Database management systems are highly specialized to efficiently organize and process huge amounts of data in a transactional manner. During the last years, however, database management systems have been evolving as a central hub for the integration of mostly heterogeneous and autonomous data sources to provide homogenized data access. The next step in pushing database technology forward to play the role of an information marketplace is to actively notify registered users about incoming messages or changes in the underlying data set. Therefore, notification services may be seen as a generic term for subscription systems or, more general, data stream systems which both enable processing of standing queries over transient data. This article gives a comprehensive introduction into the context of notification services by outlining their differences to the classical query/response-based communication pattern, it illustrates potential application areas, and it discusses requirements addressing the underlying data management support. In more depth, this article describes the core concepts of the PubScribe project thereby choosing three different perspectives. From a first perspective, the subscription process and its mapping onto the primitive publish/subscribe communication pattern is explained. The second part focuses on a hybrid subscription data model by describing the basic constructs from a structural as well as an operational point of view. Finally, the PubScribe notification service project is characterized by a storage and processing model based on relational database technology. To summarize, this contribution introduces the idea of notification services from an application point of view by inverting the database approach and dealing with persistent queries and transient data. Moreover, the article provides an insight into database technology, which must be exploited and adopted to provide a solid base for a scalable notification infrastructure, using the PubScribe project as an example.

Förskolan och hemmet har ett ömsesidigt ansvar för förskolebarnet, den gemensamma nämnaren som förenar de två uppfostringsarenorna. Tidigare forskning visar att samverkan kan beskrivas på olika vis och kommer med förutsättningar för en fungerande samverkan. Dock har samverkan en central plats i förskolan för att bejaka barnets behov. Syftet med studien är att öka kunskapen om vårdnadshavares uppfattningar om samverkan mellan hemmet och förskolan. Studien bygger på kvalitativa intervjuer med 14 vårdnadshavare. Studiens tillämpade teoretiska begrepp är isärhållandets princip och partnerskapsprincipen. Resultatet i studien visar att vårdnadshavarna beskriver en samverkan i likhet med partnerskapsprincipen. Dock redovisar resultatet att vårdnadshavarna önskade samverkan ligger i linje med både partnerskapsprincipen och isärhållandets princip. Vårdnadshavarnas prioritet inomsamverkan är daglig och muntlig information om det egna barnet vid hämtning eller lämning. Resultatet redovisar vidare att vårdnadshavarna inte önskar samverka i frågor berörande förskolans organisation. Vårdnadshavarna beskriver även upplevda önskade och oönskade gränssättningar inom samverkan mellan hemmet och förskolan. Studiens slutsats är att samverkan kan beskrivas olika och innefattar individuella förväntningar, därför är det nödvändig att diskutera samverkan gemensamt med alla individuella parter. Vidare är studiens slutsats även att vårdnadshavarna önskar en samverkan dels i linje med partnerskapsprincipen men även i linje med isärhållandets princip

Es wird die enantioselektive Synthese eines substituierten Cyclopentanfragmentes beschrieben, welches zur Synthese einer Vielzahl von Diterpenen aus Euphorbiaceae genutzt werden kann. Schlüsselschritt hierbei ist eine intramolekulare Carbonyl-En-Reaktion. In zwei verschiedenen Syntheseansätzen wurde versucht, dieses zu einem Jatrophan-Diterpen umzusetzen. Versuche hinsichtlich einer Nozaki-Hiyama-Kishi-Kupplung werden beschrieben. Im zweiten Ansatz, wurde über eine Ringschlussmetathese bzw. eine Relay-Ringschlussmetathese versucht entsprechende Jatrophane herzustellen. Dies gelang bei einem Substrat, welches eine zweifach substituierte Doppelbindung beinhaltet. Somit konnte ein nichtnatürliches 17-Norjatrophan enantioselektiv synthetisiert werden. / The enantioselective synthesis of a highly substituted cyclopentan, useful for the synthesis of diterpenes from Euphorbiaceae is described. Key step is a intramolecular carbonyl-en reaction. Two different approaches towards Jatrophanes were examined. The first one envisioning a Nozaki-Hiyama-Kishi coupling didn´t work. The second one employed a ring-closing-metathesis which was successful in the case of a disubstituted double bond formed. The use of an relay-ring-closing-metathesis was also examined. The enantioselective synthesis of a nonnatural 17-Norjatrophane is described in all details.

