The purpose of this thesis was to design and implement a hierarchical approach to visualization of the chemical space. Such visualization is a challenging yet important topic used in diverse fields ranging from material engineering to drug design. Especially in drug design, modern methods of high- throughput screening generate large amounts of data that would benefit from hierarchical analysis. One possible approach to hierarchical classification of molecules is a structure based classification based on molecular scaffolds. The scaffolds are widely used by medicinal chemists to group molecules of similar properties. A few scaffold-based hierarchical visualization methods have been proposed. However, to our best knowledge, there exists no tool that would provide a scaffold-based hierarchical visualization of molecular data sets on the background of known chemical space. In this thesis, such tool was created. First, a scaffold tree hierarchy based on ring topologies was designed. Next, this hierarchy was used to analyze frequency of scaffolds extracted from molecules in PubChem Compound database. Subsequently, the PubChem Compound scaffold frequency data was used as a background for visualization of molecular data sets. The visualization is performed by a client-server application implemented as a part of...

Title: Theory of aggregates of photosynthetic molecules: spectroscopy, structure, transport phenomena Author: Ján Lalinský Institute: Institute of Physics of Charles University Supervisor of the master thesis: RNDr. Tomáš Mančal, PhD., Institute of Physics of Charles University Abstract. A theory of absorption of light in an isotropic solution of molecules was formulated on the basis of electromagnetic theory of par- ticles with attention to relativistic nature of their interaction and its im- pact on the spectrum of circular dichroism. Calculations of the absorption spectra of simple systems were performed to demonstrate the properties of the mathematical model. Also calculations of the absorption spectra of the models of the bacteriochlorophyll dimer which were proposed as possible basic unit in the lamellar model of the interior of a chlorosome were performed. The experimental spectra of solution of non-aggregated bacteriochlorophyll were used to fit the parameters of the mathematical model of the molecule and for these parameters the spectra of the pro- posed models of a dimer were calculated. It has been found that the new non-electrostatic terms in the description of the mutual interaction of the parts of the molecule are negligible for calculations of ordinary absorption spectrum, but they have...

This thesis considers atom`s attributes, which affects shape of molecules. It describes rules that are basic for molecule creation. This text features basic attributes and rules, which affects the final shape of molecule. Next part of this text explains several ways to display molecule. Following parts of this thesis describes several ways how to store and represent atom and molecules in computer technology along with solution of these problems that are used for this thesis.

The work summarizes basic theory of relaxation, energy transfer and decoher- ence in photosynthetic molecular aggregates described as open quantum systems and basic theory of third order coherent non-linear spectroscopy. The work presents two methods for calculation of photo-induced dynamics of molecular aggregates. The methods relax certain approximations of the theories commonly used to model the relaxation and energy transfer in the molecular systems on the sub-picosecond time scale. The first theory derived in the formalism of para- metric projection operators accounts for correlations in a second-order non-linear response-function that are usually neglected in the formalism of master equations. The second theory represents stochastic model of exact dynamics via the cumulant expansion. The work also presents an analysis of importance of the secular and the Markov approximations in the description of dynamics derived in the second-order perturbation theory in the system-bath coupling with emphasis on the excitonic coherence lifetime.

Supported lipid bilayers have been used as an artificial model of biological membranes and their interaction with 5 selected antimicrobial peptides was studied by several experimental techniques, mainly ellipsometry, laser scanning microscopy and fluorescence correlation spectroscopy. The thesis explains basic principles of the applied techniques focusing on their aspects relevant to characterization of lipid bilayers. The biological significance of antimicrobial peptides, their modes of interaction with membranes and the basic characteristics of the selected peptides are briefly discussed. The following text describes the main types of experimental studies performed and the interpretation of their results. Peptide-induced changes in lipid bilayer morphology were characterized by ellipsometry and laser scanning microscopy. Most interesting effects were observed in the case of melittin, which induced formation of long lipid tubules protruding from the bilayer. Lipid lateral diffusion measured by fluorescence correlation spectroscopy can provide information on bilayer organization on length-scales below resolution of optical microscopy.

