Hypoxia-inducible factors (HIFs) are a highly conserved group of transcriptional regulators responsible for cellular and systemic O2 homeostasis in animals. However, how HIFs are involved in basic adaptive ventilatory and metabolic responses to acute and chronic hypoxia remains incompletely characterized. Naked mole rats are among the most hypoxia tolerant mammals identified. As opposed to the typical hyperventilatory response of most adult mammals, naked mole rats exhibit a unique decline in ventilation, matching their substantial decrease in metabolic rate. Naked mole rats therefore provide an excellent model in which to investigate adaptations to hypoxic ventilatory and metabolic responses (HVR and HMR, respectively). Interestingly, naked mole rats possess a mutation within the von Hippel-Lindau (VHL) binding domain—a protein necessary for proteasomal degradation of HIF subunits in normal O2 concentrations—suggesting they retain elevated baseline expression of HIF and thus an upregulation of downstream gene targets. In designing our experiment, we focused on sustained hypoxia and HIF1, which is typically the first responder subunit upon exposure to low O2 stress. We sought to determine how increased HIF1 expression might contribute to the distinct HVR and HMR of naked mole rats, first by confirming the observed VHL mutation translates into increased HIF1 protein expression via immunoblotting. HIF1 protein expression was found to be 3-fold higher in naked mole rat brain than mouse brain and 4-fold higher than in mouse liver tissue (p < 0.05). We then investigated how elevated HIF1 levels might contribute to the HVR and HMR by treating naked mole rats with two different HIF1 inhibitors (either echinomycin; 0.5 and 1.0 mg kg-1, or PX-478; 80.0 mg kg-1) and subsequently examined changes in ventilatory and metabolic parameters in awake animals exposed to sustained hypoxia (7% O2; 1 hour). In control naked mole rats, minute ventilation (V̇E) reversibly decreased by 32% in hypoxia (1298.3 ± 188.5 to 882.6 ± 117.0 mL min-1 kg-1) because of changes in both breathing frequency (fR) and tidal volume (VT). Conversely, the HVR was not significantly affected in any of our three treatment groups however, normoxic ventilation increased in naked mole rats treated with low dose echinomycin (0.5 mg kg-1) by 72% (from 1298.3 ± 188.5 to 2239.5 ± 221.1 mL min-1 kg-1). Consistent with previous findings, metabolic rate in control naked mole rats decreased 70% (from 40.1 ± 5.0 to 11.9 ± 0.9 mL O2 min-1 kg-1). Again, treatment with our pharmacological agents did not significantly alter this response but did result in a 43% decrease in basal metabolic rate (V̇O2 and V̇CO2) in both high-dose echinomycin and PX-478 treated naked mole rats (40.1 ± 5.0 to 22.5 ± 3.6 and 23.0 ± 1.88 mL O2 min-1 kg-1 respectively, p < 0.05), dulling the magnitude of the HMR. As a result of unmatched changes in V̇E and V̇O2, HIF1 deficient naked mole rats treated with both low-dose echinomycin and PX-478 experienced an atypical increase in their air convection requirement (ACR; V̇E:V̇O2-1) in hypoxia (from 77.4 ± 11.3 to 159.2 ± 34.63 and 123.5 ± 35.5 respectively, p < 0.05), resembling a hyperventilation response closer to that of hypoxia-intolerant mammals. To further determine how increased HIF1 availability affects the HMR and HVR, we administered hypoxia-intolerant mice with a pharmacological HIF1 agonist (3,4- EDHB; 180 mg kg-1) and used identical experimental design to measure downstream ventilatory and metabolic responses. Mice exhibit similar reductions in metabolic rate during hypoxic exposure (from 60.3 ± 2.4 to 21.8 ± 1.8 mL O2 min-1 kg-1, p < 0.05) but experience a 30% increase in fR (from 157.5 ± 9.5 to 200.4 ± 10.8 breaths min-1, p < 0.05). In contrast, mice treated with EDHB and to exposed 7% O2 exhibited a 20% increase in fR (200.4 ± 10.8 to 236.5 ± 14.1 breaths min-1, p < 0.05) and a 30% reduction in the magnitude of their HMR (from 38.5 ± 2.8 to 27.8 ± 3.6 ΔV̇O2). No other significant trends were observed in any of the other parameters measured. We conclude metabolic and ventilatory control in naked mole rats and mice may partially depend on increased HIF1 expression.