Es wird die enantioselektive Synthese eines substituierten Cyclopentanfragmentes beschrieben, welches zur Synthese einer Vielzahl von Diterpenen aus Euphorbiaceae genutzt werden kann. Schlüsselschritt hierbei ist eine intramolekulare Carbonyl-En-Reaktion. In zwei verschiedenen Syntheseansätzen wurde versucht, dieses zu einem Jatrophan-Diterpen umzusetzen. Versuche hinsichtlich einer Nozaki-Hiyama-Kishi-Kupplung werden beschrieben. Im zweiten Ansatz, wurde über eine Ringschlussmetathese bzw. eine Relay-Ringschlussmetathese versucht entsprechende Jatrophane herzustellen. Dies gelang bei einem Substrat, welches eine zweifach substituierte Doppelbindung beinhaltet. Somit konnte ein nichtnatürliches 17-Norjatrophan enantioselektiv synthetisiert werden. / The enantioselective synthesis of a highly substituted cyclopentan, useful for the synthesis of diterpenes from Euphorbiaceae is described. Key step is a intramolecular carbonyl-en reaction. Two different approaches towards Jatrophanes were examined. The first one envisioning a Nozaki-Hiyama-Kishi coupling didn´t work. The second one employed a ring-closing-metathesis which was successful in the case of a disubstituted double bond formed. The use of an relay-ring-closing-metathesis was also examined. The enantioselective synthesis of a nonnatural 17-Norjatrophane is described in all details.

