réalisé en cotutelle avec le Dr. Marie Kmita et Dr. Marco Horb / Chez l’humain, les maladies congénitales cardiaques (MCC) sont présentes chez 3-4% des nouveaux nés et sont une cause importante de mortalité infantile et de morbidité dans le monde. La majorité des MCCs implique les valves et les septums, qui proviennent des cellules endocardiques. Les valves aortiques bicuspides (VAB) sont la MCC la plus fréquente chez l’humain, avec un taux estimé de 1-2% dans la population. Cependant, les gènes et les mécanismes moléculaires qui causent cette malformation demeurent obscures. Le facteur de transcription GATA5 est exprimé dans les cellules et les coussins endocardiques de façon transitoire durant la septation et la formation des compartiments cardiaques. Chez le poisson zèbre, des mutations dans le gène Gata5 causent des malformations cardiaques sévères incluant l’absence de cellules endocardiques. In vitro, l’inhibition de Gata5 bloque la différentiation endocardique. Ces études suggéraient donc un rôle important de GATA5 dans la formation du cœur. Dans le cadre de ce projet de doctorat, nous avons analysé le rôle de GATA5 dans le développement du cœur en produisant des lignées de souris chez lesquelles le gène Gata5 était inactif soit dans toutes les cellules ou uniquement dans les cellules endocardiques. Les souris possédant 2 allèles mutées du gène Gata5 étaient viables mais plus de 26% des souris Gata5-/- ont développé des VABs. Par ailleurs, une incidence similaire de VABs a été obtenue chez les souris ayant une délétion spécifique de Gata5 des cellules endocardiques, obtenue en croisant les souris Gata5WT/Flox avec les souris transgéniques Tie2-Cre. Sur le plan mécanistique, une réduction significative de JAG1, un corécepteur pour Notch1, ainsi qu’une augmentation marquée de Rbj un répresseur de cette voie, ont été détectés chez les souris Gata5-/- et Tie2- cre+;Gata5Flox/Flox, suggérant qu’une dérégulation de la voie Notch dans les cellules endocardiques puisse être la cause des VABs. Ces résultats démontrent l’importance de GATA5 pour le développement endocardique et la formation de la valve aortique. De plus, ils identifient GATA5 comme gène candidat de MCCs chez l’humain. Environ 12-14% des MCCs sont causés par le développement anormal de la voie de chasse, menant aux malformations telles que la transposition des grandes artères, la tétralogie de Fallot ou le syndrome du ventricule droit à double issue. Des mutations dans Gata4 et Gata6 sont associés à des défauts de la voie de chasse, dans plusieurs espèces incluant l’humain. Nous avons examiné si GATA5 interagit avec GATA4 ou GATA6 dans le développement de la voie de chasse. Alors que les souris hétérozygotes pour Gata5, Gata4 ou Gata6 ont des défauts cardiaques subtiles et sont viables, les embryons Gata4+/-Gata5+/- et Gata5+/-Gata6+/- démontrent une létalité embryonnaire et périnatale due à des défauts cardiaques, tel qu’un ventricule droit à double issue et des défauts de septation ventriculaire. Ces résultats indiquent l'importance des interactions génétiques entre GATA5 et les autres facteurs GATA pour la rotation et l’alignement de la voie de chasse au cours du développement cardiaque et soulèvent la possibilité que des changements subtiles de l'activité de 2 facteurs GATA puissent mener à des MCCs chez l'humain. / Congenital heart defect (CHD) in humans occur in 3-4% of live birth and is a major cause of infant mortality and morbidity in the world. The majority of CHD involves the valves and septa, which originate from endocardial cells. Bicuspid aortic valve (BAV) is the most common CHD in humans with an estimated rate of 1-2% in the population. However, very few genes have been linked to this defect and the mechanisms underlying BAV formation remain undefined. GATA5, a member of the GATA family of transcription factors, is expressed in a spatial and temporal manner in the developing heart where it is predominantly found in endocardial cells and endocardial cushions (ECs) of the outflow tract (OFT) and atrioventricular canal between E9.5-E12.5 in the mouse. Mutations in the Gata5 gene in zebrafish (faust mutants) cause cardia bifida and lead to endocardial cell depletion. In vitro studies using antisense mRNA against Gata5 revealed a critical role for this gene in differentiation of endocardial cells. In the context of the present doctoral research project, we investigated the role of GATA5 in mammalian heart development by generating a mouse line with a null Gata5 allele. Gata5 null mice are viable but over 26% of them developed BAVs. Endocardial specific deletion of Gata5 