Advertising plays a vital role in supporting free websites and smart- phone apps. Click-spam, i.e., fraudulent or invalid clicks on online ads where the user has no actual interest in the advertiser's site, results in advertising revenue being misappropriated by Click-spammers. This revenue also funds malware authors through adware and malware crafted specifically for click-spammers. While some ad networks take active measures to block Click-spam today, the effectiveness of these measures is largely unknown, as they practice security-through-obscurity for fear of malicious parties reverse-engineering their systems. Moreover, advertisers and third parties have no way of independently estimating or defending against Click-spam. This work addresses the click-spam problem in three ways. It proposes the first methodology for advertisers to independently measure Click-spam rates on their ads. Using real world data collected from ten ad networks, it validates the method to identify and perform in-depth analysis on seven ongoing Click-spam attacks not currently caught by major ad networks, high- lighting the severity of Click-spam. Next, it exposes the state of Click-spam defenses by identifying twenty attack signatures that mimic Click-spam attacks in the wild (from Botnets, PTC sites, scripts) that can be easily detected by ad networks, and implements these attacks, and shows that none of the ad networks protect against all the attacks. This also shows that it's possible to reverse engineer click-fraud rules employed by ad networks in spite of the security-through-obscurity practices prominent today. Finally, it shows that it is not just possible, but also desirable to create Click-spam algorithms that do not rely on security-through-obscurity but instead on invariants that are hard for click-spammers to defeat, as such algorithms are inherently more robust and can catch a wide variety of click-fraud attacks. / text

In the first part of the thesis, a series of six modified 2'-deoxyadenosine triphosphates, bearing small functional groups (chloro, amino, methyl, vinyl, ethynyl and phenyl) at position 2 of adenine, was designed and synthesised. They were then tested as substrates for DNA polymerases in enzymatic synthesis of minor-groove modified DNA. The 2-phenyl modified dATP was the only triphosphate unable to be incorporated, meaning that the phenyl group is already too big for minor-groove incorporations. All of the other tested nucleotides were good substrates for tested DNA polymerases [KOD XL, Vent(exo-) and Bst LF] affording minor- groove modified DNA bearing one or four modifications. The vinyl- and ethynyl-modified DNAs were then used for post-synthetic modification of DNA minor groove with fluorescent labels utilising click reactions. Ethynyl group reacted in copper-catalysed alkyne-azide cycloaddition (CuAAC), whereas the vinyl group participated in thiol-ene reaction. This procedure allowed for the attachment of big functional groups otherwise unable to be installed into the DNA minor groove using direct enzymatic incorporation. The second part of the thesis was devoted to the study of 2-alkylamino-2'- deoxyadenosine triphosphates and their use in enzymatic synthesis of base-modified ONs and DNA....

A range of copper(I) alkynyl ladder polymers have been prepared via a simple single step microwave reaction at 100 °C for 2 minutes, using copper hydroxyacetate (Cu2(OH)3Ac.H2O) as the copper source, all with yields in excess of 80 %. A variety of functional groups were chosen ranging from a simple aromatic phenol ring, substituted aromatic groups, groups with a long carbon chain, and an example of 2 alkynyl units in one chain. The polymeric structure of these materials has been elucidated by powder X-ray diffraction, the results of which confirm that by changing the R groups on the copper ladder chains the structure of the ladder itself is altered to accommodate the variety of sizes and shapes. This was further detailed using a series of methyl substituted phenyl rings as the R group (ortho, meta and para), which were further examined by solid state NMR, and Raman spectroscopy. The raman data confirmed that the copper copper distance in the ladder backbone varied based on the side group present. The NMR results suggest that not only are there variations to copper backbone, but also there are different possible positions for the aromatic group to stack in based on the substitution on the aromatic ring. All data collected indicates the crystallinity of the polymer is strongly affected by the choice of alkyne. The range of ladder polymers has been used to catalyse a series of dipolar cycloaddition reactions of terminal alkynes and organic azides, with the aim to obtain additional mechanistic information on the alkyne-azide click reactions. These reactions were carried out using a simple microwave method requiring an excess of alkyne (1.5 eq) to azide (1 eq), using 10 mol% of the ladder polymer as catalyst for 10 minutes at 100 °C. These conditions were then modified slightly to allow for on water catalysis of the click reactions using copper(I) alkynyl ladder polymers. Triazole products were obtained in excellent yields ranging from approximately 60 -95%. Using similar conditions it was also possible to introduce an iodo group to the triazole product when starting with iodoacetylene rather than a terminal alkyne, with only slightly reduced yields of 50-70%. Flow chemistry was briefly tested and was shown to be a viable option for the synthesis of 1,2,3-traizoles using copper(I) alkynyl ladder polymer catalysts. The support material copper on carbon was investigated for comparison with the copper(I) alkynyl ladder polymers. The support material was found to actually be a composition of copper hydroxynitrate, a layered material capable of forming copper(I) ladder polymers, and carbon. A series of these materials were made using different supports using the same method as carbon, and all resulted in a mixture of copper hydroxynitrate and support material. An impurity was discovered in specific carbon batches (depending on the carbon preparation method) and was identified as libethenite (copper hydroxyphosphate). A series of click reactions were carried out using these copper hydroxynitrate/carbon mixtures and excellent yields of 80-90% were obtained, the impurity libethenite was also tested but found to not catalyse the click reaction.