The door closing action is a recurrent situation when using a vehicle, and its sound is therefore a common sensation, which would elicit pleasant feelings. Sensory pleasantness is an important aspect in terms of customer’s perspective, and it can be a contributing factor when deciding to buy or not a specific vehicle. The first contact between a prospective customer and the automobile usually happens in car salons or at the car retailer. The initial impression of the vehicle might be sight-based, and the door may commonly be the first physical contact. Depending on the car brand and type, doors differ in terms of mass, structure, dimension. Furthermore, there are differences regarding the latching system and the door sealing structure, in terms of material and construction. The closing sound produced when slamming the door is related to all these parameters. Auditory pleasantness can be described by characteristics of the sound that are described through psychoacoustics. Loudness, sharpness, roughness, and tonality are important auditory parameters to objectively describe this complex sensation. The aim of car doors would be to generate an enthusiastic, low-pitched, and saturated sound, which would elicit feelings of solidity, robustness, and security. On the other side, a metallic, high-pitched, fragmented sound could be a source of annoyance and produce feelings of insecurity and cheap vehicle.The present work aims to provide a broad picture on the mechanics and acoustics of door closing for automobiles. In specific, the closing sound was evaluated in relation to the door gaskets and their sealing performance over time. The sealing performance was analyzed in energy and force terms. The door closing motion was studied as a quasi-static problem, as well as a dynamic problem, where the former is related to the latching capability of the door, the latter is connected to the slamming action. The measurement results include the sealing performance trend from fresh to aged gaskets. From these measurements, the rubber non-linear behaviour could then be evaluated from a sound quality perspective. The acoustic analysis revealed inconsistencies of the psychoacoustic parameters in the description of the hearing sensations. Spectral analysis was also implemented to capture the door closing phenomenon, and the Wavelet transform emerged as the method with the highest resolution in the description of the sound wave progression.Several measurements were performed in order to assess all the established points, and methods were implemented for the sealing stiffness analysis and the acoustic analysis. The severe transiency of the door closing event was put in evidence. The stiffness analysis method showed also potential in helping to adjust the end of line tuning of the vehicle. Finally, benchmarking was included in the project, which enabled comparisons with competitor cars. / Dörrstängning är en återkommande händelse när ett fordon används, och ljudet bör därför ge ett positivt intryck och korrekt information till brukaren. Ett behagligt intryck är en viktig aspekt ur kundens perspektiv och kan vara ett var flera bidragande faktorer när beslut tas om att köpa eller inte köpa ett fordon. Den första kontakten mellan en potentiell kund och bilen sker vanligtvis i bilsalonger eller hos bilhandlare. Det första intrycket av fordonet kan vara visuellt, och dörren är ofta den första fysiska kontakten. Beroende på biltyp och fabrikat skiljer sig dörrarna åt när det kommer till massa, struktur och dimensioner. Dessutom kan det finnas skillnader i låssystem och dörrtätningskonstruktion såsom i både material och utformning. Stängningsljudet som uppstår när dörren slås igen är relaterat till alla dessa parametrar. Ett ljuds upplevda behaglighet i det beror på ljudets egenskaper, som beskrivs med hjälp av psykoakustik. Ljudstyrka, skärpa, råhet och tonalitet är viktiga auditiva parametrar för att objektivt beskriva detta komplexa intryck. Målet med bildörrar bör vara att generera ett dovt och mättat ljud, för att framkalla känslor av soliditet, robusthet och säkerhet. Å andra sidan kan, ett metalliskt, högfrekvent och skramligt ljud vara en källa till irritation och ge känslor av osäkerhet och låg kvalité.Syftet med detta arbete är att ge en övergripande beskrivning av dörrstängning och akustiken kring detta. I synnerhet utvärderades stängningsljudet i förhållande till dörrpackningarna och deras tätningsprestanda mätt över tiden. Tätningsprestanda analyserades i energi- och krafttermer. Dörrens stängningsrörelse studerades både som ett kvasistatiskt problem och som ett dynamiskt problem. Det förstnämnda är relaterat till dörrens låsningsförmåga, medan det sistnämnda är kopplat till smällar i dörren. Mätresultaten visade hur tätningsprestandan förändras över tiden. Gummits icke-linjära beteende har också utvärderats med ett ljudkvalitetsperspektiv. En spektralanalys genomfördes av ljudet från dörrstängningar och Wavelet-transformen visade sig vara den lösning som gav bäst kvalitet. Flera mätningar utfördes för att bedöma alla fastställda punkter och metoder infördes för analysen av tätningens styvhet och för den akustiska analysen. Den kraftiga transiensen i dörrstängningen kunde ses i resultaten. Styvhetsanalysen visade även hur den utvecklade metoden skulle kunna bidra till att justera fordonets end-of-line inställningar. Slutligen ingick benchmarking i projektet vilket möjliggjorde jämförelser med konkurrentbilar.

Chapter 1 gives background information on proteases and discusses the concept of protease inhibition as a therapeutic strategy for humans. It introduces the key concept that conformation defines biological activity. It also outlines how proteases almost universally bind their substrate/inhibitors in an extended β-strand conformation. The use of calpain as a prototype protease for the testing of β-strand mimics synthesised later in the thesis is also discussed. Chapter 2 describes how molecular modeling was used to rationalise the structure based activity relationships (SAR) of known calpain inhibitors. Molecular modeling was then used to successfully design a number of acyclic β-strand mimics. The synthesis and testing of eight such inhibitors is described. The most potent β-strand mimic prepared was 2.13. This was determined to have an IC₅₀ of 30 nM against calpain II. Chapter 3 outlines the history and application of ring closing metathesis (RCM) to the synthesis of cyclic compounds. The attempted synthesis of an eight membered cyclic nitrogen to nitrogen conformationally constrained dipeptide is described. The synthesis of a conformationally constrained β-amino acid calpain inhibitor (3.73) is also described. A novel calpain inhibitor motif was designed in Chapter 4. On the basis of this an in-silico combinatorial library of two hundred and eighty eight possible β-strand templates was prepared. Conformational analysis of this library was performed and from this a number of excellent β-strand templates were identified and selected for synthesis. The preparation of ten β-strand templates is described. New microwave irradiation methodology was developed to achieve this. vii The formation of a six-membered catalyst deactivating chelate is also proposed to explain why some dienes fail to undergo RCM. Two methods to circumvent the formation of such a chelate are outlined. The addition of Lewis acid chloro-dicyclohexyl borane to the RCM reaction mixture and chain length alteration are investigated. Chapter 5 describes the design of macrocyclic β-strand mimics using induced fit molecular modelling. The physicochemical properties of these were calculated in-silico. From this analysis a number of Tyr-XX-Gly based and Tyr-XX-Cys based macrocyclic calpain inhibitors were selected for synthesis. The preparation and testing of these are described. In the Tyr-XX-Gly macrocyclic system a number of variables were investigated and numerous SAR implications concluded. Aldehyde 5.14 was identified as the best electrophilic warhead macrocyclic calpain inhibitor with an IC₅₀ against calpain II of 27 nM. The best non-electrophilic warhead macrocycle (5.13) had an IC₅₀ against calpain II of 704 nM. Chapter 6 describes synthetic optimisation for the preparation of calpain inhibitors 2.13, 5.14 and 5.17. Multi-gram quantities of each were prepared. Aldehydes 2.13 and 5.14 were evaluated as anti-cataract agents using in-vivo cataract sheep model. Both of these β-strand mimics were demonstrated to retard cataract development. Macrocycle 5.14 was found to be the most effective, decreasing the rate of cataract development between forty four and forty nine per cent relative to control. Chapter 7 outlines the attempted development of RCM methodology for the chiral synthesis of α-α disubstituted amino acid lactams. In addition, methodology for the stereoselective incorporation of a C-N constrained β-amino acid carbocycle into a peptide or peptidomimetic is described.