obtained by crossing mice with floxed (Flox) Gata5 alleles with Tie2-cre transgenic mice resulted in a similar incidence of BAVs. RNA profiling revealed that Jag-1, a co-receptor for Notch1, is significantly downregulated in both Gata5 null and Tie2-cre+;Gata5Flox/Flox mice, suggesting that disruption of Notch signaling in endocardial cells may be the underlying mechanism of disease. These findings reveal an important function for GATA5 in endocardial cell development and aortic valve formation and identify GATA5 as an important candidate CHD causing gene. Abnormal development of the OFT accounts for about 12-14% of all CHDs, leading to malformations such as persistent truncus arteriosus (PTA), tetralogy of Fallot (TOF), double outlet right ventricle (DORV) and transposition of the great arteries (TGA). Both GATA4 and GATA6 play important role in OFT development. We tested whether GATA5 might interact genetically with GATA4 and GATA6 for proper heart morphogenesis. We found that, whereas mice lacking a single copy of Gata5, Gata4 or Gata6 have subtle cardiac defects, the Gata4+/-Gata5+/- and Gata5+/-Gata6+/- mutant embryos show embryonic and perinatal lethality due to severe heart defects, including double outlet right ventricle and ventricular septal defects. These findings reveal the importance of genetic interactions between GATA5 and the other cardiac GATA factors in the normal rotation and patterning of the OFT during heart development in vivo. The results raise the possibility that subtle alterations in the level or activity of 2 cardiac GATA factors might lead to congenital heart disease in human.

Introdução: obstrução gastroduodenal maligna é uma condição frequente em neoplasias gástricas e pancreáticas em estágio avançado. O tratamento paliativo visa a melhora dos sintomas e da qualidade de vida, sendo realizado pelas técnicas cirúrgicas ou endoscópicas. Embora a terapêutica cirúrgica seja consagrada, as complicações relacionadas ao procedimento e as condições clínicas desfavoráveis dos pacientes devem ser consideradas. Apesar dos avanços do tratamento endoscópico e da possibilidade de oferecer um tratamento menos invasivo, deve-se considerar as complicações e a taxa de reintervenção desta modalidade terapêutica. Novas tecnologias foram desenvolvidas para minimizar as complicações relacionadas ao uso de próteses e demandam uma análise pormenorizada. O objetivo desta revisão sistemática é comparar o tratamento endoscópico com próteses cobertas e não cobertas e o cirúrgico com gastrojejunoanastomose para obstrução gastroduodenal. Métodos: ensaios clínicos randomizados foram identificados nas bases de dados do MEDLINE, Embase, Cochrane, LILACS, SCOPUS e CINAHL. A comparação entre as próteses metálicas cobertas e não cobertas incluiu o sucesso técnico, sucesso clínico, complicações, obstrução, migração, sangramento, perfuração, fratura das próteses e reintervenção. Os desfechos usados na comparação da terapêutica cirúrgica com gastrojejunoanastomose e endoscópica com próteses foram o sucesso técnico, complicações e reintervenção. A avaliação da patência não pode ser incluída devido à falta de uniformidade dos dados extraídos. Resultados: oito artigos foram selecionados, três comparando gastrojejunostomia e próteses e cinco comparando próteses cobertas e não cobertas. A metanálise dos estudos sobre gastroenteroanastomose e próteses não demonstrou diferença significativa no sucesso técnico e número absoluto de complicações. O tratamento com próteses apresentou uma maior taxa de reintervenção que a terapêutica cirúrgica (DR = 0,26, IC 95% = 0,05 a 0,47, NNH = 4). A metanálise que comparou próteses metálicas cobertas e não cobertas não demonstrou diferença estatística significativa considerando o sucesso técnico, sucesso clínico, complicações, fratura das próteses, perfuração, sangramento e necessidade de reintervenção. Uma maior taxa de migração foi atribuída à terapêutica com próteses cobertas (DR = 0,09, IC 95% = 0,04 a 0,14, NNH = 11). Entretanto, o tratamento com próteses cobertas apresenta menor taxa de obstrução em relação às não cobertas (DR = -0,21, IC 95% = -0,27 a -0,15, NNT = 5). Uma análise de subgrupo de estudos com próteses metálicas que incluíram apenas pacientes com câncer gástrico demonstrou resultado semelhante à metanálise com todos os artigos. Conclusões: o tratamento endoscópico paliativo da obstrução gastroduodenal maligna com próteses cobertas apresenta maior taxa de migração e menor número de obstruções quando comparado com o uso de próteses não cobertas. A terapêutica cirúrgica com gastrojejunoanastomose associa-se