Denna studie är baserat på flertal olika studier som diskuterar ämnet webbanalysering. Webbanalysering är något som har vuxit enormt eftersom flera vill kunna se hur effektiv en webbplats faktiskt fungerar ute på internet. Genom att samla in data kunna se hur en webbplats används och kunna optimera den eller enbart samla data för intressets skulle. Frågan som detta arbete tar upp är, hur mycket påverkar svarstiderna webbplatsen, när en handskriven webbanalyserings applikation är implemeterad. Verktyget kombinera flera olika slags tekniker för att samla in data kontinuerligt för den ansvarige. Resultatet visar att verktyget inte påverkar svarstiderna så att användarens vistelse på webbplatsen skulle bli negativ.

The Safety of passwords has been in question for over 40 years, long before the Internet. While improvements have been made to ensure security nothing has changed with passwords since the emergence of the Internet. Passwords need to be long and complex to be secure and users should not reuse their passwords. In a world where there are thousands of services on the internet requiring authentication to keep passwords safe users will have to remember a lot of passwords. Studies show however that users are prone to both create bad passwords but to also reuse their passwords on different sites. A lot of different alternatives to passwords has been proposed but none has become dominant. Is there a good alternative to text-based passwords? Can a graphical password be that alternative? The purpose of this thesis is to create a prototype of a CCP-like system and to conduct a memorability and usability test with it. The test results suggest that CCP is easy to use for users new to the concept of graphical passwords. A CCP-password also seems memorable with most participants recalling their passwords after a week with ease. PCCP can be a good substitute for passwords since it is easy to use, easy to remember and potentially more secure than text-based passwords.

All known living cells contain a complex set of molecular machinery to support their growth and replication. However, the earliest cells must have been much simpler, consisting of a compartment and a genetic material to allow for Darwinian evolution. To study these intermediates, plausible model `protocells' must be synthesized in the laboratory since no fossils remain. Recent work has shown that fatty acids can self-assemble into vesicles that are able to grow and divide through simple mechanisms. However, a self-replicating protocell genome has not yet been developed. Here we discuss studies of systems that allow for the copying of nucleic acid templates without enzymes and how they could be developed into a genetic material.

Carbon monoxide (CO) is an endogenous signaling molecule and has therapeutic values. However, the application of CO in the development of therapeutic options is hampered by the lack of pharmaceutically acceptable delivery methods. Inhalation of CO is not an ideal option for wide-spread clinical applications. Existing CO releasing molecules (CORMs) are mostly metal complexes, which have toxicity concerns to overcome. Some metal free CORMs have been developed. However, they all require light as a trigger to release CO, which limits their applications in vivo. Herein, we describe a metal-free CO prodrug approach using an intramolecular inverse electron-demanded Diels-Alder reaction. Such prodrugs can release CO spontaneously under physiological conditions with tunable release rates with the concomitant formation of a fluorescent reporter after CO releases. This intramolecular “click and release” strategy represents a milestone in the development of CO based therapeutics.

