Background: Cough is extremely common in childhood and a tool to objectively measure cough frequency would be clinically beneficial. To date paediatric cough monitoring systems have relied on manual cough counting which is time consuming and costly. The VitaloJAK™ (Vitalograph, UK) is a custom built 24hr semi-automated cough monitoring device that has been used successfully to quantify cough in adults. This thesis consists of a series of studies using the VitaloJAK™ monitor system in children. Methods: Firstly, we tested the feasibility of using the VitaloJAK™ for 24 hr cough recordings in children and tested existing compression software for cough quantification. The VitaloJAK™ system was then used to to assess and compare the cough frequency, variation and circadian distribution of cough in children with asthma, CF, and PCD during stable periods of disease and during an exacerbation. Finally, we used modelling to assess whether cough events are random events, or are clustered in time; the time intervals between coughs for each patient were calculated and fitted to an exponential model of random recurrences and a Weibull model for clustered recurrences. Results: The majority of children were able to wear the monitor for almost 24 hours without too much difficulty; overall, children wore the monitor for a median of 22.25 hours (0.38 – 24hrs). Using the compression software, a median of 100% (91-100) of coughs was retained and 24-hour records were reduced down to around 10% of their original size. There was no significant difference in cough frequency between the three disease groups. The median (range) cough frequency per hour was 3 (0.2 to 18) coughs/hour (c/h), 4 (0.5 to 37) c/h, and 4 (0.5 to 27) c/h for asthma, CF, and PCD groups respectively (p=0.3). Cough frequency in children was significantly greater during the day and reduced during sleep in all disease groups. There was a significant difference in the 24-hour cough frequency between the exacerbation and stable asthma group (median 11 (0-27) vs. 3 (0-5), p=0.004). The 24-hour pattern revealed a substantial variability in peak timing of cough in each respiratory disease. Children with asthma peaked in the early evening, those with CF in the morning, and those with PCD in the afternoon. No difference was found in the circadian cough rate, when divided into 6 4-hour time periods, either between the three diseases (p=0.18) or between stable and exacerbation phases among the asthmatic children (p=0.14). A significant difference was seen in the 24-hour total cough frequency between asthmatic children (median 4c/h; range 1-18) and adults (median 1 c/h; range 0.3-16); p=0.001. The temporal pattern of recurrence of cough events is non-randomly distributed over time, and this was best described by the Weibull model in the majority of the 24hr cough, day-time cough and night-time cough recordings in children and adults. The cough events appear to cluster together in time, with the probability of a second cough being initially high and decreasing with time. Conclusion: This thesis has demonstrated that the VitaloJAK™ semi-automated cough monitor provides an accurate estimate of cough frequency in children (sensitivity 100%) while significantly reducing the time required for analysis. A substantial variability in the timing of peak cough frequency exists in each respiratory disease and this might reflect different mechanisms of cough in each disease. Sleep appears to significantly reduce cough in all the diseases studied, both when disease is stable and exacerbating. In both asthmatic children and adults, the recurrence pattern of coughs is clustered and can be described by a Weibull distribution. This work has set a foundation for further investigation of the cough frequency and 24 hour cough circadian patterns in children.

