A preorganised amino acid derivative containing a cyclopropyl constraint was designed to orient an amino acid into its bound conformation. This constrained mimic was determined by ITC to be equally potent to the native Phe derivative. It was found that a more favorable enthalpy of binding was compensated by an equally unfavorable entropy compared to the native ligand. In order to properly ascertain the effects of the cyclopropane constraint, a flexible control containing the same number of heavy atoms was synthesized and tested, and it was found to be at least 200 fold less potent than the constrained analog. However, without structural data of the flexible control, it is difficult to infer if the differences in ligand binding affinity arose from the ligand constraint or some other unknown complexity to binding. We studied the thermodynamic and structural effects of modifying alkyl chains of n-alka(e)nol and phenylalka(e)nol binders to MUP-I by both the removal of a rotor via deletion of a methylene unit and restriction of a rotor via the installation of an internal olefin. In general, we observed that a similar thermodynamic signature accompanies modifications for both the n-alka(e)nol and phenylalka(e)nol ligands: A favorable T[delta][delta]Sºo̳b̳s̳ is compensated by an unfavorable T[delta][delta]Hºo̳b̳s̳ such that T[delta][delta]Gºo̳b̳s̳ for both removal of a methylene and insertion of an internal olefin are unfavorable and equipotent, respectively. The insertion of an internal olefin into an alkyl chain led to significantly more favorable entropies than does methylene removal, yet enthalpy-entropy compensation leads to nearly equipotent binding energetics. However, we did find a strong correlation between [delta]Ho̳b̳s̳° and buried apolar Connolly Surface Area (CSA). The intrinsic free energies of introducing an internal olefin into the n-alkanols and phenylalkanols differ markedly from the observed data. It was observed that intrinsic affinities are more favorable than the observable because a favorable T[delta][delta]S⁰i̳n̳t̳ dominates an unfavorable [delta][delta]Hºi̳n̳t̳. Also, we discovered that the intrinsic entropies of inserting an internal olefin are nearly double that of removing a methylene group, suggesting that the insertion of an internal olefin results in the restriction of more C-C rotors. We have shown through ITC analysis that the added substituents probed in this study provided binding increases to our Grb2 SH2 ligands as expected, but that the thermodynamic driving force of binding affinities depended greatly upon the specific nature and flexible mobility of the ligands in the binding pocket. Through a combination of X-ray and ITC studies it was shown that ligands containing rigid and aromatic functional groups bound with a higher [delta]H° than the more flexible alkyl ligands, and that this effect correlates well with more direct vdW contacts made in the pocket. Finally, we described a case study where a strict adherence to the Topliss operational schemes led to an expedient development of novel MUP-I binding analogs. The validity of the schemes was also depicted through the synthesis and testing of ligands that were correctly predicted to be weaker/equipotent to the starting ligand. Of important note is that the degree to which the schemes led to affinity boost depended greatly on the starting potency of the initial compound. / text

Proteins from the lipocalin family play significant roles during the transport of chemical signals. These globular proteins (molecular mass: 17,7 - 21,7 kDa) are able to bind a wide spectrum of volatile ligands. Since they decay continuously, the scent impact is prolonged. Major urinary proteins (MUPs) are lipocalins, typically found in the urine and used during olfactory communication in the house mouse. But the urine is not the only source of chemical signals. Many species of mammals perform selfgrooming - a technique in which saliva is transported into the fur. The goal of the thesis is to identify main proteins that are involved in chemical communication by selected species of the genus Apodemus, and to discover the source of production (i.e. saliva or urine). The Experion capillary electrophoresis system was used to confirm the absence of lipocalins in the urine in two Apodemus species (A. uralensis, A. sylvaticus). Furthermore, a lot of lipocalins is present in the saliva of above-mentioned species. The quantity and types of salivary lipocalins was identified by 2D electrophoresis along with mass spectrometry analyses (MALDI MS/MS) in three species of the genus Apodemus (A. uralensis, A. sylvaticus and A. flavicollis). The conclusion of this inter-specific comparison suggests, that sociality...

Viena labiausiai paplitusių internetinių informacinių sistemų rūšių yra intranetas. Tai organizacijos tinklas, grindžiamas interneto protokolų rinkiniu TCP/IP. Pagrindinė intraneto paskirtis – komunikacija ir bendradarbiavimas tarp organizacijos narių, ir paprastai kiekvienas jų, priklausomai nuo savo atliekamų funkcijų, turi skirtingas naudojimosi intranetu teises. Magistrinio darbo tikslas - sukurti informacinę sistemą „Ei-tinklas“ gimnazijoje – intranetą – kaip vieną iš priemonių, skirtų šiuolaikinei vadybai bei mokymui(-si), realizuoti. / One of the most prevalent types of Internet Information Systems is Intranet. It is an organization network based on the collection TPC/IP of internet records. The main purpose of the Intranet is communication and cooperation among members of an organization, and usually each of them, depending on their accomplishing functions, has different rights of the Intranet’s usage. The aim of Master Degree Work is to create an information system “Ei-network” in the gymnasium – Intranet – as one of the means designed for implementing modern management and teaching (learning).

