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In the last two decades, new unpredicted charmonium-like states with extraordinary characteristics have been observed experimentally. These states also known as the XYZ states, e.g., the Y(4260) or the X(3872), are mostly interpreted as QCD allowed exotic hadrons. One of the leading hadron physics experiments in the world, the Beijing Electron Spectrometer III (BESIII) at the Beijing Electron-Positron Collider II (BEPCII) is aiming towards revealing the internal structure of these states. It has brought numerous breakthrough discoveries including the discovery of the charged Zc(3900). In order to understand the nature of the Y(4260) state and its decay patterns, an inclusive analysis is performed for different recoil systems (π+π−,K+K− and K±π∓) using the BESIII data samples for center of mass energies above 4 GeV collected between 2013 and 2019. The aim of this analysis is twofold: on one hand, we search for new unobserved charmonium-like decay channels using the missing mass technique and on the other hand, it provides an accurate inclusive cross section measurement for e+e−→X π+π−, with the X being the J/ψ, hc and ψ(2S), respectively. Two resonant structures, the Y(4220) and the Y(4390), are observed in the inclusive energy dependent Born cross section of e+e−→hc π+π−, which is consistent with the BESIII exclusive measurements. Moreover, the energy dependent cross section of e+e−→J/ψ π+π− is investigated, in which two resonances have consistently been observed with the previous BESIII exclusive studies, namely, the Y(4220) and the Y(4320). In the (K±π±) recoil system, possible Y(4260) open charm decay channels are investigated. Two enhancements are observed in the inclusive energy dependent cross section of e+e−→DD above 4.13GeV, which could possibly be the ψ(4160)and the ψ(4415).
An investigation of photoelectron angular distributions and circular dichroism of chiral molecules
(2021)
The present work demonstrates the capability of several type of molecular frame photoelectron angular distributions (MFPADs) and their linked chiroptical phenomenon the photoelectron circular dichroism (PECD) to map in great detail the molecular geometry of polyatomic chiral molecules as a function of photoelectron energy. To investigate the influence of the molecular potential on the MFPADs, two chiral molecules were selected, namely 2-(methyl)oxirane (C3H6O, MOx, m = 58,08 uma) and 2-(trifluoromethyl)oxirane (C3H3F3O, TFMOx, m = 112,03 uma). The two molecules differs in one substitutional group and share an oxirane group where the O(1s) electron was directly photoionized with the use of synchrotron radiation in the soft X-ray regime. The direct photoionization of the K-shell electron is well localized in the molecule and it induces the ejection of two or more electrons; the excited system separates into several charged (and eventually neutral) fragments which undergo Coulomb explosion due to their charges. The electrons and the fragments were detected using the COLd Target Recoil Ion Momentum Spectroscopy (COLTRIMS) and the momentum vectors calculated for each fragment belonging from a single ionization. The former method gives the possibility to post-orient molecules in space, giving access to the molecular frame, thus the MFPAD and its related PECD for multiple light propagation direction.
Stereochemistry (from the Greek στερεο- stereo- meaning solid) refers to chemistry in three dimensions. Since most molecules show a three-dimensional structure (3D), stereochemistry pervades all fields of chemistry and biology, and it is an essential point of view for the understanding of chemical structure, molecular dynamics and molecular reactions. The understanding of the chemistry of life is tightly bounded with major discoveries in stereochemistry, which triggered tremendous technical advancements, making it a flourishing field of research since its revolutionary introduction in late 18th century. In chemistry, chirality is a brunch of stereochemistry which focuses on objects with the peculiar geometrical property of not being superimposable to their mirror-images. The word chirality is derived from the Greek χειρ for “hand”, and the first use of this term in chemistry is usually attributed to Lord Kelvin who called during a lecture at the Oxford University Junior Scientific Club in 1893 “any geometrical figure, or group of points, “chiral”, and say that it has chirality if its image in a plane mirror, ideally realized, cannot be brought to coincide with itself.”