Universitätspublikationen
Refine
Year of publication
Document Type
- Article (10808)
- Doctoral Thesis (1567)
- Preprint (1554)
- Working Paper (1438)
- Part of Periodical (564)
- Conference Proceeding (511)
- Report (299)
- Part of a Book (107)
- Review (92)
- Book (60)
Language
- English (17089) (remove)
Has Fulltext
- yes (17089) (remove)
Keywords
- inflammation (92)
- COVID-19 (89)
- SARS-CoV-2 (62)
- Financial Institutions (47)
- Germany (45)
- climate change (45)
- aging (43)
- ECB (42)
- cancer (42)
- apoptosis (41)
Institute
- Medizin (5096)
- Physik (2985)
- Wirtschaftswissenschaften (1643)
- Frankfurt Institute for Advanced Studies (FIAS) (1575)
- Biowissenschaften (1399)
- Informatik (1249)
- Center for Financial Studies (CFS) (1136)
- Sustainable Architecture for Finance in Europe (SAFE) (1059)
- Biochemie und Chemie (855)
- House of Finance (HoF) (700)
Nineteen-channel EEGs were recorded from the scalp surface of 30 healthy subjects (16 males and 14 females, mean age: 34 years, SD: 11.7 years) at rest and under trains of intermittent photic stimulation (IPS) at rates of 5, 10 and 20 Hz. Digitalized data were submitted to spectral analysis with fast fourier transformation providing the basis for the computation of global field power (GFP). For quantification, GFP values in the frequency ranges of 5, 10 and 20 Hz at rest were divided by the corresponding data obtained under IPS. All subjects showed a photic driving effect at each rate of stimulation. GFP data were normally distributed, whereas ratios from photic driving effect data showed no uniform behavior due to high interindividual variability. Suppression of alpha-power after IPS with 10 Hz was observed in about 70% of the volunteers. In contrast, ratios of alpha-power were unequivocal in all subjects: IPS at 20 Hz always led to a suppression of alpha-power. Dividing alpha-GFP with 20-Hz IPS by alpha-GFP at rest (R = a-GFPIPS/a-GFPrest) thus resulted in ratios lower than 1. We conclude that ratios from GFP data with 20-Hz IPS may provide a suitable paradigm for further investigations. Key words: EEG, Brain mapping, Intermittent photic stimulation, IPS, Global field power ratios
In this proceeding the emergence of a composite, adjoint-scalar field as an average over (trivial holonomy) calorons and anti-calorons is reviewed. This composite field acts as a background field to the dynamics of perturbative gluons, to which it is coupled via an effective, gauge invariant Lagrangian valid for temperatures above the deconfinement phase transition. Moreover a Higgs mechanism is induced by the composite field: two gluons acquire a quasi-particle thermal mass. On the phenomenological side the composite field acts as a bag pressure which shows a linear dependence on the temperature. As a result the linear rise with temperature of the trace anomaly is obtained and is compared to recent lattice studies.
Background: Pathogenic bacteria infecting both animals as well as plants use various mechanisms to transport virulence factors across their cell membranes and channel these proteins into the infected host cell. The type III secretion system represents such a mechanism. Proteins transported via this pathway (‘‘effector proteins’’) have to be distinguished from all other proteins that are not exported from the bacterial cell. Although a special targeting signal at the N-terminal end of effector proteins has been proposed in literature its exact characteristics remain unknown. Methodology/Principal Findings: In this study, we demonstrate that the signals encoded in the sequences of type III secretion system effectors can be consistently recognized and predicted by machine learning techniques. Known protein effectors were compiled from the literature and sequence databases, and served as training data for artificial neural networks and support vector machine classifiers. Common sequence features were most pronounced in the first 30 amino acids of the effector sequences. Classification accuracy yielded a cross-validated Matthews correlation of 0.63 and allowed for genome-wide prediction of potential type III secretion system effectors in 705 proteobacterial genomes (12% predicted candidates protein), their chromosomes (11%) and plasmids (13%), as well as 213 Firmicute genomes (7%). Conclusions/Significance: We present a signal prediction method together with comprehensive survey of potential type III secretion system effectors extracted from 918 published bacterial genomes. Our study demonstrates that the analyzed signal features are common across a wide range of species, and provides a substantial basis for the identification of exported pathogenic proteins as targets for future therapeutic intervention. The prediction software is publicly accessible from our web server ( www.modlab.org ).