Aplikace pro vizualizaci a modelování molekul nejsou dosud příliš poznamenány současným hardware vyvinutým pro potřeby počítačových her. Cílem projektu je navrhnout intuitivní rozhraní s novými widgety specializovanými na atomové struktury a vizualizací využívající moderní hardware grafických karet. Důležitou částí je také dosažení vysoké přesnosti modelování, obvykle dostupné pouze u profesionálních CAD programů.

<p>UVOD: Gojaznost je hronično, multifaktorijalno i kompleksno oboljenje povezano sa povećanim rizikom od aterosklerotskih kardiovaskularnih bolesti (KVB). Disfunkcija vaskularnog endotela predstavlja rani događaj u patofiziolo&scaron;kom kontinuumu aterosklerotskog procesa, a produženo izlaganje vaskularnog endotela faktorima rizika za aterosklerozu udruženim sa gojaznosti (insulinska rezistencija, dislipidemija, proinflamatorno/protrombozno stanje), može doprineti procesima aktivacije/disfunkcije endotela i progresiji ateroskleroze u supkliničku, odnosno kliničku formu bolesti. CILJ: Uporediti koncentracije solubilne forme adhezionih molekula &ndash; intracelularnog adhezivnog molekula &ndash;1 (sICAM&ndash;1) i E selektina (sE&ndash;selektin), između ispitanika sa hiperalimentacionim tipom gojaznosti i normalno uhranjenih zdravih ispitanika, kao i utvrditi eventualno postojanje razlika u koncentraciji sICAM&ndash;1 i sE&ndash;selektina između ispitanika kod kojih je merenjem debljine kompleksa intima medija karotidne arterije (IMK) uočen supklinički stadijum ateroskleroze i ispitanika koji imaju normalnu debljinu IMK. Ispitati povezanost parametara telesne kompozicije (ukupne masne mase tela i masne mase abdominalnih depoa), cirkuli&scaron;ućih koncentracija biomarkera disfunkcije vaskularnog endotela (sICAM&ndash;1 i sE&ndash;selektina) i IMK kod ispitanika sa hiperalimentacionim tipom gojaznosti. MATERIJAL I METODE: U istraživanje je uključeno 60 ispitanika sa hiperalimentacionim tipom gojaznosti bez pridruženih komorbiditeta i 30 zdravih normalno uhranjenih učesnika usklađenih sa ispitanicima po godinama života i polu koji su činili kontrolnu grupu. Svim ispitanicima su urađena antropometrijska merenja, analiza komponenata telesne kompozicije (bioelektrična impedansna analiza, Tanita Body Composition Analyzer BC &ndash; 418 MA III), laboratorijska analiza uzoraka krvi na automatizovanim analizatorskim sistemima sa određivanjem parametara metabolizma glukoze (bazalno i 2 h u toku oralnog glukoza tolerans testa), lipida i lipoproteina, inflamacije i homocisteina. Određivanje serumske koncentracije sICAM&ndash;1 i sE&ndash;selektina je vr&scaron;eno ELISA tehnikom (R&amp;D Systems, Inc. Minneapolis, USA). Vrednosti IMK&ndash;a su određivane pomoću karotidnog dupleks ultrazvuka (Aloka SSD&ndash;650 US system, Tokyo), a na osnovu izmerenih (IMK) i normalno očekivanih vrednosti IMK za svakog ispitanika je izračunavan IMK Z&ndash;skor. Supklinički stadijum ateroskleroze je definisan kao vrednost IMK Z&ndash;skora veća od 1 (&scaron;to odgovara vrednosti IMK većoj od 95 percentila normalno očekivane vrednosti u odnosu na pol i godine života ispitanika). REZULTATI: Ispitanici sa hiperalimentacionim tipom gojaznosti su imali statistički značajno vi&scaron;e vrednosti medijane serumske koncentracije sE&ndash;selektina u poređenju sa medijanom serumske koncetracije sE&ndash;selektina učesnika u kontrolnoj grupi (36,2 (33,21&ndash;43.7) vs. 25,14 (23,1&ndash;29,48) ng/mL, P=0,00). Gojazni ispitanici III stepena gojaznosti su imali statistički značajno vi&scaron;u medijanu serumske koncenracije sE&ndash;selektina u odnosu na medijanu sE&ndash;selektina u ispitanika I stepena gojaznosti (41,5 (36,58&ndash;49,48) vs. 34,34 (22,49&ndash;36,62) ng/mL, P=0,00), odnosno medijanu sE&ndash;selektina u ispitanika II stepena gojaznosti (41,5 (36,58&ndash;49,48) vs. 32,1 (26,1&ndash;43,64) ng/mL, P=0,00). Nije uočena