The atmospheres of exoplanets are being characterised in increasing detail by observational facilities and will be examined with even greater clarity with upcoming space based missions such as the James Webb Space Telescope (JWST) and the Wide Field InfraRed Survey Telescope (WFIRST). A major component of exoplanet atmospheres is the presence of cloud particles which produce characteristic observational signatures in transit spectra and influence the geometric albedo of exoplanets. Despite a decade of observational evidence, the formation, dynamics and radiative-transport of exoplanet atmospheric cloud particles remains an open question in the exoplanet community. In this thesis, we investigate the kinetic chemistry of cloud formation in hot Jupiter exoplanets, their effect on the atmospheric dynamics and observable properties. We use a static 1D cloud formation code to investigate the cloud formation properties of the hot Jupiter HD 189733b. We couple a time-dependent kinetic cloud formation to a 3D radiative-hydrodynamic simulation of the atmosphere of HD 189733b and investigate the dynamical properties of cloud particles in the atmosphere. We develop a 3D multiple-scattering Monte Carlo radiative-transfer code to post-process the results of the cloudy HD 189733b RHD simulation and compare the results to observational results. We find that the cloud structures of the hot Jupiter HD 189733b are likely to be highly inhomogeneous, with differences in cloud particle sizes, number density and composition with longitude, latitude and depth. Cloud structures are most divergent between the dayside and nightside faces of the planet due to the instability of silicate materials on the hotter dayside. We find that the HD 189733b simulation in post-processing is consistent with geometric albedo observations of the planet. Due to the scattering properties of the cloud particles we predict that HD 189733b will be brighter in the upcoming space missions CHaracterising ExOPlanet Satellite (CHEOPS) bandpass compared to the Transiting Exoplanet Space Survey (TESS) bandpass.

This thesis answers the question “Why does security cooperation occur between Western states?”. The basic answer is: “Because most state actors do not want their states to integrate”. In other words, cooperation occurs as a coping mechanism, as an imperfect substitute for integration. But the thesis does not only investigate the reasons for cooperation, what Aristotle called the final cause. The thesis also examines the material, formal and efficient causes of cooperation. Such an unorthodox causal explanation of cooperation is based on a Critical Realist philosophy of social science. The application of this philosophy to the empirical study of International Relation is rare, making this thesis original. Beyond the philosophy of social science, the thesis' research design, many of the cases, and much of the data are also rarely used. The research design is an embedded multiple-case study. The states studied are the United States of America, France and Luxembourg. Within each state, the embedded subcases are three types of state security organisations: the armed forces, law enforcement and intelligence agencies. Rarely have these three types of security organisations been compared. Similarly, Luxembourg is seldom studied. Comparing different types of states and different types of state security organisations has not only allowed the main research question to be answered. It has also allowed temporal, spatial, national, and functional variation in cooperation to be identified and theorised. The empirical evidence studied includes participant observation (at the North Atlantic Treaty Organisation) and documents (e.g. state policy documents, annual reports by organisations, reports by parliaments and non-governmental organisations, autobiographies, books by investigative journalists, articles by newspapers and magazines). The thesis is also based on a score of elite interviews (e.g. with ambassadors, diplomatic liaisons, ministerial advisors, foreign ministry officers, military commanders, etc.), and the careful study of both declassified and classified archival records.

