Le vieillissement vasculaire est caractérisé par une dysfonction de l’endothélium. De nombreux facteurs de risque cardiovasculaire tels que l’obésité et l’hypertension prédisposent l’endothélium à un stress oxydant élevé aboutissant à une dysfonction endothéliale, celle-ci étant communément accompagnée d’une diminution de la biodisponibilité du monoxyde d’azote. Bien que la fonction endothéliale soit un déterminant majeur de la prédiction du risque cardiovasculaire des patients, son évaluation individuelle reste très limitée. En conséquence, il existe un intérêt scientifique grandissant pour la recherche de meilleurs biomarqueurs. L’Angiopoiétine like-2 (angptl2), une protéine identifiée récemment, joue un rôle pro-inflammatoire et pro-oxydant dans plusieurs désordres causés par une inflammation chronique allant de l’obésité à l’athérosclérose. L’inflammation et un stress oxydant accru ont été établis comme des mécanismes sous-jacents à l’apparition d’une dysfonction endothéliale, c’est pourquoi ce travail met l’accent sur le rôle de l’angptl2 dans la dysfonction endothéliale. Plus précisément, ce travail vise à: 1) déterminer les effets aigus de l’angptl2 sur la fonction endothéliale, 2) caractériser la fonction endothéliale et la contribution des différents facteurs relaxants dérivés de l'endothélium (EDRF) dans plusieurs lits vasculaires, et ce, dans un modèle de souris réprimant l’expression de l’angptl2 (knock-down, KD), et 3) examiner si l'absence d'expression angptl2 protège contre la dysfonction endothéliale induite par un régime riche en graisses (HFD) ou par perfusion d'angiotensine II (angII) chez la souris. Dans la première étude, l’incubation aigue avec de l’angptl2 recombinante induit une dysfonction endothéliale dans les artères fémorales isolées de souris de type sauvage (WT), probablement en raison d’une production accrue d'espèces réactives oxygénées. Les artères fémorales de souris angptl2 KD présentent une meilleure fonction endothéliale en comparaison aux souris WT, vraisemblablement par une plus grande contribution de la prostacycline dans la vasodilatation. Après 3 mois d’une diète HFD, les principaux EDRF respectifs des artères fémorales et mésentériques sont conservés uniquement dans les souris angptl2 KD. Cette préservation est associée à un meilleur profil métabolique, une moindre accumulation de triglycérides dans le foie et des adipocytes de plus petite taille. De plus, l’expression de gènes inflammatoires dans ces tissus adipeux n’est augmentée que chez les souris WT. Dans la seconde étude, l’absence d’angptl2 résulte en une production accrue de monoxyde d’azote dans les artères cérébrales isolées par rapport à celles des souris WT. La perfusion chronique d’angII provoque, seulement chez les souris WT, une dysfonction endothéliale cérébrale probablement par le biais d’une augmentation de la production d’espèces réactives oxygénées, probablement dérivé des NADPH oxydase 1 et 2, ainsi que l'augmentation des facteurs constricteurs dérivés de l’endothélium issus de la cyclo-oxygénase. En revanche, l’apocynine réduit la dilatation cérébrale chez les souris KD traitées à l’angII, ce qui suggère le recrutement potentiel d’une voie de signalisation compensatoire impliquant les NADPH oxydases et qui aurait un effet vaso-dilatateur. Ces études suggèrent fortement que l’angptl2 peut avoir un impact direct sur la fonction endothéliale par ses propriétés pro-inflammatoire et pro-oxydante. Dans une optique d’application à la pratique clinique, les niveaux sanguins d’angptl2 pourraient être un bon indicateur de la fonction endothéliale. / Vascular aging is characterized by changes in the endothelium. Common cardiovascular risk factors, including obesity and hypertension, predispose the endothelium to increased oxidative stress, leading to endothelial dysfunction commonly characterized by diminished nitric oxide bioavailability. Although endothelial function can be a major determinant of cardiovascular risk prediction in patients, individual testing is still limited in clinical settings and thus there is increasing scientific interest in finding better biomarkers. Angiopoietin like-2 (angptl2), a recently identified protein, is a pro-inflammatory and pro-oxidative protein involved in chronic inflammatory disorders ranging from obesity to atherosclerosis. As inflammation and increased oxidative stress are established underlying mechanisms by which endothelial dysfunction occurs, this work focuses