statistički značajna razlika u medijani serumske koncentracije sE&ndash;selektina između ispitanika I i II stepena gojaznosti (34,34 (22,49&ndash;36,62) vs. 32,1 (26,1&ndash;43,64) ng/mL, P=0,12). Gojazni ispitanici su imali statistički značajno vi&scaron;e vrednosti medijane serumske koncentracije sICAM&ndash;1 u poređenju sa medijanom serumske koncetracije sICAM&ndash;1 učesnika u kontrolnoj grupi (266,8 (245,8&ndash;326,73) vs.183,32 (167,9&ndash;208,57), P=0,00). U ispitivanoj grupi gojaznih uočena je statistički značajna razlika u medijani koncentracije sICAM&ndash;1 između ispitanika u I, II i III stepena gojaznosti (200,6 (190,26 - 264,4) vs. 278,5 (219,54 - 343,24) vs. 329,6 (259,2 - 350,34) ng/mL, P=0,00). Učestalost IMK Z&ndash;skor &gt; 1 je bila statistički značajno eća u gojaznih ispitanika u odnosu na kontrolnu grupu (36/60 vs. 7/30, P=0,00). Ispitanici sa IMK Z&ndash;skor &gt; 1 su imali statistički značajno vi&scaron;u medijanu koncentracije sICAM&ndash;1 u odnosu na ispitanike kod kojih je IMK Z&ndash;skor &le; 1 (295,4 (238,46&ndash;340,38) vs. 244,2 (227,35&ndash;260,38), P=0.00). Regresionom analizom (R2=0,71, korigovani R2=0,59) je utvrđeno da su parametri hsCRP (&beta;=0,45, P=0,00), HOMA&ndash;IR (&beta;=0,44, P=0,035) i ISI (&beta;=&ndash;0,36, P=0,028) nezavisno i statistički značajno povezani sa serumskom koncentracijom sE&ndash;selektina. Regresionom analizom (R2=0,65, korigovani R2=0,56) je utvrđeno da parametri ITM (&beta;=0,55, P=0,00), trigliceridi (&beta;=0,30, P=0,00), HDL holesterol (&beta;=&ndash;0,31, P=0,00), odnos TG/HDL&ndash;holesterol (&beta;=0,33, P=0,01), hsCRP (&beta;=0,31, P=0,00) i fibrinogen (&beta;=0,34, P=0,00) su nezavisno i statistički značajno povezani sa serumskom koncentracijom sICAM&ndash;1. U faktorskoj analizi je izdvojeno pet faktora &ldquo;gojaznost&rdquo;, &ldquo;insulinska rezistencija&rdquo;, &ldquo;aterogeni faktor&rdquo;, &ldquo;endotelna disfunkcija i vaskularna inflamacija&rdquo; i &ldquo;metabolički faktor&rdquo; koji obja&scaron;njavaju 69.72% ukupne varijanse ispitivanog uzorka. U multivarijabilnom modelu sa svim faktorima zajedno kojim je obja&scaron;njeno ukupno 75% varijanse, jedino je faktor gojaznost imao statički značajan i nezavistan uticaj na vrednost IMK Z&ndash;skor &gt; 1 (OR=2,74 (CI 1,18&ndash;6,33), P=0,019). U faktoru gojaznost su se izdvojili parametri: FAT trunk (%), FAT (%), OS (cm), ITM (kg/m2), LDL &ndash; holesterol (mmol/L), SP (mmHg), HOMA1&ndash;%B, fibrinogen (g/L), ApoB/apoA-I i hsCRP (mg/L). Univarijantom logističkom regresijom je uočeno da porast u koncentraciji LDL&ndash;H (OR=5,33 (CI 1,9&ndash;14,2), P=0,02) i koncentraciji hsCRP&ndash;a (OR=2,53 (CI 1,3&ndash;3,98),P=0,017) povećava rizik za postojanje vrednosti IMK Z&ndash;skor &gt; 1. ZAKLJUČAK: Cirkuli&scaron;uće serumske koncentracije biomarkera disfunkcije vaskularnog endotela, sE&ndash;selektina i sICAM&ndash;1, su značajno vi&scaron;e kod ispitanika sa hiperalimentacionim tipom gojaznosti u odnosu na njihove koncentracije u normalno uhranjenih ispitanika. U gojaznih ispitanika, koncentracija sE&ndash;selektina je povezana sa vrednostima indeksa insulinske rezistencije i biomarkera inflamacije, dok je koncentracija sICAM&ndash;1 značajno povezana sa udelom masne mase u ukupnoj telesnoj masi, vrednostima biomarkera inflamacije i proaterogenih lipidskih parametara. Ispitanici kod kojih postoji uvećanje abdominalnih masnih depoa i ukupnog udela masnog tkiva u telesnoj masi, vrednosti SKP, koncentracije LDL &ndash; holesterola, vrednosti lipoproteinskog indeksa ApoAI/apoB, bazalne insulinemije i biomarkera inflamacije, imaju trostruko povećan rizik od supkliničkog stadijuma ateroskleroze. U gojaznih osoba prilikom procene rizika od aterosklerotskih KVB, potrebno je utvrditi fenotipske osobine vaskularnog endotela i eventualno postojanje supkliničkog stadijuma ateroskleroze, da bi se definisale adekvatne preventivne mere i sagledale potencijalne terapijske mogućnosti.