Tese de mestrado integrado. Engenharia Electrotécnica e de Computadores. Faculdade de Engenharia. Universidade do Porto. 2010

Layer-by-layer assembly has received much attention over the last fifteen years. This assembly process can be carried out using different methods including hydrogen-bonding, electrostatic, and to a lesser extent, covalent interactions. However, these assemblies are rarely seen on polyolefin substrates due to the lack of functionality on the surface. “Click” chemistry has become very popular in recent years as a means to join modular compounds together. This thesis is the first published report to use “click” chemistry as a means for layer-by-layer assembly on a polymeric substrate. By designing polymers that contain alkyne or azide groups, it is possible to assemble them layer-by-layer on a polyethylene substrate. Polymers based on tert-butyl acrylate were initially designed for use in organic solvents such as tetrahydrofuran. The copper catalyst that facilitated the 1,3-dipolar cycloaddition was air sensitive and expensive. To capture the true essence of “click” chemistry, a new system was designed based on N-isopropyl acrylamide (NIPAM)-based polymers. These polymers were water soluble and allowed for “click” chemistry to be performed in water and open to air in benign conditions. With the development of a water soluble polymer system that could be modified to contain either azide groups or alkyne groups, layer-by-layer assembly was carried out in water. A polyethylene film was modified in a series of reactions to have an alkyne-functionalized surface. The poly(N-isopropyl acrylamide)-based polymers were layered in an alternating fashion to form multilayer assemblies. A series of control reactions were also performed, showing that these layers were interconnected via triazole linkages. These assemblies were monitored by attenuated total reflectance spectroscopy. Once the layers were assembled, the polyvalent nature of the polymers allowed for further functionalization. Various surface functionalizations were established using fluorescence microscopy and contact angle analysis. By using spectroscopic and chemical means, layer-by-layer assembly on polyethylene films was proven. Control reactions showed the necessity of components for triazole formation. Therefore, layer-by-layer assembly using “click” chemistry was achieved.

Layer-by-layer assembly has received much attention over the last fifteen years. This assembly process can be carried out using different methods including hydrogen-bonding, electrostatic, and to a lesser extent, covalent interactions. However, these assemblies are rarely seen on polyolefin substrates due to the lack of functionality on the surface. “Click” chemistry has become very popular in recent years as a means to join modular compounds together. This thesis is the first published report to use “click” chemistry as a means for layer-by-layer assembly on a polymeric substrate. By designing polymers that contain alkyne or azide groups, it is possible to assemble them layer-by-layer on a polyethylene substrate. Polymers based on tert-butyl acrylate were initially designed for use in organic solvents such as tetrahydrofuran. The copper catalyst that facilitated the 1,3-dipolar cycloaddition was air sensitive and expensive. To capture the true essence of “click” chemistry, a new system was designed based on N-isopropyl acrylamide (NIPAM)-based polymers. These polymers were water soluble and allowed for “click” chemistry to be performed in water and open to air in benign conditions. With the development of a water soluble polymer system that could be modified to contain either azide groups or alkyne groups, layer-by-layer assembly was carried out in water. A polyethylene film was modified in a series of reactions to have an alkyne-functionalized surface. The poly(N-isopropyl acrylamide)-based polymers were layered in an alternating fashion to form multilayer assemblies. A series of control reactions were also performed, showing that these layers were interconnected via triazole linkages. These assemblies were monitored by attenuated total reflectance spectroscopy. Once the layers were assembled, the polyvalent nature of the polymers allowed for further functionalization. Various surface functionalizations were established using fluorescence microscopy and contact angle analysis. By using spectroscopic and chemical means, layer-by-layer assembly on polyethylene films was proven. Control reactions showed the necessity of components for triazole formation. Therefore, layer-by-layer assembly using “click” chemistry was achieved.

AN ABSTRACT OF THE THESIS OF SUSANNE BÖHM, for the Master of Arts degree in LINGUISTICS, presented on APRIL 12, 2010, at Southern Illinois University Carbondale. TITLE: CLICKS IN XHOSA AND NAMA: A COMPARATIVE ANALYSIS MAJOR PROFESSOR: Dr. Karen Baertsch ABSTRACT. This study is a comparative analysis of Xhosa and Nama clicks. It contains an acoustic pilot study for which one Nama speaker and one Xhosa speaker were recorded. Differences and similarities in place of articulation and accompaniment were measured between clicks in word-initial position for both languages. Previous studies showed that clicks with the same accompaniment are similar across both languages. For the clicks measured in the study, this was not exclusively the case. Overall, measuring differences and similarities between clicks of the two languages, a larger sample with more speakers is needed, which exceeds the scope of this thesis.

