The objective of this research is to investigate the effects of tip clearance on the stage and component performance in a high-speed centrifugal compressor. The experimental data were compared against results from a numerical model to assess the ability of the numerical simulation to predict the effects of tip clearance. Experimental data were collected at Purdue University on the Single Stage Centrifugal Compressor (SSCC), a high-speed, high-pressure ratio test compressor sponsored by Honeywell Aerospace. Numerical simulations were completed using the ANSYS CFX software suite and part of the research computing clusters located at Purdue University.<div><br></div><div>Two tip clearances were tested, the nominal tip clearance and a tip clearance that is 66% larger than the nominal clearance, at speeds from 60% to 100% corrected speed. To compare data points with different tip clearances, various parameters were evaluated, and one was chosen. The value of TPR/inlet corrected mass flow rate best represented similar loading conditions, and thus similar incidences, for each tip clearance and was chosen as the best method for comparing similar data points taken with different clearances. Stage and component performance were focused on the sensitivity of each performance parameter to the changing of the tip clearance. The stage total pressure ratio and stage efficiency showed moderate sensitivity while the stage work factor showed much lower sensitivity. The impeller is more sensitive to changing tip clearances than the stage is, showing greater changes when comparing data from each tip clearance. The diffuser was on the same order of sensitivity as the impeller, with marginally higher sensitivities for some parameters. It was found that by the typical performance metrics, the diffuser performs worse at the nominal clearance than at the larger clearance. Upon further investigation though, the impeller is providing a higher static pressure and therefore, more diffusion, at the nominal clearance so the diffuser must perform less diffusion during nominal clearance operation.<br></div><div><br></div><div>To assess the validity of a prediction of the performance and sensitivity of the stage and components to the tip clearance, a numerical model was developed and validated. The numerical model was able to reasonably predict the stage performance with better comparisons of performance in the impeller and worse in the diffuser. The instrumentation in the experiment was replicated in the software to calculate performance the same way it is calculated experimentally so that the results would be comparable. While the performance of the stage and components was lacking in some areas, the trends predicted were similar to those calculated from the experimental data. As with the performance, the trends in the impeller matched very well between the experiment and the numerical simulation. The trends in stage and diffuser performance were predicted more accurately than the stage and diffuser performance maps and were able to capture the magnitude of the change in performance caused by changing the tip clearance. <br></div>

付記する学位プログラム名: 充実した健康長寿社会を築く総合医療開発リーダー育成プログラム / 京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第22396号 / 薬科博第118号 / 新制||薬科||13(附属図書館) / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 髙倉 喜信, 教授 山下 富義, 教授 小野 正博 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