. Although the latter is usually considered as the birth of the word chirality, the concept underlying it was already present in several fields of science (above all mathematics), already proving the already multidisciplinary relevance of chirality across many field of science and beyond. Nature shows great examples of chiral symmetry on all scales. Empirically, it is possible to observe it at macroscopic scale (e.g. distribution of rotations of galaxies), down to the microscopic scale (e.g. structure of some plankton species), but it is at the molecular level where the number gets remarkable: most of the pharmaceutical drugs, food fragrances, pheromones, enzymes, amino acids and DNA molecules, in fact, are chiral. Moreover, the concept of chirality goes far beyond the mere spatial symmetry of objects being crucially entangled with the fundamental properties of physical forces in nature. The symmetry breaking, namely the different physical behaviour of a two chiral systems upon the same stimuli, is considered to be one of the best explanation for the long standing questions of homochirality in biological life, and ultimately to the chemical origin of life on Earth as we know it. Our organism shows high enantio-selectivity towards specific compounds ranging from drugs, to fragrances. Over 800 odour molecules commonly used in food and fragrance industries have been identified as chiral and their enantiomeric forms are perceived to have very different smells, as the well-know example of D- and L- limonene. Similarly, responses to pharmaceuticals drugs can be enantiomer specific, and in fact about 60 % the drugs currently on the market are chiral compounds, and nearly 90 % of them are sold as racemates. The same degree of enantio-selectivity is observed in the communications systems of plants and insects. Plants produce lipophilic liquids with high vapour pressure called plant volatiles (PVs) which are synthesized via different enzymes called tarpene synthases that are usually chiral. Chiral molecules and chiral effects have a strong impact on all the fields of science with exciting developments ranging from stereo-selective synthesis based on heterogeneous enantioselective catalysis, to optoelctronics, to photochemical asymmetric synthesis, and chiral surface science, just to cite a few.
Chiral molecules come in two forms called enantiomers. Their almost identical chemical and physical properties continue to pose technical challenges concerning the resolution of racemic mixtures, the determination of the enantiomeric excess, and the direct determination of the absolute configuration of an enantiomer. ...
While high-quality climate reconstructions of some past warm periods in the Cenozoic era now exist, the geological processes responsible for driving the observed longterm changes in atmospheric CO2 are not sufficiently well understood. The long-term change in atmospheric CO2 across the Cenozoic has been proposed to be driven by processes such as terrestrial weathering, organic carbon production and burial, reverse weathering, and volcanic degassing. One way of constraining the relative importance of the various driving forces proposed so far is to better understand the degree to which ocean chemistry has changed because the chemistry of seawater responds to geologic processes that drive atmospheric CO2. In addition, knowledge of the concentration of the major elements in seawater is crucial for accurately applying proxies such as those based on the boron isotopic composition and Mg/Ca of marine carbonates (a proxy for palaeo pH/CO2 and palaeotemperature, respectively). Previously reported records of seawater composition are primarily derived from fluid inclusions in marine evaporites; however, the results are sparse due to the limited availability of such deposits. In this thesis, changes in the Eocene seawater chemistry were reconstructed using trace element (elements/Ca) and isotopic (δ26Mg) proxies in a Larger Benthic Foraminifera (LBFs), i.e., Nummulites sp., to constrain the driving processes of long-term changes in seawater chemistry.
To achieve the objective of this thesis, first, a measurement protocol was established using LA-ICPMS to measure the K/Ca ratio simultaneously with other element/calcium ratios, which is challenging due to the interference of ArH+ on K+. Utilising this newly established measurement protocol, laboratory-cultured Operculina ammonoides grown at different seawater calcium concentrations ([Ca2+]), repeated at different temperatures, as well as modern O. ammonoides collected from different regions exhibiting a range of seawater parameters, were investigated. A significant correlation was observed between K/Casw and K/CaLBF, allowing K/CaLBF to potentially be used as a proxy for seawater major ion reconstructions. In addition, modern O. ammonoides demonstrated no significant influence of most seawater parameters (temperature, salinity, pH, or [CO32-]) on K/CaLBF. Modern O.
ammonoides were also assessed for their Mg isotopic composition (δ26Mg), revealing no significant effect of temperature or salinity on δ26MgLBF. Furthermore, the Mg isotopic fractionation in O. ammonoides was found to be close to that of inorganic calcite, indicating minimal vital effects in these large benthic foraminifera.
