Congenital heart defects due to the aberrant development of the atrioventricular (AV) valves and septum are among the most common developmental abnormality in newborns and cause significant neonatal morbidity and mortality. A key point in cardiac morphogenesis occurs when cells within the endocardial cushions (ECCs), the precursors for the AV valvoseptal complex, delaminate and undergo an epithelial-to-mesenchymal transformation (EMT). The mesenchymal cells then proliferate and the cushion area elongates to form the AV valves and portions of the AV septae. The signals that initiate region-specific EMT during heart development are unknown. Cilia, known for their role in establishing left-right (LR) asymmetry, function to receive and integrate extracellular signals, including fluid flow, in a range of other organ systems. We hypothesize that cilia could also have a direct role in heart development outside of their role in LR development. Using immunohistochemistry, we demonstrated the presence of cilia on the myocardium, epicardium, and ECCs of wild-type mouse hearts at embryonic day (e) 9.5 and e12.5. To characterize the potential role of these cilia, we compared mice with mutations affecting ciliary biogenesis, motility, and mechanosensation. Using bright field microscopy and in situ hybridization, we analyzed the embryonic heart structure and the expression pattern of Gata4, an EMT transcription factor. We showed that compared to mice with immotile but structurally normal cilia, the mice without cilia had hypocellular ECCs, a thinned compact myocardium (CM), and an up-regulated expression of Gata4. These observations suggest that a subset of cilia called cardiac cilia have a role in cardiogenesis outside of their role in LR development and affect Gata4 expression. One possible function of cardiac cilia is as mechanosensors, integrating fluid flow and influencing cardiac morphogenesis including EMT and development of the CM.

No description available.

Building envelopes are elements with a long lifetime, which provide a barrier between internal and external space and contribute to the internal environmental conditions provision. Their complex role ensures a large impact on the environmental and energy performance of a building and the occupant perception of a space. This study looks at the use of novel materials and processes to help reduce the environmental impact of buildings by improving facade and transparent roof design. There are three main strands to the work. First, novel building components, ETFE foil cushions were examined. Physical testing has shown that ETFE foil cushions compare favourably to double glazing in terms of thermal and daylighting performance which was also noted as one of the most likeable feature by occupants. Environmental impact analysis has indicated that ETFE foils can reduce the environmental impact of a building through reduced environmental burden of both the construction and operation of the building. Secondly, a cradle-to-gate Life Cycle Analysis (LCA) was carried out for float glass, which considered the environmental impacts of glass manufacture. The embodied energy was calculated to be 13.4 ± 0.5 GJ per tonne while the total number of eco-points 243 ± 11 per tonne. It is shown that float glass is comparable to the use of steel, and highly preferable to the use of aluminium as a cladding panel. Finally, a concept design tool (FACADE) was developed by defining a large number of office facade models and employing dynamic thermal, daylighting and environmental impact modelling to create a database which can be accessed through a user friendly interface application. A parametric analysis has indicated that using natural ventilation where possible can reduce the environmental impact of offices by up to 16%. Improving the standard of the facade and reducing the internal heat loads from lighting and equipment can reduce environmental impact up to 22%. This study makes a significant contribution to understanding the environmental impact of building envelope individual and integrated components.