During the summer, buildings in hot dry climates have the inevitable problem of cooling. These climates are characterized by hot summer days with cold nights, a high degree of solar radiation, low humidity and with a nearly fixed seasonal and daily pattern of wind. These natural phenomena could be exploited by nocturnal ventilation to cool the building fabric, thus saving energy during the day and providing comfort at night. The procedures to evaluate thermal performance of buildings with special reference to nocturnal ventilation are studied. Various approaches to building thermal response are first reviewed. Dynamic thermal simulation computer models are developed to predict hourly 'internal temperatures'. These are used to study the various constituents of models. They are based on: -the Admittance Method (as suggested by the CIBSE Guide); -a similar procedure but with higher harmonics; -the Response Factor Method (suggested by ASHRAE); -and the Finite Difference Method. A room surrounded by similar rooms in a multi-storey building, having only one external wall, was simulated in the laboratory. It was subjected to typical variations of a hot climate. Predictions of the computer simulations are compared with laboratory results and it is shown that -the closest agreement was obtained with the Response Factor and Finite Difference methods which are equally good; -for higher rates of ventilation, representation of a room by a simple three nodes model thermal network will give sufficiently accurate results; while for lower rates of ventilation a more detailed model gives more accurate results; -the standard Admittance Method gives adequate results, especially with higher rates of ventilation. It could also be used for hourly temperature-, calculations and variable ventilation without loosing significant accuracy; -a fuller treatment in the Admittance Method of time-lag and time-lead, associated with the dynamic thermal factors, will not greatly improve the results. An increase in the number of harmonics in the procedure did not also result in significant improvements, especially with a high rate of ventilation. Natural ventilation into rooms through open windows in these climates is theoretically investigated. It is shown that the rate of natural air flow obtained may be sufficient to meet the requirements of passive cooling by nocturnal ventilation. A computer program is developed to calculate the rate of air flow in multi-zone buildings, and a new relationship is suggested, which will reduce the complexity of natural air flow calculations in multi-zone buildings subjected to cross ventilation.

Mobility has become a substantial part in our society. Since we spend a lot of our available time on the road, we expect the automotive environment to provide similar comfort levels than residential buildings. Within this context, this research thesis especially focuses on automotive thermal comfort control. The automotive cabin is a very special environment, which is characterized by extreme inhomogeneity and overall transient behavior. Thermal comfort is a very vague and a very subjective term, which depends on physiological and psychological variables. Theories for thermal comfort in transient environments have not been fully established yet and researchers are still busy with its investigation. At present, automotive industry relies on extensive thermal comfort models, manikins and powerful simulation tools to assess and control thermal comfort. This thesis studies the application of artificial intelligence and proposes a blackbox approach which aims for extracting thermal comfort knowledge directly from human's interaction with the HVAC controls. This methodology avoids the use of human physiological and psychological thermal comfort models and does not require any a-priori knowledge. A novel comfort acquisition tool has been developed and has been integrated into a research vehicle in order to gather the required data for system learning. Data has been collected during spring, autumn and summer conditions in Southern Africa. Methods of data mining have been applied and an intelligent implementation using artificial neural networks has been proposed. The achieved results are promising and allow for about 87 perecent correct classification. It is concluded that methods of artificial intelligence perform well and are far superior compared to conventional approaches. These methods can be used as a powerful tool for the development process of vehicle air-conditioning controls and have great potential for time and cost reduction.

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Postoperative pulmonale Komplikationen (PPK) gehören zu den häufigsten Ursachen, die zu einem verlängerten Krankenhausaufenthalt, steigenden Kosten und einer erhöhten Morbidität und Mortalität führen. Die pulmonale elektrische Impedanztomographie (EIT) ermöglicht die bettseitige Visualisierung der regionalen Lungenventilation in Echtzeit in der transversalen Elektrodenebene. Insbesondere dorsale Atelektasen oder Pleuraergüsse können eine Verschiebung der Ventilation nach ventral bewirken. Als Hypothese wurde angenommen, dass postoperativ bei spontanatmenden Patienten nach einem peripheren Eingriff eine Umverteilung der Ventilation nach ventral auftritt und dadurch die Vitalkapazität der Lunge abnimmt. In die prospektive Beobachtungstudie wurden 27 Patienten eingeschlossen, die sich einem elektiven peripheren Eingriff in Allgemeinnarkose (mit oder ohne Regionalanästhesie) unterzogen und ein erhöhtes Risiko für PPK‘s aufwiesen. Die Lungenfunktion der Patienten wurde präoperativ sowie am ersten und dritten postoperativen Tag mittels EIT in Spontanatmung und einem forcierten Atemmanöver erfasst. Dabei wurde das Center of Ventilation (COVy) berechnet. Periphere Eingriffe in Allgemeinnarkose führten nicht zu einer signifikanten ventralen Verschiebung der regionalen pulmonalen Ventilation in Spontanatmung gemäß pulmonalem EIT am ersten und dritten postoperativen Tag. Die FVC%Soll war lediglich am ersten postoperativen Tag vermindert. Bei zwei Patienten traten postoperative pulmonale Komplikationen auf. Insgesamt zeigte die Kohorte nur geringe Veränderungen der Vitalkapazität, was einen Einfluss der Eingriffslokalisation auf die Umverteilung der pulmonalen Ventilation nahelegt. / Postoperative pulmonary complications (PPCs) increase morbidity and mortality of surgical patients, duration of hospital stay and costs. Pulmonary electrical impedance tomography (EIT) enables the bedside visualization of regional ventilation in real-time within a transversal section of the lung. Dorsal atelectasis or effusions might cause a ventral redistribution of ventilation. We hypothesized the existence of ventral redistribution in spontaneously breathing patients during their recovery from peripheral surgery and that vital capacity is reduced if regional ventilation shifts to ventral lung regions. This prospective observational study included 69 adult patients undergoing elective peripheral surgery with an expected intermediate or high risk for PPCs. Patients received general anesthesia with and without additional regional anesthesia. On the preoperative, the first and the third postoperative day, EIT was performed at rest and during spirometry (forced breathing). The center of ventilation in dorso-ventral direction (COVy) was calculated. A significant redistribution of pulmonary ventilation was not observed after peripheral surgery on the first and third postoperative day. FVC%predicted was only decreased on the first postoperative day. In two patients occurred pulmonary complications after peripheral surgery. The cohort showed only minor changes in vital capacity, suggesting a role of the location of surgery for postoperative redistribution of pulmonary ventilation.