Operculina ammonoides is the nearest living relative of the abundant Eocene genus Nummulites, enabling the reconstruction of seawater chemistry using the calibration based on O. ammonoides. The trace elemental/calcium proxies, including Na/Ca, K/Ca, and Mg/Ca, as well as the δ26Mg proxy, were investigated in Eocene Nummulites. The result showed that during the Eocene, [Ca2+]sw was 1.6-2 times higher, while [K+]sw was ~2 times lower than the modern seawater composition. Furthermore, [Mg2+]sw decreased from the early Eocene (54.3− +9 7..69 mmol kg-1 at ~55 Ma) to Late Eocene (37.8− +4 4..3 4 mmol kg-1 at ~31 Ma), followed by
an increase toward modern seawater [Mg]. In contrast, the variability in δ26Mgsw values remained within a narrow range of ~0.3 ‰ throughout the Cenozoic. The reconstructed [Ca2+]sw agrees with the suggestion that Cenozoic seawater chemistry changes can be explained via a change in the seafloor spreading rate. When combined with existing records, the observed minimal change in δ26Mgsw with an increase in [Mg2+]sw suggests an additional possible role of a decrease in the formation of authigenic clay minerals coincident with the Cenozoic decline in deep ocean temperature, which is also supported by the increase in the [K+]sw reconstructed here for the first time. This finding highlights that the reduction in seafloor-spreading rate and decline in reverse weathering during the Cenozoic era has played a significant role in the evolution of seawater chemistry, emphasizing the importance of these processes in driving long-term changes in the carbon cycle.
A large number of chemicals are constantly introduced to surface water from anthropogenic and natural sources. Although substantial efforts have been made to identify these chemicals (e.g potentially anthropogenic contaminants) in surface waters using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS), a large number of LC-HRMS chemical signals often with high peak intensity are left unidentified. In addition to synthetic chemicals and transformation products, these signals may also represent plant secondary metabolites (PSMs) released from vegetation through various pathways such as leaching, surface run-off and rain sewers or input of litter from vegetation. While this may be considered as a confounding factor in screening of water contaminants, it could also contribute to the cumulative toxic risk of water contamination. However, it is hardly known to what extent these metabolites contribute to the chemical mixture of surface waters. Thus, reducing the number of unknowns in water samples by identifying also PSMs in significant concentrations in surface waters will help to improve monitoring and assessment of water quality potentially impacted by complex mixtures of natural and synthetic compounds. Therefore, the main focus of the present study was to identify the occurrence of PSMs in river waters and explore the link between the presence of vegetation along rivers and detection of their corresponding PSMs in river
water.
In order to achieve the goals of the present thesis, two chemical screening approaches, namely, non-target and target screening using LC-HRMS were implemented. (1) Non-target analysis involving a novel approach has been applied to associate unknown peaks of high intensity in LC-HRMS to PSMs from surrounding vegetation by focusing on peaks overlapping between river water and aqueous plant extracts (Annex A1). (2) LC–HRMS target screening in river waters were performed for about 160 PSMs, which were selected from a large phytotoxin database (Annex A2 and A3) considering their expected abundance in the vegetation, their potential mobility, persistence and toxicity in the water cycle and commercial availability of standards.
In non-target screening (Annex A1), a high number of overlapping peaks has been found in between aqueous plant extracts and water from adjacent location, suggesting a significant impact of vegetation on chemical mixtures detectable in river waters. The chemical structures were assigned for 12 pairs of peaks while several pairs of peaks
whose MS/MS spectra matched but no structure suggestion were made by the implemented software tools for retrieving possible chemical structure. Nevertheless, the pairs of peaks with matching spectra represented the same chemical structure. The identified compound belonged to different compound classes such as coumarins, flavonoids besides others. For the identified PSMs individual concentration up to 5 µg/L were measured. The concentration and the number of detected PSMs per sample were correlated with the rain event and vegetation coverage.
Target screening unraveled the occurrence of 33 out of 160 target compounds in river waters (Annex A2 and A3). The identified compounds belonged to different classes such as alkaloids, coumarins, flavonoids, and other compounds. Individual compound concentrations were up to several thousand ng/L with the toxic alkaloids narciclasine and
lycorine recording highest maximum concentrations. The neurotoxic alkaloid coniine from poison hemlock was detected at concentrations up to 0.4 µg/L while simple coumarins
esculetin and fraxidin occurred at concentrations above 1 µg/L. The occurrence of some PSMs in river water were correlated to the specific vegetation growing along the rivers while the others were linked to a wide range of vegetation. As an example, narciclasine and lycorine was emitted by the dominant plant species from Amaryllidaceae family (e.g. Galanthus nivalis (snow drop), Leucojum vernum and Anemone nemorosa) while intermedine and echimidine were from Symphytum officinale. The ubiquitous occurrence of simple coumarins fraxidin, scopoletin and aesculetin could be linked to their presence in a wide range of vegetation.
