Millimeter emission from protoplanetary disks : dust, cold gas, and relativistic electrons

Star formation occurs when a dense cloud of interstellar gas and dust gravitationally collapses. Rotation during this collapse leads naturally to the formation of a flattened circumstellar disk around the forming star. These disks are additionally known as protoplanetary disks because the orbiting circumstellar dust and cold gas represent the building blocks for planets. How long this material survives and how it evolves in this time will determine the propensity for (and the diversity of) planetary systems. This thesis is split into three parts that analyze different aspects of disk evolution and the circumstellar environment. In part one, we use observations at millimeter wavelengths to probe (and then model and compare) the dust and gas properties around low-mass Sun-like stars. We conclude that high-resolution spatial and spectral imaging of optically thinner molecular lines will provide the most robust description of the disk structure and evolution using future instrumentation. During these routine observations, we report recurring millimeter flares resulting in part two. We attribute this phenomenon to synchrotron emission from relativistic electrons trapped in the (colliding) magnetospheres of a young binary system. Finally, we present a microgravity experiment to probe the collisional growth mechanism for the first steps of planet formation.UBL - phd migration 201

Inhibition of cyclooxygenase 2 expression by diallyl sulfide on joint inflammation induced by urate crystal and IL-1β

SummaryObjectiveInvestigation of the effects of diallyl sulfide (DAS), a garlic sulfur compound, on joint tissue inflammatory responses induced by monosodium urate (MSU) crystals and interleukin-1β (IL-1β).DesignThe HIG-82 synovial cell line was used to establish the experimental model and DAS regime. Primary cultures of articular chondrocytes and synovial fibroblasts obtained from patients undergoing joint replacement for osteoarthritis were used in experimental studies. Cyclooxygenase (COX) expression following MSU crystal and IL-1β stimulation with/without DAS co-incubation was assessed by reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunocytochemistry and nuclear factor-kappa B (NF-κB) activation determined by electrophoretic mobility shift assay. Prostaglandin E2 (PGE2) production was measured by enzyme-linked immunosorbent assay (ELISA). DAS effects on COX gene expression in an MSU crystal-induced acute arthritis in rats were assessed by RT-PCR.ResultsMSU crystals upregulated COX-2 expression in HIG-82 cells and this was inhibited by co-incubation with DAS. DAS inhibited MSU crystal and IL-1β induced elevation of COX-2 expression in primary synovial cells and chondrocytes. Production of PGE2 induced by crystals was suppressed by DAS and celecoxib. MSU crystals had no effect on expression of COX-1 in synovial cells. NF-κB was activated by MSU crystals and this was blocked by DAS. Increased expression of COX-2 in synovium following intraarticular injection of MSU crystals in a rat model was inhibited by co-administration of DAS.ConclusionsDAS prevents IL-1β and MSU crystal induced COX-2 upregulation in synovial cells and chondrocytes and ameliorates crystal induced synovitis potentially through a mechanism involving NF-κB. Anti-inflammatory actions of DAS may be of value in treatment of joint inflammation

Differential cartilaginous tissue formation by human synovial membrane, fat pad, meniscus cells and articular chondrocytes

Objective: To identify an appropriate cell source for the generation of meniscus substitutes, among those which would be available by arthroscopy of injured knee joints. Methods: Human inner meniscus cells, fat pad cells (FPC), synovial membrane cells (SMC) and articular chondrocytes (AC) were expanded with or without specific growth factors (Transforming growth factor-betal, Fibroblast growth factor-2 and Plate let-derived growth factor bb, TFP) and then induced to form three-dimensional cartilaginous tissues in pellet cultures, or using a hyaluronan-based scaffold (Hyaff(R)-11), in culture or in nude mice. Human native menisci were assessed as reference. Results: Cell expansion with TFP enhanced glycosaminoglycan (GAG) deposition by all cell types (up to 4.1-fold) and messenger RNA expression of collagen type II by FPC and SMC (up to 472-fold) following pellet culture. In all models, tissues generated by AC contained the highest fractions of GAG (up to 1.9 were positively stained for collagen type II (specific of the inner avascular region of meniscus), type IV (mainly present in the outer vascularized region of meniscus) and types I, III and VI (common to both meniscus regions). Instead, inner meniscus, FPC and SMC developed tissues containing negligible GAG and no detectable collagen type II protein. Tissues generated by AC remained biochemically and phenotypically stable upon ectopic implantation. Conclusions: Under our experimental conditions, only AC generated tissues containing relevant amounts of GAG and with cell phenotypes compatible with those of the inner and outer meniscus regions. Instead, the other investigated cell sources formed tissues resembling only the outer region of meniscus. It remains to be determined whether grafts based on AC will have the ability to reach the complex structural and functional organization typical of meniscus tissue. (C) 2006 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights rese

The type 2 cannabinoid receptor regulates susceptibility to osteoarthritis in mice

