Application and Development of Charge Transfer Simulations in Biological and Organic Systems

Diese Arbeit zeigt eine theoretische Untersuchung von lichtinduzierten Ladungstransferprozessen in der Proteinfamilie der Photolyasen/Cryptochrome, als prominentes Beispiel. Während Photolyasen lichtinduzierte DNA-Schäden reparieren, sind Cryptochrome Signalmoleküle, welche die Lichtreaktion vermitteln. Beide haben eine homologe Proteinstruktur und einen Flavin-Adenin-Dinukleotid Kofaktor, der ihre biologischen Funktionen durch Ladungstransferprozesse ermöglicht. Diese weisen einen signifikanten nicht-gleichgewichts Charakter auf, welcher es für die etablierten Ladungstransfertheorien schwierig macht die richtige Kinetik vorherzusagen. Daher wird in diese Arbeit eine hybride Multi-Skalen Simulationsmethode verwendet, die klassische und Quantendynamikansätze kombiniert und nicht auf der Annahme von Gleichgewichtsprozessen basiert ist. Dieses Multi-Skalen Methode wurde angewendet, gebenchmarkt und weiterentwickelt, um die Genauigkeit der Quantenbeschreibung zu untersuchen und zu erhöhen. Dies erhöhte auch die Übertragbarkeit auf Studien zum Ladungstransfer in anderen molekularen Systemen. Darüber hinaus bietet diese Methode eine praktikable Alternative zu teuren zeitaufgelösten Spektroskopie-Verfahren, hinsichtlich der Charakterisierung von Ladungstranferprozessen in den Photolyasen und Cryptochromen. In experimentellen Studien mit PhrB, einer Photolyase von A. tumefaciens, war es nicht möglich, die Kinetik der Ladungstranferprozesse aufzulösen. Daher wurde in dieser Arbeit die Multi-Skalen Methode verwendet, um den Ladungstransfer in PhrB zu charakterisieren. Insbesondere das Vorhandensein von einem Tyrosin, anstelle von Tryptophan, im Ladungstransfer Pfad wurde untersucht. Daher wurden Molekulardynamik-Simulationen von Mutanten genutzt um eine Struktur-Funktionsbeziehung zu erstellen und ein getunnelter Ladungstransfer wurde vorgeschlagen, der die erste Aminosäure des Pfades involviert. Weitere Simulationen zeigten, dass das angrenzende Wasser einen Transfer entlang des energetisch ungünstigen Tyrosins ermöglicht, während ein Tryptophan den Rücktransfer erleichtert. PhrA, eine weitere Photolyase von A. tumefaciens, wurde untersucht, um die Ladungstranferprozesse entlang alternativer Pfade aufzuklären. Es wurden unterschiedliche Verhaltensweisen der Kinetik des Ladungstransfers beobachtet. Ein Pfad bietet einen schnellen Transfer, während der Andere eine bessere Stabilisierung der Ladung ermöglicht. Der Ladungstransfer in Photolyasen und Cryptochromen löst weitere Prozesse aus, wie zum Beispiel einen Protonentransfer zum Kofaktor oder strukturelle Umlagerungen des Reaktionszentrums. In der E. coli Photolyase kann der Kofaktor protoniert werden, jedoch ist der Protonendonator und der Mechanismus unklar. Darüber hinaus zeigten experimentelle Mutationsstudien, dass die Einbringung eines Protonendonators in die Tasche des Kofaktors die Protonierung verhindert. Daher wurden klassische und Quantendynamik Simulationen durchgeführt und ein Protonentransfermechanismus bestimmt. Simulationen einer Mutante zeigten, dass die Flexibilität und die Coulomb-Wechselwirkungen der Tasche nicht durch den Austausch von einer oder zwei Aminosäuren verändert werden kann. Somit kann eine Protonentransferfähigkeit nicht eingeführt werden, auch wenn die Mutanten scheinbar die entscheidenden strukturellen Muster aufweisen

Substitutions over infinite alphabet generating (-\beta)-integers

This contribution is devoted to the study of positional numeration systems with negative base introduced by Ito and Sadahiro in 2009, called (-\beta)-expansions. We give an admissibility criterion for more general case of (-\beta)-expansions and discuss the properties of the set of (-\beta)-integers. We give a description of distances within this set and show that this set can be coded by an infinite word over an infinite alphabet, which is a fixed point of a non-erasing non-trivial morphism.Comment: In Proceedings WORDS 2011, arXiv:1108.341

Biological relevance of charge transfer branching pathways in photolyases

In PhrA, a class III CPD photolyase, two branching tryptophan charge transfer pathways have been characterized in the mechanism of FAD photoreduction. To provide a molecular explanation of the charge transfer abilities of both pathways, we performed simulations where the protein motion and the positive charge are simultaneously propagated. Our computational approach reveals that one pathway drives a very fast charge transfer whereas the other pathway provides a very good thermodynamic stabilization of the positive charge. During the simulations, the positive charge firstly moves on the fast triad, allowing the stabilization of reduced FAD. After one nanosecond, we observe a nearly equal probability to find the charge at ending tryptophan of either pathway. Our results highlight the role of the protein environment, which manages the association of a kinetic and a thermodynamic pathways to trigger a fast and efficient FAD photoreduction