The antiviral or anticancer activities of C-5 modified pyrimidine nucleoside analogues validate the need for the development of their syntheses. In the first half of this dissertation, I explore the Pd-catalyzed cross-coupling reaction of allylphenylgermanes with aryl halides in the presence of SbF5/TBAF to give various biaryls by transferring multiple phenyl groups, which has also been applied to the 5-halo pyrimidine nucleosides for the synthesis of 5-aryl derivatives. To avoid the use of organometallic reagents, I developed Pd-catalyzed direct arylation of 5-halo pyrimidine nucleosides. It was discovered that 5-aryl pyrimidine nucleosides could be synthesized by Pd-catalyzed direct arylation of N3-free 5-halo uracil and uracil nucleosides with simple arenes or heteroaromatics in the presence of TBAF within 1 h. Both N3-protected and N3-free uracil and uracil nucleosides could undergo base-promoted Pd-catalyzed direct arylation, but only with electron rich heteroaromatics. In the second half of this dissertation, 5-acetylenic uracil and uracil nucleosides have been employed to investigate the hydrogermylation, hydrosulfonylation as well as hydroazidation for the synthesis of various functionalized 5-vinyl pyrimidine nucleosides. Hydrogermylation of 5-alkynyl uracil analogues with trialkylgermane or tris(trimethylsilyl)germane hydride gave the corresponding vinyl trialkylgermane, or tris(trimethylsilyl)germane uracil derivatives. During the hydrogermylation with triphenylgermane, besides the vinyl triphenylgermane uracil derivatives, 5-[2-(triphenylgermyl)acetyl]uracil was also isolated and characterized and the origin of the acetyl oxygen was clarified. Tris(trimethylsilyl)germane uracil derivatives were coupled to aryl halides but with decent yield. Iron-mediated regio- and stereoselective hydrosulfonylation of the 5-ethynyl pyrimidine analogues with sulfonyl chloride or sulfonyl hydrazine to give 5-(1-halo-2-tosyl)vinyluracil nucleoside derivatives has been developed. Nucleophilic substitution of the 5-(β-halovinyl)sulfonyl nucleosides with various nucleophiles have been performed to give highly functionalized 5-vinyl pyrimidine nucleosides via the addition-elimination mechanism. The 5-(β-keto)sulfonyluracil derivative has also been synthesized via the aerobic difunctionalization of 5-ethynyluracil analogue with sulfinic acid in the presence of catalytic amount of pyridine. Silver catalyzed hydroazidation of protected 2'-deoxy-5-ethynyluridine with TMSN3 in the presence of catalytic amount of water to give 5-(α-azidovinyl)uracil nucleoside derivatives was developed. Strain promoted Click reaction of the 5-(α-azidovinyl)uracil with cyclooctyne provide the corresponding fully conjugated triazole product.

Pas de résumé disponible. / No abstract available.

This paper is focused on analysis of internet advertising and its role in marketing communication. The paper determines general methods and instruments of internet marketing and describes internet advertisement in comparison with traditional advertising media. In more detail the paper is focused on description and explanation of effect of Pay-Per-Click advertisement campaigns. The options of their usage and recognized differences are explicated by practical instance of marketing strategies of real companies.

This thesis focuses on the effectiveness of marketing tools available in Czech internet environment. The theoretical part describes typical attributes and advantages of individual tools and observes the possibilities of achieving marketing and commercial goals by using these tools. In the application part, the surveyed e-shop is introduced and it's marketing tools are analyzed using web analytics. Either behaviour of customers of this e-shop or financial indicators, which are crucial for evaluating performance, are analyzed in this thesis. The synergic effect of using these marketing channels is evaluated using the assisted conversions analysis. The main goals of this thesis is evaluation of the efficiency of used marketing tools using web analytics and consider suitability of their use for this specific e-shop. Another aim is comparing the performance of individual marketing sources and proposing measures to help increase efficiency of tools used by this e-shop.