Due to lack of aquatic toxicity data for the identified PSMs (in both target and non-target) and extremely scarce exposure data, no reliable risk assessment was possible.
Alternatively, risk estimation was performed using the threshold for toxicological concern (TTC) concept developed for drinking water contaminants. Many of the identified PSMs
exceeded the TTC value (0.1 µg/L) thus caution should be taken when using such surface waters for drinking water abstraction or recreational use.
This thesis provides an overview of the occurrence of PSMs in river water impacted by the massive presence of vegetation. Concentration for many of the identified PSMs are well within the range of those of synthetic environmental contaminants. Thus, this study adds to a series of recent results suggesting that possibly toxic PSMs occur in relevant concentrations in European surface waters and should be considered in monitoring and risk assessment of water resources. Aquatic toxicity data for PSMs are extensively lacking but are required to include these compounds in the assessment of risks to aquatic organisms and for eliminating risks to human health during drinking water production.
Die Purinanaloga Cladribin und Fludarabin sowie die Pyrimidinanaloga Cytarabin und Gemcitabin sind wichtige Bestandteile in der Behandlung Iymphoproliferativer und hämatologischer Erkrankungen. Die zwei Hauptmechanismen der zytostatisch wirksamen Medikamente sind zum einen die Induktion der Apoptose und zum anderen die Hemmung der ZeIlproliferation. Beide Wege führen am Ende zum Untergang der Zelle und damit zur Tumorregression. In verschiedenen klinischen Studien wurde die klinische Wirksamkeit der Nukleosidanaloga demonstriert. Das Ziel der Kombinationen etablierter Substanzen mit neuen Medikamenten ist der Erhalt additiver und synergistischer Effekte, resultierend in einer Erhöhung der klinischen Effektivität. 2-CdA, ein Purinanalogon, zeigte bisher Aktivitäten als Einzelsubstanz in der Behandlung niedrigmaligner Lymphome. Chow et al untersuchten die Induktion der Apoptose durch die Einzelgabe von 2-CdA und durch 2-CdA in Kombination mit anderen antineoplastischen Medikamenten. Die Messungen der Apoptoserate (Durchflußzytometrie) induziert durch die alleinige Gabe von Cladribin, ergab eine von der Dosis abhängigen Kurvenverlaur 3x Mit Steigerung der Dosis erhöhte sich die Apoptoserate in den normalen wie in den neoplastischen Zellen. Hier wurde nun untersucht, ob sich durch die Steigerung der extrazellulären 2-CdA Konzentration, dessen intrazellulären Metabolismus erhöhen lässt und damit die Menge des aktiven Metaboliten 2-CdA TP. Als Methode eignete sich hierfür die HPLC. Die Ergebnisse zeigten, daß mit zunehmender extrazellulärer Konzentration die intrazelluläre Phosphorylierung des Cladribins in seine aktiven Metabolite signifikant anstieg. Es ist daher anzunehmen, daß höhere Dosen in vivo in der Behandlung niedrigmaligner Lymphome in einer größeren klinischen Effektivität resultieren könnte. Die klinische Effektivität könnte auch durch die Kombination mit anderen neoplastischen Substanzen erhöht werden. Untersucht wurde daher die Kombination von 2-CdA mit dem neuen Pyrimidinanalogon Gemcitabin (dFdC), welches bisher vielversprechende Aktivitäten gegenüber myeloischen und lymphatischen leukämischen Zellen gezeigt hat. Es wirkt dabei als Modulator auf den Metabolismus anderer Nukleoside, wenn diese durch die Deoxycytidinkinase phosphoryliert werden. Analysiert wurden unterschiedliche Inkubationsbedingungen (simultane und sequentielle Inkubation) an zwei myeloischen (Hel, HL 60) und an zwei lymphatischen (JURKAT, HUT 78) Zellinien. Der Einfluss von dFdC auf den intrazellulären Metabolismus des 2-CdA wurde mit Hilfe der HPLC untersucht. Es wurde beobachtet, daß eine simultane Applikation beider Substanzen zu einer antagonistischen Wirkung führte, während