The present work consists of two parts: experimental study of natural ventilation in a model room and the flow associated with a source-sink pair. The first part describes the natural ventilation of a model room of size 300mmx 300mm x 300mm with water as the fluid medium. It is insulated by air gaps on the four sides and at the top. A constant heat flux of 3148W/m2 has been maintained on the bottom surface of the room. This ‘room’ is surrounded by a large exterior tank containing water. The changes in temperature of the bottom, the interior and the exterior have been measured using T-type thermocouples. There are three openings each on two opposing sides of the model room. For any experiment, only one opening on each side is kept open. Fluid enters or leaves these openings and the flow is driven entirely by buoyancy forces. Three configurations have been studied: (1) The bottom opening at the inlet side and the top opening at the outlet side are open, (2) the bottom opening at the inlet side and the middle opening at the outlet side are open, and (3) the middle opening at the inlet side and the top opening at the outlet side are open. Shadowgraph technique is used for visualization. The buoyancy causes flow to enter through the bottom opening and leave through the top opening. At the openings, buoyant jets are observed and which have higher or lower relative densities. The buoyant jet at the inlet interacts with the plumes on the heated bottom plate. From these visualizations, it appears that free convection at bottom plate will be affected by the buoyant jets at the openings and the degree to which it is affected depends on the position and size of openings and distance between inlet and outlet. The flow rate due to the natural ventilation depends on the bottom surface heat flux and the height difference between the openings. The temperatures of the floor, the interior and the exterior are calculated using a simple mathematical model (Hunt and Linden [1999]). The mathematical model assumes well mixed conditions within the room and accounts for losses at the openings. The values of temperatures obtained in the experiments are reasonably well predicted by the mathematical model. The second part of the work is concerned with the interaction of a source -sink pair. The source consists of fluid issuing out of a nozzle in the form of a jet and the sink is a pipe that is kept some distance from the source pipe. Such source -sink pairs are observed in many situations including data centers, and collection of fresh water from a large reservoir that has also a discharge of pollutants. The main parameters of the problem are source and sink flow rates, the axial and lateral separations of the source and sink, and the angle between the axes of source and sink. Of concern is the percentage of source fluid that enters the sink as a function of these parameters. The experiments have been carried in a large glass water tank. The source nozzle diameter is 6mm and the sink pipe diameter is either 10mm or 20mm. The horizontal and vertical separations and angles between these source and sink pipes are adjustable. The Reynolds numbers of the source jet is about 3200. Experiments were done with the sink flow rate equal to, lower or higher than the source flow rate. The flow was visualized using KMnO4 dye and planar Laser Induced Fluorescence (LIF). The velocity fields for some cases were obtained using Particle Image Velocitymetry (PIV). To obtain the efficiency (that is percentage of source fluid entering the sink pipe), titration method is used. A small amount of hydrochloric acid (HCL) is added in the jet fluid through the overhead tank and the fluid collected at the sink is titrated with the Sodium hydroxide (NaOH) as base and Phenolphthalein as the pH indicator. The main characteristics of the jet, without a sink, were measured using PIV. The velocity profiles, jet widths and volume flow rates at various axial locations were obtained and compared with results reported in the literature for similar Reynolds number jets. For 100%, 70%, 50% and 25% efficiencies or removals and for zero lateral separations, the sink flow rate is about 1.5 times the flow rate predicted on the basis of jet properties at that point in the absence of a sink. The sink flow rate to obtain a certain efficiency increase dramatically with lateral separation; for example, when the lateral separation is about one half jet width, the required sink flow rate to obtain a certain efficiency increases by about five times. The sink diameter and the angle between source and the sink axes don’t influence efficiencies as much as the lateral separation. Data from our all experiments have been consolidated in the form of correlations that can be used for design of appropriate sinks for removal of heat and pollutants.

published_or_final_version / abstract / Mechanical Engineering / Doctoral / Doctor of Philosophy