La thèse concerne les aspects inorganiques de la réaction des alcynes terminaux avec les azotures, la principale des réactions dites ”click”. La catalyse de cette réaction par des dendrimères centrés sur le cuivre (I) nous a permis de mettre en évidence des effets dendritiques originaux. Les assemblages dendritiques et polymériques fonctionnels réalisés à l’aide cette réaction “click”, en particulier avec des carboranes, nous ont conduits à la stabilisation de nanoparticules d’or et de palladium à partirde cations coordonnés aux triazoles “click”. La catalyse très efficace dans aqueux milieu et dans les conditions ambiantes de formation de liaison carbone-carbone a été réalisée à l’aide de très faibles quantités de ces nanoparticulesde palladium stabilisées. / The thesis concerns aspects of inorganic reaction between organic azides and terminal alkynes, the main “click” reactions. Catalysis of this reaction by copper (I)-centered dendrimers allowed us to highlight the dendritic effects originals. The dendritic and polymeric functional assemblies produced using the "click" reaction, especially with carboranes, led us to the stabilization of gold nanoparticles and palladium from cation-coordinated "click" triazole. The highly efficient catalysis in aqueous medium under ambient conditions of formation of carbon-carbon was carried out using very small amounts of stabilized palladium nanoparticles.

The purpose of this paper is to investigate consumers’ attitudes against the technique one-click purchasing. One-click purchasing is a method allowing the customers to transact a purchase with only one click. The customer has entered the payment information necessary to complete the purchase at a previous occasion. Within the next buying opportunity, the customer can purchase products with one single click. The analysis and conclusions is based on both primary and secondary sources. The primary sources represent the result of a questionnaire performed with 200 respondents. The top findings in this study are that the one-click purchasing method is used on a regular basis and most of the consumers’ trust that the method correctly cares for personal information. However the conclusion is that the demand of the method is not high and it seems like the consumers does not care if the method is available upon payment completions or not.

Cette thèse se concentre sur le design et la synthèse de molécules fluorescentes contenant un motif triazole et un squelette benzothiadiazole (BTD), coumarine, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacène (BODIPY) ou dicyanométhylène-4H-pyran (DCM) par chimie "click" et l’étude de leurs propriétés et applications en biologie et en chimie analytique. Dans le but de synthétiser des peptides fluorescents et d'étudier leurs applications, des acides aminés fluorescents contenant BTD, coumarine et BODIPY ont été préparés par réaction "click", et incorporés dans la somatostatine par synthèse peptidique en phase solide. Les peptides fluorescents synthétisés pourront être utilisés pour le développement d'un test de "binding" des analogues de la somatostatine. Des dérivés de BTD et BODIPY ont également été conçus et synthétisés pour servir de mimes de coudes beta- qui conduisent à des peptides courts qui pourraient être facilement détectés et étudiés en utilisant des techniques de fluorescence. La capacité des composés obtenus à former des liaisons hydrogène intramoléculaires a été étudiée par spectroscopie infrarouge. En outre, une série de macrocycles à base de BODIPY contenant un C-glucopyranoside conjugué ou non à des acides aminés tels que glycine, acid aspartique ou méthionine ont été synthétisés avec succès en utilisant une réaction "click" comme étape de macrocyclisation. Certains des composés synthétisés présentent des propriétés de reconnaissance sélective vers Cu2+, Fe3+, F- et CN- dans l'acétonitrile. Enfin, un nouveau capteur fluorescent, qui est capable de reconnaître les cations et anions d'une manière coopérative, a été conçu et synthétisé par chimie "click". Ce composé est très sensible à des combinaisons de Cu2+, F- et / ou Br- d’une manière séquence- et halogénure-dépendante. / This thesis is focused on the design and synthesis of triazole-containing fluorescent molecules based on benzothiadiazole (BTD), coumarin, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) or dicyanomethylene-4H-pyran (DCM) by “click” chemistry and investigation of their properties and applications in biology and analytical chemistry. In the aim to synthesize fluorescent peptides and investigate their applications, fluorescent amino acids containing BTD, coumarin and BODIPY were prepared by “click” reaction, and incorporated into somatostatin through solid phase peptide synthesis. The resulting fluorescent peptides could be used for the development of a binding assay for somatostatin analogues. BTD and BODIPY derivatives have also been designed and synthesized to act as beta-turn mimics which lead to short conformationally restricted peptides that could be easily detected and studied using fluorescence techniques. The ability of the synthesized compounds to form intramolecular hydrogen bond was studied by infrared spectroscopy. Moreover, a series of BODIPY-based macrocycles containing a C-glucopyranoside conjugated or not with various amino acids such as glycine, aspartic acid or methionine have been successfully synthesized by using “click” reaction as the macrocyclization step. Some of the synthesized compounds exhibited selective recognition properties towards Cu2+, Fe3+, F- and CN- in acetonitrile. Finally, a new fluorescent sensor, which has the ability to recognize cations and anions in a cooperative way, was designed and synthesized by “click” chemistry. This compound was highly sensitive to combinations of Cu2+, F– and/or Br– in a sequence- and halide-dependent way.