Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) is the ninth member of the Ca+2-dependent mammalian proprotein convertase super family of serine endoproteases that is structurally related to the bacterial subtilisin and yeast kexin enzymes. It plays a critical role in the regulation of lipid metabolism and cholesterol homeostasis by binding to and degrading low-density lipoprotein-receptor (LDL-R) which is responsible for the clearance of circulatory LDL-cholesterol from the blood. Owing to this functional property, there is plenty of research interest in the development of functional inhibitors of PCSK9 which may find important biochemical applications as therapeutic agents for lowering plasma LDL-cholesterol. The catalytic domain of PCSK9 binds to the EGF-A domain of LDL-R on the cell surface to form a stable complex and re-routes the receptor from its normal endosomal recycling pathway to the lysosomal compartments leading to its degradation. Owing to these findings, we propose that selected peptides from PCSK9 catalytic domain, particularly its disulphide (S-S) bridged loop1 323-358 and loop2 365-385, are likely to exhibit strong affinity towards the EGF-A domain of LDL-R. Several regular peptides along with corresponding all- dextro and retro-inverse peptides as well as the gain-of-function mutant variants were designed and tested for their regulatory effects towards LDL-R expression and PCSK9-binding in human hepatic HepG2 and mouse hepatic Hepa1c1c7 cells. Our data indicated that disulfide bridged loop1-hPCSK9323-358 and its H357 mutant as well as two short loop2-hPCSK9372-380 and its Y374 mutant peptides modestly promote the LDL-R protein levels. Our study concludes that specific peptides from the PCSK9 catalytic domain can regulate LDL-R and may be useful for development of novel class of therapeutic agents for cholesterol regulation.

Abstracts in English and Zulu / Airline choice is of interest to both airline product development and marketing personnel and academics. While most of the studies airline choice/service quality only identify airlines service attributes essential to customers, this study employed personal values to extend and provide the reasons why airline service attributes are not or essential to passengers. Personal values are presented in the literature as the ultimate life goals individuals seek to attain in all aspects of their lives; hence, guide their behaviour. Based on this, the main objective of this study was to examine and identify the consumer (passenger) personal values that underpin the evaluation of airline service attributes used to choose an airline within the South African domestic passenger market. To achieve this objective, together with the secondary objectives, a quantitative descripto-explanatory research design was employed to guide data collection and analysis. A sample of 324 respondents was selected using a hybrid technique of convenience, and snowball sampling techniques and data were collected using both an online and hardcopy questionnaire. Data obtained were sorted and cleaned for analysis using the Statistical Product and Service Solutions (SPSS 26) and the Analysis of a Moment Structures (AMOS Version 26) software. Exploratory factor analysis (EFA) was conducted to assess factor structures of observed variables and identify latent constructs. The factorability of portrait value questionnaire (PVQ) items was determined using the confirmatory factor analysis (CFA). Hypotheses were tested using the backward multiple regression analysis, Whitney-Mann test, Spearman correlation and hierarchical regression with Hayes’ Process Macro. The study identified five of Schwartz’s 19 refined values as significantly influencing the evaluation and prioritisation of airline service attributes. A state