Several available free software audio solutions were analyzed, and Jackdmp—a C++ reimplementation of the renowned JACK Audio Connection Kit—was selected as the most appropriate solution for a real-time audio architecture on DROPS. The JACK sound architecture provides the lowest processing latency possible on a desktop computer for a given set of sound card parameters. It reduces the latency jitter caused by software to zero and synchronizes streams at sample accuracy. A real-time admission scheme for JACK clients is proposed. The execution time of different typical JACK clients was analyzed with measurements to validate the assumptions the proposal is based on, but also to gain further knowledge about their timing behavior. The measurements showed that the condition set by Paul Davis—the time to process a client must be a linear function of the buffer size—holds for all tested clients. Jackdmp was ported to DROPS. The developed design of the port and its implementation is documented here. Measurements showed that—although the real-time performance of the Linux kernel is continuously being improved in the mainline and on special external branches—DROPS can provide a signaling latency that is two times lower on average than the values that can be achieved on the same machine running with a low latency patched Linux kernel. Thus, it can be stated that DROPS is well-suited for real-time audio processing and that the pursued path to use it as the foundation of a truly real-time capable audio workstation should be followed. / Wenn man heute digitale Audiotechnik zum Aufnehmen oder Abmischen von Musik oder anderen Audiodaten verwenden möchte, steht man vor der Wahl, entweder auf eine sehr spezialisierte Hardwarelösung zurückzugreifen oder aber sich eines gewöhnlichen Desktopsystems mit entsprechender Audiosoftware zu bedienen. Der Vorteil eines Desktopsystems ist neben seinem deutlich niedrigeren Preis vor allem die Flexibilität. Bezüglich seines Echtzeitverhaltens bietet ein Computer mit einem Standard-Desktop-Betriebssystem aber bei weitem nicht dieselbe Verlässlichkeit einer spezialisierten Hardwarelösung oder analoger Technik. Die Architektur von DROPS --- mit dem echtzeitfähigen Fiasco- Mikrokern auf der einen Seite sowie der Unterstützung von Legacy-Anwendungen durch L4Linux auf der anderen Seite --- birgt die Hoffnung, die Vorteile von den beiden eben beschriebenen Welten auf einem System mit DROPS kombinieren zu können. Die Motivation meiner Arbeit war es, für dieses langfristige Ziel einen ersten Grundstein zu legen. Dazu war es meine Aufgabe, verschiedene Open-Source- Lösungen hinsichtlich ihrer Eignung als Echtzeit-Audioarchitektur für DROPS zu analysieren und die am besten geeignete auf L4Env zu portieren. Meine Wahl fiel dabei auf das in der Linux-Audio-Szene wohlbekannte Jack Audio Connection Kit (JACK). Desweiteren konnte ich in der Arbeit untersuchen, wie sich die JACK Audioarchitektur in ein globales Echtzeit-Scheduling --- z.B. eines von DROPS --- einbetten ließe, und schlage eine generische Methode dafür vor.

Several available free software audio solutions were analyzed, and Jackdmp—a C++ reimplementation of the renowned JACK Audio Connection Kit—was selected as the most appropriate solution for a real-time audio architecture on DROPS. The JACK sound architecture provides the lowest processing latency possible on a desktop computer for a given set of sound card parameters. It reduces the latency jitter caused by software to zero and synchronizes streams at sample accuracy. A real-time admission scheme for JACK clients is proposed. The execution time of different typical JACK clients was analyzed with measurements to validate the assumptions the proposal is based on, but also to gain further knowledge about their timing behavior. The measurements showed that the condition set by Paul Davis—the time to process a client must be a linear function of the buffer size—holds for all tested clients. Jackdmp was ported to DROPS. The developed design of the port and its implementation is documented here. Measurements showed that—although the real-time performance of the Linux kernel is continuously being improved in the mainline and on special external branches—DROPS can provide a signaling latency that is two times lower on average than the values that can be achieved on the same machine running with a low latency patched Linux kernel. Thus, it can be stated that DROPS is well-suited for real-time audio processing and that the pursued path to use it as the foundation of a truly real-time capable audio workstation should be followed. / Wenn man heute digitale Audiotechnik zum Aufnehmen oder Abmischen von Musik oder anderen Audiodaten verwenden möchte, steht man vor der Wahl, entweder auf eine sehr spezialisierte Hardwarelösung zurückzugreifen oder aber sich eines gewöhnlichen Desktopsystems mit entsprechender Audiosoftware zu bedienen. Der Vorteil eines Desktopsystems ist neben seinem deutlich niedrigeren Preis vor allem die Flexibilität. Bezüglich seines Echtzeitverhaltens bietet ein Computer mit einem Standard-Desktop-Betriebssystem aber bei weitem nicht dieselbe Verlässlichkeit einer spezialisierten Hardwarelösung oder analoger Technik. Die Architektur von DROPS --- mit dem echtzeitfähigen Fiasco- Mikrokern auf der einen Seite sowie der Unterstützung von Legacy-Anwendungen durch L4Linux auf der anderen Seite --- birgt die Hoffnung, die Vorteile von den beiden eben beschriebenen Welten auf einem System mit DROPS kombinieren zu können. Die Motivation meiner Arbeit war es, für dieses langfristige Ziel einen ersten Grundstein zu legen. Dazu war es meine Aufgabe, verschiedene Open-Source- Lösungen hinsichtlich ihrer Eignung als Echtzeit-Audioarchitektur für DROPS zu analysieren und die am besten geeignete auf L4Env zu portieren. Meine Wahl fiel dabei auf das in der Linux-Audio-Szene wohlbekannte Jack Audio Connection Kit (JACK). Desweiteren konnte ich in der Arbeit untersuchen, wie sich die JACK Audioarchitektur in ein globales Echtzeit-Scheduling --- z.B. eines von DROPS --- einbetten ließe, und schlage eine generische Methode dafür vor.