on the role of angptl2 in endothelial dysfunction, a topic that is largely unexplored. Specifically, this work aims to 1) determine the acute effects of angptl2 on endothelial function, 2) characterize endothelial function and contribution of different endothelium-derived relaxing factors in various vascular beds in a newly generated angptl2 knock-down (KD) mouse model, and 3) examine whether the lack of angptl2 expression protects against endothelial dysfunction induced by either a high-fat diet (HFD) or angiotensin II (angII) infusion in mice. In the first study, we show that a recombinant angptl2 acutely evokes endothelial dysfunction in the femoral artery isolated from wild-type (WT) mice, likely due to increased production of reactive oxygen species. Also in the femoral artery, angptl2 KD mice display better endothelial function compared to WT, which may be a result of greater prostacyclin contribution to vasodilation. After a 3-month HFD, the main respective endothelium-derived relaxing factors in the femoral and mesenteric arteries are preserved in angptl2 KD mice only, which was associated with a better metabolic profile, such as lower total cholesterol-to-high-density lipoprotein and low-density-to-high-density lipoprotein ratios compared to WT mice. After a HFD, KD mice have less triglyceride accumulation in the liver and smaller adipocytes in their mesenteric and epididymal white adipose tissues compared to WT mice, while inflammatory gene expressions in adipose tissues increase in WT mice only. In the second study, we reveal that the lack of angptl2 in KD mice results in greater nitric oxide production compared to WT mice in their isolated cerebral arteries. Chronic infusion of pro-inflammatory and pro-oxidative angII results in cerebral endothelial dysfunction only in WT mice, which is acutely ameliorated with either N-acetylcysteine, apocynin, or indomethacin, suggesting increased reactive oxygen species, likely derived from the NADPH oxidases 1/2, and increased cyclooxygenase-derived endothelium-derived contracting factors. In contrast, apocynin reduces cerebral dilation in angII-treated KD mice, suggesting recruitment of a potential compensatory dilatory NADPH oxidase pathway. These studies are the first to explore angptl2 contribution to endothelial dysfunction in different vascular beds, and strongly suggest that angptl2 can directly impair endothelial function by its pro-inflammatory and pro-oxidative properties. Translating this to the clinical setting, expression levels of angptl2 may be an indicator of endothelial function, and lowering angptl2 levels could become a potential therapeutic approach in the treatment of chronic inflammatory disorders including cardiovascular diseases.

The purpose of the projection was creating an object which offers enough space for social activities with possibility of free time spending. The floor projection of irregular shape allows the object of the golf club to be splitted into dispositionally detached parts. The object consists of three-storey main building and two-storey relaxing section. Whole object has a basement. It is situated in sloping terrain on the outskirts of the Dolní Dobrouč village. The basement of main building has the shape of irregular rectangle. It is imbedded into the ground and technical background of main object is situated here. The relaxing section is connected to this space by small passage which is used for technical background of this section. The floor projection of the first floor exceeds over the basement. In a guests section, there is a main entrance, a restaurant and a shop. The staff section adjoins to this section. On the second floor, there are conference rooms, administrative section, the other floor of the restaurant and a garage. The basement of the relaxing section as much as its first floor are designed for the guests‘ relaxation. The shed roof construction of the main building and the relaxing section is made of glued laminated truss. The garage has a shed roof too with the construction built of thin-walled domestic roof trusses. In the construction point of view the object was projected with aspect to cooperation of materials and systems and so allows effective use of different parts. The building does not invade the character of the environment due to its shape solution when object almost copies the terrain. However, the whole complex of golf club including golf course, creates a distinctive landscaping object.