of indifference among customers was found when the impact of airline service attributes was tested, with only onboard services found to significantly influence post-purchase outcomes such as satisfaction, loyalty and repeat purchase behaviour. It was also found that passengers did not distinguish between low-cost and full-service carriers. Income only moderated the influence of stimulation and self-direction thought values on airline service attributes while marketing communications effort was found to have a direct than a moderating role. In the main, these findings bring a novel and rich way of explaining airline choice through personal values. The results are essential for airline market segmentation, positioning and the development of airline products or features that match passenger desired life goals (personal values) which are touted as a guide to their choice behaviour. / Ukuqoka inkampani yezindiza ozoyisebenzisa kumayelana nokuthuthukisa umkhiqizo nabasebenzi bokumaketha kanye nabacwaningi. Phezu kokuba ukucwaninga ngezindiza nokuqokwa kwazo/ ikhwalithi yesevisi kukhomba kuphela izimfanelo zesevisi ezibalulekile kumakhasimende, lolu cwaningo lumbandakanye okungamagugu abantu ukunweba nokuletha izizathu zokuthi kungani izimfanelo zesevisi zenkampani yezindiza zingabalulekile noma zibalulekile kubagibeli. Okungamagugu abantu kwethulwe ngemibhalo kwaba ngamaphupho ekusasa ahlonzwayo ezimpilweni, ngakho,ebe eqondisa indlela yokuziphatha kwabo. Kuncike kulokhu, eyona nhlosongqangi yalolu cwaningo kwaku wukuhlola nokuhlonza okungamagugu omuntu ongumthengi (umgibeli) ukusekela ukuhlolwa kwezimfanelo zesevisi ezisetshenziswa ukukhetha inkampani yezindiza azoyisebenzisa ezimakethe zalezi ezihambela ngaphakathi eNingizimu Afrika. Ukufezekisa le nhlosongqangi kanye nezinye izizathu zocwaningo, idizayini yokucwaningo ye’quantitative descripto-explanatory’ isetshenziswe ukuqokelela idatha nokuhlaziya ulwazi. Isampula yababambe iqhaza abangama-324 ikhethiwe kusetshenziswa i hybrid technique of convenience, kanye nendlela yesampula yemihlathi eyazanayo (snowball sampling), kanti idatha iqoqwe ngakho kokubili, ‘online’ namaphepha anemibuzo ebuzelwa ukuthola okuthile. Idatha etholakele ihlukanisiwe yenzelwa ukuhlaziyeka kahle kusetshenziswa iStatistical Product neService Solutions (SPSS 26) kanye ne-Analysis of a Moment Structures (AMOS Version 26) software. I-Exploratory factor analysis (EFA) yenziwe ukuze kuhlolwe ukuthi izakhiwo eziyizimiso ukuqaphela okuguqukayo kwabuye kwaqashelwa ne-identify latent constructs. I- factorability yeportrait value questionnaire (PVQ) izinto zanqunywa kusetshenziswa iconfirmatory factor analysis (CFA). Umbono ube usuhlolwa kusetshenziswa ibackward multiple regression analysis, Whitney-Mann test, Spearman correlation ne hierarchical regression ene Hayes’ Process Macro. Lolu cwaningo lube nezinkomba ezinhlanu zika’Schwartz’s 19’ ezingamagugu acwengisisiwe abe nomthelela wazo ethonyeni lokuhlola nokubeka phambili kwezinkampani zezindiza izimfanelo zesevisi. Kutholwe isimo sokunganaki kubagibeli uma kuhlolwa izimfanelo zesevisi yenkampani yezindiza, kuphela nje isevisi yangaphakathi endizeni ithathwa njengebaluleke kakhulu enomthelela emiphumeleni yokuthenga kamuva okubalwa kukho ukwaneliseka kwabagibeli, ukwethembeka nokuphinda kuthengwe amanye ngokuzayo. Kutholakele ukuthi abagibeli abakwazanga ukwahlukanisa phakathi kosizo olusezingeni eliphansi nalolo olusezingeni eliphezulu. Inzuzo ibe nomthelela kuphela ekukhuthazeni isiqondiso ngasinye ngokwamagugu okuziphatha ezinsizeni zesevisi yenkampani yezindiza ngakolunye uhlangothi ezokuxhumana kwezezimakethe kuyimizamo etholakele kube neqondile kuneqhaza elisezingeni elilinganayo. Ngokwesidingo, lokhu okutholakele kwethula indlela entsha ecebileyokuchaza ukuqokwa kwezinkampani zezindiza ezisethenziswa abantu abawuhlobo oluthile. Imiphumela ibalulekile emakethe yezinkampani zezindiza ukuze kwahlukaniswe, kubekwe endaweni, kuthuthukiswe imikhiqizo yezinkampani zezindiza noma izinto ezithandwa abagibeli nezidingo zabo zempilo okuyizona eziwumhlahlandlela wokuqoka inkampani abazoyisebenzisa / Business Management / D. Com. (Business Management)