a uma menor taxa de reintervenção em relação ao uso de próteses / Introduction: malignant gastric outlet obstruction is a frequent condition in advanced gastric and pancreatic neoplasms. Palliative treatment can be performed by endoscopic or surgical techniques. Palliation aims to relief symptoms and increase quality of life. Although surgical therapy is the established treatment, the complication rate of the procedure and the unfavorable clinical conditions must be considered. Despite the advances in the endoscopic treatment and the possibility to offer a minimally invasive therapy, complication rate and need of reintervention must be reminded. New technologies have been developed to minimize the complications related to the use of stents and require a detailed analysis. This systematic review aims to compare surgery and covered and uncovered stent treatments for gastric outlet obstruction. Methods: randomized clinical trials were identified in MEDLINE, Embase, Cochrane, LILACs, BVS, SCOPUS and CINAHL databases. Comparison of covered and uncovered stents included: technical success, clinical success, complications, obstruction, migration, bleeding, perforation, stent fracture and reintervention. The outcomes used to compare Gastrojejunostomy and stents were technical success, complications and reintervention. Patency rate could not be included because of lack of uniformity of the extracted data. Results: eight studies were selected, three comparing gastrojejunostomy and stents and five comparing covered and uncovered stents. The meta-analysis of surgical and endoscopic stent treatment showed no difference in the technical success and overall number of complications. Stents had higher reintervention rates than surgery (RD: 0.26, 95% CI [0.05, 0.47], NNH: 4). There is no significant difference in technical success, clinical success, complications, stent fractures, perforation, bleeding and the need for reintervention in the analyses of covered and uncovered stents. There is a higher migration rate in the covered stent therapy compared to uncovered self-expanding metallic stents in the palliation of malignant gastric outlet obstruction (RD: 0.09, 95% CI [0.04, 0.14], NNH: 11). Nevertheless, covered stents had lower obstruction rates (RD: -0.21, 95% CI [-0.27, - 0.15], NNT: 5). A subgroup analysis with studies that included only patients with gastric cancer showed similar results when compared with the analysis with all trials. Conclusions: in the palliation of malignant gastric outlet obstruction, covered stents had higher migration and lower obstruction rates when compared with uncovered stents. Gastrojejunostomy is associated with lower reintervention rates than stents

Introdução: obstrução gastroduodenal maligna é uma condição frequente em neoplasias gástricas e pancreáticas em estágio avançado. O tratamento paliativo visa a melhora dos sintomas e da qualidade de vida, sendo realizado pelas técnicas cirúrgicas ou endoscópicas. Embora a terapêutica cirúrgica seja consagrada, as complicações relacionadas ao procedimento e as condições clínicas desfavoráveis dos pacientes devem ser consideradas. Apesar dos avanços do tratamento endoscópico e da possibilidade de oferecer um tratamento menos invasivo, deve-se considerar as complicações e a taxa de reintervenção desta modalidade terapêutica. Novas tecnologias foram desenvolvidas para minimizar as complicações relacionadas ao uso de próteses e demandam uma análise pormenorizada. O objetivo desta revisão sistemática é comparar o tratamento endoscópico com próteses cobertas e não cobertas e o cirúrgico com gastrojejunoanastomose para obstrução gastroduodenal. Métodos: ensaios clínicos randomizados foram identificados nas bases de dados do MEDLINE, Embase, Cochrane, LILACS, SCOPUS e CINAHL. A comparação entre as próteses metálicas cobertas e não cobertas incluiu o sucesso técnico, sucesso clínico, complicações, obstrução, migração, sangramento, perfuração, fratura das próteses e reintervenção. Os desfechos usados na comparação da terapêutica cirúrgica com gastrojejunoanastomose e endoscópica com próteses foram o sucesso técnico, complicações e reintervenção. A avaliação da patência não pode ser incluída devido à falta de uniformidade dos dados extraídos. Resultados: oito artigos foram selecionados, três comparando gastrojejunostomia e próteses e cinco comparando próteses cobertas e não cobertas. A metanálise dos estudos sobre gastroenteroanastomose e próteses não demonstrou diferença significativa no sucesso técnico e número absoluto de complicações. O tratamento com próteses apresentou uma maior taxa