Indiana University-Purdue University Indianapolis (IUPUI) / Neural crest cells (NCC) are a multipotent population of cells that form at the dorsal region of neural tube, migrate and contribute to a vast array of embryonic structures, including the majority of the head, the septum of the cardiac outflow tract (OFT), smooth muscle subpopulations, sympathetic nervous system and many other organs. Anomalous NCC morphogenesis is responsible for a wide variety of congenital defects. Importantly, several individual members of the TGFβ superfamily have been shown to play essential roles in various aspects of normal NCC development. However, it remains unclear what role Smad7, a negative regulator of TGFβ superfamily signaling, plays during development and moreover what the spatiotemporal effects are of combined suppression of TGFβ superfamily signaling during NCC formation and colonization of the developing embryo. Using a cre/loxP three-component triple transgenic system, expression of Smad7 was induced via doxycycline in the majority of pre- and post-migratory NCC lineages (via Wnt1-Cre mice). Further, expression of Smad7 was induced via doxycycline in a subset of post-migratory NCC lineages (via Periostin-Cre mice, after the NCC had reached their target organs and undergone differentiation). Induction of Smad7 within NCC significantly suppressed TGFβ superfamily signaling, as revealed via diminished phosphorylation levels of both Smad1/5/8 and Smad2/3 in vivo. This resulted in subsequent loss of NCC-derived craniofacial, pharyngeal and cardiac OFT cushion tissues. ROSA26r NCC lineage mapping demonstrated that cardiac NCC emigration and initial migration were unaffected, but subsequent colonization of the OFT was significantly reduced. At the cellular level, increased cell death was observed, but cell proliferation and NCC-derived smooth muscle differentiation were unaltered. Molecular analysis demonstrated that Smad7 induction resulted in selective increased phospho-p38 levels, which in turn resulted in the observed initiation of apoptosis in trigenic mutant embryos. Taken together, these data demonstrate that tightly regulated TGFβ superfamily signaling is essential for normal craniofacial and cardiac NCC colonization and cell survival in vivo.

No description available.

The United States averages 40,000 traffic fatalities annually. The American Association of State Highway and Transportation Officials (AASHTO) Roadside Design Guide cites run-off-the-road crashes as contributing greatly to this statistic, with about one-third of all traffic deaths [1]. This number has remained relatively constant over the past four decades, and despite a major increase in vehicle miles traveled (VMT), the rate of fatalities per 100 million vehicle miles traveled has declined. However, this relatively large number of run-off-the-road crashes should remain a major concern in all roadway design. The Highway Safety Act of 1966 marks a defining moment in the history of roadside safety [ ]. Before this point, roadways were only designed for motorists who remained on the roadway, with no regard for driver error. As there was no legislation or guidelines concerning roadside design, roadways constructed prior to 1966 are littered with fixed objects directly off of the edge of pavement. Fortunately, many of these roads have reached their thirty year design lives and have become candidates for improvement. The following report examines roadside crashes on nine Atlanta urban arterial roadways. Accident type, severity, and location for all crashes on these were evaluated. It is found roadside collisions with utility poles and trees were more prone to occur at intersection locations than midblock locations. Also for the studied roadway corridors, on average, roadside collisions were more likely to result in serious injury or fatality. Based on these findings initial recommendations are offer for improving clear zone requirements.

Transportation safety is a highly contentious issue in the design of cities and communities. To enhance community livability, urban designers, architects and city planners often encourage the placement of street trees, aesthetic street lights, and other roadside features in a buffer zone between the pedestrian realm and the vehicle travelway. While such designs clearly enhance the aesthetic quality of a roadway, conventional geometric design practice regards roadside features located in the clear zone as fixed-object hazards, and strongly discourages their use. This study examines roadside safety in urban environments to better understand the nature of urban fixed-object crashes, as well as the safety impacts of livable streetscape treatments. While the prevailing assumption is that livable street treatments have a negative impact on a roadways safety performance, the existing empirical evidence indicates that such designs are much safer than more conventional roadside designs. Current safety objections to the use of livable street treatments are not based on empirical evidence, but are instead the result of a design philosophy that systematically overlooks the real-world operating behavior of road users. This study details the origin and evolution of this philosophy, termed passive safety, and subjects it to an empirical test to evaluate its applicability to urban arterial roadways. It finds that passive safety assumptions do not meaningfully explain empirical observations of crash frequency and severity. To enhance contemporary geometric design practice, this study then proceeds to more thoroughly examine the nature and characteristics of urban roadside crashes, and proposes a new design approach, termed positive design that better addresses the twin goals of safety and livability.