Neuromuscular disorders change the underlying structure and function of motor units within a muscle, and are detected using needle electromyography. Currently, inferences about the presence or absence of disease are made subjectively and are largely impression-based. Quantitative electromyography (QEMG) attempts to improve upon the status quo by providing greater levels of precision, objectivity and reproducibility through numeric analysis, however, their results must be transparently presented and explained to be clinically viable. The probabilistic muscle characterization (PMC) model is ideally suited for a clinical decision support system (CDSS) and has many analogues to the subjective analysis currently used. To improve disease characterization performance globally, a hierarchical classification strategy is developed that accounts for the wide range of MUP feature values present at different levels of involvement (LOI) of a disorder. To improve utility, methods for detecting LOI are considered that balance the accuracy in reporting LOI with its clinical utility. Finally, several aggregation methods that represent commonly used human decision-making strategies are considered and evaluated for their suitability in a CDSS. Four aggregation measures (Average, Bayes, Adjusted Bayes, and WMLO) are evaluated, that offer a compromise between two common decision making paradigms: conservativeness (average) and extremeness (Bayes). Standard classification methods have high specificity at a cost of poor sensitivity at low levels of disease involvement, but tend to improve with disease progression. The hierarchical model is able to provide a better balance between low-LOI sensitivity and specificity by providing the classifier with more concise definitions of abnormality due to LOI. Furthermore, a method for detecting two discrete levels of disease involvement (low and high) is accomplished with reasonable accuracy. The average aggregation method offers a conservative decision that is preferred when the quality of the evidence is poor or not known, while the more extreme aggregators such as Bayes rule perform optimally when the evidence is accurate, but underperform otherwise due to outlier values that are incorrect. The methods developed offer several improvements to PMC, by providing a better balance between sensitivity and specificity, through the definition of a clinically useful and accurate measure of LOI, and by understanding conditions for which each of the aggregation measures is better suited. These developments will enhance the quality of decision support offered by QEMG techniques, thus improving the diagnosis, treatment and management of neuromuscular disorders.

Neuromuscular disorders change the underlying structure and function of motor units within a muscle, and are detected using needle electromyography. Currently, inferences about the presence or absence of disease are made subjectively and are largely impression-based. Quantitative electromyography (QEMG) attempts to improve upon the status quo by providing greater levels of precision, objectivity and reproducibility through numeric analysis, however, their results must be transparently presented and explained to be clinically viable. The probabilistic muscle characterization (PMC) model is ideally suited for a clinical decision support system (CDSS) and has many analogues to the subjective analysis currently used. To improve disease characterization performance globally, a hierarchical classification strategy is developed that accounts for the wide range of MUP feature values present at different levels of involvement (LOI) of a disorder. To improve utility, methods for detecting LOI are considered that balance the accuracy in reporting LOI with its clinical utility. Finally, several aggregation methods that represent commonly used human decision-making strategies are considered and evaluated for their suitability in a CDSS. Four aggregation measures (Average, Bayes, Adjusted Bayes, and WMLO) are evaluated, that offer a compromise between two common decision making paradigms: conservativeness (average) and extremeness (Bayes). Standard classification methods have high specificity at a cost of poor sensitivity at low levels of disease involvement, but tend to improve with disease progression. The hierarchical model is able to provide a better balance between low-LOI sensitivity and specificity by providing the classifier with more concise definitions of abnormality due to LOI. Furthermore, a method for detecting two discrete levels of disease involvement (low and high) is accomplished with reasonable accuracy. The average aggregation method offers a conservative decision that is preferred when the quality of the evidence is poor or not known, while the more extreme aggregators such as Bayes rule perform optimally when the evidence is accurate, but underperform otherwise due to outlier values that are incorrect. The methods developed offer several improvements to PMC, by providing a better balance between sensitivity and specificity, through the definition of a clinically useful and accurate measure of LOI, and by understanding conditions for which each of the aggregation measures is better suited. These developments will enhance the quality of decision support offered by QEMG techniques, thus improving the diagnosis, treatment and management of neuromuscular disorders.

Major Urinary Proteins (MUP) are pheromonal transmitters involved in chemical communication in rodents. Complexes of MUPs and ligands mediate information about genetical background of an individual and co-create individual scent profile. They play a significant role in kinship determination, the crucial factor in the choice of a mating partner. It is assumed that the MUP production is energetically demanding due to the pressure of sexual selection, and the transmitted signal is thus supposed to be honest. This theory hasn't yet been experimentally tested, neither was proven the effect of another intense selection pressure- a parasitic infection. In my thesis, I describe the effect of an infection of a parasite Toxoplasma gondii on MUP production. The results suggest that the production is altered in both sexes, the production decreasing in males to the level of male castrates (or the female level). Considering the results of more detailed analysis of the infection we assume that the energetical demands of the MUP production doesn't allow the production of ordinary amounts if MUPs during the first phase of the infection as the energy is primarily devoted to the infection control. The increased production in latter phase can be attributed to the importance of scent communication. Decreased levels of...

