This thesis tested the hypothesis that ethanol suppresses respiratory muscle activity by effects at the central motor pool and/or by state-dependent regulation of motor activity via influences on sleep/arousal processes. Ten rats were implanted with electroencephalogram and neck electrodes to record sleep-wake states, and genioglossus and diaphragm electrodes for respiratory recordings. Studies were performed following intraperitoneal injection of ethanol (1.25g/kg) or vehicle. The effects on genioglossus activity of ethanol (0.025-1M) or vehicle applied directly to the hypoglossal motor nucleus were also determined in sixteen isoflurane-anaesthetized rats. The results of these studies suggest that ethanol at physiologically relevant concentrations promoted sleep, and altered electroencephalogram and postural motor activities indicative of a sedating effect. The lack of effect on genioglossus activity with ethanol applied directly to the hypoglossal motor pool suggests that the suppression observed with systemic administration may be mediated via effects on state-dependent processes rather than direct effects at the motor pool per se.

The mechanisms underlying the generation of rapid eye movement (REM) sleep are poorly understood. Despite a lack of direct support, neurons maximally active during REM sleep (REM sleep-active) located in the pedunculopontine tegmental nucleus (PPTn) are hypothesized to generate this state and its component phenomenology. This hypothesis has never been directly tested, since the results of selectively inhibiting this cell-group have never been determined. Using microdialysis, electrophysiology, histochemical and pharmacological methods in freely-behaving rats (n=22) instrumented for sleep-wake state and respiratory muscle recordings, I selectively inhibited REM sleep-active PPTn neurons. Contrary to the prevailing hypothesis, I showed that REM sleep-active PPTn neurons suppress REM sleep by limiting the frequency of its onset. These neurons also shape the impact of REM sleep on breathing. REM sleep-active PPTn neurons restrain behavioural activation of upper-airway musculature during REM sleep, while depressing breathing rate and respiratory activation of the upper-airway musculature across sleep-wake-states.

This thesis tested the hypothesis that ethanol suppresses respiratory muscle activity by effects at the central motor pool and/or by state-dependent regulation of motor activity via influences on sleep/arousal processes. Ten rats were implanted with electroencephalogram and neck electrodes to record sleep-wake states, and genioglossus and diaphragm electrodes for respiratory recordings. Studies were performed following intraperitoneal injection of ethanol (1.25g/kg) or vehicle. The effects on genioglossus activity of ethanol (0.025-1M) or vehicle applied directly to the hypoglossal motor nucleus were also determined in sixteen isoflurane-anaesthetized rats. The results of these studies suggest that ethanol at physiologically relevant concentrations promoted sleep, and altered electroencephalogram and postural motor activities indicative of a sedating effect. The lack of effect on genioglossus activity with ethanol applied directly to the hypoglossal motor pool suggests that the suppression observed with systemic administration may be mediated via effects on state-dependent processes rather than direct effects at the motor pool per se.

The mechanisms underlying the generation of rapid eye movement (REM) sleep are poorly understood. Despite a lack of direct support, neurons maximally active during REM sleep (REM sleep-active) located in the pedunculopontine tegmental nucleus (PPTn) are hypothesized to generate this state and its component phenomenology. This hypothesis has never been directly tested, since the results of selectively inhibiting this cell-group have never been determined. Using microdialysis, electrophysiology, histochemical and pharmacological methods in freely-behaving rats (n=22) instrumented for sleep-wake state and respiratory muscle recordings, I selectively inhibited REM sleep-active PPTn neurons. Contrary to the prevailing hypothesis, I showed that REM sleep-active PPTn neurons suppress REM sleep by limiting the frequency of its onset. These neurons also shape the impact of REM sleep on breathing. REM sleep-active PPTn neurons restrain behavioural activation of upper-airway musculature during REM sleep, while depressing breathing rate and respiratory activation of the upper-airway musculature across sleep-wake-states.