Les acides biliaires sont des composés naturels existants dans le corps humain. Leur biocompatibilité, leur caractère amphiphile et la rigidité de leur noyau stéroïdien, ainsi que l’excellent contrôle de leurs modifications chimiques, en font de remarquables candidats pour la préparation de matériaux biodégradables pour le relargage de médicaments et l'ingénierie tissulaire. Nous avons préparé une variété de polymères à base d’acides biliaires ayant de hautes masses molaires. Des monomères macrocycliques ont été synthétisés à partir de diènes composés de chaînes alkyles flexibles attachées à un noyau d'acide biliaire via des liens esters ou amides. Ces synthèses ont été réalisées par la fermeture de cycle par métathèse, utilisant le catalyseur de Grubbs de première génération. Les macrocycles obtenus ont ensuite été polymérisés par ouverture de cycle, entropiquement induite le catalyseur de Grubbs de seconde génération. Des copolymères ont également été préparés à partir de monolactones d'acide ricinoléique et de monomères cycliques de triester d’acide cholique via la même méthode. Les propriétés thermiques et mécaniques et la dégradabilité de ces polymères ont été étudiées. Elles peuvent être modulées en modifiant les différents groupes fonctionnels décorant l’acide biliaire et en ayant recours à la copolymérisation. La variation des caractéristiques physiques de ces polymères biocompatibles permet de moduler d’autres propriétés utiles, tel que l’effet de mémoire de forme qui est important pour des applications biomédicales. / Bile acids are natural compounds in the body. Their biocompatibility, facial amphiphilicity, rigidity of steroid nucleus, and ease of chemical modification make them excellent candidates as building blocks for making biodegradable materials used in drug delivery and tissue engineering applications. We have prepared main-chain bile acid-based polymers having high molecular weights. Macrocyclic monomers were synthesized from dienes, which consist of flexible alkyl chains attached to a bile acid core through either ester or amide linkages, via ring closing metathesis using first-generation Grubbs catalyst. They were polymerized using entropy-driven ring-opening metathesis polymerization using second-generation Grubbs catalyst. Copolymers were also prepared from monolactone of ricinoleic acid and cholic acid-based cyclic triester monomer via the same method. The thermal and mechanical properties and degradation behaviours of these polymers have been investigated. The properties can be tuned by varying the chemical linking with the bile acid moiety and by varying the chemical composition of the polymers such as copolymerization with ricinoleic acid lactones. The tunability of the physical properties of these biocompatible polymers gives access to a range of interesting attributes. For example, shape memory properties have been observed in some samples. This may prove useful in the design of materials for biomedical applications.