Ionenbewegungen über das Atemwegsepithel bilden die Grundlage einer definierten Zusammensetzung intraluminaler pulmonaler Flüssigkeit. Ein perinataler Anstieg maternaler und damit einhergehend fetaler Glukokortikoid (GC)-Serumlevel ist vergesellschaftet mit einer Veränderung im epithelialen Ionentransport der Lunge. So erfährt das respiratorische Epithel in einer perinatalen Anpassungsreaktion eine Transition fetaler Fruchtwasserproduktion hin zu überwiegend flüssigkeitsabsorbierenden Vorgängen. In den distalen Abschnitten spiegelt sich dies in einer Aktivierung flüssigkeitsabsorptiv wirkender epithelialer Natriumkanäle (ENaC) wider. Vor Beginn der Transition überwiegt ein sekretorisch aktiver, apikaler Chloridkanal, der cystic fibrosis transmembrane conductance regulator (CFTR). Als Gegenspieler zum ENaC gewährleistet der CFTR einen transepithelialen Flüssigkeitsstrom in das Lumen des respiratorischen Systems. Diese Prozesse ermöglichen den pulmonalen Gastaustausch sowie die Bereitstellung eines periziliären Flüssigkeitsfilms, welcher die postnatale mukoziliäre Clearance (MCC) gewährleistet. Während bereits gezeigt werden konnte, dass GC den ENaC vor allem in distalen Atemwegsepithelien in Expression und Aktivität steigern (Thome et al. 2003; Venkatesh und Katzberg 1997), gibt es bisher nur wenige Daten zum Einfluss von GC auf den CFTR. Zusammenfassend kann durch die vorliegende Arbeit gezeigt werden, dass es durch GC zu einer Zunahme des CFTR-abhängigen Ionentransportes kommt und dass dieser aktivitätssteigernde Einfluss von der PI3K sowie der AKT abhängig ist, während die SGK1 nicht wesentlich in diesen Wirkmechanismus involviert zu sein scheint. Es ließ sich nachweisen, dass es durch GC zu einer gesteigerten Phosphorylierung von AKT, SGK1 sowie NEDD4L kommt, woraus eine Aktivitätssteigerung der AKT und der SGK1 sowie ein Rückgang in der NEDD4L-Aktivität resultieren. Eine AKT-Inhibition verhindert die zunehmende NEDD4L Phosphorylierung, während eine Inhibition der SGK1 keinen Einfluss auf den NEDD4L-Phosphorylierungsstatus zeigt. Des Weiteren ergibt sich ein stimulierender Einfluss von GC auf die CFTR-Aktivität innerhalb von 30 Minuten. Im Gegensatz zum Ionentransport zeigten GC keinen Einfluss auf den Epithelwiderstand und damit die Barrierefunktion der Zellkultur.:1. Abkürzungsverzeichnis S. 3 2. Abbildungsverzeichnis S. 5 3. Bibliographische Beschreibung S. 6 4. Einleitung S. 7 4.1. Der CFTR und seine Rolle im epithelialen Chloridtransport S. 7 4.2.Die Struktur und Regulation des CFTR S. 8 4.3.Die (Patho-)Physiologie des CFTR S. 10 4.4.Alternative Chloridkanäle S. 11 4.5.Methodik – Etablierung der Methode S. 12 5. Originalpublikation 5.1. “Glucocorticoids Distinctively Modulate the CFTR Channel with Possible Implications in Lung Development and Transition into Extrauterine Life” S. 14 5.2. “Signaling Cascade involved in Rapid Stimulation of Cystic Fibrosis Conductance Regulator (CFTR) by Dexamethasone” S. 36 6. Zusammenfassung der Ergebnisse S. 52 6.1 Hintergrund und Ziel S. 52 6.2 Ergebnisse S. 53 7. Diskussion der Ergebnisse S. 54 8. Literaturverzeichnis S. 57 9. Anmerkungen zur Originalpublikation – Darstellung des eigenen Beitrags S. 64 10. Erklärung über die eigenständige Abfassung der Arbeit S. 65 11. Curriculum vitae S. 66 12. Danksagung S. 68

While community-oriented policing was touted as a new paradigm in American policing, little data reflects its success in reducing crime and/or increasing crime clearance rates. Researchers have failed to definitively describe community policing as a successful style of policing, leaving much more research to be done on its effectiveness as a crime reduction method. Using Trojanowicz's seminal conceptualization of community-oriented policing as the foundation, the purpose of this correlational study was to determine whether there are statistically significant associations between community-oriented policing, crime rates, and crime clearance rates for the 9 municipalities of Carteret County, North Carolina. Data for community-oriented policing methods were collected from the police agencies via personal contact with an agency representative, while data for violent crime, property crime, violent crime clearance rates, and property crime clearance rates were obtained from the State Bureau of Investigation and the Federal Bureau of Investigation's Uniform Crime Report. The results of Spearman's rho and a chi-square test for independence indicated that there was a statistically significant relationship between community-oriented policing and the violent crime rate (p = .03), the violent crime clearance rate (p = .03) and the property crime clearance rate (p = .009). This study may enhance positive social change for police agencies in North Carolina by providing specific recommendations to better implement successful community policing strategies in their communities.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20979号 / 医博第4325号 / 新制||医||1026(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 妻木 範行, 教授 戸口田 淳也, 教授 柳田 素子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Cystic fibrosis is the most common fatal recessive hereditary disease and affects about one out of every 3,000 newborns. There is no cure for this disease. Patients rely on treatment on a daily basis like medical treatment with both tablets and inhaled medication, airway clearance therapy and physical exercise to slow the decline in lung function and prolong their lives.