Background: Aerosol therapy has been established as an efficient form of drug delivery to pediatric and adult patients with respiratory diseases; however, aerosol delivery to the pediatric population is quite challenging. While some studies compare jet nebulizer (JN), vibrating mesh nebulizer (VMN), or JN and pMDI, there is no study comparing these three devices in pediatric and young children. The aim of this study quantifies aerosol deposition using JN, VMN, and pMDI/VHC in a simulated pediatric with active and passive breathing patterns. Methods: Each aerosol generator was placed between manual resuscitator bag (Ambu SPUR II Disposable Resuscitator, Ambu Inc, Glen Burnie, MD) and infant facemask (Mercury Medical, Cleanwater, FL), which was held tightly against the SAINT model. Breathing parameters used in this study were Vt of 100 mL, RR of 30 breaths/min, and I:E ratio of 1: 1.4. Active and passive breathing patterns were used in this study with aerosol device; active breathing pattern was created using a ventilator (Esprit Ventilator, Respironics/Philips Healthcare, Murrysville, PA) connected to a dual chamber test lung (Michigan Instruments, Grand Rapids, MI), which was attached to an absolute filter (Respirgard II, Vital Signs Colorado Inc, Englewood, CO), to collect aerosolized drug, connected to the SAINT model. Pediatric resuscitator bag was run at 10 L/min of oxygen and attached to aerosol generator with facemask. In passive breathing pattern, SAINT model was attached to test lung and ventilated using the resuscitator bag with the same breathing parameters. Each aerosol device was tested three times (n=3) with each breathing patterns. Drug was eluted from the filter and analyzed using spectrophotometry. The amount of drug deposited on the filter was quantified and expressed as a percentage of the total drug dose. To measure the differences in the inhaled drug mass between JN, VMN, and pMDI/VHC in active or passive breathing, one-way analysis of variance (one-way ANOVA) was performed. To quantify the difference in aerosol depositions between the two breathing patterns, independent t-test was performed. A p < 0.05 was considered to be statistically significant. Results: Although the amount of aerosol deposition with the JN was the same in passive and active breathing without any significant difference, the VMN was more efficient in active breathing than the JN (p = 0.157 and p = 0.729, respectively). pMDI/VHC had the greatest deposition in the simulated spontaneous breathing (p=0.013) Conclusion: Aerosol treatment may be administered to young children using JN, VMN, or pMDI/VHC combined with resuscitator bag. Using pMDI/VHC with resuscitator bag is the best choice to deliver albuterol in spontaneously breathing children. Further studies are needed to determine the effectiveness of these aerosol generators with different type of resuscitator bag and different breathing parameters.

The pre-Botzinger complex (pBC) is a sub-circuit of the respiratory central pattern generator. The pBC is required for eupnea and is contained in a transverse slice of the ventrolateral medulla. In the slice, pBC cells are responsible for generating the respiratory rhythm, and hypoglossal motoneurons (HMs) are responsible for transmitting the rhythm out of the brainstem to the muscles. Understanding how the transverse slice rhythm is generated and transmitted is a first step in understanding how this process occurs in vivo. To understand this network, we developed ionic current models of the individual network components and explored how the various ion channels affect single-cell firing characteristics and network dynamics. First, we used the considerable amounts of experimental data from neonatal HMs to develop an HM model. The model was used to explore the roles of ion channels in shaping the complex dynamics of the neonatal HM action potential (AP) and to investigate the age-dependent changes in HMs. We used a genetic algorithm to optimize the HM model to more closely fit experimental measures of AP shape. A comparison of feature-based and template-based fitness functions revealed that a feature-based fitness function performs best when optimizing the HM model to fit characteristics of the neonatal HM AP. Next, we used our existing pBC models to understand how different ionic currents affect rhythmogenesis in the pBC. Our results indicate that intrinsic bursters increase the robustness of rhythm generation in the pBC. Finally, we developed an improved pBC neuron model and explored how various ion channels affect bursting dynamics at the single-cell level. The HM and pBC models developed in this study will be used in future network models of the transverse slice.

The problem of the performance decay and the factors affecting on the DMFC performance for long-term operation are studied in this thesis. First, the influence of the initial treatments of MEA and the exposure of MEA in the atmosphere on the water content are measured. In addition, the effects of the pressure of the MEA hot press conditions, the treatments and preservation of MEA, and the operative conditions on the performance are also examined. Eventually, we expect that the best way to increase the DMFC performance and avoid the performance can be found. These can provide for references when a portable DMFC need to be designed and manufactured in future. In order to solve the problem of methanol crossover leading to the cathode poisoned, cells are operated only under the proper methanol concentration and discharged thoroughly before finishing the whole experiment. It is also necessary to maintain MEAs in proper wetness so that the performance of stack will not decay too quickly. In the initial treatment, firstly, a MEA is immersed in 3M MeOH and then boiled with 80oC DI water for an hour, respectively. The experimental conditions of this passive single-cell DMFC are pumpless in anode chamber, air-breathing, and room temperature. The power density of this DMFC with these test conditions can reach a value about 33mW/cm2. This value is about 106% higher than that of the untreated MEA. If MEA boiled with 0.5M H2SO4 for an hour and then boiled with 80oC DI water for an hour, its power density is about 75% higher than that of the untreated MEA.