Bacterial autotransporters represent a diverse family of proteins that autonomously translocate across the inner membrane of Gram-negative bacteria via the Sec complex and across the outer bacterial membrane. They often possess exceptionally long N-terminal signal sequences. We analyzed 90 long signal sequences of bacterial autotransporters and members of the two-partner secretion pathway in silico and describe common domain organization found in 79 of these sequences. The domains are in agreement with previously published experimental data. Our algorithmic approach allows for the systematic identification of functionally different domains in long signal sequences. Keywords: bacterial autotransporter, sequence analysis, pattern, protein targeting, signal peptide, protein trafficking
In my dissertation I study the transmission of monetary and fiscal policy in New Keynesian DSGE models. In the first chapter we revisit the exchange rate channel in a two-country model of the U.S. and a panel of industrialized countries to analyse how monetary policy transmission in the U.S. changes if it becomes more trade integrated. We find that more openness lowers the sacrifice ratio, although the effect is quantitatively small and depends on the pricing of the firms. In the second chapter we simulate the impact of the U.S. fiscal stimulus package in 2009 on GDP. We find that the government spendingmultiplier is well below 1. The finding is robust to including rule-of-thumb consumers and simulating the stimulus in the recent recession. In the third chapter we collect the fiscal stimulus measures in the eleven biggest countries of the euro area. Then we do a robustness study by simulating the european package in five different models of the euro area. The macroeconomic models vary in terms of backward-looking decision making of the agents and openness. Our findings provide no support for a Keynesian multiplier. Instead they suggest that additional government spending will reduce private spending for consumption and investment purposes. If government spending faces an implementation lag, the initial effect on GDP may even be negative. In the fourth chapter I estimate a DSGE model for Germany and compute forecasts for the debt-to-GDP ratio. I find that the expected economic recovery will lead to a decrease in Germany’s indebtedness in the medium-term given that policy makers stick to the fiscal policy rules.
We propose a theory characterizing information systems (IS) as language communities which use and develop domain-specific languages for communication. Our theory is anchored in Language Critique, a branch of philosophy of language. In developing our theory, we draw on Systems Theory and Cybernetics as a theoretical framework. "Organization" of a system is directly related to communication of its sub-systems. "Big systems" are self-organizing and the control of this ability is disseminated throughout the system itself. Therefore, the influence on changes of the system from its outside is limited. Operations intended to change an organization are restricted to indirect approaches. The creation of domain-specific languages by the system itself leads to advantageous communication costs compared to colloquial communication at the price of set-up costs for language communities. Furthermore, we demonstrate how our theoretical constructs help to describe and predict the behavior of IS. Finally, we discuss implications of our theory for further research and IS in general. Keywords: Language Critique, language communities, communication, self-organization, IS research
Lipid rafts are specialized plasma membrane micro-domains highly enriched in cholesterol, sphingolipids and glycosylphosphatidylinositol (GPI) anchored proteins. Lipid rafts are thought to be located in the exofacial leaflet of plasma membranes. Functionally, lipid rafts are involved in intracellular trafficking of proteins and lipids, secretory and endocytotic pathways, signal transduction, inflammation and in cell-surface proteolysis. There has been substantial interest in lipid rafts in brain, both with respect to normal functioning and with certain neurodegenerative diseases. Based on the impact of lipid rafts on multitude biochemical pathways, modulation of lipid rafts is used to study related disease pathways and probably offers a target for pharmacological intervention. Lipid rafts can be targeted by modulation of its main components, namely cholesterol and sphingolipids. Other approaches include the modulation of membrane dynamics and it has been reported that protein-lipid interactions can vary the occurrence and composition of these membrane micro-domains. The present review summarizes the possibilities to modulate lipid rafts with focus on neuronal cells. Keywords: Lipid raft, cholesterol, membrane fluidity, statin, cyclodextrine, docosahexaenoic acid.