[EN] Wheelchair users represent around 1% of the population. This group is characterised through the number of hours spent each day in a seated position. This can lead to health problems linked mainly to the development of pressure ulcers. In addition, the position in the wheelchair is critical in order to be able to perform different activities comfortably. The aim of the cushions, integrated in the whole seating system, is to contribute to the prevention, positioning and comfort of the person in a wheelchair. Incorporating the user adequately into the assessment, prescription and development of new cushions is a key aspect, clearly identified in the bibliography, which requires the use of innovation models to produce this incorporation systematically. This research paper adopts the cause-effect model, successfully used in other fields such as the car or shoe making industries, but to date not used in the field of tissue management cushions. The use of this model has allowed for the identification of different links between the consequences of the interaction person-cushion (developed perception of the user) with the cushion and person characteristics, as well as with the physiological and biomechanical response resulting from this interaction. This was a necessary step to obtain design and selection criteria for the cushions. The physiological and biomechanical variables which have been analysed are pressure and microclimate. To study the consequences of this interaction we have considered the user perception obtained by means of a questionnaire. Thirty-six wheelchair users have participated in this study which includes the assessment of twenty-five cushions. The main criteria for the inclusion of users in the study has been the risk level of risk of developing pressure ulcers. The inclusion of cushions was based on the market representation and consideration of the different typologies. From the point of view of the user's opinion this research paper has allowed for the identification of the quality perception factors (F1. Stability, F2.Heat-pain, F3. Fitting, F4. Collapse, F5. Size-aesthetics and F6. Weight-cold) and for the calculation of their weight on the global factors of goodness and evolution of the cushions. In addition, the comparison of the pressure values obtained directly from the wheelchair users and those measured using the dummy highlights a clear divergence between both behaviour. We have also defined design criteria and limit values, admissible and recommendable, for a group of variables, as well as the relation of the subjective variables with these quality factors. The results of this research support the importance of a comprenhensive approach to the cushions, including the design, development and prescription processes whereby the users may become more of a protagonist than they have been so far. / [ES] Las personas en silla de ruedas representan alrededor del 1% de la población. Este colectivo se caracteriza por pasar muchas horas al día sentado. Esto puede comportar problemas de salud vinculados principalmente al desarrollo de úlceras por presión. Por otra parte, el posicionamiento en la silla de ruedas es crítico para poder realizar actividades diversas de forma confortable. El objetivo de los cojines, integrados dentro del sistema de sedestación, es contribuir a la prevención, el posicionamiento y el confort de la persona en la silla de ruedas. Incorporar el usuario de forma adecuada en la evaluación, prescripción y desarrollo de nuevos cojines es un aspecto clave, identificado claramente en la bibliografía, que requiere el uso de modelos de innovación que faciliten esta incorporación de forma sistemática. En este trabajo de investigación se ha adoptado el modelo de evaluación causa-efecto, empleado con éxito en ámbitos como la automoción o el calzado, pero que hasta el momento no se había utilizado en el campo de los cojines antiescaras. El uso de este modelo ha permitido la identificación de diversos encadenamientos entre las consecuencias de la interacción cojín-persona (percepción desarrollada en el usuario) con las características del cojín y la persona, así como con la respuesta fisiológica y biomecánica resultante de esta interacción. Éste era el paso previo para poder obtener criterios de diseño y selección de cojines. Las variables fisiológicas y biomecánicas analizadas han sido la presión y el microclima. Para estudiar las consecuencias de la interacción hemos considerado la percepción del usuario obtenida mediante cuestionarios. Treinta y seis personas en silla