eine konsekutive Gabe einen synergistischen Effekt bewirkte, unabhängig von der Inkubationsdauer und dem Ursprung der Zellen (myeloisch oder lymphatisch). Die gewonnenen Daten legen nahe, daß eine gleichzeitige Kombinationstherapie von Cladribin und Gemcitabin nicht zu einer Verbesserung der klinischen Effektivität führt. In vielen Standardregimes werden Purin- und Pyrimidinanaloga zur Verbesserung der klinischen Effektivität miteinander kombiniert. Untersucht wurde bisher nur der Metabolismus der Standardtherapieschemata. Das Ziel dieser Arbeit bestand nun darin die Effektivität auf die Induktion der Apoptose, auf die Zellproliferation, auf den Zusammenbruch der Mitochondrienmembranpotentials und auf die Expression apoptoserelevanter Proteine zu analysieren. Die Hemmung der Zellproliferation und die Induktion der Apoptose sind die Hauptmechanismen der Zytotoxizität der antineoplastisch wirksamen Agenzien.65 Daher wurde hier analysiert, ob Ara-C in Kombination mit Purinanaloga einen synergistischen oder antagonistischen Effekt auf die Zellproliferation und auf die Induktion der Apoptose in AML Zellinien (HL 60 und HEL) ausübt. Daneben wurden die Effekte der Kombination von Ara-C mit Bendamustin, einem neuen bifunktionellen Agenz mit alkylierender Aktivität und mit den Eigenschaften der Purinanaloga, geprüft. Die Ergebnisse zeigen, daß Ara-C kombiniert mit Fludarabin oder Bendamustin sowohl zu antagonistischen Effekten auf die Hemmung der Zellproliferation, auf die Induktion der Apoptose als auch auf die Ruptur der Mitochondrienmembran führen, unabhängig von einer simultanen oder konsekutiven Applikation (Purinanaloga vor Ara-C), im Gegensatz zur Kombination von Cytarabin mit Cladribin. Während der Induktion der IC 50 Levels der Apoptose, konnte weder bei den antagonistischen noch bei den synergistischen Zytostatikakombinationen ein spezifisches Expressionsmuster der Apoptose assoziierten Proteine, wie der pro- oder antiapoptotischen Bcl-2-Familienmitgliedern, der Exekutionscaspasen, der IAPs, des proapoptotischen PAR-4, PARP oder p53, beobachtet werden. Zusammenfassend lässt sich sagen, daß die Effektivität der Medikamentenkombinationen Ara-C plus Purinanaloga abhängig ist von dem gewählten Purinanalogon, wohingegen die Inkubationsbedingungen (gleichzeitig oder sequentiell) oder die Dosiseskalation keine Rolle spielen.
Im Rahmen der Versuchsanordnung der vorliegenden In-vitro-Studie wurden insgesamt sieben Abformmaterialien (zwei Polyether und fünf A-Silikone) hinsichtlich ihrer Dimensions- und Lagerungsstabilität sowie ihres Rückstellvermögens untersucht. Mit den Abformmaterialien erfolgte die Untersuchung der Einphasen- und Doppelmischmethode, sowie der Korrektur- und Folientechnik, so dass acht verschiedene Kombinationen (Abformmaterial/ -methode) resultierten. Für die Untersuchung wurde auf Grundlage eines Frasaco-Modells ein speziell angefertigtes, aus V2A-Stahl bestehendes, Präzisionsmodell hergestellt. Dieses wies vier stilisierte Präparationspfeiler auf. Jeder dieser Pfeiler wurde mit fünf CNC gefrästen Kreuzen versehen, die zur späteren Vermessung herangezogen wurden. Mit jeder Material-Methoden-Kombination wurden 12 Abformungen unternommen. Die Abformungen wurden ohne Einsatz eines Modellwerkstoffes direkt optisch vermessen. Dafür wurde das Präzisionsmodell nach jedem Abformvorgang mit einer definierten Kraft mittels Zugprüfmaschine in vertikaler Richtung aus der Abformküvette gezogen. Jede Abformung wurde anschließend lageidentisch in einer speziell dafür aufgestellten Messeinrichtung positioniert und optisch mit der Digitalkamera Axio Cam HRc abgelichtet. Für die Vermessung wurden 11 Messstrecken innerhalb der Abformung bestimmt. Darunter befanden sich drei okklusale und acht zervikale Messstrecken. Die okklusalen Messstrecken verliefen zwischen den okklusal an den Pfeilern angebrachten Vermessungskreuzen. Die