At one point or another we have all felt overwhelmed or stressed. It is part of human nature and can at times be beneficial as it can boost our performance and make us more alert. However when it becomes a part of daily life to worry about everything, it turns into a hindrance. This is where Iyashikei, the japanese word referring to the feeling of calm and relaxed, comes into play. We explore what makes a medium “Iyashikei” and define a design methodology based on those findings. The design methodology consists of three parts in which feelings and Iyashikei have been the main focus when deciding what to include. This design methodology is then evaluated by using it to design a game. The game is a small proof of concept design and can be expanded upon further to increase its calming effect. However we believe that it is sufficient as proof of concept.

El presente trabajo de investigación trata de la producción mediante servicio de maquila y la comercialización de tés de 45 gr. con la marca Hibiscus que es una mezcla de hojas deshidratadas de planta aromáticas, medicinales que mantienen sus nutrientes y propiedades funcionales, tales como: digestivo, relajante y antioxidante como una solución para mejorar la salud y bienestar del consumidor. Además, para simplificar el proceso de preparación del filtrado del té, la presentación del producto trae un infusor de té para taza. En este sentido, para posicionar el producto en el consumidor, se buscará que la experiencia del consumidor relacione el producto con la salud en el segmento de varones y mujeres de 25 a 55 años de edad del nivel socioeconómico A y B que residen en Lima Moderna de Lima Metropolitana, con estilo de vida sofisticado y moderno, que cuidan su imagen personal y prefieren productos saludables que les facilite ahorro de tiempo en la preparación. Cabe indicar, el negocio Hibiscus tiene potencial crecimiento por la tendencia de la alimentación saludable, el crecimiento promedio de la venta anual es 4%. Hibiscus Té será distribuido por el canal directo a través de módulo de venta en Jockey Plaza y Marketplace de Facebook y por el canal indirecto en tiendas saludables como son: Sanahoria, Flora y Fauna, Ecotienda, y plataformas webs: ecotienda.pe, limaorganica.pe y mercadillo.pe. también, se contará con delivery para la entrega del pedido en 24 horas. / He following business research paper deals with the production process, marketing and sales of 45 gr. packed teas under the brand ‘Hibiscus’. The teas contain a mixture of dehydrated, aromatic, medicinal plant leafs that maintain their nutrients and functional properties, such as: digestive, relaxing and antioxidant. They serve as a solution to improve consumer health and well-being. In addition, to simplify the process of preparing the tea (filtering), the product presentation comes with a tea infuser. In this sense, to adequately position the product in the market, we must provide a great consumer experience, making our customers relate the product with good health. Our range of consumers belong to the segment of 25 to 55 year old men & women, of the socioeconomic levels A and B, who reside in the metropolitan, modern area of Lima. They have a sophisticated and modern lifestyle, take care of their personal image and prefer healthy products that facilitate saving time in preparation. It should be noted that the Hibiscus business has good potential growth due to the trend of healthy eating. The average growth of annual sales is projected at 4%. Hibiscus Tea will be distributed through a direct channel by the sales module in Jockey Plaza, via Facebook Marketplace, and through the indirect channel in a variety of healthy stores. These include: Sanahoria, Flora and Fauna, Ecotienda, and web platforms such as ecotienda.pe, limaorganica.pe and mercadillo.pe. Finally, there will be a delivery service for orders made during a 24 hours scale. / Trabajo de investigación

Several studies suggest that diabetes affects male and female vascular beds differently. However, the mechanisms underlying the interaction of sex and diabetes remain to be investigated. This study investigates whether there are 1) sex differences in the development of abnormal vascular responses and 2) changes in the relative contributions of endothelium-derived relaxing factors (EDRFs) in modulating vascular reactivity of mesenteric arteries taken from streptozotocin (STZ)-induced diabetic rats at early and intermediate stages of the disease (one and eight weeks, respectively). We also investigated the mesenteric expression of the mRNAs for endothelial nitric oxide synthase (eNOS) and NADPH oxidase (Nox) in STZ-induced diabetes in both sexes. Vascular responses to acetylcholine (ACh) in mesenteric arterial rings pre-contracted with phenylephrine were measured before and after pretreatment with indomethacin (cyclooxygenase inhibitor), L -NAME (NOS inhibitor), or barium chloride (K IR blocker) plus ouabain (Na + -K + ATPase inhibitor). We demonstrated that ACh-induced relaxations were significantly impaired in mesenteric arteries from both male and female diabetic rats at one and eight weeks. However, at eight weeks the extent of impairment was significantly greater in diabetic females than diabetic males. Our data also showed that in females, the levels of eNOS and Nox2- and Nox4-dependent NADPH oxidase mRNA expression and the relative importance of NO to the regulation of vascular reactivity were substantially enhanced, while the importance of endothelium-derived hyperpolarizing factor (EDHF) was significantly reduced at both one and eight weeks after the induction of diabetes. This study reveals the predisposition of female rat mesenteric arteries to vascular injury after the induction of diabetes, may be due to a shift away from a putative EDHF, initially the major vasodilatory factor, towards a greater reliance on NO, and the interaction of oxidative stress with elevated NO.