Planning problems, like real-world planning and scheduling problems, are complex tasks. As an efficient strategy for handing such problems is the ‘divide and conquer’ strategy has been identified. Each sub problem is then solved independently. Typically the sub problems are solved in a linear way. This approach enables the generation of sub-optimal plans for a number of real world problems. Today, this approach is widely accepted and has been established e.g. in the organizational structure of companies. But existing interdependencies between the sub problems are not sufficiently regarded, as each problem are solved sequentially and no feedback information is given. The field of coordination has been covered by a number of academic fields, like the distributed artificial intelligence, economics or game theory. An important result is, that there exist no method that leads to optimal results in any given coordination problem. Consequently, a suitable coordination mechanism has to be identified for each single coordination problem. Up to now, there exists no process for the selection of a coordination mechanism, neither in the engineering of distributed systems nor in agent oriented software engineering. Within the scope of this work the ECo process is presented, that address exactly this selection problem. The Eco process contains the following five steps. • Modeling of the coordination problem • Defining the coordination requirements • Selection / Design of the coordination mechanism • Implementation • Evaluation Each of these steps is detailed in the thesis. The modeling has to be done to enable a systemic analysis of the coordination problem. Coordination mechanisms have to respect the given situation and the context in which the coordination has to be done. The requirements imposed by the context of the coordination problem are formalized in the coordination requirements. The selection process is driven by these coordination requirements. Using the requirements as a distinction for the selection of a coordination mechanism is a central aspect of this thesis. Additionally these requirements can be used for documentation of design decisions. Therefore, it is reasonable to annotate the coordination mechanisms with the coordination requirements they fulfill and fail to ease the selection process, for a given situation. For that reason we present a new classification scheme for coordination methods within this thesis that classifies existing coordination methods according to a set of criteria that has been identified as important for the distinction between different coordination methods. The implementation phase of the ECo process is supported by the CoPS process and CoPS framework that has been developed within this thesis, as well. The CoPS process structures the design making that has to be done during the implementation phase. The CoPS framework provides a set of basic features software agents need for realizing the selected coordination method. Within the CoPS process techniques are presented for the design and implementation of conversations between agents that can be applied not only within the context of the coordination of planning systems, but for multiagent systems in general. The ECo-CoPS approach has been successfully validated in two case studies from the logistic domain.
Therapy of hemorrhagic shock with following resuscitation-induced liver injury : in vivo study
(2010)
Shock resulting from life-threatening blood-loss (hemorrhagic shock) represents the most frequent injury pattern after a traumatic insult. Hemorrhagic shock induces inflammatory changes, characterized by highly complex pathophysiological pathways often resulting in death. In this study, we establish an experimental in vivo model of H/R in rats and study the mechanisms which determine the hepatic injury after H/R. Furthermore, we show that hemorrhagic shock with following resuscitation is accompanied with release of systemic and local pro-inflammatory mediators, increased infiltration of hepatic neutrophils in the liver, increased oxidative and nitrosative stress, enhanced cell death of both types, apoptosis and necrosis, conspicuous cytoskeletal rearrangements, loss of hepatic integrity and finally high general mortality rates, up to 80%. In addition, the effects of two potential therapeutic interventions to prevent the H/R induced liver injury are explored in a model of H/R in rats. First, the role of JNK and its inhibition by D-JNKI-1 in preservation of hepatic integrity following H/R was analyzed. Second, we investigated the potential of simvastatin to prevent the disturbed inflammatory response and hepatic injury after H/R. The effects of both therapeutic interventions were studied by looking at several inflammatory parameters, markers of oxidative and nitrosative stress, cytoskeleton integrity, microcirculatory parameters, underlying signaling cascades, liver damage and mortality. Highly specific blockade of JNK with the potent, inhibitory peptide D-JNKI-1 revealed the crucial role of the JNK signaling pathway in the H/R induced pathophysiology and strong protective effects of DJNKI- 1 in H/R induced liver injury, when the peptide was applied before and even after hemorrhagic shock. The other therapeutic intervention tested in this study was the use of simvastatin which also revealed protective effects after H/R and even a remarkable improvement in survival after H/R. We show that H/R induced release of pro-inflammatory cytokines, hepatic PMNL infiltration, increased oxidative and nitrosative stress, apoptosis and necrosis can be diminished by treatment with D-JNKI-1 but also with simvastatin in vivo. Furthermore, simvastatin reduces H/R induced cytoskelatal rearrangements, loss of liver integrity and the mortality rate after H/R. The key pathway which underlies these beneficial effects of simvastatin is the Rho kinase pathway. Identification of both mechanisms as well as the effectiveness of both substances provide new insights in the close interaction between hypoxia and the immune system and present a promising basis for the anti-inflammatory, hepatoprotective treatment after H/R.