The aim of this thesis was to investigate the effect of clearance and tolerance in bolted joints when there is a mismatch between the bolt holes. A parametric study with seven different cases was analyzed in this project; four double bolt configuration and three triple bolt configuration, with variation of the size of the bolt hole misalignment, the diameter of the bolt and the thickness of the plates. All analyses were performed with the aid of the FEM commercial software Abaqus, all the models were modelled with 3D brick elements. Despite bolted connections being subject of several investigations, no study about this matter for structural engineering purposes had been performed before. The results indicate that for connections with a low number of bolts a misalignment of the bolt clearance can cause a serious reduction in the ultimate bearing capacity of a joint and it indicates that the Eurocode 1993 1-8 might be overestimating the ultimate bearing capacity for some cases.

The construction of cities involves the use of land for new spaces and infrastructure. Construction on undeveloped land poses a dilemma on how to deal with the natural resources found on the construction site. Circular economy could provide guidelines on how to harness these resources, so they become products that circulate through as many cycles as possible, therefore decreasing resource consumption and waste. This research aims to explore alternatives to harness the natural materials extracted during the land clearance process of a new urban district: Sollihøgda plussby. Additionally, a new method to examine the circularity of the suggested products will be tested: the longevity indicator. The method of this thesis consists of three parts: (1) an inventory to define which natural materials are found in the construction site and their main characteristics, (2) interviews with industry experts to gain a technical insight on the possible uses for the materials, and (3) a longevity indicator to measure the circularity of the proposed uses. This research found that the forest in Avtjerna consists of Norway spruce, Scots pine and birch. The sediments are mostly humus with a turf sheet cover, while most of Avtjerna’s bedrock is categorized as rhomb porphyry lava. Norway spruce and rhomb porphyry lava have the required quality to become high-quality products for the construction industry, and they could be used directly in the project. High-quality products have longer lifetimes and more possibilities of recycling and reuse, therefore they scored higher when calculating the longevity indicator, which means a higher material retention. The other materials (Scots pine, birch, other sediments and rocks) have also possibilities of becoming products that could be used in Sollihøgda Plussby, but the longevity indicator for these materials was lower than those of Norway spruce and rhomb porphyry. Despite the usefulness of the longevity indicator to provide a preliminary assessment, this method needs to be upgraded so it incorporates other CE parameters. There should be a distinction on how many times the material is recycled, the lifetime of the recycled products, and the quality of the products obtained from the recycling process. Inventorying the natural resources on a construction site is a practice that should become common, since it allows to determine how materials can be harnessed, but also which areas should be preserved due to their ecological value. Additionally, the longevity indicator should not be used in isolation, but the environmental impacts of each suggested product should be assessed too.