</p> / <p>INTRODUCTION: Obesity is a chronic, multifactorial and complex disease associated with an increased risk of atherosclerotic cardiovascular diseases (CVD). Vascular endothelial dysfunction is an early event in the pathophysiological continuum of atherosclerotic process. The prolonged exposure of vascular endothelium to classical and obesity associated risk factors (insulin resistance, dyslipidemia, proinflammatory state) could further promote deterioration of endothelial function and progression of atherosclerosis to subclinical or clinical form of disease. OBJECTIVE: The aim of the study was to compare the concentration of soluble forms of adhesion molecules, intracellular adhesion molecule-1 (sICAM-1) and E-selectin (sE-selectin), between obese subjects and normal weight healthy subjects, as well as to determine the possible existence of differences in concentration of sICAM-1 and sE-selectin among subjects with subclinical stage of atherosclerosis (assessed by measuring the thickness of the intima media complex of the carotid artery (IMT)), and subjects who have a normal value of IMT. Also, the aim was to determine the association between the parameters of body composition (total body fat mass and fat mass intra-abdominal depots), circulating concentrations of sICAM-1 and sE-selectin, and value of IMT in obese subjects. MATERIALS AND METHODS: The study included 60 obese nondiabetic subjects, without preexisting CVD and other associated comorbidity, and 30 healthy normal weight age and sex matched participants. All subjects underwent anthropometric measurements, analysis of the components of body composition (bioelectrical impedance analysis, Tanita Body Composition Analyzer BC - 418 MA III), laboratory analysis of blood samples (automated analyzer systems) with determining the parameters of glucose metabolism (basal and 2 h during the oral glucose tolerance test), lipids and lipoproteins, inflammation and homocysteine. Serum concentrations of sICAM-1 and sE-selectin were determined by ELISA (R &amp; D Systems, Inc., Minneapolis, USA). The values of IMK were determined by carotid duplex ultrasound (Aloka &ndash; ProSound ALPHA 10). IMK Z-score was calculated using the measured and the normal expected values of IMT for each patient. Subclinical stage of atherosclerosis was defined as the value of IMT Z-score greater than 1 (corresponding to the 95th sex-age-specific percentile of IMT measurements). RESULTS: Obese subjects had significantly higher median sE-selectin serum concentrations compared to median serum concentrations of sE-selectin in the normal weight subjects (36.2 (33.21-43.7) vs 25.14 (23.1-29.48) ng/mL, P=0.00). Morbid obesity subjects had significantly higher sE-selectin median serum concentration compared to the median sE-selectin concentration in moderate obese subjects (41.5 (36.58-49.48) vs 34.34 (22.49-36.62) ng/mL, P=0.00), and compared to the median sE-selectin concentration in severely obese subjects (41.5 (36.58-49.48) vs. 32.1 (26.1-4364) ng / mL, P=0.00). Obese subjects had significantly higher median sICAM-1 serum concentration compared to median sICAM-1 serum concentration in the control group (266.8 (245.8-326.73) vs. 183.32 (167.9-208.57), P=0.00). In the obese group, we observed a statistically significant difference in median sICAM-1 serum concentrations between moderate, severely and morbid obese subjects (200.6 (190.26-264.4) vs. 278.5 (219.54-343.24) vs. 329.6 (259.2-350.34) ng/mL, P=0.00). The frequency of IMT Z-score&gt; 1 was significantly higher in the obese group compared to control group (36/60 vs. 7/30, P=0.00). Subjects with IMT Z-score&gt; 1 had significantly higher median concentrations of sICAM-1 compared to those in which the IMK Z-score &le; 