Sepsis is a systemic inflammatory response to infection, which may ultimately lead to multi-organ failure. Sepsis causes millions of deaths each year and creates tremendous financial burdens on the health care system, yet there is no effective cure for sepsis. Even years after the onset of sepsis, patients who have clinically recovered still die from sepsis-related complications due to chronic immune dysfunction. Neutrophils, the most dominant leukocytes in human circulatory systems, play a critical role in not only promoting inflammation to fight against microbe invasion but also facilitating inflammation resolution to restore immune homeostasis. While dysfunctional/exhausted neutrophils have been implicated in the long-term morbidity and mortality of sepsis, the cause of neutrophil exhaustion and the system to rejuvenate the dysregulated immunity are understudied. To fill in the missing piece here, we conducted our trilogy-like projects. First, we established an in vitro culture system to mimic sepsis-like conditions: murine neutrophils prolonged-stimulated with LPS exhibit exhaustion-related phenotype with the elevated expression of both proinflammatory and immunosuppressive makers on the cell surface as well as dysregulated swarming patterns. We found that by knocking out TRAM (TICAM2), an adaptive molecule regulating TLR4 downstream MyD88-independent signaling pathway, neutrophils exhibit attenuated exhaustion on both phenotypic and functional levels. Of note, TRAM contributes to the development of exhausted neutrophils through activating Src family kinases (SFKs)-STAT1 cascade, and deficiency in TRAM provides protective effects on systemic inflammation, reduces tissue injury, and improves survival in a murine colitis-induced sepsis model. Next, in my second project, we reported that neutrophils can be clustered into three subpopulations even at their naïve state based on the single-cell RNA sequencing (scRNAseq) analyses. Of note, neutrophils in one of the clusters are more mature but less apoptotic with the elevated expression of resolving-associated markers Cd86 and Cd200r, hence we termed these neutrophils as 'resolving neutrophils'. We found that the resolving neutrophil population can be expanded via pharmacologically reprogramming with sodium 4-phenylbutyrate (4-PBA) or genetic deletion of TRAM. Resolving neutrophils not only secrete more pro-resolving mediators, such as ResolvinD1 and SerpinB1, but also exert enhanced phagocytic and bactericidal capacities. Mechanistically, we discovered that the development of resolving phenotype in neutrophils is mediated by the PPARγ/LMO4/STAT3 signaling circuitry, which is constitutively suppressed by TRAM. To explore the translational applications of resolving neutrophils, in my third and final project, we conducted adoptive transfer experiments to examine the effects of TRAM-deficient resolving neutrophils in cecal slurry (CS)-induced septic mice. We found that TRAM-deficient mice are more resilient to severe sepsis with reduced tissue injury and less compromised lung integrity as compared to wild-type (WT) mice, and splenic neutrophils from TRAM deficient septic mice better preserve resolving-related features. Moreover, transfusing TRAM deficient neutrophils in WT septic mice renders therapeutic effects with alleviated lung and kidney damage. We also observed TRAM-deficient neutrophil-mediated resolving memory propagation in vitro to promote resolving features of neutrophils, monocytes, and T cells, as well as to strengthen endothelial cell barrier function. In terms of the mechanism, we reported that TRAM is critical for the secretion of neutrophil elastase, a potent protein to compromise endothelium; hence, endothelial cells cocultured with TRAM deficient neutrophils maintain higher levels of adhesion/tight junction markers than cocultured with WT neutrophils. Taken together, our trilogy projects better define exhausted and resolving neutrophils. And most importantly, our works demonstrate that TRAM, an underappreciated molecule, is responsible for inducing neutrophil exhaustion and suppressing resolving neutrophil generation. / Doctor of Philosophy / A 'good' inflammation upon the infection should include two steps: the initial proinflammatory response to combat invading pathogens followed by the later resolution process to repair damage and restore the balance of the host's immune system. The harmony of these reactions is essential to maintain immune homeostasis, and the disruption of immune homeostasis may lead to different pathogenic conditions, including sepsis. Neutrophils are the most dominant white blood cells in human circulation, and they play a critical role in both promoting proinflammatory response and facilitating inflammation resolution. While the dysfunction of neutrophils is associated with the pathogenesis of sepsis and implicated in long-term sepsis-related death, approaches to rejuvenate dysregulated/exhausted neutrophils to restore immune homeostasis in septic patients are still lacking. In our projects, we better defined the characteristics of exhausted neutrophils in a sepsis-mimicking condition and unveiled the underlying mechanisms of neutrophil exhaustion. In addition, we demonstrated that neutrophils with pro-resolving features can be expanded concurrently with the decrease of exhausted neutrophils by a genetic modification approach. Finally, we showed that neutrophils with pro-resolving features can offer therapeutic effects in sepsis mice to alleviate tissue injury and organ dysfunction.