de reintervenção que a terapêutica cirúrgica (DR = 0,26, IC 95% = 0,05 a 0,47, NNH = 4). A metanálise que comparou próteses metálicas cobertas e não cobertas não demonstrou diferença estatística significativa considerando o sucesso técnico, sucesso clínico, complicações, fratura das próteses, perfuração, sangramento e necessidade de reintervenção. Uma maior taxa de migração foi atribuída à terapêutica com próteses cobertas (DR = 0,09, IC 95% = 0,04 a 0,14, NNH = 11). Entretanto, o tratamento com próteses cobertas apresenta menor taxa de obstrução em relação às não cobertas (DR = -0,21, IC 95% = -0,27 a -0,15, NNT = 5). Uma análise de subgrupo de estudos com próteses metálicas que incluíram apenas pacientes com câncer gástrico demonstrou resultado semelhante à metanálise com todos os artigos. Conclusões: o tratamento endoscópico paliativo da obstrução gastroduodenal maligna com próteses cobertas apresenta maior taxa de migração e menor número de obstruções quando comparado com o uso de próteses não cobertas. A terapêutica cirúrgica com gastrojejunoanastomose associa-se a uma menor taxa de reintervenção em relação ao uso de próteses / Introduction: malignant gastric outlet obstruction is a frequent condition in advanced gastric and pancreatic neoplasms. Palliative treatment can be performed by endoscopic or surgical techniques. Palliation aims to relief symptoms and increase quality of life. Although surgical therapy is the established treatment, the complication rate of the procedure and the unfavorable clinical conditions must be considered. Despite the advances in the endoscopic treatment and the possibility to offer a minimally invasive therapy, complication rate and need of reintervention must be reminded. New technologies have been developed to minimize the complications related to the use of stents and require a detailed analysis. This systematic review aims to compare surgery and covered and uncovered stent treatments for gastric outlet obstruction. Methods: randomized clinical trials were identified in MEDLINE, Embase, Cochrane, LILACs, BVS, SCOPUS and CINAHL databases. Comparison of covered and uncovered stents included: technical success, clinical success, complications, obstruction, migration, bleeding, perforation, stent fracture and reintervention. The outcomes used to compare Gastrojejunostomy and stents were technical success, complications and reintervention. Patency rate could not be included because of lack of uniformity of the extracted data. Results: eight studies were selected, three comparing gastrojejunostomy and stents and five comparing covered and uncovered stents. The meta-analysis of surgical and endoscopic stent treatment showed no difference in the technical success and overall number of complications. Stents had higher reintervention rates than surgery (RD: 0.26, 95% CI [0.05, 0.47], NNH: 4). There is no significant difference in technical success, clinical success, complications, stent fractures, perforation, bleeding and the need for reintervention in the analyses of covered and uncovered stents. There is a higher migration rate in the covered stent therapy compared to uncovered self-expanding metallic stents in the palliation of malignant gastric outlet obstruction (RD: 0.09, 95% CI [0.04, 0.14], NNH: 11). Nevertheless, covered stents had lower obstruction rates (RD: -0.21, 95% CI [-0.27, - 0.15], NNT: 5). A subgroup analysis with studies that included only patients with gastric cancer showed similar results when compared with the analysis with all trials. Conclusions: in the palliation of malignant gastric outlet obstruction, covered stents had higher migration and lower obstruction rates when compared with uncovered stents. Gastrojejunostomy is associated with lower reintervention rates than stents

Chez l’humain, les maladies congénitales cardiaques (MCC) sont présentes chez 3-4% des nouveaux nés et sont une cause importante de mortalité infantile et de morbidité dans le monde. La majorité des MCCs implique les valves et les septums, qui proviennent des cellules endocardiques. Les valves aortiques bicuspides (VAB) sont la MCC la plus fréquente chez l’humain, avec un taux estimé de 1-2% dans la population. Cependant, les gènes et les mécanismes moléculaires qui causent cette malformation demeurent obscures. Le facteur de transcription GATA5 est exprimé dans les cellules et les coussins endocardiques de façon transitoire durant la septation et la formation des compartiments cardiaques. Chez le poisson zèbre, des mutations dans le gène Gata5 causent des malformations cardiaques sévères incluant l’absence de