1 (295.4 (238.46-340.38) vs. 244.2 ( 227.35-260.38), P=0.00). In regression analysis (R2=0.71, adjusted R2=0.59), hsCRP (&beta;=0.45, P=0.00), HOMA-IR (&beta;=0.44, P=0.035) and ISI (&beta;=-0.36, P=0.028) were independently and significantly associated with serum sE-selectin concentration. In regression analysis (R2=0.65, adjusted R2=0.56), BMI (&beta;=0.55, P=0.00), triglycerides (&beta;=0.30, P=0.00), HDL cholesterol (&beta;=-0.31, P=0.00), the ratio of TG/HDL-cholesterol ratio (&beta;=0.33, P=0.01), hsCRP (&beta;=0.31, P=0.00 ) and fibrinogen (&beta;=0.34, P=0.00) were independently and significantly associated with serum sICAM-1 concentration. In the Factor analysis, five factors &quot;obesity&quot;, &quot;insulin resistance&quot;, &quot;atherogenic factor,&quot; &quot;endothelial dysfunction and vascular inflammation&quot; and &quot;metabolic factor&quot; explained 69.72% of the total variance of the test sample. In a multivariate model with all the factors together (75% of the total variance), &quot;obesity&quot; factor was significantly and independently associated with IMT Z-score&gt; 1 (OR=2.74 (CI 1.18-6.33), P=0.019). The &quot;obesity&quot; factor consisted of parameters: trunk fat (%), fat (%), waist (cm), BMI (kg/m2), LDL &ndash; cholesterol (mmol/L), systolic blood presure (mmHg), HOMA1-% B, fibrinogen (g/L), Apo B/apoA-I and hsCRP (mg/L). Logistic regression analysis showed that independent predictors of IMT Z-score&gt; 1 were LDL-cholesterol (OR=5.33(CI 1.9-14.2), P=0.02) and hsCRP (OR=2.53 (CI 1.3-3.98), P=0.017). CONCLUSION: Circulating serum concentrations of endothelial dysfunction biomarkers, sE-selectin and sICAM-1, were significantly higher in obese subjects compared to concentration in the normal weight subjects. In obese subjects, the concentration of sE-selectin was associated with insulin resistance and biomarkers of inflammation, whereas sICAM-1 concentration was associated with fat mass, inflammation biomarkers and the proatherogenic lipid parametars. In individuals with increased abdominal fat depots and total proportion of fat mass in the body weight, values of SBP, LDL-C, ApoB/apoA-I, basal insulin levels and biomarkers of inflammation, there is threefold increased risk of subclinical stages of atherosclerosis. In order to define an adequate preventive measures and possible therapeutic options for atherosclerotic CVD in obese subjects, it is necessary to assess the phenotypic characteristics of vascular endothelium and possible presence of subclinical stage of atherosclerosis.</p>

Biochemistry is usually the last taught discipline of chemistry. In the Czech Republic, grammar school students study biochemistry during the third or fourth grade. This can sometimes cause problems because there is often little time left for biochemistry when compared to other chemical disciplines. The content of the biochemical curriculum is often limited only to memorization of the most important facts and there is no time enough to point out the important relationships of biochemistry to everyday life. In the last year of study, many students have already decided whether or not to study chemistry in the future and it is then difficult to find some topics that would attract the attention of those who do not want to continue studying chemistry. This thesis is focused on the solving this situation. The first part gives an overview on the theoretical background, which forms the framework for the following parts - Analysis of selected textbooks, which was done to map the current state of teaching biochemistry in Czech schools, and Creation of new didactic materials that can complement current textbooks and help teachers explain the basics of biochemistry more clearly and in the context of contemporary everyday life. The last part of this diploma thesis summarizes the experiences with use of the...