Inhibition of enzymes in the isoprenoid biosynthetic pathway (IBP) plays an important role in the treatment of bone diseases and lowering cholesterol. The IBP begins with the enzyme HMG-CoA reductase catalyzing the conversion of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid. Mevalonic acid is then converted to isopentenyl pyrophosphate (IPP) via the intermediate mevalonate-5-diphosphate. Three molecules of IPP are joined by the enzyme farnesyl diphosphate synthase (FDPS), which yields the intermediate farnesyl pyrophosphate (FPP). FPP is an important substrate and represents the branch point in the pathway. Compounds which disrupt this pathway at FDPS include risedronate, lovastatin, and zoledronate. It is believed these compounds express their pharmacological effects on a further downstream enzyme. Further downstream from FDPS the IBP includes the key enzymes geranylgeranyl diphosphate synthase (GGDPS), which is responsible for the production of geranylgeranyl pyrophosphate (GGPP) and necessary for protein prenylation of the proteins Ras, Rho, and Rab. The second key enzyme is geranylgeranyl transferase II (GGTase II), which is responsible for the transfer of GGPP to Rab proteins. Rab proteins, which play an essential role for both protein secretion and trafficking, are of great interest as a therapeutic target for the bone disease multiple myeloma. Multiple myeloma is a disorder of malignant plasma cells, characterized by the overproduction of monoclonal protein, antibodies, or light chains, which can ultimately thicken the blood. Targeting the prevention of geranylgeranylation of the Rab proteins by the enzyme GGTase II can happen through two different strategies. The first would be an indirect route, which would aim to inhibit the enzymes upstream from GGTase II. This could include the enzymes HMG-CoA reductase, FDPS, and GGDPS. Drugs that inhibit the earlier steps in the IBP indirectly prevent protein geranylgeranylation but they also limit formation of other key processes further downstream. The second approach would be a direct inhibition of the enzyme responsible for protein prenylation, GGTase II. There are very few know inhibitors of GGTase II. One such inhibitor is a carboxyphosphonate 3-PEHPC, a mimic of the bisphosphonate risedronate. Unfortunately, 3-PEHPC does not display an attractive potency. Efforts to develop a more potent inhibitor of the enzyme GGTase II, have focused on the preparation of a family of carboxyphosphonates containing a triazole core, and these compounds were prepared via click chemistry. Their activity has been studied, but the salts that were successfully made were ultimately inactive in comparison to 3-PEHPC. Previous attempts at forming isoprene-containing triazole carboxyphosphonates, as isoprene chains were shown to help increase activity towards GGTase II, proved difficult and unsuccessful. Focus was then switched to alteration of isoprene bisphosphonate triazoles as GGDPS inhibitors in attempts to increase activity towards this enzyme. The biological activity of these bisphosphonates was found to be selective and potent inhibitors of GGDPS, with little to no activity towards the GGTase II enzyme. In an effort to develop more potent inhibitors, isoprene triazole carboxyphosphonates were produced in an attempt to enhance the biological activity towards GGTase II. Along with forming a family of isoprene bisphosphonate compounds to increase the biological activity towards GGDPS in comparison to other previously made bisphosphonates. These carboxyphosphonate and bisphosphonate compounds were prepared through click chemistry and tested for their activity toward GGTase II and GGDPS.

<div><p>The cellular protein pool exists in a state of dynamic equilibrium, such that a balance between protein synthesis and degradation is maintained to sustain protein homeostasis. This equilibrium is essential for normal cellular functions and hence alteration in protein dynamics has several pathological implications in developing and adult tissues. Recent progress in mass spectrometry (MS) and metabolic labeling techniques has advanced our understanding of the mechanisms of protein regulation in cultured cells and less complicated multicellular organisms. However, methods for the analysis of the dynamics of intra- and extra-cellular proteins in embryonic and adult tissues remain lacking.</p><p>To address this gap, we developed a metabolic labeling technique that enables labeling the nascent murine proteome via injection of non-canonical amino acids (ncAAs), which can be selectively enriched by “clickable” tags for identification and quantification. Using this technique, we developed a MS-based method for the selective identification and quantification of the intra- and extra-cellular newly synthesized proteins in developing murine tissues. We then applied this technique to study the dynamic regulation of extracellular matrix (ECM) proteins during embryonic and adolescent musculoskeletal development. We show that the applied technique enables resolving differences in the nascent proteome of different developmental time points with high temporal resolution. The technique can also reveal protein dynamic information that cannot be captured by the traditional proteomic techniques. Additionally, we identified key ECM components that play roles in musculoskeletal development to provide insights into the mechanisms of musculoskeletal tissue regeneration.</p><p>To fully characterize our labeling technique, we developed a mathematical model to describe the biodistribution kinetics of azidohomoalanine (Aha), the most widely used ncAA, in murine tissues. The model enabled measuring the relative rates of protein synthesis and turnover in different tissues and predicting the effect of different dosing regimens of Aha on the degree of protein labeling. Finally, we analyzed the plasma metabolome of Aha-injected mice to investigate the impact of Aha incorporation on normal physiology. The analysis revealed that Aha administration into mice does not significantly perturb metabolic functions. Taken together, the findings presented in this dissertation demonstrate the utility of the ncAA labeling technique in mapping protein dynamics in mammalian tissues. This will ultimately have a significant impact on our understanding of protein regulation in health and disease. </p></div><br>