cellules endocardiques. In vitro, l’inhibition de Gata5 bloque la différentiation endocardique. Ces études suggéraient donc un rôle important de GATA5 dans la formation du cœur. Dans le cadre de ce projet de doctorat, nous avons analysé le rôle de GATA5 dans le développement du cœur en produisant des lignées de souris chez lesquelles le gène Gata5 était inactif soit dans toutes les cellules ou uniquement dans les cellules endocardiques. Les souris possédant 2 allèles mutées du gène Gata5 étaient viables mais plus de 26% des souris Gata5-/- ont développé des VABs. Par ailleurs, une incidence similaire de VABs a été obtenue chez les souris ayant une délétion spécifique de Gata5 des cellules endocardiques, obtenue en croisant les souris Gata5WT/Flox avec les souris transgéniques Tie2-Cre. Sur le plan mécanistique, une réduction significative de JAG1, un corécepteur pour Notch1, ainsi qu’une augmentation marquée de Rbj un répresseur de cette voie, ont été détectés chez les souris Gata5-/- et Tie2- cre+;Gata5Flox/Flox, suggérant qu’une dérégulation de la voie Notch dans les cellules endocardiques puisse être la cause des VABs. Ces résultats démontrent l’importance de GATA5 pour le développement endocardique et la formation de la valve aortique. De plus, ils identifient GATA5 comme gène candidat de MCCs chez l’humain. Environ 12-14% des MCCs sont causés par le développement anormal de la voie de chasse, menant aux malformations telles que la transposition des grandes artères, la tétralogie de Fallot ou le syndrome du ventricule droit à double issue. Des mutations dans Gata4 et Gata6 sont associés à des défauts de la voie de chasse, dans plusieurs espèces incluant l’humain. Nous avons examiné si GATA5 interagit avec GATA4 ou GATA6 dans le développement de la voie de chasse. Alors que les souris hétérozygotes pour Gata5, Gata4 ou Gata6 ont des défauts cardiaques subtiles et sont viables, les embryons Gata4+/-Gata5+/- et Gata5+/-Gata6+/- démontrent une létalité embryonnaire et périnatale due à des défauts cardiaques, tel qu’un ventricule droit à double issue et des défauts de septation ventriculaire. Ces résultats indiquent l'importance des interactions génétiques entre GATA5 et les autres facteurs GATA pour la rotation et l’alignement de la voie de chasse au cours du développement cardiaque et soulèvent la possibilité que des changements subtiles de l'activité de 2 facteurs GATA puissent mener à des MCCs chez l'humain. / Congenital heart defect (CHD) in humans occur in 3-4% of live birth and is a major cause of infant mortality and morbidity in the world. The majority of CHD involves the valves and septa, which originate from endocardial cells. Bicuspid aortic valve (BAV) is the most common CHD in humans with an estimated rate of 1-2% in the population. However, very few genes have been linked to this defect and the mechanisms underlying BAV formation remain undefined. GATA5, a member of the GATA family of transcription factors, is expressed in a spatial and temporal manner in the developing heart where it is predominantly found in endocardial cells and endocardial cushions (ECs) of the outflow tract (OFT) and atrioventricular canal between E9.5-E12.5 in the mouse. Mutations in the Gata5 gene in zebrafish (faust mutants) cause cardia bifida and lead to endocardial cell depletion. In vitro studies using antisense mRNA against Gata5 revealed a critical role for this gene in differentiation of endocardial cells. In the context of the present doctoral research project, we investigated the role of GATA5 in mammalian heart development by generating a mouse line with a null Gata5 allele. Gata5 null mice are viable but over 26% of them developed BAVs. Endocardial specific deletion of Gata5 obtained by crossing mice with floxed (Flox) Gata5 alleles with Tie2-cre transgenic mice resulted in a similar incidence of BAVs. RNA profiling revealed that Jag-1, a co-receptor for Notch1, is significantly downregulated in both Gata5 null and Tie2-cre+;Gata5Flox/Flox mice, suggesting that disruption of Notch signaling in endocardial cells may be the underlying mechanism of disease. These findings reveal an important function for GATA5 in endocardial cell development and aortic valve formation and identify GATA5 as an important candidate CHD causing gene. Abnormal development of the OFT accounts for about 12-14% of all CHDs, leading to malformations such as persistent truncus arteriosus (PTA), tetralogy of Fallot (TOF), double outlet right ventricle (DORV) and transposition of the great arteries (TGA). Both GATA4 and GATA6 play important role in OFT development. We tested whether