de ruedas han participado en este estudio que ha incluido la valoración de veinticinco cojines. El principal criterio para la inclusión de usuarios en el estudio ha sido el nivel de riesgo de desarrollar úlceras por presión. La inclusión de los cojines se ha basado en la representatividad del mercado y la inclusión de tipologías diferentes. Desde el punto de vista de la opinión de los usuarios este trabajo de investigación ha permitido identificar los factores de calidad percibida (F1. Estabilidad, F2. Calor-dolor, F3. Encajonamiento, F4. Colapso, F5. Tamaño-estética y F6. Peso-frío) y calcular el peso de ellos sobre los factores globales de bondad y evolución de los cojines. Por otra parte, la comparación de los valores de presión obtenidos con las personas en silla de ruedas y los medidos con el maniquí constata una clara divergencia en el comportamiento. También se han definido criterios de diseño y valores límite, admisibles y recomendables, para un conjunto de variables, así como su relación con los factores de calidad y las variables subjetivas agrupadas en estos factores. Los resultados de este trabajo apoyan la importancia de una aproximación global a los cojines, que incluya los procesos de diseño, desarrollo y prescripción, donde los usuarios sean mucho más protagonistas de lo que han sido hasta ahora. / [CA] Les persones en cadira de rodes representen al voltant de l'1% de la població. Aquest col·lectiu es caracteritza per passar moltes hores al dia damunt la cadira, cosa que pot comportar problemes de salut vinculats principalment al desenvolupament d'úlceres per pressió. Per altra banda, el posicionament en la cadira de rodes és crític per poder realitzar activitats diverses i que aquestes puguen fer-se de forma confortable. L'objectiu dels coixins, integrats dins del sistema de sedestació, és contribuir a la prevenció, el posicionament i el confort de la persona en la cadira de rodes. Incorporar l'usuari de forma adequada en l'avaluació, prescripció i desenvolupament de nous coixins és un aspecte clau, identificat clarament a la bibliografia, que requereix l'ús de models d'innovació que faciliten aquesta incorporació de forma sistemàtica. En aquest treball d'investigació s'ha adoptat el model d'avaluació causa-efecte, emprat amb èxit en àmbits com l'automoció o el calcer, però que fins al moment no s'havia utilitzat en el camp dels coixins antiescares. L'ús d'aquest model ha permès la identificació de diversos encadenaments entre les conseqüències de la interacció coixí-persona (percepció desenvolupada en l'usuari) amb les característiques del coixí i la persona, així com amb la resposta fisiològica i biomecànica resultant d'aquesta interacció. Aquest era el pas previ per poder obtenir cri teris de disseny i selecció de coixins. Les variables fisiològiques i biomecàniques analitzades han estat la pressió i el microclima. Per a estudiar les conseqüències de la interacció hem considerat la percepció de l'usuari obtinguda mitjançant l'ús de qüestionaris. Trenta-sis persones en cadira de rodes han participat en aquest estudi que ha inclòs la valoració de vint-i-cinc coixins. El principal criteri per a la inclusió d'usuaris en l'estudi ha estat el nivell de risc de desenvolupar úlceres per pressió. Per a la inclusió dels coixins s'ha buscat la representativitat del mercat i la inclusió de tipologies diferents. Des del punt de vista de l'opinió dels usuaris aquest treball d'investigació ha permès identificar els factors de qualitat percebuda (F1. Estabilitat, F2. Calor-dolor, F3. Encaixament, F4. Col·lapse, F5. Grandària-estètica i F6. Pes-fred) i calcular el pes d'ells sobre els factors globals de bondat i evolució dels coixins. Per altra banda, la comparació dels valors de pressió obtinguts amb les persones en cadira de rodes i els mesurats amb el maniquí constata una clara divergència en el comportament. També s'han definit criteris de disseny i valors límit, admissibles i recomanables, per a un conjunt de variables i la seua relació amb els factors de qualitat i les variables subjectives. Els resultats d'aquest treball suporten la importància d'una aproximació global als coixins, que incloga els processos de disseny, desenvolupament i prescripció, on els usuaris siguen molt més protagonistes del que ho han estat fins ara. / Barbera Guillem, R. (2016). Identificació de criteris de disseny i selecció de coixins antiescares, a partir d'aspectes funcionals dels coixins i les característiques particulars i preferències dels usuaris [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/61463