The freshwater fish species Schistura robertsi and Paracanthocobitis zonalternans belong to the family Nemacheilidae, which is distributed across whole Eurasia and with one species in northeast Africa. P. zonalternans occurs in lowland habitats through western Southeast Asia from Central Myanmar until northern Malaysia. The distribution area is of biogeographic interest, because it crosses several known biogeographic barriers, namely the border between Indian and Indochinese freshwater fauna along the Salween River, the Isthmus of Kra, the Krabi - Surat Thani line and the Kangar - Pattani line. In the present study, around 250 specimens of P. zonalternans from 62 localities across the whole distribution area were investigated using genetic (nuclear and mitochondrial sequences), morphologic and geologic data. The genetic data reveal the existence of seven major clades within the analysed material, each of them with a distinct geographic distribution area and only few cases of overlap, but with occurrence of some cases of secondary contact. Divergence time estimations suggested that P. zonalternans is about 18 my old, and a biogeographic analysis located the region of origin in the Tenasserim region (nowadays southern Myanmar). The global sea level fluctuations seem to have had a strong impact on the...

Potato is one of the most important agricultural crops and there is an attempt to increase and improve yields of tubers, among other things, by elucidation of the mechanisms that regulate the process of tuber induction. Potato tuberization is a morphogenetic process in which the tubers are formed from the underground parts of the stem - stolons. The correct timing of this process is controlled by a complex regulatory network and influenced by many internal and external factors. Under favourable conditions, an inductive signal is generated in the leaves and it is transported to the stolon by a "phloem information superhighway" driven by carbohydrates flow. The signal triggers cell division, expansion, and changes in the cell growth orientation in the stolon. The development of tubers is influenced by number of biochemical and morphological processes driven by a regulatory network of genes that are expressed in different parts of plants. This work was focused on Solanum tuberosum, Lada cultivar and its derived D69 mutant line with lacking isoform of manganese-stabilizing protein (MSP), which is so far the only dissimilarity identified under all tested conditions. I aimed to map the processes related to the production of carbohydrates in leaves (photosynthetic characteristics - rate of photosynthesis...

The master's thesis deals with answer of distribution of countries, which was determined in 1965 in the theoretical concept by John Hajnal, in contemporary Europe. The main aim was to reanalyze the original division of countries using cluster analysis on the basis demographic indicators: average age at first marriage men and women, the average age of a woman at first child birth, the number of divorces per 100 marriages, the proportion of live births in marriage and out of marriage. The data used came from the Eurostat database from 1990 to 2015. Cluster analyzes of European countries were also performed according to the value orientations of their inhabitants in the area of social relations and life expectations. Respondents' statements came from the European Social Survey from 2002 to 2018. Cluster analysis of selected demographic indicators did not confirm two models of Hajnal's concept of marital behavior. Cluster analyzes of respondents' value orientations confirmed the existence of two value approaches to life priorities - a preference for traditionally accepted values and a preference for a dynamic and efficient lifestyle. Keywords Hajnal line, family, marriage, divorce rate, ESS research project, K-means cluster analysis, values