This thesis concerns my theoretical calculations and simulations in comparison with experimental measurements acquired by means of surface science techniques on bare surfaces and molecules adsorbed on surfaces. In the beginning of the thesis I briefly describe the density functional theory (DFT) method, which is used for calculations of geometric and electronic structure of surfaces and absorbed molecules. It is followed by a quick overview of the scanning probe microscopy (SPM) and X-ray spectroscopy techniques that provided experimental context for my calculations. In the later part of my thesis I introduce publications on which I participated. In these works, direct results of my DFT calculations or simulations based on DFT outputs helped to reveal geometric and electronic structure of acetophenone adsorbed on Si(111) surface, on-surface oligomerized organic molecules and boron atoms used for substitational doping of graphene. The simulations also enable us to probe a laser initiated CO hydrogenation in real time. A big part of my work was the development of some simulation methods for SPM imaging of molecules on surfaces with flexible tip apexes. These simulation methods helped to create a comprehensive overview of SPM techniques performed with flexible tip apexes. 1

Two gas-phase ion-molecule reaction systems are presented here based on measurements done in a temperature variable 22-pole trapping machine. In the first case, the proton affinity of methane is determined based on a new technique for measuring the equilibrium constant of the HCO2+ + CH4 <=> CH5+ + CO2 reaction. The second case reports to the (Ar + N2 )+ reaction system, with reaction rate temperature dependencies measurements made both in the forward and reverse direction with different and complementary methods. The temperature variable 22-pole trapping machine allows one to determine equilibrium constants and reaction rate coefficients over a wide range of temperatures. The coupling of an effusive beam to the setup overcomes the problem of neutral gas wall condensation and extends the temperature range measurements beyond condensation point. The introduction (Chapter 1) gives a short overview about the rf technology and parallel experimental techniques developed in order to better characterize and understand the several mechanisms related to ion-molecule reactions. It also focuses some aspects of reaction rate temperature dependencies determination as well as thermodynamical equilibrium in laboratory environment. A short description of the setup and experimental methods are presented in Chapter 2. Based on equilibrium constant measurements, Chapter 3 is dedicated to the proton affinity of methane. This concept has applications on several fields such as atmospheric and combustion modelling, or testing empirical and ab initio theories for electronic structures. The (Ar − N2 )+ system presented in Chapter 4, is known for being a good case study for inferring the role of vibrational excitation in reaction dynamics and to the existence of non-adiabatic coupling. The experimental results here presented for the N2+ + Ar reaction demonstrate that it is possible to avoid parallel reactions with first vibrational excited state of nitrogen (N2 (ν = 1)). On the other hand, the reverse reaction experiments confirm the existence of a minimum of the reaction rate in the 30 to 300 K range, due to the existence of two reaction channels. The question of the high rate coefficient towards lower temperatures being related to the N2 rotational ground state population is raised. A summary and outlook are presented in Chapter 5, where some new possible paths of investigation are pointed out.