GATA5 might interact genetically with GATA4 and GATA6 for proper heart morphogenesis. We found that, whereas mice lacking a single copy of Gata5, Gata4 or Gata6 have subtle cardiac defects, the Gata4+/-Gata5+/- and Gata5+/-Gata6+/- mutant embryos show embryonic and perinatal lethality due to severe heart defects, including double outlet right ventricle and ventricular septal defects. These findings reveal the importance of genetic interactions between GATA5 and the other cardiac GATA factors in the normal rotation and patterning of the OFT during heart development in vivo. The results raise the possibility that subtle alterations in the level or activity of 2 cardiac GATA factors might lead to congenital heart disease in human. / réalisé en cotutelle avec le Dr. Marie Kmita et Dr. Marco Horb

The work focuses on outlet of the electrical power from power plants operating in urban areas. After a short analysis of the general possibility of leading out electric power from power plants of various types, thesis continues to describe of outlet electrical power from PPC Červený Mlýn. Subsequently, are calculated short-circuit conditions in the main switching station. It follows an analysis of power lines. The last part dealt with the issue of reliability of sources in connection with random transition processes in the electrical network and the light of the operational reliability of electrical power equipment.

The Master’s thesis on the theme „Multi function house“ is drafted as a building documentation according to the relevant laws and standards. The project processes a documentation of a new multi fiction apartment house construction with overall 16 flats. Their sizes are from a flat 2+1 to a flat with 4 rooms and kitchenette. Every flat has a garage and a cellar in the first floor. In the house there are 2 offices with a capacity about 12 employees and also 3 commercial premises. Hairdressing parlor and an Apple store are going to by situated into two smaller premises. In the last premise with 263 m2 of floorspace there is going to be a cycling shop. The project is designed as a brick building without basement. The building has two parts with four floors and these parts are united by a single-storey part. The whole building is symetric. The roof is designed as a platform with tend of 3%. On top of the first floor there is going to be a vegetation roof and a roof teracce with a flagging. On the fourth floor there are going to be roof teracces with ceramic pavement. Over the fourth floor there is going to be a roof cllading laden by pebbles. The house is situated in the town Kroměříž, in the pacific neighbourhood near to the historical town center. The neighbourhood of the object is determined for a building-up of family houses. Nearby the house there is a primary school and an athletic ground. The brick object is designed by a construction system Livetherm on the wall footings. The ceiling constructions are from concrete. The Master’s thesis is made as a project realization of building construction part with studies and design fundamentals. The part of the thesis is also the thermal technical recognition, fire recognition of the object and concept of canalization.

The aim of this work was the analysis of air current from the right outlet, using the smoke method and the subsequent determination of a method for application. A further task was to establish a method for determining the upper and lower vertical routing, yaw angle (ß) and angle of inclination (?) of the air current. The experiment aims to approximate conditions as close to those experienced in the actual vehicle. After assembling a track with a soot blower (outlet) in the laboratory and defining the coordinates of the vehicle, the air current was subjected to visualization within the range of five positions of the vanes. Visualization was achieved by the use of technology for the smoke method. We used a light plane with a customized system of coordinates, a smoke generator for visualizing the air current being emitted and a camera for recording images. During our research we established the upper and lower cut off at the specific closures of the horizontal vanes of the soot blower. We determined a common analogy between the experimental track used in the experiment and the circumstances in the actual vehicle. We acquired the yaw angles (ß) and the angles of inclination (?) in the light plane and, after conversion, in the system of coordinates of the vehicle for all five settings of the vanes. The assessment of the given soot blower was undertaken according to the values achieved.