Primary care and the early phases of schizophrenia in the Czech Republic

Aim - To explore knowledge, treatment setting, attitudes and needs associated with patients in early phases of psychosis among general practitioners (GPs) in Prague, andto compare results with GPs from 6 countries participating in the International GP Study (IGPS) on Early Psychosis (Canada, Australia, New Zealand, England, Norway,Austria). Methods - Survey questionnaires were mailed to 648 GPs in the city of Prague. Results - The response rate was 19.9%. Prague GPs showed significantly lower diagnostic knowledge of early phases of psychosis compared to their international colleagues. They frequently indicated depression/anxiety and somatic complaints as early warnings of psychosis. They more often considered their behaviour to be problematic and more commonly handed them over to specialists. The majority of Prague GPs wished specialized outpatient services for low-threshold referrals of such patients. Conclusions - Along the mental health reforms in the Czech Republic which emphasis the role of primary care, GPs' knowledge of the early warning signs of psychosis needs to be improved. Declaration of Interest: The study was supported by an unrestricted grant from Sanofi-Synthélabo SA, Switzerland, to the principal investigators of the IGPS (AES, DU). The authors have stated that there are none; all authors are independent from the funding body and the views expressed in this paper have not been influenced by the funding sourc

Primary care and the early phases of schizophrenia in the Czech Republic

Aim – To explore knowledge, treatment setting, attitudes and needs associated with patients in early phases of psychosis among general practitioners (GPs) in Prague, andto compare results with GPs from 6 countries participating in the International GP Study (IGPS) on Early Psychosis (Canada, Australia, New Zealand, England, Norway,Austria). Methods – Survey questionnaires were mailed to 648 GPs in the city of Prague. Results – The response rate was 19.9%. Prague GPs showed significantly lower diagnostic knowledge of early phases of psychosis compared to their international colleagues. They frequently indicated depression/anxiety and somatic complaints as early warnings of psychosis. They more often considered their behaviour to be problematic and more commonly handed them over to specialists. The majority of Prague GPs wished specialized outpatient services for low-threshold referrals of such patients. Conclusions – Along the mental health reforms in the Czech Republic which emphasis the role of primary care, GPs' knowledge of the early warning signs of psychosis needs to be improved

Unambiguous 1-Uniform Morphisms

A morphism h is unambiguous with respect to a word w if there is no other morphism g that maps w to the same image as h. In the present paper we study the question of whether, for any given word, there exists an unambiguous 1-uniform morphism, i.e., a morphism that maps every letter in the word to an image of length 1.Comment: In Proceedings WORDS 2011, arXiv:1108.341

The symmetric Radon-Nikod\'ym property for tensor norms

We introduce the symmetric-Radon-Nikod\'ym property (sRN property) for finitely generated s-tensor norms $\beta$ of order $n$ and prove a Lewis type theorem for s-tensor norms with this property. As a consequence, if $\beta$ is a projective s-tensor norm with the sRN property, then for every Asplund space $E$, the canonical map $\widetilde{\otimes}_{\beta}^{n,s} E' \to \Big(\widetilde{\otimes}_{\beta'}^{n,s} E \Big)'$ is a metric surjection. This can be rephrased as the isometric isomorphism $\mathcal{Q}^{min}(E) = \mathcal{Q}(E)$ for certain polynomial ideal \Q. We also relate the sRN property of an s-tensor norm with the Asplund or Radon-Nikod\'{y}m properties of different tensor products. Similar results for full tensor products are also given. As an application, results concerning the ideal of $n$-homogeneous extendible polynomials are obtained, as well as a new proof of the well known isometric isomorphism between nuclear and integral polynomials on Asplund spaces.Comment: 17 page

Magnetic resonance elastography in nonlinear viscoelastic materials under load.

Characterisation of soft tissue mechanical properties is a topic of increasing interest in translational and clinical research. Magnetic resonance elastography (MRE) has been used in this context to assess the mechanical properties of tissues in vivo noninvasively. Typically, these analyses rely on linear viscoelastic wave equations to assess material properties from measured wave dynamics. However, deformations that occur in some tissues (e.g. liver during respiration, heart during the cardiac cycle, or external compression during a breast exam) can yield loading bias, complicating the interpretation of tissue stiffness from MRE measurements. In this paper, it is shown how combined knowledge of a material's rheology and loading state can be used to eliminate loading bias and enable interpretation of intrinsic (unloaded) stiffness properties. Equations are derived utilising perturbation theory and Cauchy's equations of motion to demonstrate the impact of loading state on periodic steady-state wave behaviour in nonlinear viscoelastic materials. These equations demonstrate how loading bias yields apparent material stiffening, softening and anisotropy. MRE sensitivity to deformation is demonstrated in an experimental phantom, showing a loading bias of up to twofold. From an unbiased stiffness of [Formula: see text] Pa in unloaded state, the biased stiffness increases to 9767.5 [Formula: see text]1949.9 Pa under a load of [Formula: see text] 34% uniaxial compression. Integrating knowledge of phantom loading and rheology into a novel MRE reconstruction, it is shown that it is possible to characterise intrinsic material characteristics, eliminating the loading bias from MRE data. The framework introduced and demonstrated in phantoms illustrates a pathway that can be translated and applied to MRE in complex deforming tissues. This would contribute to a better assessment of material properties in soft tissues employing elastography