zervikalen Messstrecken erstreckten sich in mesio-distaler, sowie vestibulo-oraler Richtung der Pfeiler. Anfangs- und Endpunkt jeder Strecke wurden jeweils als ein bestimmter Kreuzungspunkt zweier Schenkel der angebrachten Vermessungskreuze definiert. Die Vermessung der Strecken fand an vier verschiedenen Messzeitpunkten statt. Der erste Zeitpunkt stellte den frühesten Zeitpunkt der Modellherstellung dar, der vom Hersteller angegeben wurde. Der zweite Messzeitpunkt wurde 3 Stunden, der dritte 24 Stunden und der vierte 48 Stunden nach der Entformung vorgenommen. Die Ergebnisse zeigten, dass alle gemessenen Strecken zu jedem Zeitpunkt kleiner waren als die Messstrecken des Präzisionsmodells. Sowohl die statistische als auch die deskriptive Analyse ergaben, dass der Unterschied zum Präzisionsmodell bei den okklusalen Strecken größer war als bei den zervikalen Strecken. Die statistische Datenanalyse ergab bei den zusammengefassten okklusalen Strecken (ab, bc, cd), den zusammengefassten zervikalen Strecken (a1, a2, b1, b2, c1, c2, d1, d2) sowie den zervikalen mesio-distalen Messstrecken (a1, b1, c1, d1) und den zervikalen vestibulo-oralen Messstrecken (a2, b2, c2, d2) bei keinem Abformmaterial und zu keinem Messzeitpunkt einen signifikanten Unterschied zum Präzisionsmodell. Signifikante Unterschiede zwischen den einzelnen Materialien und dem Präzisionsmodell wurden bei den einzeln betrachteten okklusalen Strecken ab, bc und cd festgestellt. Zwischen den Messzeitpunkten zeigten mit Ausnahme von Aquasil und Honigum alle Materialien das gleiche Verhalten. Dabei konnte zwischen dem ersten und zweiten Messzeitpunkt eine Kontraktion der Abformmaterialien beobachtet werden. Zum dritten und vierten Messzeitpunkt hin fand eine Expansion statt. Bei den Materialien Aquasil und Honigum wurde zwischen dem ersten und vierten Messzeitpunkt eine stetige Expansion beobachtet. Unter den bestehenden Versuchsbedingungen waren die Ergebnisse der Korrekturmethoden mittels Panasil binetics putty soft und Korsil zu jedem Messzeitpunkt und fast allen Messstrecken am detailgenauesten. Nur bei der okklusalen Messstrecke bc ließen die Polyethermaterialien Impregum Penta Soft und Impregum Penta Duo Soft zu jedem Zeitpunkt die geringsten Abweichungen zum Präzisionsmodell erkennen. Die Doppelmischmethode mit dem Material Aquasil und die Folientechnik mittels Panasil binetics putty soft erbrachten geringfügig ungünstigere Ergebnisse. Größere Abweichungen zum Präzisionsmodell resultierten bei den Doppelmischabformungen mit Impregum Penta Duo Soft und Honigum. Die größten Abweichungen wurden bei der Einphasenabformung mittels Impregum Penta Soft und der Doppelmischmethode mit Panasil tray soft beobachtet. Hinsichtlich des Zeitpunktes der Modellherstellung stellte sich heraus, dass der von den Herstellern angegebene, früheste Zeitpunkt der Modellherstellung zu guten Modellergebnissen führt. Die zum zweiten Messzeitpunkt hin beobachtete Kontraktion konnte von einigen Abformmaterialien z. B. Impregum Penta Soft (Strecke ab) und Panasil tray soft (Strecke ab) selbst nach 24 Stunden nicht kompensiert werden. Bei diesen Materialien sollte zu diesem Zeitpunkt auf eine Modellherstellung verzichtet und stattdessen weitere 24 Stunden abgewartet werden. Zwischen dem dritten und vierten Messzeitpunkt konnten jedoch bei den meisten Abformmaterialien nur noch sehr geringe Dimensionsänderungen festgestellt werden. Daher konnten alle Abformmaterialien auch bei längerer Lagerung als sehr dimensionsstabil angesehen werden. Eine Modellherstellung kann somit auch 48 Stunden nach der Entformung stattfinden. Der zweite Messzeitpunkt, der 3 Stunden nach der Entformung stattfand, sollte zur Modellherstellung vermieden werden, da infolge der Materialexpansion ungünstige Modellergebnisse in Form stark verkleinerter Modellstümpfe und Pfeilerdistanzen resultieren könnten.