One of the earliest and most striking observations made about HIV is the extensive genetic variation that the virus has within individual hosts, particularly in the hypervariable regions of the env gene which is divided into 5 variable regions (V1-V5) and 5 more constant (C1-C5) regions. HIV evolves at any time over the course of an individual’s infection and infected individuals harbours a population of genetically related but non-identical viruses that are under constant change and ready to adapt to changes in their environment. These genetically heterogeneous populations of closely related genomes are called quasispecies [65]. Tuberculosis or tubercle forming disease is an acute and/or chronic bacterial infection that primarily attacks the lungs, but which may also affect the kidneys, bones, lymph nodes, and brain. The disease is caused by Mycobacterium tuberculosis (MTB), a slow growing rod-shaped, acid fast bacterium. It is transmitted from person to person through inhalation of bacteria-carrying air droplets. Worldwide, one person out of three is infected with Mycobacterium tuberculosis – two billion people in total. TB currently holds the seventh place in the global ranking of causes of death [73]. In 2008, there were an estimated 9.4 (range, 8.9–9.9 million) million incident cases (equivalent to 139 cases per 100 000 population) of TB globally [75]. A complex biological interplay occurs between M. tuberculosis and HIV in coinfected host that results in the worsening of both pathologies. HIV promotes progression of M. tuberculosis either by endogenous reactivation or exogenous reinfection [77, 78] and, the course of HIV-1 infection is accelerated subsequent to the development of TB [80]. Active TB is associated with an increase in intra-patient HIV-1 diversity both systemically and at the infected lung sites [64,122]. The sustainability or reversal of the HIV-1 quasispecies heterogeneity after TB treatment is not known. Tetanus toxoid vaccinated HIV-1 infected patients developed a transient increase in HIV-1 heterogeneity which was reversed after few weeks [121]. Emergence of a heterogeneous HIV-1 population within a patient may be one of the mechanisms to escape strong immune or drug pressure [65,128]. The existence of better fitting and/or immune escape HIV-variants can lead to an increase in HIV-1 replication [129,130]. It might be that TB favourably selected HIV-1 variants which are sources for consistent HIV-1 replication. Understanding the mechanisms underlying the impacts of TB on HIV-1 is essential for the development of effective measures to reduce TB related morbidity and mortality in HIV-1 infected individuals. In the present study we studied whether the increase in HIV-1 quasispecies diversity during active TB is reversed or preserved throughout the course of antituberculous chemotherapy. For this purpose Two time point HIV-1 quasispecies were evaluated by comparing HIV-1 infected patients with active tuberculosis (HIV-1/TB) and HIV-1 infected patients without tuberculosis (HIV-1/non TB). Plasma samples were obtained from the Frankfurt HIV cohort and HIV-1 RNA was isolated. C2V5 env was amplified by PCR and molecular cloning was performed. Eight to twenty five clones were sequenced from each patient. Various phylogenetic analyses were performed including tree inferences, intra-patient viral diversity and divergence, selective pressure, co-receptor usage prediction and two time point identity of quasispecies comparison using Mantel’s test. We found out from this study that: 1) Active TB sustains HIV-1 quasispecies diversity for longer period 2. Active TB increases the rate of HIV-1 divergence 3) TB might slow down evolution of X4 variants And we concluded that active TB has an impact on HIV-1 viral diversity and divergence over time. The influence of active TB on longitudinal evolution of HIV- 1 may be predominant for R5 viruses. The use of CCR5-coreceptor inhibitors for HIV-1/TB patients as therapeutic approach needs further investigation.