Cystic fibrosis (CF) is the most common autosomal recessive genetic disease in Caucasian populations. CF affects multiple organ systems including pancreas, liver, intestines, sweat glands, and male reproductive organs, however the leading cause of morbidity and mortality in CF patients is chronic lung disease. CF is caused by a mutant cystic fibrosis transmembrane conductance regulator (CFTR) gene which leads to chloride (Cl-) and bicarbonate (HCO3-) anion dysregulation at the airway surface. Without adequate anion exchange, thick, viscous mucus accumulates at the airway surface allowing bacterial colonization to occur. Complementing CFTR in the appropriate airway cells restores the anion channel activity in CFTR-deficient cells. The ultimate goal for CF gene therapy is to design an integrating vector that would lead to persistent and efficient expression of CFTR in the airways. Performing gene therapy experiments is dependent upon a relevant animal model. The CF pig is a large animal model similar in size, anatomy, and physiology to humans. Importantly, the CF pig recapitulates human lung disease. From the CF pig, we have learned much about CF lung disease and have developed relevant assays to measure anion channel correction. We have learned that loss of CFTR leads to a decreased airway surface ASL pH, bacterial killing ability, and increased mucus viscosity. Standardized assays have been developed to evaluate the change in current by Ussing chambers, ASL pH, bacterial killing in vivo and ASL pH and viscosity on primary airway cultures in vitro. Ultimately, these metrics allow us to make conclusions about the efficiency of CFTR restoration. Viral vectors are promising candidates for CF gene therapy. Viral vectors such as adenovirus (Ad), adeno-associated virus (AAV), and pseudotyped lentiviral vectors such as feline immunodeficiency virus (FIV) or human immunodeficiency virus (HIV) can efficiently transduce airway cells and express CFTR. Ad and AAV have both been tested in CF clinical trials, but CFTR expression was transient, if detected at all. Understanding vector biology and overcoming barriers in the lung have allowed us to improve vector delivery to the airways. However, the next major hurdle was achieving persistent expression. Ad and AAV are both transiently expressing vectors, and vector readministration is implausible due to the presence of neutralizing antibodies that develop against the vector. Creating a hybrid nonviral/viral vector in which the integrating nonviral piggyBac transposon system is delivered by an Ad or AAV vector has allowed us to achieve persistent expression in mice. In a third integrating vector system, lentiviral vectors have historically been challenging to work with due to low titer levels. However, improvement in vector purification methods have allowed us to validate a lentiviral vector as a viable gene therapy option. In total, we have validated three integrating vector systems by restoring CFTR to CF pigs to correct the phenotypic defect.

Pseudomonas aeruginosais an opportunistic pathogen that infects cystic fibrosis (CF) patients contributing to their high morbidity and mortality. P. aeruginosaundergoes a phenotypic conversion in the CF lung, from nonmucoid to mucoid, by constitutively producing a polysaccharide called alginate. These mucoid strains often revert to nonmucoid in vitrodue to second-site suppressor mutations. We hypothesized that mapping these mutations would lead to the identification of novel genes involved in alginate production. In a previous study, a mucoid strain, PDO300 (PAOmucA22), was used to isolate suppressors of alginate phenotype (sap). One of the uncharacterized nonmucoid revertants, sap27, is the subject of this study. The mucoid phenotype in sap27was restored by pMO012217 from a minimal tiling path cosmid library. The cosmid pMO012217 harbors 18 P. aeruginosaopen reading frames (ORF). The cosmid was mutagenized with a transposon to map the contributing gene. It was mapped tolptD(PA0595) encoding lipopolysaccharide transport protein. E. coliLptD transports lipopolysaccharide to the outer leaflet of the outer membrane. The Alg+phenotype was restored upon complementation with P. aeruginosa lptDalone, suggesting that sap27likely harbor a chromosomal mutation inlptD. Sequencing analysis of sap27showed the presence of a mutation not in lptDbut in algO, which encodes a periplasmic protease protein. This suggests LptD is able to bypass analgO mutation by positively regulating alginate production. The lptD is a part of a three-gene operon lptD-surA-pdxA. SurA is an essential protein for survival in starvation and a major chaperone protein for all outer membrane proteins and PdxA is a NAD-dependent dehydrogenase and is involved in the vitamin B6biosynthetic pathway. Pyridoxal 5’-phosphate (PLP) is the active form of vitamin B6.P. aeruginosagrown in a media supplemented with PLP increased production of pyocyanin, a virulence factor. The PLP and aromatic amino acids are synthesized from a common precursor chorismic acid. We demonstrated an increase in pyocyanin production when the bacteria were cultured supplemented by the aromatic amino acids phenylalanine. We concluded that the lptDoperon plays a role in the P. aeruginosavirulence by regulating alginate and pyocyanin production.