Software evolves. Developers and programmers manifest the needs that arise due to evolving software by making changes to the source code. While developers make such changes, reusing old code and rewriting existing code are inevitable. There are many challenges that a developer faces when manually reusing old code or rewriting existing code. Software tools and program transformation systems aid such reuse or rewriting of program source code. But there are significantly occuring development tasks that are hard to accomplish manually, where the current state-of-the-art tools are still not able to adequately automate these tasks. In this thesis, we discuss some of these unexplored challenges that a developer faces while reusing and rewriting program source code, the significance of such challenges, the existing automation support for these challenges and how we can improve upon them.
Modern software development relies on code reuse, which software developers
typically realize through hand-written abstractions, such as functions,
methods, or classes. However, such abstractions can be challenging to
develop and maintain. An alternative form of reuse is \emph{copy-paste-modify}, in which developers explicitly duplicate source code to adapt the duplicate for a new purpose. Copy-pasted code results in code clones, i.e., groups of code fragments that are similar to each other. Past research strongly suggests that copy-paste-modify is a popular technique among software developers. In this paper, we perform a small user study that shows that copy-paste-modify can be substantially faster to use than manual abstraction.
One might propose that software developers should forego hand-written abstractions in favour of copying and pasting. However, empirical evidence also shows that copy-paste-modify complicates software maintenance and increases the frequency of bugs. Furthermore, the developers in an informal poll we conducted strongly preferred to read code written using abstractions. To address the concern around copy-paste-modify, we propose a tool that merges similar pieces of code and automatically creates suitable abstractions. Our tool allows developers to get the best of both worlds: easy reuse together with custom abstractions. Because different kinds of abstractions may be beneficial in different contexts, our tool provides multiple abstraction mechanisms, which we selected based on a study of popular open-source repositories.
To demonstrate the feasibility of our approach, we have designed and implemented a prototype merging tool for C++ and evaluated our tool on a number of clones exhibiting some variation, i.e near clones, in popular Open Source packages. We observed that maintainers find our algorithmically created abstractions to be largely preferable to existing duplicated code. Rewriting existing code can be considered as a form of program transformation, where a program in one form is transformed into a program in another form. One significant form of program transformation is data representation migration that involves changing the type of a particular data structure, and then updating all of the operations that has a control or data dependence on that data structure according to the new type. Changing the data representation can provide benefits such as improving efficiency and improving the quality of the computed results. Performing such a transformation is challenging, because it requires applying data-type specific changes to code fragments that may be widely scattered throughout the source code connected by dataflow dependencies. Refactoring systems are typically sensitive to dataflow dependencies, but are not programmable with respect to the features of particular data types. Existing program transformation languages provide the needed flexibility, but do not concisely support reasoning about dataflow dependencies.
To address the needs of data representation migration, we propose a new approach to program transformation that relies on a notion of semantic dependency: every transformation step propagates the transformation process onward to code that somehow depends on the transformed code. Our approach provides a declarative transformation specification language, for expressing type-specific transformation rules. We further provide scoped rules, a mechanism for guiding rule application, and tags, a device for simple program analysis within our framework, to enable more powerful program transformations.
We have implemented a prototype transformation system based on these ideas for C and C++ code and evaluate it against three example specifications, including vectorization, transformation of integers to big integers, and transformation of array-of-structs data types to struct-of-arrays format. Our evaluation shows that our approach can improve program performance and the precision of the computed results, and that it scales to programs of at least 3700 lines.
A sound and well-functioning legal system will encourage growth in investment and create opportunities for investors. Trademarks as part of intellectual property play an important role in the future development of a country. A mark or symbol is needed in order to give products and services identity and to distinguish them and their qualities from identical or similar products and services of a competitor.
This research studies, examines and analyses the degree, nature and function of trademark protection within the legal system of Afghanistan and compare them with the Paris, Madrid and TRIPs agreements. It has been divided into four chapters: Chapter one provides general information and an overview of the current legal system of Afghanistan. Chapter two studies and analyses international agreements pertaining to the legal protection of trademark. It also critically assesses the ATML compatibility with these agreements: and answers the research question of to what extent the ATML provisions are compatible with them. Chapter three provides information on the different purposes of trademarks from a development perspective and compares the purposes provided by the ATML. Finally, chapter four assesses and examines the acquisition, assignment and termination of trademarks. The conclusions and findings of the thesis are the final section of this research.
Afghanistan, as a transitioning economy, has not developed a solid legal and practical foundation for providing comprehensive protection mechanisms for trademarks as have been articulated in developed countries and international agreements. Accordingly, the Afghan government has not entirely integrated these needs into its legal system and there are some inconsistencies of the ATML with these agreements.