This thesis examines restoration of Garry oak ecosystems in Southwestern British Columbia, Canada. Before the arrival of European settlers, Coast Salish peoples practiced intensive stewardship and cultivation practices that heavily shaped Garry oak ecosystems. These long-standing stewardship practices are responsible for the abundance of culturally important plants found in Garry oak ecosystems today. In addition to their cultural value to Coast Salish peoples, Garry oak ecosystems also support unique biodiversity, including numerous at-risk species. These ecosystems and the values they embody came under threat with the arrival of European settlers, who introduced non-native plants and excluded Coast Salish peoples and their stewardship practices from these ecosystems. Today, Garry oak ecosystems have been reduced to a fraction of their pre-colonial distribution and remaining patches are typically heavily invaded by both native and non-native plants. Their cultural and biological values coupled with ongoing degradation has motivated both Indigenous and non-Indigenous land managers to implement restoration programs in Garry oak ecosystems. To inform future restoration efforts, this thesis examines ecological impacts of a long-term restoration program and a wildfire in a lək̓ʷəŋən Garry oak ecosystem at Mill Hill Regional Park near Langford, British Columbia. In Project 1, vegetation responses to a 13-year invasive species removal program were quantified to determine if native plant populations were successfully bolstered by the removal efforts. In Project 2, impacts of an unintended wildfire on the relative cover of native and non-native plants were examined. This attempted to explore potential ecosystem shifts that may occur as wildfires increase in frequency and severity as predicted by climate models. In Project 1, the greatest change observed after invasive species removal was an increase in other introduced species, while increases in native species were not statistically significant. In Project 2, introduced Anthoxanthum odoratum was facilitated by fire while native Camassia spp. were reduced by it. Taken together, these results demonstrate the complexity of restoring Indigenously managed ecosystems where multiple introduced species have existed for long periods. Invasive species, specifically Anthoxanthum odoratum, showed greater responses to removal efforts and wildfire than native species. Intensive, long-term restoration programs that utilize multiple tools, including low-intensity fire, invasive removal, herbicide, and seeding of native species appear necessary to bolster native species without unintentional facilitation of introduced species. Coast Salish peoples and stewardship practices were integral in maintaining these ecosystems before the arrival of European settlers and should play a key role in their restoration today, though traditional practices will likely need adapted to account for environmental changes caused by colonization. Furthermore, to avoid continuing the cultural damage that began with colonization, it is vital that Coast Salish First Nations lead or be directly involved in restoration of these ecosystems, which continue to hold irreplaceable cultural value. / Graduate / 2023-01-14