Background: New drugs are constantly sought after to improve the survival of patients with malignant gliomas. The ideal substance would selectively target tumor cells without eliciting toxic side effects. Here, we report on the anti-proliferative, anti-migratory, and anti-invasive properties of the natural, nontoxic compound Curcumin observed in five human glioblastoma (GBM) cell lines in vitro. Methods: We used monolayer wound healing assays, modified Boyden chamber trans-well assays, and cell growth assays to quantify cell migration, invasion, and proliferation in the absence or presence of Curcumin at various concentrations. Levels of the transcription factor phospho-STAT3, a potential target of Curcumin, were determined by sandwich-ELISA. Subsequent effects on transcription of genes regulating the cell cycle were analyzed by quantitative real-time PCR. Effects on apoptosis were determined by caspase assays. Results: Curcumin potently inhibited GBM cell proliferation as well as migration and invasion in all cell lines contingent on dose. Simultaneously, levels of the biologically active phospho-STAT3 were decreased and correlated with reduced transcription of the cell cycle regulating gene c-Myc and proliferation marking Ki-67, pointing to a potential mechanism by which Curcumin slows tumor growth. Conclusions: Curcumin is part of the diet of millions of people every day and is without known toxic side effects. Our data show that Curcumin bears anti-proliferative, anti-migratory, and anti-invasive properties against GBM cells in vitro. These results warrant further in vivo analyses and indicate a potential role of Curcumin in the treatment of malignant gliomas.
This dissertation introduces in chapter 1 a new comparative approach to model-based research and policy analysis by constructing an archive of business cycle models. It includes many well-known models used in academia and at policy institutions. A computational platform is created that allows straightforward comparisons of models’ implications for monetary and fiscal stabilization policies. Chapter 2 applies business cycle models to forecasting. Several New Keynesian models are estimated on historical U.S. data vintages and forecasts are computed for the five most recent recessions. The extent of forecast heterogeneity for models and professional forecasts is analysed. Chapter 3 extends the forecasting analysis to a long sample and to the evaluation of density forecasts. Weighted forecasts are computed using a variety of weighting schemes. The accuracy of forecasts is evaluated and compared to professional forecasts and forecasts from nonstructural time series methods. Chapter 4 adds a new feature to existing business cycle models. Specifically, a medium-scale New Keynesian model is constructed that allows for strategic complementarities in price-setting. The role of trade integration for monetary policy transmission is explored. A new dimension of the exchange rate channel is highlighted by which monetary policy directly impacts domestic inflation. Chapter 5 tests whether simple symmetric monetary policy rules used in most business cycle models are a sufficient description of reality. I use quantile regressions to estimate policy parameters and find asymmetric reactions to inflation, the output gap and past interest rates.
In the following Magisterarbeit I am going to develop a Concept Empiricist model of conceptual thought, which is in its technical core primarily inspired and motivated by Larry Barsalou‘ s Perceptual Symbol Systems Theory (PSST) (1999, 2008a). But it is not a theory of concepts in the genuine sense only, but it also expands naturally on related topics like the ontology of mind and the problem of intentionality. This is not arbitrarily chosen, but a natural consequence of any contemporary Concept Empiricist theory, for those theories are in kind direct outgrowths of an embodied approach to cognition which yields these consequences – the natural extension to related topics – as will be shown. The roadmap for the Magisterarbeit is going to look like this: First I will delineate the embodied cognition framework. Within embodied cognition there is a plethora of differing attempts at explaining the diverse phenomena of higher and lower cognition which differ in the meanwhile tremendously from each other. Therefore it will be very useful to set clear boundaries between the differing approaches, which range from strong neural embodiment on the one side to a very promiscuous extended mind hypothesis on the other side, in order to make a clear case for Concept Empiricism. It will be also very helpful to set my favoured version of grounded cognition off against classical attempts at the phenomena which are to be explained. Following that I am going to present Larry Barsalou‘s Perceptual Symbol Systems Theory in more detail. I will do that to an extent which allows for an appropriate discussion of concept related phenomena, but which is not too lengthy. I will spare the reader with unnecessary psychological or neurobiological details as long as it is not really necessary for explaining or clarifying the phenomena with which I deal here. Having done this I will discuss at great length conceptual meaning. In doing so I will present a presentational theory of meaning which is anti-realist, internalist and imaginistic. In advertising for this theory I will recur to conceptual methods, intuition as well as to the empirical record. Next and related to this I will develop a resemblance based theory of intentionality which differs also widely from the already established theories of intentionality so far given. Indeed it possess a feature which makes it very distinct and this is, besides its reliance on pattern mapping, the statistical grounding of