This thesis addresses designing Product Lines (PLs) of Graphical Editors (GEs). It provides a feasible top-down design approach specialized on such Graphical Editor Product Lines (GEPLs), which can be configured dynamically. Furthermore, the end product's features are implemented modular, which has numerous positive effects on the development and maintenance processes for the family. These effects reach from decreasing the complexity of big PLs, allowing to delegate split up development tasks onto multiple isolated working teams, easier debugging and flexibility to extend or specialize a family of products as well as being able to use functionalities developed by third-party vendors. While design methods avoiding monolithic architectures and implementations exist for many PL domains, there are none known for GEPLs. Yet, the domain of those offers many challenges as GEPLs are actually comprised of Software Product Lines (SPLs) and Language Product Lines (LPLs), which is a combination untackled by any modular design approach known to me. Additionally, products in the domain require to implement multiple distinct and specific concerns, leading to artifacts which differ significantly but have to be located and managed in a single component. Overall, this justifies the need for specialized design approaches for the GEPL domain. In regard to this need, this thesis gives an overview of the existing landscape of approaches to design PLs, analyzing solutions offered by other researchers. Furthermore, a requirement analysis for the GEPL domain is conducted. Its results are the foundation for the presentation of a top-down design approach for dynamically configurable GEPLs, which are implemented feature modularly. Finally, a case study documenting the development of such a family of GEs is providing a proof of its feasibility.:1 Introduction 1.1 Motivation 1.2 Problem Definition 1.3 Outline 1.4 Terminology 2 Survey on Software and Language Product Line Design 2.1 Classification Scheme 2.1.1 Domain 2.1.2 Configuration 2.1.3 Design Method 2.1.4 Modularity 2.2 Overview 2.3 Discussion 2.3.1 Evaluation 2.3.2 Results 3 Requirements of Graphical Editor Product Lines 32 3.1 Functional Requirements 3.1.1 Edit Concerns 3.1.2 Language Family Concerns 3.2 Non-Functional Requirements 3.2.1 User Requirements 3.2.2 Development Requirements 4 Design of Graphical Editor Product Lines 4.1 Characteristics 4.2 Design Approach 4.2.1 Edit Concerns 4.2.2 Language Family Concerns 4.3 Discussion 4.3.1 Techniques 4.3.2 Evaluation 5 Case study: Modularization of a Family of Graphical Editors 5.1 Background 5.1.1 Compartment Role Object Model 5.1.2 Full-fledged Role Modeling Editor 5.1.3 Reusable Technology 5.2 Realization 5.2.1 Edit Concerns 5.2.2 Language Family Concerns 5.3 Discussion 5.3.1 Requirements 5.3.2 Limitations of the Modularization 5.3.3 Results 6 Conclusion 6.1 Summary 6.1.1 Desired Properties 6.1.2 Feasibility 6.2 Contributions 6.3 Future Work 6.3.1 Bottom-Up Design Method 6.3.2 Requirements 6.3.3 Modularization

Die vorliegende Studie befasste sich mit zwei Fragestellungen. Im ersten Teil wurde die Projektionsabhängigkeit von radiologischen Landmarken im konventionellen Röntgenbild der Schulter und damit deren klinische Anwendbarkeit untersucht. Im zweiten Teil wurde das Auftreten von sog. röntgenhellen Linien (RLL) bei Glenoidersatz im konventionellen Röntgen und im CT untersucht. Beide Fragestelllungen sind in der Beurteilung von Landmarken von Glenoidkomponenten in der Endoprothetik der Schulter von Bedeutung. Zur Beantwortung der ersten Frage wurden 6 mit Markierungen versehene humane Scapula-Leichenpräparate in 25 Projektionen geröntgt und der Einfluss der Projektionen auf gängige Landmarken gemessen. Die Landmarken wurden an der Margo lateralis, Margo medialis, knöchernen Glenoid, Coracoidbasis, Fossa supraspinata und oberen Linie der Spina scapulae festgelegt. Zur Beantwortung der zweiten Frage wurden 10 humane Glenoid-Leichenpräparate mit einzementierter Glenoidkomponente im konventionellen Röntgen und im CT untersucht. Alle gewonnenen radiologischen Bilder wurden von zwei Untersuchern vermessen und die Interobserverreliabilität errechnet. Die Ergebnisse des ersten Teiles sowohl der Messwerte der Landmarken als auch der Interobserverreliabilität zeigten, dass die Margo medialis des Schulterblattes die zuverlässigsten Ergebnisse bei der Robustheit gegen Verkippung zur Beurteilung des Kunststoff Glenoids aufwiesen. Im klinischen Alltag ist diese Landmarke jedoch auf vielen Röntgenbildern der Schulter nicht mit abgebildet. Es zeigte sich, dass die am wenigsten projektionsabhängige Landmarke, die regelmässig auf Schulteraufnahmen abgebildet ist, die Margo lateralis scapulae ist. Als Ergebnis des