Goal of this master´s thesis is to experimentally analyse air jet from ventilation outlet of a passenger car dashboard using smoke visualization and to describe this air jet. Air flow was set at 30 m3/h according to requirements from Škoda Auto s.r.o. from previous experiments on a similar ventilation outlet. First type of measuring rig which was developed for previous experiments was disassembled and replaced with a new modern measuring rig which is supposed to be used for next visualizations and experiments. Visualization was performed using smoke method and laser light plane. Air jet was photographed for five defined ventilation outlet adjustments and that for a jet to free space and for a jet flowing along a wall. The wall represented a front left door of a car. Results were processed by computer and presented as pictures and tables. Resulting angles were transformed to the main coordinate system of a car. Ventilation outlet functionality with respect to the air distribution in a car was evaluated afterwards.

This thesis describes the methods and procedures used in designing production lines, focusing on the production line for machining of train wheels. The thesis also describes the basic types of railway wheels, their design and important design elements. It also deals with the complete manufacturing process of train wheel from material selection through the technological processes of forming, heat treatment, mechanical tests, machining and non-destructive testing and measuring. Suitable equipment for the construction of automatic lines for machining, inspection and measurement of train wheels is selected according to the specified parameters of the wheel types, manufacturing productivity and production shop dimensions, These devices include vertical machining center, single-purpose machine for grease outlet drilling, device for ultrasonic inspection, magnetic particle inspecton device, measuring station and train wheel balancing machine. Several variants of the production line including detailed specification of manipulation cycle times is created. These variants are mutually compared and evaluated to find the optimal solution.

I dagens industrier förekommer det ofta flaskhalsar och onödiga förluster i produktionslinjer. Det medför att en implementering av underhållsarbete i form av förebyggande underhåll och optimering av delar i produktionen är viktiga för att bibehålla en effektiv och hög kvalite. I Scania så försöker man ständigt förbättra produktionen med att införa automation, automatisering och optimering på alla aspekter när det gäller resultat och även hälsa för individen. För att eliminera alla slöserier skapar Scania grunden för ett kvalitativt förarbete inom förbättrings lägen och Scania har gjort detta ända sen företaget startade under tidigt 1900-tal. Denna rapport ämnar sig åt att jämföra nuläget för kylsystemet i det norra området i Scania med potentialen till ett förbättrings läge. Hela Scanias processkyla och komfortkyla försörjs av en kylcentral i det norra området och med vatten från mälaren förses det norra området med den kyla som processerna i produktionen kräver. Rapporten kommer bara att ägna tid och resurser att frambringa potential och optimerings punkter för processkyla, och inte komfortkyla som är tillägnad för kontor och arbetsrum. Litteraturstudien har utförts med datainsamling genom Scanias tidigare media utredningar, arkiv, och även gå&se på Scanias olika byggnader där kartläggning av process kylan har varit i fokus. Resultaten säkerställde att variationer av förbättringslägen kan medföra en optimerad process för hur processkyla(ΔT) kan höjas och därmed höja nyttjandegraden för Scanias fjärrkyla i det norra området. Slutsatserna som studien påvisar är förbättringslägen för fyra slutanvändare som använder fjärrkylan idag och en optimerad framledningen utav kylan så att process kylan används på ett så optimalt sätt som möjligt. / In today's industries, there are often bottlenecks and unnecessary losses in production lines. This means that an implementation of maintenance work in the form of preventive maintenance and optimization of parts in production are important to maintain efficiency and high quality.Scania constantly strives to improve production by introducing automation and optimization in all aspects in terms of results and also for the health of the individual. To eliminate all waste, Scania creates the basis for qualitative preparation in areas for improvement, and Scania has done this ever since the company started in the early 20th century. This report aims to compare the current situation for the cooling system in the northern area of Scania with the potential for an improvement. The entire Scania process cooling and comfort cooling is supplied by a cooling center in the northern area and with water from the lake Mälaren, the northern area is supplied with the cooling that the processes in production require. The report will only have the time and resources to generate potential and optimization points for the process cooling, and not the comfort cooling that is for offices and workrooms, etc. The literature study has been carried out with data collection through Scania's previous media investigations, archives, and also go&look at Scania's various buildings where mapping of the cooling process has been in focus. The results ensured that variations in improvement modes can lead to an optimized process for how process cooling can be increased and thereby increase the utilization rate of Scania's district cooling in the northern area. The conclusions that are studied show improvement modes for four end users who use the district cooling today and improve the flow out of the cold water so that the process cooling is used in the most optimal way possible.