Retrotransposons are major components of plant genomes influencing their genome size, organization and evolution. In the frame of this work, retrotransposons of the Beta vulgaris genome have been identified by molecular methods and whole genome bioinformatics approaches. Neither belonging to the rosids nor asterids, B. vulgaris (cultivated beet including sugar beet, beet root and mangold) is taxonomically placed at a key position at the root of the core eudicots, and considerably different from traditional plant model species such as thale cress or rice. Its genome has been sequenced, and annotation is under way. In order to compare different evolutionary lineages of B. vulgaris retrotransposons, long terminal repeat (LTR) and non-LTR retrotransposon family have been analyzed in detail. Full-length members have been isolated and characterized by bioinformatics, Southern and fluorescent in situ hybridization. Hallmarks of the LTR retrotransposon family Cotzilla are an additional env-like open reading frame (ORF), homogeneity of the members and the very high abundance. Most family members are evolutionarily young, and have most likely been created during recent bursts of amplification during species radiation. In contrast, the non-LTR retrotransposon family BNR has fewer copies and is much more diverged. Although the BNR ORF2 resembles previously analyzed long interspersed nuclear elements (LINEs) of the L1 clade, its ORF1 sequence differs strongly. It lacks the zinc finger domain described for plant LINEs, but contains instead an RNA recognition motif (RRM) likely to have an RNA-binding function. Database searches revealed the presence of similar LINE families in higher plant genomes such as poplar, lotus and soybean. Comparing their reverse transcriptase regions with other retrotransposons, these BNR-like LINEs form a separate group of L1 LINEs designated as BNR subclade. Availability of the B. vulgaris genome sequence allowed retrotransposon analyses on a genome-wide scale. A Hidden Markov Model-based detection algorithm has been developed in order to retrieve retrotransposon information directly from the database. Nearly 6000 B. vulgaris reverse transcriptase sequences have been isolated and classified into LTR retrotransposons of the Ty3-gypsy and Ty1-copia type, and non-LTR retrotransposons of the LINE type. As a result, a comprehensive overview of the retrotransposon spectrum of the B. vulgaris genome has been generated. Since plant LINEs have been only rarely investigated, the B. vulgaris LINE composition was studied in detail. Out of 28 described LINE clades, only members of the L1 and RTE clades have been identified. Based on a minimal shared sequence identity of 60 %, they form at least 17 L1 families and one RTE family. Full-length members of all investigated L1 families have been analyzed regarding their sequence, structure and diversity. In order to transfer the algorithm tested in B. vulgaris to other angiosperm genomes, twelve additional plant genomes have been queried for LINE reverse transcriptases. Key finding is the presence of only two LINE clades (L1 and RTE) in the analyzed genomes of higher plants. Whereas plant L1 LINEs are highly diverse and form at least seven subclades with members across species borders, RTE LINEs are extremely homogenized and constitute most likely only a single family per genome. In summary, this work’s results help to gain an understanding of the different strategies of retrotransposon evolution in plants, whereas the generated data directly contributes to the B. vulgaris genome annotation project. / Retrotransposons sind eine wesentliche Komponente von Pflanzengenomen, die sowohl die Größe und Organisation als auch die Evolution dieser Genome wesentlich beeinflussen können. Im Rahmen dieser Arbeit wurden verschiedene Gruppen von Retrotransposons des Beta vulgaris Genoms mittels molekularer und bioinformatischer Methoden identifiziert. Innerhalb der dikotyledonen Blütenpflanzen