zweiten Teiles zeigte sich, dass im konventionellen Röntgen sichtbare RLL im CT nicht alle zur Darstellung kamen und somit als Artefakte zu werten waren. Aufgrund der klinisch schwierig durchzuführenden Röntgentechnik kann nicht immer eine exakte AP Aufnahme im konventionellen Röntgen gewonnen werden, wodurch auch projektionsbedingt Doppellinien erscheinen können. Diese wurden vermutlich durch die konvexe Form des PE Glenoids und Zementfehlern verursacht. Zur Beurteilung einer Lockerung sollte also eine Computertomografie angefertigt werden. Weiterhin zeigte sich aber auch im CT, dass frisch implantierte Glenoidkomponenten trotz optimaler Bedingungen RLL aufweisen. Dies zeigte deutlich, dass die Zementiertechnik auch in ihrer modernen Form noch nicht voll ausgereift war und deshalb weiterhin nach Verbesserungsmöglichkeiten gesucht werden sollte. / The aim of this study was to evaluate the reliability of different bony landmarks on radiographs after implantation of a total shoulder arthroplasty when the scapula is tilted compared with the ideal ap view. To assess loosening of the glenoid component, serial evaluation of ap radiographs of the scapula has been established as the 'gold standard. This study also verified the incidence of radiolucent lines (RLL) in radiographs and on CTscans to show different measurements of localization and appearance of the RLL. For the first aim of this study glenoid components were implanted into 6 human cadaveric scapulae. Radiographs were taken exactly anterior-posterior in the frontal plane, as well as craniocaudal tilted (±15° and ±30°) and mediolateral tilted (±10° and ±20°). The following landmarks were evaluated: lateral margin of the scapula, medial margin of the scapula, floor of the fossa supraspinatus line, spine of the scapula line, glenoid fossa line, and coracoid base line. In the second part of this study, 10 glenoid components were implanted into human cadaveric glenoids and a CT-scan as well as radiographs were made in an exact anteriorposterior view. The images were compared to evaluate the localization, incidence and form of the RLL. Every X-ray was measured by two different examiners to show the interobserver reliability. Regarding robustness against glenoid tilt, the medial margin of the scapula had the best intraobserver and interobserver reliability, whereas the lateral margin of the scapula had an acceptable intraobserver and interobserver reliability. In measuring medial migration, the glenoid fossa line had a significantly lower intraobserver and interobserver reliability than the coracoid base line. Because conventional radiographs were hardly done in exact ap direction despite the laboratory within, RLL were seen on X-ray although no RLL actually existed. The CT-scans highlighted the existence of artefacts, which looked like RLL on conventional radiography. The curved form of the glenoid component can cause double lines, which look like RLL on X-rays. However, the conventional radiography can still be used to detect an increase of RLL in postoperativ control X-rays. To be absolutely sure whether RLL do exist a CT-scan has to be done. This study shows that, even under best conditions for an implantation of glenoid components RLL can be viewed due to false cementation technique. The results underline that the cement implantation can still be improved to minimize the incidence of RLL.

Konforme Feldtheorien (CFT) spielen eine Schlüsselrolle in der modernen theoretischen Physik. Mit CFT beschreibt man reale physikalische Systeme bei Kritikalität. Dank der AdS/CFT-Korrespondenz spielt sie auch bei der Untersuchung der Quantengravitation eine zentrale Rolle. Auf der Seite der CFT steht die N=4 supersymmetrische Yang-Mills (SYM) Theorie. Diese Arbeit dreht sich hauptsächlich um die supersymmetrische Wilson-Linie und ihre Interpretation als konformer Defekt in N=4 SYM. Insbesondere konzentrieren wir uns auf Anregungen, die auf dem Defekt lokalisiert sind, sogenannte Einfügungen, deren Korrelatoren durch eine eindimensionale CFT beschrieben werden. Das erste Hauptergebnis dieser Arbeit ist ein effizienter Algorithmus zur Berechnung von Mehrpunkt Korrelationsfunktionen von Skalareinfügungen auf der Wilson-Linie bis zur nächsten Ordnung bei schwacher Kopplung kodieren. Es werden verschiedene Berechnungen solcher