The master‘s thesis deals with a line of a new tram track, which will merge the current tracks in the street Kounicova and in the street Štefánikova. The track continues through the area of Jasels barracks, through the street Dělostřelecká, where its ended by a tram loop. A part of the thesis was also a design of the new stop layout.

The aim of the diploma thesis is to design the extension of tram line no. 12 from the current terminal station Technologicky park to the city district Brno-Medlanky. The tram track is situated on the separate road bed outside the built up urban area. Directional and elevational solution of the track is designed in several variants, after the evaluation the best variant is selected and elaborated. The diploma thesis contains the design of the tram stop and the terminal station with baloon loop, including access paths. Adjustment of the crossed road and the drainage system solution is part of the thesis as well.

This thesis deals with the relocation of the tram line No. 12 from Kounicova to Veveří Street in Brno city. The No. 12 line will run together with lines No. 3 and No. 11. The proposed line is run in the local communications area. At the intersection of Veveří with Pod Kaštany Street, line No. 12 will be disconnected using the tram triangle, then it will run along Pod Kaštany and Šumavská Streets to Kounicova Street, where it will be reconnected to the original line and with the help of another tram triangle there will be a possibility to continue by the planned track along Šumavská Street. The goal of this thesis is to propose a design of tram superstructure construction, provide a solution for surrounding roads and propose the location of stops, including access to them.

Master's Thesis is focused on urban public transport, specifically on tram network in Prague. The first part introduces the transport, with focus on personal transport, its transport routes and means of transport. Next part describes Prague tram network, its history from the very beginning of the first tram lines till present and that is broken up into the detail on particular tram lines which are now operated. Further the transportation survey of Prague integrated transport from the year 2016 is introduced. The information from this survey are consequently used for two different drafts on solution of tram network. The first draft suggests tracing the lines with the biggest possible amount of lines while the second one suggests tracing with as many direct offers as possible. The last part of the thesis compares and valuates both suggested drafts.

The implementation of grass tracks is uncommon in Stockholm compared to Central Europe where it is more popularized. As more tram projects are planned in the future such as the Spårväg Syd project, the aim of this study is to explore the role of grass tracks in the public transport sector by theoretically conceptualising grass tracks as a green infrastructure strategy. The research questions were to study how residents perceive the grass track between Sicka Udde and Sickla Station, and how the grass track could contribute to noise concerns, traffic safety, and financial resource in the Spårväg Syd project. Qualitative methods were used in which online surveys were sent out to residents in Hammarby Sjöstad and interviews with the municipality and county workers from Lund, Norrköping and Stockholm were conducted. The result showed that the resident was more positive about the grass track compared to the municipality and county workers which highlighted the additional cost and work effort to provide the public with a well-maintained and visually attractive grass track. The conclusion of this study has covered previous and new discoveries which open discussions for further reflection on what project planners shall consider before deciding to implement grass tracks in future tram projects.

Wiener Linien’s tram network is one of the largest and busiest of its kind worldwide. Maintaining and improving the Level of Service (LoS) is one of the major tasks of the operations division. To direct these improvements efficiently to lines and sections of lines in need, tram line performance needs to be assessed. In this master thesis a Python-based model is developed to assess tram line performance using ideal operational constraints. Furthermore, the model is capable of computing the energy consumption for this optimal case. The tool computes Undisturbed Optimal Travel Times (UOTTs) which serve as a benchmark for tram line performance. Therefor it builds on track alignment data (curves and radii, gradients and switches), speed restriction data and a set of optimal parameters (no traffic, constant acceleration, etc.). Furthermore, train resistance, curve speeds and vehicle type are taken into consideration. These parameters are investigated and selected based on literature studies, interviews with employees of Wiener Linien, as well as field tests. Finally, the model results are compared to real world data for evaluation. A discussion of the results regarding further applications and improvements is performed. / Spårvagnsnätet i Wiener Linien är ett av de största och mest trafikerade i sitt slag i världen. Att underhålla och förbättra servicenivån är en av de viktigaste uppgifterna för driftsavdelningen. För att dessa förbättringar ska kunna riktas effektivt till de linjer som mest behöver det måste spårvagnarnas prestanda bedömas. I detta exjobb utvecklas en Python-baserad modell för att bedöma spårvagnslinjens prestanda med hjälp av ideala trafikparametrar. Dessutom kan modellen beräkna energiförbrukningen för dessa optimala scenarier.Verktyget beräknar Ostörda Optimala Restider (UOTTs) som blir referenser för spårvagnslinjernas prestanda. Metoden bygger på spårutformning (kurvor och radier, lutningar och växlar), hastighetsbegränsningar, och en uppsättning optimala parametrar (ingen vägtrafik, konstant acceleration osv.). Dessutom tas hänsyn till rullmotstånd, hastighet i kurvor och fordonstyp. Dessa parametrar undersöks och väljs ut genom litteraturstudier, intervjuer med anställda vid Wiener Linien samt fälttester.Modellresultaten jämförs med uppmätta restidsdata för utvärdering av den dagliga driften. En diskussion av ytterligare tillämpningar och förbättringar förs.

