (NN) interactions J(ij). The effect of external electric fields (EFs) on the stability of NC magnetic order has been quantified for representative monoatomic free-standing and deposited chains. We find that an external EF, which is applied perpendicular to the chains, favors non-collinear order in V chains, whereas it stabilizes the ferromagnetic (FM) order in Fe chains. Moreover, our calculations reveal a change in the magnetic order of V chains deposited on the Cu(110) surface in the presence of external EFs. In this case the NC spiral order, which was unstable in the absence of EF, becomes the most favorable one when perpendicular fields of the order of 0.1 V/Å are applied. As a final application of the theory we study the magnetic interactions within monoatomic TM chains deposited on graphene sheets. One observes that even weak chain substrate hybridizations can modify the magnetic order. Mn and Fe chains show incommensurable NC spin configurations. Remarkably, V chains show a transition from a spiral magnetic order in the freestanding geometry to FM order when they are deposited on a graphene sheet. Some TM-terminated zigzag graphene-nanoribbons, for example V and Fe terminated nanoribbons, also show NC spin configurations. Finally, the magnetic anisotropy energies (MAEs) of TM chains on graphene are investigated. It is shown that Co and Fe chains exhibit significant MAEs and orbital magnetic moments with in-plane easy magnetization axis. The remarkable changes in the magnetic properties of chains on graphene are correlated to charge transfers from the TMs to NN carbon atoms. Goals and limitations of this study and the resulting perspectives of future investigations are discussed.

Protein Folding Simulations: Confinement, External Fields and Sequence Design

The present Thesis looks at the problem of protein folding using Monte Carlo and Langevin simulations, three topics in protein folding have been studied: 1) the effect of confining potential barriers, 2) the effect of a static external field and 3) the design of amino acid sequences which fold in a short time and which have a stable native state (global minimum). Regarding the first topic, we studied the confinement of a small protein of 16 amino acids known as 1NJ0 (PDB code) which has a beta-sheet structure as a native state. The confinement of proteins occurs frequently in the cell environment. Some molecules called Chaperones, present in the cytoplasm, capture the unfolded proteins in their interior and avoid the formation of aggregates and misfolded proteins. This mechanism of confinement mediated by Chaperones is not yet well understood. In the present work we considered two kinds of potential barriers which try to mimic the confinement induced by a Chaperon molecule. The first kind of potential was a purely repulsive barrier whose only effect is to create a cavity where the protein folds up correctly. The second kind of potential was a barrier which includes both attractive and repulsive effects. We performed Wang-Landau simulations to calculate the thermodynamical properties of 1NJ0. From the free energy landscape plot we found that 1NJ0 has two intermediate states in the bulk (without confinement) which are clearly separated from the native and the unfolded states. For the case of the purely repulsive barrier we found that the intermediate states get closer to each other in the free energy landscape plot and eventually they collapse into a single intermediate state. The unfolded state is more compact, compared to that in the bulk, as the size of the barrier decreases. For an attractive barrier modifications of the states (native, unfolded and intermediates) are observed depending on the degree of attraction between the protein and the walls of the barrier. The strength of the attraction is measured by the parameter $\epsilon$. A purely repulsive barrier is obtained for $\epsilon=0$ and a purely attractive barrier for $\epsilon=1$. The states are changed slightly for magnitudes of the attraction up to $\epsilon=0.4$. The disappearance of the intermediate states of 1NJ0 is already observed for $\epsilon =0.6$. A very high attractive barrier ($\epsilon \sim 1.0$) produces a completely denatured state. In the second topic of this Thesis we dealt with the interaction of a protein with an external electric field. We demonstrated by means of computer simulations, specifically by using the Wang-Landau algorithm, that the folded, unfolded, and intermediate states can be modified by means of a field. We have found that an external field can induce several modifications in the thermodynamics of these states: for relatively low magnitudes of the field ($<2.06 \times 10^8$ V/m) no major changes in the states are observed. However, for higher magnitudes than ($6.19 \times 10^8$ V/m) one observes the appearance of a new native state which exhibits a helix-like structure. In contrast, the original native state is a $\beta$-sheet structure. In the new native state all the dipoles in the backbone structure are aligned parallel to the field. The design of amino acid sequences constitutes the third topic of the present work. We have tested the Rate of Convergence criterion proposed by D. Gridnev and M. Garcia ({\it work unpublished}). We applied it to the study of off-lattice models. The Rate of Convergence criterion is used to decide if a certain sequence will fold up correctly within a relatively short time. Before the present work, the common way to decide if a certain sequence was a good/bad folder was by performing the whole dynamics until the sequence got its native state (if it existed), or by studying the curvature of the potential energy surface. There are some difficulties in the last two approaches. In the first approach, performing the complete dynamics for hundreds of sequences is a rather challenging task because of the CPU time needed. In the second approach, calculating the curvature of the potential energy surface is possible only for very smooth surfaces. The Rate of Convergence criterion seems to avoid the previous difficulties. With this criterion one does not need to perform the complete dynamics to find the good and bad sequences. Also, the criterion does not depend on the kind of force field used and therefore it can be used even for very rugged energy surfaces.