The diploma thesis is concerned with the swimming pool compound which is situated in the area of the Czech-Moravian Highlands, in the town Humpolec and it contains the complete documentary materials (documentation) for the execution of the project, fire safety solution to the building with respect to building physics, structural assess of wooden constructions and air- conditioning of the swimming hall. In the swimming compound there is a swimming hall with five swimming pools with the total water area of 605,4 m2 (swimming pool, the swimming pool for non-swimmers, relaxing swimming pool, whirpool, wading pool) and other additional services – four saunas with bar, massages,solarium and two buffets. The capacity of the swimming hall is 286 persons, the capacity of the whole compound is 418 persons. As for the shape of the building, it is designed as five rectangulars of different heights embedded into each other. Under the part of the swimming centre there is a basement and its external ground plan size is 61,33m*52,83. The basement serves as utility rooms of the whole building. The load-bearing construction of the swimming hall is designed using beam girders and pillars, made of glued laminated timber. In the rest of the building there is a brick construction system. Around the swimming hall there is a glass fronted facade.

This thesis summarizes my work on a new apartment building in Slovany, neighbourhood in Pilsen. My primary responsibility was to develop documentation for the project´s design and implementation. The building consists of four floors above ground, an underground floor and a flat roof. The building´s L-shaped plan, rebound 4th floor above ground and balconies lighten the mass of the building. The structural system of the building combined reinforced concrete system of the underground floor, column system of the 1st up to the 3rd floor above ground and wall system of the 4th floor above ground. The building is designed for six residential units with cellars, two garages, a relaxation room and a gym. The thesis includes the preparatory and study reports, architectural and construction solutions, and fire-safety building and construction site equipment solutions.

Thèse de doctorat présenté en vue de l'obtention du doctorat en psychologie - recherche intervention, option neuropsychologie clinique (Ph.D) / Les traumatismes craniocérébraux (TCC) peuvent entraîner de lourdes conséquences physiques, cognitives, émotionnelles et comportementales. Parmi celles-ci, l’agitation est très fréquente et se caractérise par une hyperactivité motrice, une désorientation, des problèmes d'attention, une labilité émotionnelle, une désinhibition et de l’agressivité. Elle interfère avec le rétablissement et les processus de réadaptation, mais il n'existe pas à ce jour de consensus sur son traitement, outre la contention physique ou la prise de médicaments, qui peuvent respectivement causer des blessures ou entraver la récupération. De récentes données suggèrent que les interventions musicales peuvent réduire l’agitation chez les patients TCC mais la capacité des patients TCC à percevoir et traiter la musique pendant la phase aiguë post-blessure n'a pas été établie. Le premier article de cette thèse visait à évaluer la perception musicale chez les patients TCC hospitalisés en phase aiguë. Dans la présente étude, 42 patients ayant subi un TCC ont été comparés à un groupe témoin. Tous les participants ont complété les tests de Scale et Rhythm de la Montreal Battery of Evaluation of Amusia pour mesurer la perception musicale, et le test d’empan numérique pour mesurer la mémoire verbale à court terme. Comparativement au groupe témoin, les patients TCC ont obtenu des performances significativement inférieures; 43% d'entre eux présentaient des déficits de traitement de la hauteur et 40% des déficits de traitement du rythme. Les patients présentant des lésions à l'hémisphère droit ont obtenu des résultats plus faibles que ceux présentant des lésions à l'hémisphère gauche. Les déficits de traitement de la hauteur et du rythme coexistaient dans 31% des cas, ce qui suggère l'existence de réseaux neuronaux partiellement dissociables. Le deuxième article est une revue non systématique dont l’objectif était de caractériser l'agitation et son traitement. Plusieurs types d’interventions comportementales, dont les interventions musicales, ont été explorées dans cette revue. Les limites méthodologiques ont été discutées et des recommandations ont été