This master’s degree thesis is aiming to provide design solution within extension of tram line no.5 in the town of Brno,which nowadays ends by balloon loop at Štefánikova čtvrť stop at Merhautova street in Černá Pole district. Proposed tram line is designed in the limits of local urban roads and ends by newly designed balloon loop at Okružní street in Lesná district. Within the framework of this thesis new tram super structure is designed together with surrounding urban rous and connection to Halasova náměstí.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Este trabalho consiste em analisar historicamente o bonde em Fortaleza no perÃodo entre 1913 e 1947, pondo em relevo as relaÃÃes que os habitantes estabeleciam com a cidade em face da presenÃa desses equipamentos modernos; observando o uso que as diferentes classes sociais faziam do espaÃo urbano, sobretudo a partir da chegada do bonde, iniciado no ano de 1913, pela companhia inglesa Cearà Tramway Light, e encampado pelo poder pÃblico local em 1947. Nesses anos, o bonde foi muito mais do que uma simples mÃquina, representava a existÃncia do moderno na capital e se constituÃa em espaÃo de convivÃncia entre as diferentes classes sociais. Durante esse perÃodo, houve um crescimento acentuado da populaÃÃo e, apÃs os anos 1930, os equipamentos urbanos nÃo acompanharam o novo ritmo da cidade. A pesquisa tambÃm apresenta como o sistema de transporte define os espaÃos urbanos, a configuraÃÃo de bairros e as disputas por locais prÃximos ao centro. Com uma sÃrie de irregularidades, paralisaÃÃes, dificuldades na circulaÃÃo, o bonde alterou o cotidiano dos habitantes de Fortaleza na percepÃÃo da velocidade, do espaÃo, do tempo e, principalmente, no caminhar pela urbe.

This thesis aim is to study the planning documents for the tramway in Lund from a perspective of power and rationality. The empirical material used has been studied using critical discourse analysis, departing from the ideas of Fairclough (2010), Winther Jørgensen and Philips (2000) and Watt Bolsen (2007). The discourse analysis resulted in four themes that were predominant in the empirical material. These themes are passenger attraction, economic rationalities, prognosis and attractive urban environment. These are used as the base for the analysis of power and rationality.The analysis of power and rationality depart from a Foucauldian perspective of power. The main perspective used in this thesis is inspired by Flyvbjerg’s (1998) ten propositions of the relation between power and rationality. Where power influence rationality and rationality is embedded by power. The relation between power and rationality is according to Flyvbjerg asymmetrical, and when rationality and reason are confronted, reason yields to power (Flyvbjerg, 1998, p. 228ff). The findings of the analysis of power and rationality present examples from the empirical material where power seeks to define knowledge and reality, as well as examples of powers strategy to blur the line between rationality and rationalisation. This view on the strategies, operations and rationalities of power are also shared by scholars such as Richardson (2004) and Fox-Rogers and Murphy (2014). The ambition of the analysis of power and rationality is not to find out a ‘what’ but to understand ‘how’ power and rationality is presented in the planning documents related to the development of a tramway in Lund. Finally, this thesis discusses the findings from both the discourse analysis as well as the analysis of rationality and power from a wider social perspective. Placing the findings of the discourse analysis into a societal and institutional process, as well as arguing for other rationalities than the one found in the analysis of power and rationality to be valued more in the planning process.