Vier-, Fünf- und Sechspunkt-Korrelatoren gezeigt und ihre Eigenschaften diskutiert. Darüber hinaus wird am Beispiel der Vierpunkt-Funktion die Leistungsfähigkeit der Ward-Identitäten veranschaulicht, die für die Ableitung eines Ergebnisses nächster, vorletzter und führender Ordnung entscheidend sind. Dank dieser perturbativen Ergebnisse vermuten wir eine Mehrpunkt-Erweiterung der Ward-Identitäten, die von den Vier-Punkt-Funktionen erfüllt werden. Diese nichtperturbativen Beschränkungen erweisen sich als fundamentale Bestandteile des Bootstraps einer Fünfpunkt-Funktion bei starker Kopplung. Zum Abschluss dieser Arbeit definieren wir eine inhärent eindimensionale Mellin-Amplitude auf der nichtperturbativen Ebene mit geeigneten Subtraktionen und analytischen Fortsetzungen. Die Effizienz des 1d-Mellin-Formalismus zeigt sich auf der perturbativen Ebene. Man findet einen Ausdruck in geschlossener Form für die Mellin-Transformation von Kontaktwechselwirkungen führender Ordnung, den man verwendet, um CFT-Daten zu extrahieren. / Conformal field theory (CFT) plays a key role in modern theoretical physics. Through CFT we describe real physical systems at criticality and fixed points of the renormalization group flow. It is also central in the study of quantum gravity, thanks to the AdS/CFT correspondence. This thesis originates in the context of the N=4 supersymmetric Yang-Mills (SYM) theory, which represents the CFT side of this correspondence. This work mainly revolves around the supersymmetric Wilson line and its interpretation as a conformal defect in N=4 SYM. Particularly, we focus on excitations localized on the defect called insertions, whose correlators are described by a one-dimensional CFT. The first main result of this work is an efficient algorithm for computing multipoint correlation functions of scalar insertions on the Wilson line, consisting of recursion relations encoding the possible interactions up to next-to-leading order at weak coupling. We show various computations of such four-, five- and six-point correlators, and discuss their properties. Moreover, we use the four-point function case to illustrate the power of the Ward identities, which are crucial in deriving a next-to-next-to-leading order result. Thanks to these perturbative results, we find a family of differential operators annihilating our correlation functions, which we conjecture to be a multipoint extension of the Ward identities satisfied by the four-point functions. These non-perturbative constraints are shown to be fundamental ingredients in the bootstrap of a five-point function at strong coupling. To conclude this thesis, we define an inherently one-dimensional Mellin amplitude at the non-perturbative level with appropriate subtractions and analytical continuations. The efficiency of the 1d Mellin formalism is manifest at the perturbative level. We find a closed-form expression for the Mellin transform of leading order contact interactions and use it to extract CFT data.

Colon cancer causes approximately seven percent of all cancer-related deaths in the world and presumably due to modern lifestyle, it is also one of the most frequently diagnosed cancers. The inefficiency of standard treatment indicates the need for intensive research of molecular mechanisms of cancer development. The canonical Wnt signaling pathway is essential for maintenance of the progenitor phenotype of stem cells in crypts of the intestine and controls repopulation of the epithelia, in physiological conditions. However, aberrant activation leads to tumor formation. Although Wnt signaling in cancer has been subjected to thorough investigation, there is still a lot of questions concerning further branching of the pathway. As a model of Wnt/β-catenin triggered colorectal cancer, we use mice with mutated APC, which is the tumor suppressor involved in this pathway. Previous expression profiling of the intestinal tumors from relevant mice revealed two transcription factors: ETV4 and MSX1 which are significantly overexpressed in cancer cells. In this project we elucidate whether the overexpression is really tumor restricted and Wnt dependent or there is a crosstalk with another signal transduction pathway. We investigate the function and regulation of these transcription factors by synthetic reporter assays,...