gehört B. vulgaris (kultivierte Rübe einschließlich Zuckerrübe, Roter Beete und Mangold) weder zu den Rosiden noch zu den Asteriden, sondern nimmt eine Schlüsselposition innerhalb der Kerneudikotyledonen ein. Somit zeigt das Rübengenom wesentliche Unterschiede zu traditionellen Modellpflanzen wie Arabidopsis thaliana oder Oryza sativa. Das Genom ist bereits sequenziert, die Annotation jedoch noch nicht abgeschlossen. Um verschiedene evolutionäre Linien von B. vulgaris Retrotransposons vergleichend zu untersuchen wurden insbesondere Long Terminal Repeat (LTR)- und Non-LTR-Retrotransposon-Familien detailliert analysiert. Vollständige Mitglieder wurden isoliert und mittels bioinformatischer Methoden, Southern- und Fluoreszenz-in situ-Hybridisierung untersucht. Die LTR-Retrotransposon-Familie Cotzilla ist durch einen zusätzlichen env-ähnlichen offenen Leserahmen (ORF), Homogenität ihrer Mitglieder und eine hohe Abundanz gekennzeichnet. Die meisten Cotzilla-Kopien sind evolutionär jung und wurden wahrscheinlich innerhalb eines kurzen Zeitraumes während der Artentstehung stark amplifiziert. Im Gegensatz zur Cotzilla-Familie besitzt die Non-LTR-Retrotransposon-Familie BNR weniger Kopien und ist wesentlich divergierter. Während der BNR-spezifische ORF2 starke Ähnlichkeiten zu anderen pflanzlichen Long Interspersed Nuclear Elements (LINEs) der L1-Klade aufweist, unterscheidet sich der BNR ORF1 von diesen sehr stark. Im Gegensatz zu bereits beschrieben pflanzlichen LINEs kodiert er kein Zinkfingermotiv, sondern substituiert dieses durch ein RNA-Erkennungsmotiv (RRM). Durch Datenbanksuche konnten BNR-ähnliche LINEs in den Genomen höherer Pflanzen wie Soja, Lotus und Pappel identifiziert werden. Ein Vergleich der entsprechenden Reversen Transkriptasen (RT) mit den RTs anderer Retrotransposons zeigt, dass die BNR-ähnlichen LINEs eine separate Gruppe innerhalb der L1 LINEs bilden. Diese wurde daher als BNR-Subklade definiert. Die Untersuchung von Retrotransposons auf Genomebene wurde durch die B. vulgaris Genomsequenz ermöglicht. Um Retrotransposon-Informationen direkt aus dem Genom zu extrahieren, wurde ein Hidden Markov Modell (HMM)-basierter Detektions-algorithmus entwickelt. Annähernd 6000 B. vulgaris Reverse Transkriptase-Sequenzen konnten identifiziert und in LTR-Retrotransposons des Ty3-gypsy- beziehungsweise des Ty1-copia-Typs und in Non-LTR-Retrotransposons des LINE-Typs klassifiziert werden. Somit wurde ein umfassender Überblick über die Bandbreite der B. vulgaris Retrotransposons arhalten. Da pflanzliche LINEs bisher nur wenig erforscht sind, wurde die B. vulgaris LINE Zusammensetzung genauer untersucht. Von 28 beschriebenen LINE-Kladen konnten nur Mitglieder der L1- und der RTE-Klade identifiziert werden. Basierend auf einer Identität von mindestens 60 % bilden die Sequenzen 17 L1 Familien und eine RTE Familie. Vollständige Mitglieder aller L1 Familien wurden hinsichtlich ihrer Sequenz, Struktur und Diversität analysiert. Um den in B. vulgaris getesteten HMM-basierten Algorithmus auf andere Angiospermengenome zu übertragen, wurden zwölf weitere Pflanzengenome auf das Vorhandensein von LINE-spezifischen Reversen Transkriptasen untersucht. Wesentlichstes Ergebnis ist der Nachweis von nur zwei LINE-Kladen (L1 und RTE) in höheren Pflanzen. Während pflanzliche L1 LINEs hochgradig divers sind und über Artgrenzen hinaus mindestens sieben Subkladen mit Vertretern verschiedener Pflanzen bilden, sind RTE LINEs extrem homogenisiert und stellen höchstwahrscheinlich nur eine einzelne Familie pro Genom einer Art dar. Zusammenfassend ermöglichen die Ergebnisse dieser Arbeit eine Erweiterung des Verständnisses der unterschiedlichen Evolutionsstrategien von Retrotransposons in Pflanzen. Zusätzlich tragen die gewonnen Daten zur Annotation des B. vulgaris Genoms bei.