<strong>Background:</strong> Our laboratory identified ELTD1, an orphan GPCR belonging to the adhesion GPCR family (aGPCR), as a novel regulator of angiogenesis and a potential anti-cancer therapeutic target. ELTD1 is normally expressed in both endothelial cells and vascular smooth muscle cells and expression is significantly increased in the tumour vasculature. The aim of this project was to analyse ELTD1's function in endothelial cells and its role in breast cancer. <strong>Method:</strong> 62 sequenced vertebrate genomes were interrogated for ELTD1 conservation and domain alterations. A phylogenetic timetree was assembled to establish time estimates for ELTD1's evolution. After ELTD1 silencing, mRNA array profiling was performed on primary human umbilical vein endothelial cells (HUVECs) and validated with qPCR and confocal microscopy. ELTD1's signalling was investigated by applying the aGPCR ‘Stinger/tethered-agonist Hypothesis'. For this, truncated forms of ELTD1 and peptides analogous to the proposed tethered agonist region were designed. FRET-based 2^nd messenger (Cisbio IP-1;cAMP) and luciferase-reporter assays (NFAT; NFÎoB; SRE; SRF-RE; CREB) were performed to establish canonical GPCR activation. To further investigate ELTD1's role in endothelial cells, ELTD1 was stably overexpressed in HUVECS. Functional angiogenesis assays and mRNA array profiling were then performed. To investigate ELTD1 in breast cancer, a panel of cell lines representative of all molecular subtypes were screened using qPCR. Furthermore, an exploratory pilot study was performed on matched primary and regional nodal secondary breast cancers (n=43) which were stained for ELTD1 expression. Staining intensity was then scored and compared with relapse free survival and overall survival. <strong>Results:</strong> ELTD1 arose 435 million years ago (mya) in bony fish and is present in all subsequent vertebrates. ELTD1 has 3 evolutionary variants of which 2 are most common: one variant with 3 EGFs and a variant with 2 EGFs. Additionally, ELTD1 may be ancestral to members of aGPCR family 2. HUVEC mRNA expression profiling after ELTD1 silencing showed upregulation of the mitochondrial citrate transporter SLC25A1, and ACLY which converts cytoplasmic citrate to Acetyl CoA, feeding fatty acid and cholesterol synthesis, and acetylation. A review of lipid droplet (fatty acid and cholesterol) accumulation by confocal microscopy and flow cytometry (FACS) revealed no changes with ELTD1 silencing. Silencing was also shown to affect the Notch pathway (downregulating the Notch ligand JAG1 and target gene HES2; upregulating the Notch ligand DLL4) and inducing KIT, a mediator of haematopoietic (HSC) and endothelial stem cell (ESC) maintenance. Signalling experiments revealed that unlike other aGPCRs, ELTD1 does not couple to any canonical GPCR pathways (Gαi, Gαs, Gαq, Gα12/13). ELTD1 overexpression in HUVECS revealed that ELTD1 induces an endothelial tip cell phenotype by promoting sprouting and capillary formation, inhibiting lumen anastomoses in mature vessels and lowering proliferation rate. There was no effect on wound healing or adhesion to angiogenesis associated matrix components. Gene expression changes following ELTD1 overexpression included upregulation of angiogenesis associated ANTRX1 as well as JAG1 and downregulation of migration associated CCL15 as well as KIT and DLL4. In breast cancer, none of the representative breast cancer cell lines screened expressed ELTD1. ELTD1 breast cancer immunohistochemistry revealed higher levels of vascular ELTD1 staining intensity within the tumour stroma contrasted to normal stroma and expression within tumour epithelial cells. Additionally, ELTD1 expression in tumour vessels was differentially expressed between the primary breast cancer microenvironment and that of the matched regional node. Due to the small size of the pilot study population, survival comparisons between the various subgroups did not yield significant results. <strong>Conclusion:</strong> ELTD1 is a novel regulator of endothelial metabolism through its suppression of ACLY and the related citrate transporter SLC25A1. ELTD1 also represses KIT, which is known to mediate haematopoietic and endothelial progenitors stem cell maintenance, a possible mechanism through which endothelial cells maintain terminal endothelial differentiation. ELTD1 does not signal like other adhesion GPCRS with CTF and FL forms of ELTD1 not signalling canonically. Additionally, ELTD1 regulates various functions of endothelial cell behaviour and function, inducing an endothelial tip cell phenotype and is highly evolutionarily conserved. Lastly, ELTD1 is differentially expressed in tumour vessels between primary breast cancer and regional nodal metastases and is also expressed in a small subset of breast cancer cells in vivo despite no cancer cell lines expressing ELTD1. The pilot study investigating ELTD1 in the primary breast cancer and regional involved nodes will be followed up with a larger study including the investigation of ELTD1 in distant metastases.