yes / Background: Minimum toe clearance is a critical gait event because it coincides with peak forward velocity of the swing foot, and thus, there is an increased risk of tripping and falling. Trans-tibial amputees have increased risk of tripping compared to able-bodied individuals. Assessment of toe clearance during gait is thus clinically relevant. In able-bodied gait, minimum toe clearance increases with faster walking speeds, and it is widely reported that there is synchronicity between when peak swing-foot velocity and minimum toe clearance occur. There are no such studies involving lower-limb amputees. Objectives: To determine the effects of walking speed on minimum toe clearance and on the temporal relationship between clearance and peak swing-foot velocity in unilateral trans-tibial amputees. Study design: Cross-sectional. Methods: A total of 10 trans-tibial participants walked at slow, customary and fast speeds. Minimum toe clearance and the timings of minimum toe clearance and peak swing-foot velocity were determined and compared between intact and prosthetic sides. Results: Minimum toe clearance was reduced on the prosthetic side and, unlike on the intact side, did not increase with walking speed increase. Peak swing-foot velocity consistently occurred (~0.014 s) after point of minimum toe clearance on both limbs across all walking speeds, but there was no significant difference in the toe–ground clearance between the two events. Conclusion: The absence of speed related increases in minimum toe clearance on the prosthetic side suggests that speed related modulation of toe clearance for an intact limb typically occurs at the swing-limb ankle. The temporal consistency between peak foot velocity and minimum toe clearance on each limb suggests that swing-phase inter-segmental coordination is unaffected by trans-tibial amputation. Clinical relevance The lack of increase in minimum toe clearance on the prosthetic side at higher walking speeds may potentially increase risk of tripping. Findings indicate that determining the instant of peak swing-foot velocity will also consistently identify when/where minimum toe clearance occurs.

More than 300 billion cells die in the human body every day. Although there are over a dozen different death paradigms, they all produce the same result - dead and dying cells. As they are no longer actively maintained, persistent corpses can proceed to a secondary necrotic state in which its cell membrane ruptures thus releasing its contents to the extracellular milieu. As many of the intracellular contents act as damage associated molecular patterns (DAMPs), they pose a potential danger to the rest of the surrounding tissue and organism. Excessive cell death has been correlated with diseases such as atherosclerosis, Alzheimer’s, and autoimmune disorders. To avoid damage and disease associated with cell corpses, two classes of cells evolved to clear them away – professional and nonprofessional phagocytes. A professional phagocyte's primary function is to clear away dying cells and other debris. Nonprofessional phagocytes, however, have a primary role other than clearance. When nonprofessional phagocytes encounter a cell corpse, their phagocytic machinery is engaged to clear it away. Interestingly, a recent study demonstrated that most, if not all, tissues contain nonprofessional phagocytes. To investigate nonprofessional phagocytes, the model organism Drosophila melanogaster is ideal. Drosophila is a useful model system as they have orthologs for 70% of human disease genes, a simplified immune system, and a host of genetic tools. Their ovaries have three morphologically distinct cell types – 15 nurse cells and an oocyte all surrounded by an epithelial follicle cell layer. As the ovaries are immunoprivileged, the follicle cell layer acts as the ovaries’ sole phagocytes. During late stage oogenesis, a small subsection of the follicle cell layer – the stretch follicle cells – murder the nurse cells in order to produce a fully developed oocyte. As past studies of cell corpse clearance have predominantly concentrated on the professional phagocytosis in the context of apoptotic cell corpses, there are still many gaps in our knowledge of nonprofessional phagocytosis and non-apoptotic death. This dissertation focuses on the molecular mechanisms that regulate the transition of nonprofessional phagocytes from their primary role as epithelial cells to their phagocytic role in the context of a newly characterized form of non-autonomous cell death known as phagoptosis. To gain a global view of these changes, two large scale experiments were performed – a classic genetic screen of kinases using RNAi and a high-throughput translatome study. The kinase screen identified dozens of kinase genes required for proper clearance. Of the 27 kinase genes that demonstrated a severe phenotype when knocked down, two were previously uncharacterized and six produced an “undead” phenotype, a phenotype that had only been previously witnessed when genes were perturbed in the germline. A follow up study was performed on Gprk2, one of the genes that induced a severe phenotype. By comparing the phenotypes of Gprk2 knockdowns and those of the two canonical clearance pathways, a third clearance pathway was discovered. The translatome study identified over 400 genes that were statistically significantly differentially expressed between primary state and phagocytic state follicle cells, including groups affecting calcium signaling and muscle contraction. This dissertation further describes the expansion of the molecular network of nonprofessional phagocytes driven by these large-scale experiments and their follow up studies.