Ziel der vorliegenden Arbeit ist die retrospektive Beurteilung der Sicherheit und Effektivität der Leberteilresektion bei der Behandlung von Lebermetastasen des kolorektalen Karzinoms sowie der Re-Resektion bei Patienten mit Rezidivlebermetastasen. Weiterhin soll das operative Vorgehen bei synchronen Lebermetastasen hinsichtlich simultaner Resektionsverfahren und zweizeitigen Vorgehens untersucht werden. Insgesamt wurden die Ergebnisse von 660 Patienten ausgewertet, die zwischen 1988 und 2004 mit 685 Leberteilresektionen behandelt wurden. Unter diesen waren 75 Patienten, die eine Re-Resektion erhielten sowie 202 Patienten, bei denen die Lebermetastasen synchron auftraten. Neben der Analyse der postoperativen Letalität und postoperativen Komplikationen sollen prognostische Faktoren für das Langzeitüberleben und das Auftreten von Tumorrezidiven nach Leberteilresektion identifiziert werden. Da sich die Studienpopulation aus einem Zeitraum von über 15 Jahren rekrutiert, sollen außerdem verschiedene Zeitabschnitte vergleichend analysiert werden. Die Leberteilresektion ist derzeit die einzige potentiell kurative Therapie bei kolorektalen Lebermetastasen. Als prognostisch günstige Parameter in der multivariaten Analyse zeigten sich die Radikalität des Eingriffes, die Anzahl der Metastasen, vorhandene ligamentäre Lymph-knotenmetastasen sowie das Jahr der Resektion. Auch bei Rezidiven kolorektaler Lebermetastasen ist das chirurgische Vorgehen derzeit die einzige kurative Intervention. Re-Resektionen weisen ein vergleichbares operatives Risiko und vergleichbare Langzeitüberlebensraten auf wie Erstresektionen. Als einziger prognostischer Parameter für das Langzeitüberleben erwies sich in der multivariaten Analyse die Radikalität des Eingriffes. Bei synchronen Lebermetastasen sind die wichtigsten Kriterien, um eine simultane Resektion durchzuführen, die Berücksichtigung des Alters sowie des Resektionsausmaßes. Simultane Resektionen sind bei synchronen kolorektalen Lebermetastasen dann so sicher und effizient durchführbar wie Resektionen im zweizeitigen Vorgehen.

Targeting DNA has the advantage over proteins for cancer remediation because of the fewer copies of the ligands required for the desired therapeutic effect. Traditionally, covalent DNA binders like alkylating agents have been used to induce genetic instability through the formation of DNA lesions and strand breaks, leading to cellular apoptosis. The primary drawback of this treatment is the non-specific binding that affects both cancerous and non-cancerous cells. G-quadruplexes are the DNA secondary structures that are present in abundance near the promoter regions of the oncogenes and are involved in the regulation of their activities. A ligand-mediated stabilization of G-quadruplexes in the promoter regions and down-regulation of the associated oncogenes have been validated. In contrast to alkylating agents, G-quadruplex ligands induce genetic stabilization through non-covalent interactions. They can be designed to interact specifically with G-quadruplex DNA over duplex DNA, which reduce side effects arising from the off-targeting. G-quadruplex ligands invariably have the large planar aromatic moiety to interact with G-quadruplexes through π- π stacking interactions. For determining the size effect of the aromatic moiety on stabilization of G-quadruplexes, a series of ligands were synthesized by conjugating nucleobases or 1,10-phenanthroline with an aminoglycoside, neomycin. The resulting conjugates increased the binding affinity synergistically and enabled us to study the effect of the stacking moiety required for G-quadruplex stabilization. Nucleobase-neomycin conjugates did not show stabilization stabilize of human telomeric G-quadruplex. 1,10-Phenanthroline-neomycin conjugate (7b) on the other hand binds to human telomeric G-quadruplex with a Ka of (8.92.4)×108 M-1 and inhibits telomerase activity at 1.56 µM probably through G-quadruplex stabilization. Moving forward, we further enlarged the aromatic moiety by tethering two 1,10-phenantholine molecules together through a five-atom linker. The resulting molecule (2-Clip-phen) was conjugated with various amino-containing side chains. 2-Clip-phen derivatives showed at least 30 times weaker binding to duplex DNA over G-quadruplex DNA. In addition, compounds showed a preference for the antiparallel G-quadruplex conformation over parallel and hybrid G-quadruplex conformations, as shown in the CD spectroscopy studies. Ligands 11 and 13 induced the formation of an antiparallel G-quadruplex from random coils and stabilize it to 60 oC (Tm) in a salt-free condition. Mass spectrometry study showed the formation of a two-tetrad G-quadruplex with the 2-Clip-phen ligand. Docking study showed that the ligand interacts most favorably with antiparallel G-quadruplex conformation, which is supported further by the larger thermal stabilization effect on antiparallel G-quadruplex compared with other G-quadruplex conformations. Our study suggests that 2-Clip-phen can be used as a scaffold for designing G-quadruplex binding ligands that preferentially bind to antiparallel G-quadruplexes, which has never been reported before.