The work deals with communication options, the power line and particularly the use of this technology in home automation to control heating and reduction in standby mode for selected domestic appliances. The issue is outlined in detail first and then examined in detail. The publication outlines a possible variant of such a device that can detect movement in the house and on the basis of such information to adjust the energy profile. The device is from its base designed to minimize the consumption of heat and electricity.

Nombreuses sont les villes françaises à abriter des éléments d’architecture militaire (citadelles, casernes, bastions,murailles, etc.). Bien que les fonctions défensives à l’origine de ces ouvrages soient peu à peu tombées en désuétude,ceux-ci sont ancrés dans les tissus urbains des cités qui les abritent aujourd’hui encore. Ils participent des morphologiesurbaines, des schémas fonctionnels et, plus globalement, de la manière dont la notion de ville est appréhendée.Les villes font dorénavant face à de nouveaux enjeux qui poussent à renouveler les cadres au travers desquelles ellessont traditionnellement approchées. L’étalement urbain, ses conséquences, la nécessité de tendre vers un urbanismerenouvelé et plus durable amènent à porter un nouveau regard sur les fortifications urbaines. Au-delà de son aspectsymbolique, ce type d’architecture est marqué par des caractéristiques spatiales hors-normes (localisation, volumétrie,géométrie) qui engagent à l’analyser au travers des prismes méthodologiques et conceptuels que fournit la géographie.Comment l’héritage des fortifications urbaines peut-il aujourd’hui être mobilisé afin de créer un espace urbain cohérent,tant sur le plan spatial que social ou symbolique et ainsi répondre aux aspiration des villes actuelles ?La première partie de la thèse porte sur les enjeux auxquels les “villes fortes” sont aujourd’hui confrontées (modernisation,croissance étalement urbain, etc.) et la manière dont leurs “ouvrages lourds” sont affectés. La deuxième partiedu travail s’attache à caractériser le phénomène des “villes fortes” en France aujourd’hui par le biais d’approchesdescriptives, empiriques et statistiques qui permettent de formaliser et d’analyser les logiques et les règles qui régissentle devenir des anciens ouvrages défensifs. La dernière partie de la thèse étudie le potentiel d’urbanisation des zones etouvrages militaires et propose de mesurer l’impact de leur transformation en logements dans le cadre d’un scénariode renouvellement urbain compact pour la ville de Besançon. Il s’agit d’évaluer les conséquences de telles mesuressur le schéma fonctionnel des villes et les formes urbaines. L’ensemble de ces travaux montre l’intérêt du recours auxouvrages défensifs dans le cadre d’un urbanisme à la fois renouvelé, mais aussi plus “durable”, en conformité avec lesformes urbaines, les demandes contemporaines et les projets des villes. / A large number of french cities host military historical edifices (citadels, barracks, bastions, defensive walls, etc.). Although their initial defensive functions have been lost over time, these edifices remain deeply rooted in the urban fabric of their host cities. They continue exerting an impact on these cities’ urban morphology and modern-time functions as well as the way in which the concept of city is understood. Cities nowadays face some new challenges,the increasing awareness of urban sprawl and its consequences, coupled with an urge to promote a renewed and sustainable urbanism, invites us to adopt new approaches to study urban fortifications. In addition to their symbolic aspect, fortifications are characterized by their out-of-the-common spatial measure (location, volume and geometry),requiring researchers to use methodologies and geographical concepts for their academic endeavour. Against this background : how can urban fortifications be used to create urban space that is spatially, socially and symbolically coherent with their historical heritage and that also satisfies the functional need of modern cities ?The first part of this doctoral dissertation present modern-day challenges that fortified cities face (modernisation,urban expansion and sprawl, etc.), and the ways in which their “heavy buildings” are affected. The second part sheds light on the relationships between cities and their fortifications, thanks to descriptive, empirical and statistical analyses. The statistical study noticeably builds on a database to examine the rationale and rules underpinning there habilitation of ancient military edifices. The last part of the dissertation proposes an evaluation of the potential of rehabilitating ancient military edifices and spaces for modern urban usage. For this purpose the impact of transforming these fortifications into residential blocks is assessed in a fortified French city (Besançon). This assessment aims at evaluating the consequences of such urban planning measures on urban morphology and functions. Overall, the analysis provided in that doctoral dissertation demonstrates that ancient military buildings have their place in contemporary urban planning. They help to achieve a renewed and sustainable urban design in line with the urban morphology,modern social and functional requirements and the development perspectives in their host cities.