Im Rahmen eines grossangelegten Modernisierungsprogramms des CERN Beschleunigerkomplexes zur Steigerung der Intensität der Protonenstrahlen wird in einer ersten Phase der Protonenbeschleuniger Linac2 durch einen H− Ionen Beschleuniger Linac4 ersetzt. Um den Ionenstrahl an die einzelnen Beschleunigerelemente des Linac4 anzupassen sind drei Strahltransportsektionen notwendig. Diese sind aufgrund ihrer strahldynamischen Eigenschaften sensitive Stellen für ungewolltes Emittanzwachstum und Teilchenverluste und sind im Schwerpunkt dieser Thesis. Die erste Strahltransportsektion, „Low Energy Beam Transport”(LEBT), befindet sich zwischen der Teilchenquelle und dem ersten Beschleunigerelement, den Radiofrequency Quadrupole (RFQ). Im Rahmen dieser Thesis wurde das LEBT in Betrieb genommen, dessen Strahldynamik rekonstruiert und die Leistungslimitierungen experimentell bestimmt. Der zweite Teil der Thesis ist auf die Auslegung und Strahldynamik der Transfer Linie zwischen Linac4 und dem Proton Synchrotron Booster(PS-Booster) konzentriert. Die Strahldynamik der Transferlinie wurde optimiert und teilweise komplett überarbeitet. Die neue Transferlinie zeichnet sich durch eine verbesserte Emittanzerhaltung, höhere Stabilität der Strahldynamik gegenüber Aufstellungsfehlern und Feldjittern der Magnete und durch eine optimale Anpassung der Strahlparameter an die verschiedenen Injektionsschemata des PS-Boosters aus. Für eine abschließenden „Start-To-End” Simulationen wurden die Strahlcharakteristiken, die bei der Inbetriebnahme des LEBTs bestimmt worden sind, als Anfangsbedingungen für die strahldynamische Simulation von Linac4 einschließlich Transferlinie genutzt. Mit Hilfe dieser „Start-To-End” Simulationen werden kritische Positionen der Strahldynamik identifiziert, die durch Teilchenverluste oder Emittanzwachstum gekennzeichnet sind. Eine besonders kritische Sektion stellt das „Medium Energy Beam Transport” da, dessen Optik auf die neuen Strahlparameter angepasst werden musste. / In the first phase of the upgrade program of the CERN accelerator complex the proton injector Linac2 will be replaced by a new, normal-conducting H− ion Linac, Linac4, allowing a significant increase of the proton flux intensity along the downstream accelerator complex. In the design of Linac4 three beam transport sections are implemented to match the beam between the different accelerator elements and to model the longitudinal pulse structure. These three beam transport sections, which are the most critical locations in terms of beam quality preservation, are in the focus of this thesis. During the work of this thesis the Low Energy Beam Transport (LEBT), which is required to match the source beam to the radiofrequency quadrupole (RFQ), has been commissioned and its beam dynamics re-constructed. The measurement campaign used to reconstruct the LEBT beam dynamics was performed with the aim to prepare the RFQ commissioning and to maximise the LEBT performance. Downstream of the Linac4 accelerator the beam is transported along a 180m long transfer line to the Proton Synchrotron Booster (PS-Booster). The transfer line optics was studied, optimised and sections were completely re-designed. The new transfer line optics is characterised by an improved preservation of the beam emittance, higher stability of the optical solution with respect to alignment errors and field jitters of the transfer line magnets and it is matched to each of the PS-Booster injection schemes. In a concluding ”Start-To-End” simulation based on the measured beam characteristics at the LEBT exit the beam dynamics of the downstream Linac, including the transfer line, was calculated. To minimise particle losses within acceptable emittance preservation the beam optics of the Medium Energy Beam Transport (MEBT) was adapted to the measured beam parameters. This ”Start-To-End” simulation was performed to identify critical sections of the Linac4 beam dynamics and to adjust the commissioning strategies.

This diploma thesis deals with hot-formed helical compression springs. The first part of the thesis describes related problems and determines market potential. Following theoretical part describes the influence of contact line on behaviour of springs and compares it with normative regulations. Methods suitable for determination of helix shape are covered in the next part. The last part focuses on practical measurement, in which the change of helix shape during manufacture was observed. The main output of this diplomat thesis is suggestion of measures that should contribute to both optimization of manufacture and verification of FEM model.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Martin Huličiak Supervisor: PharmDr. Lukáš Červený, Ph.D Title of diploma thesis: Study of interactions of antiviral drugs with intestinal drug efflux ABC transporters P-gp, MRP2 and BCRP are efflux transporters, members of the family of ATP binding cassette (ABC) transporters. These transporters are located on the apical membrane of the intestinal epithelium, where they may limit absorption of orally administered drugs. Study of drug interactions with/on intestinal efflux transporters is necessary to provide safe and effective treatment. The Caco-2 cell line is FDA recommended in vitro model of intestinal barrier and it is used for bidirectional testing of substrates and inhibitors of ABC transporters in preclinical research. However, this methodology has several shortcomings, so the need of introduction of new experimental models is increasing and the ex vivo method based on human or rat intestine is a promising option. Precision-cut intestinal slices (PCIS) represent a mini-model of the organ and contain all types of cells of the tissue. We used both in vitro model using Caco-2 cell monolayers for drug transport study and in our lab established ex vivo method of PCIS for accumulation study...