Der Vortrag gibt einen Überblick der Neuerungen im Werkzeug Mechanism der Creo Versionen 1.0 und 2.0. Zudem werden 10 hilfreiche "Tips und Tricks" vorgestellt, welche den Mechanismuseinsatz vereinfachen.

Intra-archipelago waterways, including tidal strait networks, present a complex set of barriers to, and conduits for sediment transport between marine basins. Tidal straits may also be the least well understood tide-dominated sedimentary environment. To address these issues, currents, sediment transport pathways, and seabed sedimentology & geomorphology were studied in the central Salish Sea (Gulf and San Juan Islands region) of British Columbia, Canada and Washington State, USA. A variety of data types were integrated: 3D & 2D tidal models, multibeam bathymetry & backscatter, seabed video, grab samples, cores and seismic reflection. This dissertation included the first regional sediment transport modelling study of the central Salish Sea. Lagrangian particle dispersal simulations were driven by 2D tidal hydrodynamics (~59-days). It was found that flood-tide dominance through narrow intra-archipelago connecting straits resulted in the transfer of sediment into the inland Strait of Georgia, an apparent sediment sink. The formative/maintenance processes at a variety of seabed landforms, including a banner bank with giant dunes, were explained with modelled tides and sediment transport. Deglacial history and modern lateral sedimentological and morphological transitions were also considered. Based on this modern environment, adjustments to the tidal strait facies model were identified. In addition, erosion and deposition patterns across the banner bank (dune complex) were monitored with 8-repeat multibeam sonar surveys (~10 years). With these data, spatially variable bathymetric change detection techniques were explored: A) a cell-by-cell probabilistic depth uncertainty-based threshold (t-test); and B) coherent clusters of change pixels identified with the local Moran's Ii spatial autocorrelation statistic. Uncertainty about volumetric change is a considerable challenge in seabed change research, compared to terrestrial studies. Consideration of volumetric change confidence intervals tempers interpretations and communicates metadata. Techniques A & B may both be used to restrict volumetric change calculations in area, to exclude low relative bathymetric change signal areas. / Graduate / 2018-12-07

In the present hypercompetitive market environment of car producers established especially at the developed west european markets is very difficult to gain new customers and increase the market share. The car producing companies have to build and increase customer loyalty to ensure the sustainable growth of market share in the future. One possibility how to improve customer's loyality to brand is to provide the highest standard at both sales and service department and carefully monitor the customer satisfaction. From the satisfaction and performance indicators of the car producing company is possible to construct a mathematical model producing the market share in a given country as an output. Key indikators of customer satisfaction, sales and service and also the macroeconomical data has been used as the inputs for the model. As a target market for my analysis has been chosen Germany. This thesis presents a set of recommendations and proposals, whose implementation should ensure the improvement of the market share of the given brand on german market. The recommendation does not include only the tips for improvement of the key indicators but it also gives the overview of how to make the marketing strategy more efficient using Customer relationship management.

Der Vortrag gibt einen Überblick der Neuerungen im Werkzeug Mechanism der Creo Versionen 1.0 und 2.0. Zudem werden 10 hilfreiche "Tips und Tricks" vorgestellt, welche den Mechanismuseinsatz vereinfachen.