Accompanying with the Internet growth explosion, more and more information disseminates on the Web. The large amount of information, however, causes the information overload problem that disturbs users who desire to search and find useful information online. Information retrieval and information filtering arise to compensate for the searching and comprehending ability of the users. Recommender systems as one of the information filtering techniques emerge when users cannot describe their requirements precisely as keywords. Collaborative filtering (CF) compares novel information with common interests shared by a group of people to make the recommendations. One of its methods, the Model-based CF, generates predicted recommendation based on the model learned from the past opinions of the users. However, two issues on model-based CF should be addressed. First, data quality of the rating matrix input can affect the prediction performance. Second, most current models treat the data class as the nominal scale instead of ordinal nature in ratings. The objective of this research is thus to propose a model-based CF algorithm that considers data reliability and data scale in the model. Three experiments are conducted accordingly, and the results show our proposed method outperforms other counterparts especially under data of mild sparsity degree and of large scale. These results justify the feasibility of our proposed method in real applications.

Renewable energy is a serious alternative to deliver the energy needs of an increasing world population and improve economic activity. Wind energy provides better environmental and economic benefits in comparison with the other renewable energy sources. Wind energy is capable of providing 72 TW (TW = 10^12 W) of electric power, which is approximately four and half times the world energy consumption of 15.8 TW as reported in 2006. Since power output extracted from wind turbines is proportional to the square of the blade length and the cube of the wind speed, wind turbine size has grown rapidly in the last two decades to match the increase in power output. As the blade length increases, so does its weight opening up design possibilities to introduce hybrid glass and carbon fiber composite materials as lightweight structural load bearing alternatives. Herein, we investigate the feasibility of introducing modular composite tubulars as well as hybrid sandwich composite skins in the next generation blades. After selecting a target energy output, 8 MW with 80 m blade, airfoil geometry and the layup for the skin as well as internal reinforcements are proposed. They are incorporated into the computational blade via linear shell elements for the skin, and linear beam elements for the composite tubulars to assess the relationship between weight reduction and structural performance. Computational simulations are undertaken to understand the static and dynamic regimes; specifically, displacements, stresses, and vibration modes. The results showed that the composite layers did not exhibit any damage. However, in the balsa core of the sandwich skin, the von Mises stress exceeded its allowable at wind speeds ranging from 11.0 m/sec to 12.6 m/sec. In the blades with composite tubular reinforcement, two different types of damage are observed: a. Stress concentrations at the tubular-skin attachments, and b. Highest von Mises stress caused by the flapping bending moment. The vibration studies revealed a strong coupling mode, bending and twist, at the higher natural frequencies of the blade with tubular truss configuration. The weight saving measures in developing lighter blades in this study did not detract from the blades structural response for the selected load cases.