SummaryObjectiveCannabinoid receptors and their ligands have been implicated in the regulation of various physiological processes but their role in osteoarthritis has not been investigated. The aim of this study was to evaluate the role of the type 2 cannabinoid receptor (Cnr2) in regulating susceptibility to osteoarthritis in mice.MethodsWe analysed the severity of knee osteoarthritis as assessed by the Osteoarthritis Research Society International (OARSI) scoring system in mice with targeted deletion of Cnr2 (Cnr2−/−) and wild type (WT) littermates. Studies were conducted in mice subjected to surgical destabilisation of the medial meniscus (DMM) and in those with spontaneous age-related osteoarthritis (OA).ResultsOsteoarthritis was more severe following DMM in the medial compartment of the knee in Cnr2−/− compared with WT mice (mean ± sem score = 4.9 ± 0.5 vs 3.6 ± 0.3; P = 0.017). Treatment of WT mice with the CB2-selective agonist HU308 following DMM reduced the severity of OA in the whole joint (HU308 = 8.4 ± 0.2 vs vehicle = 10.4 ± 0.6; P = 0.007). Spontaneous age related osteoarthritis was also more severe in the medial compartment of the knee in 12-month old Cnr2−/− mice compared with WT (5.6 ± 0.5 vs 3.5 ± 0.3, P = 0.008). Cultured articular chondrocytes from Cnr2−/− mice produced less proteoglycans in vitro than wild type chondrocytes.ConclusionThese studies demonstrate that the Cnr2 pathway plays a role in the pathophysiology of osteoarthritis in mice and shows that pharmacological activation of CB2 has a protective effect. Further studies of the role of cannabinoid receptors in the pathogenesis of osteoarthritis in man are warranted

Growth accounting in economic history:Findings, lessons and new directions

There is now a large volume of growth accounting estimates covering the long run experience of advanced countries. However, most of the studies in economic history are not based on state-of-the-art methods. There is a trade-off between maintaining international comparability and achieving the best results for individual countries. A one-size-fits-all approach will not always do justice to the variety of historical experiences since the conventional assumptions may sometimes be inappropriate. Nevertheless, growth-accounting studies have produced some eye-catching results which provide food for thought both for economic historians and for growth economists. These include (1) the finding that TFP growth was comparatively slow during the First Industrial Revolution, (2) Solow's famous conclusion that TFP growth accounted for 7/8ths of American labour-productivity growth was atypical, (3) the impact of new general-purpose technologies on growth typically takes a long time to materialize, ICT being the notable exception and (4) that capital-deepening was much more important relative to TFP growth in east Asian than in western European catch-up growth. Growth accounting is undoubtedly a valuable item in the cliometrician's toolkit. Nonetheless, we anticipate the introduction of more sophisticated methods and look forward to progress in understanding what explains marked differences in TFP performance

Millimeter emission from protoplanetary disks : dust, cold gas, and relativistic electrons

Star formation occurs when a dense cloud of interstellar gas and dust gravitationally collapses. Rotation during this collapse leads naturally to the formation of a flattened circumstellar disk around the forming star. These disks are additionally known as protoplanetary disks because the orbiting circumstellar dust and cold gas represent the building blocks for planets. How long this material survives and how it evolves in this time will determine the propensity for (and the diversity of) planetary systems. This thesis is split into three parts that analyze different aspects of disk evolution and the circumstellar environment. In part one, we use observations at millimeter wavelengths to probe (and then model and compare) the dust and gas properties around low-mass Sun-like stars. We conclude that high-resolution spatial and spectral imaging of optically thinner molecular lines will provide the most robust description of the disk structure and evolution using future instrumentation. During these routine observations, we report recurring millimeter flares resulting in part two. We attribute this phenomenon to synchrotron emission from relativistic electrons trapped in the (colliding) magnetospheres of a young binary system. Finally, we present a microgravity experiment to probe the collisional growth mechanism for the first steps of planet formation

Biomechanical influence of cartilage homeostasis in health and disease

There is an urgent demand for long term solutions to improve osteoarthritis treatments in the ageing population. There are drugs that control the pain but none that stop the progression of the disease in a safe and efficient way. Increased intervention efforts, augmented by early diagnosis and integrated biophysical therapies are therefore needed. Unfortunately, progress has been hampered due to the wide variety of experimental models which examine the effect of mechanical stimuli and inflammatory mediators on signal transduction pathways. Our understanding of the early mechanopathophysiology is poor, particularly the way in which mechanical stimuli influences cell function and regulates matrix synthesis. This makes it difficult to identify reliable targets and design new therapies. In addition, the effect of mechanical loading on matrix turnover is dependent on the nature of the mechanical stimulus. Accumulating evidence suggests that moderate mechanical loading helps to maintain cartilage integrity with a low turnover of matrix constituents. In contrast, nonphysiological mechanical signals are associated with increased cartilage damage and degenerative changes. This review will discuss the pathways regulated by compressive loading regimes and inflammatory signals in animal and in vitro 3D models. Identification of the chondroprotective pathways will reveal novel targets for osteoarthritis treatments.<br/