resemblance which allows a cognitive theory of resemblance which is definite and therefore not open to the counterarguments generally mashalled against related theories, which stress the importance of resemblance. A very distinctive feature of this theory of intentionality is additionally that intentionality is seen as a capacity which emerges naturally form the mental mechanism involved. As we will see, this is a distinctive advantage of it in comparison to other proposal in the field. A discussion of the ontology of mental states follows which is however primarily a discussion of mechanistic explanations and Bechtel‘s and McCauley‘s Heuristic Identity Theory (HIT). Those theories from philosophy of science and philosophy of cognitive science do not only deliver models for the ontology of mental states, but also epistemic criteria for evaluating a theory as superior or inferior. Especially the idea of productive continuity plays a role of pivotal importance in my Magisterarbeit. It might be a bit unfortunate that that an important consideration is discussed nearly at the end of the Magisterarbeit, since I refer to it very often, however, I considered it as equally unfortunate to delay the discussion of meaning and intentionality, which is already protruded by the overview chapter and the more technical parts, even more. Therefore I plead the reader to refer to later parts of the Magisterarbeit when it is necessary in order to understand earlier parts. In the course of writing I have gotten second thoughts regarding the adequacy of an ontology of mental states altogether, especially from the background of the theory of meaning and intentionality delivered here. Therefore I tried to accommodate for ontological concepts by means of a tentative phenomenological interpretation of them. Similar ideas influenced my deliberations regarding meaning too. I hope that this transition towards Phenomenology runs smoothly and that the high level of coherence which is my primary concern and something which I always strive for first is preserved. Further, I have dedicated a main chapter of the Magisterarbeit for possible and actual critics of the ideas brought forth by me. Besides the more classic standard objections there you can find a recent critique of the authors on which I refer most often. Naturally I try to refute any single criticism brought forth and I hope that the reader will approve my objection to the objections. I will round off the Magisterarbeit with some concluding remarks and prospects for future research.
Background: The faunal and floral relationship of northward-drifting India with its neighboring continents is of general biogeographic interest as an important driver of regional biodiversity. However, direct biogeographic connectivity of India and Southeast Asia during the Cenozoic remains largely unexplored. We investigate timing, direction and mechanisms of faunal exchange between India and Southeast Asia, based on a molecular phylogeny, molecular clock-derived time estimates and biogeographic reconstructions of the Asian freshwater crab family Gecarcinucidae. Results: Although the Gecarcinucidae are not an element of an ancient Gondwana fauna, their subfamily Gecarcinucinae, and probably also the Liotelphusinae, evolved on the Indian Subcontinent and subsequently dispersed to Southeast Asia. Estimated by a model testing approach, this dispersal event took place during the Middle Eocene, and thus before the final collision of India and the Tibet-part of Eurasia. Conclusions: We postulate that the India and Southeast Asia were close enough for exchange of freshwater organisms during the Middle Eocene, before the final Indian--Eurasian collision. Our data support geological models that assume the Indian plate having tracked along Southeast Asia during its move northwards.
Background: Complex care management is seen as an approach to face the challenges of an ageing society with increasing numbers of patients with complex care needs. The Medical Research Council in the United Kingdom has proposed a framework for the development and evaluation of complex interventions that will be used to develop and evaluate a primary care-based complex care management program for chronically ill patients at high risk for future hospitalization in Germany. Methods and design: We present a multi-method procedure to develop a complex care management program to implement interventions aimed at reducing potentially avoidable hospitalizations for primary care patients with type 2 diabetes mellitus, chronic obstructive pulmonary disease, or chronic heart failure and a high likelihood of hospitalization. The procedure will start with reflection about underlying precipitating factors of hospitalizations and how they may be targeted by the planned intervention (pre-clinical phase). An intervention model will then be developed (phase I) based on theory, literature, and exploratory studies (phase II). Exploratory studies are planned that entail the recruitment of 200 patients from 10 general practices. Eligible patients will be identified using two ways of 'case finding': software based predictive modelling and physicians' proposal of patients based on clinical experience. The resulting subpopulations will be compared regarding healthcare utilization, care needs and resources using insurance claims data, a patient survey, and chart review. Qualitative studies with healthcare professionals and patients will be undertaken to identify potential barriers and enablers for optimal performance of the complex care management program. Discussion: This multi-method procedure will support the development of a primary care-based care management program enabling the implementation of interventions that will potentially reduce avoidable hospitalizations.