Magnesium alloys have attracted considerable attention owing to its low density of ~1.7 g/cm3. On the other hand, the carbon fiber (CF) reinforced polyether ether ketone (PEEK) polymer composites possess extraordinary specific strength and stiffness along the longitudinal (or fiber) direction. It follows that the combination of Mg/CF/PEEK would offer an alternative in forming a high specific strength and stiffness composite. In the first part of this study, the low density and high performance Mg-based laminated composites were fabricated by means of sandwiching the AZ31 Mg foils with the carbon-fiber/PEEK prepreg through hot pressing. Proper surface treatments of AZ31 sheet using CrO3 base etchants are necessary in order to achieve good interface bonding characteristics. The resulting Mg base laminated composite, with a low density of 1.7 g/cm3, exhibits high modulus of 75 GPa and tensile strength of 932 MPa along the longitudinal direction. The experimentally measured tensile modulus and strength data along both the longitudinal and transverse direction are within 90-100% of the theoretical predictions by rule of mixtures, suggesting that the bonding between layers and the load transfer efficiency are satisfactory. The flexural stress and modulus along the longitudinal direction are 960 MPa and 54.6 GPa, respectively, suggesting a sufficiently high resistance against bending deflection. The peel strengths are about 2.75 and 4.85 N/mm along the longitudinal and transverse directions, respectively, superior to that of the epoxy-resin-adhered and carbon-fiber-reinforced aluminum laminated composites. Polymer nanocomposites have attracted considerable attention during the past decade due to their versatile and extra-ordinary performances. The polymer nanocomposites can be prepared by the well-known sol-gel method. It is well known that PEEK is a good solvent resistant polymer. Hence, it is impossible to fabricate the PEEK nanocomposite by means of sol-gel method. In the second part of this study, the PEEK nanocomposites filled with nano-sized silica or alumina measuring 15-30 nm to 2.5-10 weight percent were fabricated by vacuum hot press molding at 400oC. The resulting nanocomposites with 5-7.5 wt% SiO2 or Al2O3 nanoparticles exhibit the optimum improvement of hardness, elastic modulus, and tensile strength by 20-50%, with the sacrifice of tensile ductility. With no surface modification for the inorganic nanoparticles, the spatial distribution of the nanopartilces appears to be reasonably uniform. There seems no apparent chemical reaction or new phase formation between the nanoparticle and matrix interface. The crystallinity degree and thermal stability of the PEEK resin with the addition of nanopartilces were examined by X-ray diffraction, differential scanning calorimetry, and thermogravity analyzer, and it is found that a slight decrease in crystallinity fraction and a higher degradation temperature would result in as compared with the prestine PEEK.

As the development of wireless networks, no doubt it brings much more convenience to us. Besides, QoS (Quality of Service) demand emerges due to the popularity of multimedia traffic. Therefore, it is quite worthwhile to do researches about how to provide QoS in wireless networks. 802.11 wireless networks are the most widespread wireless networks currently, and the main goal of 802.11e task group is to support QoS. This thesis proposes a method for further improving QoS under 802.11e environment. According to varying ratio of CBR-like / VBR-like traffic, it adaptively adjusts the proportion of CP/CF medium access mode, and selects the corresponding admission control mechanism. The basic philosophy is to choose favorable transfer ways for different traffic characteristics, hence to reduce average delay. In addition to reduce average delay, we propose another mechanism to maintain or improve system throughput as well.

Our aim was to understand mechanisms responsible for excessive electrolyte loss in the sweat gland and the potential impact on fluid balance during exercise in heat stress conditions. Human physiological testing under exercise/heat stress and immunofluorescence staining of sweat glands from skin biopsies were compared between healthy individuals (with normal and high sweat sodium chloride concentration, [NaCl]) and with cystic fibrosis patients (CF), who exhibit excessively salty sweat due to a defect of Cl- channel cystic fibrosis transmembrane conductance regulator (CFTR). Three novel findings are presented. First, excessively salty sweat may be associated with reduced expression of CFTR in the sweat gland reabsorptive duct of healthy individuals in addition to in those with CF; however, although a link to a CF gene mutation in healthy individuals with high sweat [NaCl] was not demonstrated, the possibility of an undetected CFTR mutation or polymorphism remains to be investigated as an underlying mechanism. Two, CF and healthy individuals with excessively salty sweat respond to moderate dehydration (3% body weight loss during exercise) with an attenuated rise in serum osmolality, greater relative loss in plasma volume, but similar perceived thirst compared to healthy individuals with "normal" sweat [NaCl]. However, individuals with CF respond to rehydration with hypotonic beverage by drinking less ad libitum in response to reduced serum [NaCl], suggesting that thirst-guided fluid replacement may be more appropriate for this population rather than restoring 100% of sweat loss following dehydration as is often recommended in healthy individuals.