Les vinylphosphonates fonctionnalisés représentent une classe importante de briques moléculaires utilisées en synthèse organique et suscitent un grand intérêt au niveau biologique. Ainsi, nous avons étudié différentes voies de synthèse pour accéder à ces composés. Il en ressort une méthode généralisable, faisant intervenir une réaction de substitution organocatalysée, à partir d’un substrat phosphoré original, et permettant d’obtenir de nombreux vinylphosphonates non décrits jusqu’ici. Par la suite, la synthèse de vinylphosphonates azahétérocycliques a été abordée en employant la réaction de métathèse cyclisante à partir de substrats adéquats, eux-mêmes obtenus par le biais de la méthodologie décrite précédemment.Nous avons enfin mis au point la première synthèse totale énantioselective de la molécule UPF 702 (vinylphosphonate cyclique comportant un motif acide aminé), connue pour ses propriétés biologiques notamment comme agoniste de récepteurs du glutamate et présentant ainsi un potentiel thérapeutique contre les maladies du système nerveux central. Deux voies de synthèses ont été imaginées, basées sur des réactions organocatalysées et de métathèse cyclisante. L’introduction de la chiralité a été réalisée via des réactions de désymétrisation ou de dédoublement enzymatiques et l’accès à l’amine par un réarrangement de Curtius. / Functionalized vinylphosphonates constitute an important class of building blocks used in organic synthesis and aroused great interest due to their various biological activities. Thus, we developed several synthetic methodologies to reach these compounds. The most general method entails an organocatalyzed substitution reaction using an original substrate, and allows the synthesis of numerous hitherto unknown vinylphosphonates.Then, the synthesis of azaheterocyclic vinylphosphonates was investigated using the ring closing metathesis from appropriate substrates which are obtained through the above methodology.Finally, we have set up the first enantioselective synthesis of UPF 702 (a cyclic vinylphosphonate including the amino acid moiety), known to exhibit agonist activity towards glutamate receptors, and thus potentially active against central nervous system diseases. Two synthetic approaches were devised, based on the organocatalyzed substitution followed by ring closing metathesis. The enantioselectivity was brought by enzymatic resolution or desymmetrisation, whereas the amino acid was prepared via a Curtius rearrangement.

Rituals in the school environment, specifically in small schools with composite classes, are the subject of the diploma thesis. The theoretical part describes the environment of the small schools with composite classes in the Czech Republic and the specifics of teaching work in them. They are also discussed the rituals in general terms and the relationship to the hidden curriculum in this part. Specific rituals in contemporary small schools are described in following sections. The research part is conceived as a qualitative analysis of structured interviews with teachers and directors of small schools. The diploma thesis ends with a synthesis of empirical and theoretical part and with interpretation the results. The overlap of topics related to the problem that is mentioned in the conclusion.

Esta pesquisa vem ao modo de um diálogo ou ponte entre fenomenologia e ciência geográfica. O percurso tem início com o reconhecimento da ontologia comum entre sujeito e mundo, continua com a experiência da percepção com abertura e fechamento das coisas, numa operação constituinte do meio como mundo e lugar, pela atividade humana, diante daquele instituído, passivo, acabado. Das coisas chega-se ao lugar, deste vai-se ao mundo, até que dele se retorna; um ciclo. A ontologia comum estabelecida como ontologia encarnada permite procurar no recuo ao pré-objetivo, outros atributos normalmente desconsiderados dos lugares, os quais serviram de parâmetro à sugestão de avaliação e prognóstico. Para tanto, foram realizados trabalhos de campo como oportunidade de aplicação das noções consideradas. / This research is the way of dialogue or a bridge between phenomenology and geographical science. The route begins with the common ontology between subject and world, continues with the experience of perception with opening and closing of things, a constituent of operation as a means world and place for the activity, given that up, liabilities, finished. Of the things you get to the place, this go to the world, even if it returns, is a cycle. The ontology established as common ontology makes searching in the red throwback to pre-order, the pre-purpose other attributes normally disregarded, the places, thinking on assessment and prognosis of these places. To this end, the field work was conducted as an opportunity for the application of the concepts considered.