The central difference between objectivist cognitivist semantics and embodied cognition consists in the fact that the latter is, in contrast to the former, mindful of binding meaning to context-sensitive mental systems. According to Lakoff/Johnson's experientialism, conceptual structures arise from preconceptual kinesthetic image-schematic and basic-level structures. Gallese and Lakoff introduced the notion of exploiting sensorimotor structures for higherlevel cognition. Three different types of X-schemas realise three types of environmentally embedded simulation: Areas that control movements in peri-personal space; canonical neurons of the ventral premotor cortex that fire when a graspable object is represented; the firing of mirror neurons while perceiving certain movements of conspecifics. ...
In the present work, the problem of protein folding is addressed from the point of view of equilibrium thermodynamics. The conformation of a globular protein in solution at common temperatures is quite complicated without any geometrical symmetry, but it is an ordered state in the sense of its biological activity. This complicated conformation of a single protein molecule is destroyed upon increasing the temperature or by the addition of appropriate chemical agents, as is revealed by the loss of its activity and change of the physical properties, and so on. Once the complicated native structures having biological activity are lost, it would be natural to suppose that the native structure could hardly be restored. Nevertheless, pioneers, such as Anson and Mirsky, recognized as early as in 1925 that this was not always the case. If one defines the folded and unfolded states of a protein as two distinct phases of a system, then under the variation of temperature the system is transformed from one phase state into another and vice versa. The process of protein folding is accompanied by the release or absorption of a certain amount of energy, corresponding to the first-oder-type phase transitions in the bulk. Knowing the partition function of the system one can evaluate its energy and heat capacity under different temperatures. This task was performed in this work. The results of the developed statistical mechanics model were compared with the results of molecular dynamic simulations of alanine poylpeptides. In particular, the dependencies on temperature of the total energy of the system and heat capacity were compared for alanine polypeptides consisting of 21, 30, 40, 50 and 100 amino acids. The good correspondence of the results of the theoretical model with the results of molecular dynamics simulations allowed to validate the assumptions made about the system and to establish the accuracy range of the theory. In order to perform the comparison of the results of theoretical model and the molecular dynamics simulations it is necessary to perform the efficient analysis of the results of molecular dynamics simulations. This task was also addressed in the present work. In particular, different ways to obtain dependence of the heat capacity on temperature from molecular dynamics simulations are discussed and the most efficient one is proposed. The present thesis reports the result of molecular dynamic simulations for not only alanine polypeptides by also for valine and leucine polypeptides. In valine and leucine polypeptides, it is also possible to observe the helix↔random coil transitions with the increase of temperature. The current thesis presents a work that starts with the investigation of the fundamental degrees of freedom in polypeptides that are responsible for the conformational transitions. Then this knowledge is applied for the statistical mechanics description of helix↔coil transitions in polypeptides. Finally, the theoretical formalism is generalized for the case of proteins in water environment and the comparison of the results of the statistical mechanics model with the experimental measurements of the heat capacity on temperature dependencies for two globular proteins is performed. The presented formalism is based on fundamental physical properties of the system and provides the possibility to describe the folding↔unfolding transitions quantitatively. The combination of these two facts is the major novelty of the presented approach in comparison to the existing ones. The “transparent” physical nature of the formalism provides a possibility to further apply it to a large variety of systems and processes. For instance, it can be used for investigation of the influence of the mutations in the proteins on their stability. This task is of primary importance for design of novel proteins and drug delivering molecules in medicine. It can provide further insights into the problem of protein aggregation and formation of amyloids. The problem of protein aggregation is closely associated with various illnesses such as Alzheimer and mad cow disease. With certain modifications, the presented theoretical method can be applied to the description of the protein crystallization process, which is important for the determination of the structure of proteins with X-Rays. There many other possible applications of the ideas described in the thesis. For instance, the similar formalism can be developed for the description of melting and unzipping of DNA, growth of nanotubes, formation of fullerenes, etc.