One more challenge is the lack of appropriate legal institutions for issuing, managing, administering and protecting of trademarks. The establishment of a well-functioning administrative institution will serve to fulfil the objectives of the laws. Therefore, the CBR office holds the administrative responsibility for processing the registration of trademarks.
However, the methods and facilities of the CBR office remain outdated, and the office does not have the capacity to provide applicants with up-to-date administrative and technical facilities.
Therefore, legal protection of trademark in Afghanistan is linked not only to the existence of a well functioning of laws, regulations, clear procedures, mechanism and guidelines but also to an efficient and well-functioning administrative office.
Hintergrund: Die klinische Wirksamkeit einer pharmakochirurgischen Kombinationstherapie zur Behandlung des diabetischen Makulaödems (DMÖ) bestehend aus einer posterioren Kernvitrektomie mit Entfernung von 1,5 ml liquefiziertem Glaskörper und zeitgleicher isovolumetrischer Injektion von 1,25 mg Bevacizumab und 8 mg Triamcinolon wurde in der vorliegenden Arbeit analysiert. Methodik: Daten von 73 Augen (60 Patienten; 65,4 ± 10,4 Jahre) mit einem DMÖ nach pharmakochirurgischer Kombinationstherapie wurden analysiert. Untersucht wurde neben dem Visus und der zentralen Makuladicke die Notwendigkeit von Re-Interventionen und dem Einsatz der konventionellen Verfahren (Laser, klassische 3port ppV). Wir unterschieden zwischen Gruppe I (n=38): nicht-proliferative DR (NPDR) ohne ischämische Makulopathie (I.M.); Gruppe II (n=17): NPDR mit I.M. und Gruppe III (n=18): proliferative DR mit oder ohne I.M. Die Kontrollintervalle betrugen im Median 9 Wochen (ca. 2 Monate, T1), 25 Wochen (ca. 6 Monate, T2) und 44 Wochen (ca.10 Monate, T3) nach Intervention. Ergebnisse: Die präoperativen Sehschärfen betrugen 0,52 ± 0,21 logMAR in Gruppe I, 0,99 ± 0,5 logMAR in Gruppe II, 0,77 ± 0,42 logMAR in Gruppe III. In Gruppe I verbesserte sich der Visus nach 2 Monaten zunächst auf 0,45 ± 0,21 logMAR (T1; p=0,7), nach 6 Monaten (T2) hochsignifikant auf 0,36 ± 0,16 logMAR (p<0,01) und blieb zum Zeitpunkt T3 stabil (0,36 ± 0,1 logMAR; p=1,0). Die Gruppe II zeigte zum Zeitpunkt T1 eine signifikante Visusbesserung auf 0,64 ± 0,18 logMAR (p<0,05) und war mit 0,77 ± 0,43 logMAR (T2; p>0,05) und 0,82 ± 0,4 logMAR (T3; p>0,05) leicht rückläufig. In der Gruppe III wurde zum Zeitpunkt T1 ein nicht-signifikante Visusverbesserung auf 0,53 ± 0,24 logMAR (p=0,08) erreicht, während nach 6 Monaten einen Visus von 0,62 ± 0,29 logMAR (p=0,6) und nach 10 Monaten mit 0,72 ± 0,34 logMAR (p=0,9) nahezu den Ausgangsvisus erreicht wurde. Die präoperativen Makuladicken betrugen 386,6 μm in Gruppe I, und 418,65 μm in Gruppe II und 385,17 μm in Gruppe III. Das Makulaödem konnte in allen 3 Gruppen bereits nach 2 Monaten hochsignifikant reduziert: -110μm (-28%; p<0,01) und im erreichten Niveau stabilisiert werden. 27,4 % der Augen (20/73) benötigten nach durchschnittlich 6,3 Monate eine Re-Intervention und 32,9 % benötigten im Verlauf eine Lasertherapie. Schlussfolgerung: Durch die pharmakochirurgische Kombinationstherapie konnte kurz- und mittelfristig eine Reduktion des Makulaödems mit Visusverbesserung in der Mehrzahl der Augen erreicht werden. Die Notwendigkeit von Re-Interventionen konnte zudem signifikant reduziert werden. Durch einen möglichen synergistischen Effekt kann diese Behandlungsmethode bestehende Therapieoptionen sinnvoll ergänzen und erweitern.