Este trabalho identifica e analisa as principais características econômicas da produção e comercialização de dormentes no Estado do Paraná, mais especificamente na área sob a jurisdição da Superintendência Regional de Curitiba da Rede Ferroviária Federal S.A., SR-5, com seus 3.911,44 Km de malha viária, no período 1981-6. 0 dormente de madeira e o produto, ainda, com grande utilização nesta regional, tendo-se empregado, em caráter experimental, alguns quilômetros com peças de concreto. Quanto a formatação as peças de madeira apresentam-se com a configuração prismática, porém, para o futuro ë provável a aplicação de produtos roliços ou de duas faces. 0 suprimento de dormentes para esta regional apresentou, no período 1981-6, deficiências qualitativas e quantitativas devido à crescente escassez de florestas naturais no Estado do Paraná, assim como as peças produzidas são oriundas de espécies com poucas aptidões para esse processo produtivo, proporcionando um elevado índice de substituição destes produtos nas vias. As regiões de Guarapuava (PR) e União da Vitória (PR) apresentaram grande participação no suprimento de dormente para esta regional, onde se utilizam para o desdobro o sistema semimecanizado com moto-serra. Sob o aspecto da comercialização, tem-se para este mercado as características de um oligopólio na produção e um monopsónio no consumo. A produção e consumo apresentaram-se altamente concentrados, onde 2 entre 10 fornecedores, em 1986, representaram 82,1% da produção e a SR-5 alcançou 98% do consumo dessas peças. Os preços dos dormentes sofreram, no período analisado, uma perda real em seus valores, o que proporcionou aos produtores baixos índices de lucratividade. Em função dos dormentes de madeira apresentar maior economicidade de uso, tem-se como perspectiva futura para a SR-5, no curto-prazo, que o suprimento seja realizado por áreas onde existe abundância em florestas nativas, tais como o norte do Brasil, o Paraguai ou Argentina. Com relação ao longo-prazo, é viável a SR-5 tornar-se auto-suficiente mediante a implantação de povoamentos de eucalipto, os quais apresentam potenciais de rentabilidade ao redor de 7,15% ao ano.

A presente pesquisa versa sobre a construção de Tabelas de Volume Individual Total, com e sem casca para a espécie Pinus taeda Lineu, nos principais eixos de reflorestamento do Estado do Paraná. O eixo Palmas-Guarapuava abrange as micro-regiões homogêneas 23 e 24 e compreende os Municípios de Palmas, General Carneiro, Bituruna, Pinhão, Guarapuava, Inácio Martins e Laranjeiras do Sul e o eixo Telêmaco Borba-Sengés abrange as micro-regiões homogêneas 6 e 7, compreendendo os municípios de Sengés, Jaguariaíva, Arapoti, Pirai do Sul, Tibagi e Telêmaco Borba. Foram testados cinco modelos volumétricos, para cada micro-região estudada, bem como para a massa de dados agrupados, gerando vinte e cinco equações volumétricas, sendo que a derivação das equações resultantes foi feita pelo método dos mínimos quadrados. Entre as equações testadas aquela que forneceu, em todas as ocasiões, os melhores resultados foi a gerada pelo modelo volumétrico exponencial proposto por SCHUMACHER-HALL, (vide summarium) sendo que o Erro-Padrão Residual, o índice de Furnival e o Gráfico dos Resíduos foram os principais responsáveis pela eleição da melhor equação, seguidos pelo Coeficiente de Determinação e o F calculado. Após desenvolvidas todas as equações de volume, realizou- se o teste de distribuição dos resíduos ao longo da linha de regressão através do Teste de Probabilidade Associada. Este teste demonstrou que em nove das equações testadas houve tendenciosidade na distribuição desses resíduos, sendo portanto, sumariamente excluídas. Realizou-se também, o Teste de Amplitude Múltipla de Tukey para diferentes números de repetições para as dezesseis equações remanescentes e constatou-se não haver diferença significativa, estatisticamente, entre as equações geradas ao nível de probabilidade de 0,01, o que torna válido o uso de qualquer equação dentro da área coberta por esta pesquisa. Apresentou-se neste trabalho as cinco melhores equações volumétricas testadas para Pinus taeda, com casca, bem como as Tabelas de Volume Total com casca, geradas pelas mesmas.