faites pour une approche plus systématique de la recherche utilisant des études de cas et de séries de cas chez les patients agités. Le troisième article est une étude pilote de phase II dans laquelle sont inclus des patients ayant subi un TCC modéré à sévère (n = 3) ou un accident vasculaire cérébral de l'artère cérébrale moyenne (n = 1). Ils ont été exposés à leurs musiques préférées, de la musique classique relaxante et un extrait sonore non musical (cascade) pendant la phase aiguë de récupération. Les comportements d’agitation ont été évalués à l'aide de l'Échelle d’Agitation (Agitated Behaviour Scale), de mesures actigraphiques et d’une observation qualitative. Les résultats indiquent que l’agitation a diminué lors de l’écoute de la musique classique relaxante et la cascade. L’agitation est restée stable lors de la musique préférée, mais certains patients ont exprimé des émotions positives ou présenté un comportement plus organisé, comme taper du pied ou chanter. Compte tenu des importantes limites méthodologiques dans ce champ d’études, la présente étude a permis d’explorer la faisabilité et l’effet d’une intervention musicale, ce qui permettra de guider les études futures. / Traumatic brain injury (TBI) has serious physical, cognitive, emotional, and behavioural consequences. Agitation is highly prevalent among patients with TBI, and is characterized by motor hyperactivity, disorientation, attention problems, emotional lability, disinhibition, and aggression. It often results in decreased engagement in rehabilitative treatment, and poorer functional outcomes. There is no consensus on the treatment for agitation. Most often, it is managed with medication and physical restraints, which may cause injury or impede cognitive recovery. Few studies examine novel non-pharmacological interventions for agitation in TBI patients. However, recent evidence suggests that music interventions may decrease agitated behavior in TBI patients. The ability of TBI patients to perceive and process music during the acute phase has not been established, though it may influence the efficacy of preferred music interventions. The first article of this thesis evaluated music perception in acutely hospitalized TBI patients. Music perception deficits have been identified in populations with acquired brain injury due to epilepsy, stroke, and after aneurysmal clipping. However, few studies have evaluated deficits following TBI, resulting in an underdiagnosis in this population. Forty-two patients completed the Scale and Rhythm tests of the Montreal Battery for the Evaluation of Amusia to measure music perception, and Digit Span Forward to measure verbal short-term memory. TBI patients were more often impaired than controls, with 43% demonstrating pitch processing deficits, and 40% demonstrating rhythm processing deficits. Patients with right hemisphere damage performed more poorly than those with left hemisphere damage. Pitch and rhythm deficits co-occurred 31% of the time, suggesting partly dissociable neural networks. Results are discussed in the context of current research and clinical implications. The second article was a non-systematic review in which we characterized agitation and its treatment. We explored behavioural interventions, including music interventions, occupational therapy, the Intervention Contingencies Awareness Relationship behavioural model, operant contingency management, and general therapeutic activities. The methodological limitations were discussed and recommendations made for a more systematic approach to research using case and case series studies in agitated patients. The third article was a phase-II development-of-concept pilot study in which four patients with moderate to severe TBI (n = 3), and middle cerebral artery stroke: (n = 1) were exposed to preferred music, relaxing classical music, and a nonmusical control (waterfall) during the acute phase of recovery. Agitated behaviours were assessed using the Agitated Behavior Scale, actigraphy, and qualitative observation. Agitated behaviour decreased during relaxing classical music, and waterfall. It remained stable in the preferred music condition. However, certain patients expressed positive emotions and organized behaviour such as tapping or singing along. Given important methodological limitations in current studies, a phase-II study allowed for the evaluation of outcomes and the practicality of delivering music listening interventions, which may guide future studies.