Abstract Traditional unipolar/bipolar plates, such as the metal and the graphite unipolar/bipolar plates, are expensive, weight heavy and volume large, so that it is hard to be used in the portable application. A high efficiency, low cost and lightweight portable proton exchange membrane fuel cell (called PEMFC or called HFC when using pure hydrogen fuel), which is made with a new heterogeneous composite carbon fiber bipolar plate and a MEA, is developed in our lab. There are many advantages of the new carbon fiber unipolar/bipolar plates, such as low contact resistance, low cost, lightweight and small volume. We hope that the new unipolar/bipolar plate will be able to replace the conventional metal and graphite unipolar/bipolar plates in the future. The characteristics of a portable PEMFC in different operational conditions are studied in this research. From our experimental result, we find that the factors which affect the HFC performance include the gas temperature, humidity ratio, inlet gas pressure in anode, the geometry of inlet ports, the flow channels within cell, and the oxidant flow rate etc. In addition, the contact resistances between different materials within each cell all strongly influence HFC performance. The ribs of the carbon fiber unipolar/bipolar plates is pored structure, and the gas diffusion layer is no deformation because of only slight compression in stack assembly; therefore, the reactive gas can easily flow into the most of active area. In addition, the contact resistance between the carbon fiber unipolar plate and the gas diffusion layer is lower than that between the traditional unipolar plate and the gas diffusion layer, so that the electrons in active layer is easily to exit or enter this region. The experimental result at 1.15 atm and 40 oC displays that the current density with the new unipolar plate is about twice higher than that with the graphite unipolar plate at overpotential 0.6 V. With air as an oxidizer, we find that increasing the fan rotation speed can avoid output-voltage decay in high current density, but the design with fan is unfavorable for portable application. So a front open unipolar plate and air-breathing design is adopted on the cathode. The power density of this design is slightly lower than that with fan, but it still can reach a value 160 mW/cm2 without any heating and humidification in the anode. Because this design needs little supplement device, the application in portable fuel cells of the new design will be wider than that of a traditional design.

Several disadvantages in general unipolar/bipolar plates are that cost is expensive, weight is heavy and the volume is large. The high compressing pressure is also necessary to reduce the contact resistance in making up a fuel cell stack. Therefore, it is difficult in making use general unipolar/bipolar plates to portable fuel cells. With a new heterogeneous carbon fiber bipolar plate, pumpless and air-breathing design and in cooperating with a special MEA, a portable fuel cell stacks developed in our lab have made portable applications to be possible. The structure of the DMFC stack made with the new carbon fiber bipolar plate is much more simple and weight-light than the other designs. The three portable DMFC stacks flat type, cylinder type (I), and cylinder type (II) are developed in series in our lab. The methanol solution can be stored directly in the flow channel of the anode, and does not need the extra auxiliary equipment, so it easy to apply to the portable fuel cell. The developed portable DMFC of cylinder type (II), weight is only 20g, volume is 30cm3, and the fuel stored capacity is 7.5ml. In the flat type DMFC, In anode Pt-Ru loading 3 mg/cm2, and cathode Pt loading 1 mg/cm2, methanol concentration 3 M, pumpless, air-breathing, and room temperature, the largest of output power density of the fuel cell can reach 5.27 mW/cm2, and the total power can reach 71 mW. The weight of DMFC of cylinder type (II) is far lower than DMFC of flat type in addition, so its power density 1.33mW/g is about 1.68 times of flat type 0.79 mW/g.

In this thesis the experimental method is used to study the characteristics of a DMFC when a heterogeneous carbon fiber bipolar plate is applied to it. The first main study is about the effect of the different structures of the carbon fiber bunch on the fuel cell performance. Additionally, a high temperature hot-pressing process is performed to change the inner molecular structure so that the hydrogen ion can be blocked to avoid the lateral migration between two adjacent cells. Finally, the two techniques are applied to make our new portable DMFC stack. The bipolar plates with the sawtooth or non-sawtooth carbon fiber bunches have been used in making our DMFC stack. The experimental results display that the performances of the two structures both are better than the traditional graphite bipolar plate. However, the performance of DMFC with the sawtooth bipolar plate is much better than that without sawtooth, especially in high current density. When carbon fiber bunches with sawtooth use at anode and cathode of bipolar plates, the performance can be enhanced and its power density 27.6% higher than that without sawtooth. During our study we also found that part of hydrogen ions can laterally migrate to its adjacent cathode and do not directly cross to its opposite cathode, when the banded type MEA are used to multiple cell stack. Therefore, the performance cannot be performed well due to this type ion transfer. In order to block the lateral migration, the narrow area of the membrane between two adjacent electrodes is pressed with a high temperature hot-pressing device. After a short time hot-press between two adjacent electrodes, the hydrogenion migration phenomenon reduced, and the performance had been improved about 10% higher than that without hot-press. Finally, a double layer 2x6-cell flat type DMFC is made. This 12-cell stack is composed of each electrode area 0.5x5cm2, two sheets of membrane for 6-cell using Nafion 117, the anode catalyst Pt-Ru loading 4mg/cm2, and cathode catalyst Pt loading 4mg/cm2, the methanol concentration 3M, air-breathing, and operating in room temperature. The output power of the cell can reach an average power density 8.0mW/cm2 and total power 240mW with our handmade stack. If the performance of each fuel cell is more uniform, we expect that total power can reach 480 mW. The power level should be satisfied for any kind mobile phone.