Resident tissue macrophages are an integral component of many tissues and are important in development, homeostasis and repair. Macrophages are present at sites of both pathologic bone deposition and loss, and can produce osteo-active factors. These observations link macrophages to bone disease, however their contribution to bone dynamics is poorly understood. The molecular and cellular mechanisms driving osteoblast differentiation, matrix deposition and mineralization in vivo are incompletely understood and this deficiency is translated to limited ability to clinically manipulate bone formation. The emerging understanding of the bi-directional interactions between the osseus and immune systems (osteoimmunology) provides a novel avenue to identify mechanisms involved in the regulation of bone formation. In this study, the presence and distribution of macrophages on bone surfaces was systematically analysed and their functional contribution to the bone microenvironment was investigated. Using immunohistochemistry a discrete population of mature resident tissue macrophages was demonstrated throughout resting murine osteal tissues, termed OsteoMacs. Utilising MacGreen mice (csf1r promoter drives eGFP transgene expression in macrophages and other myeloid cells), it was demonstrated that OsteoMacs were intercalated amongst other bone lining cells in both the endosteum and periosteum. OsteoMacs were TRAPneg in situ and had limited osteoclastogenic ability in vitro therefore they are unlikely to serve as the immediate physiologic osteoclast precursors in vivo. Microarray gene expression profiling demonstrated that macrophage gene expression was regulated in response to a characteristic feature of the bone microenvironment, elevated extracellular calcium. Quantitative PCR validated upregulation of sphingosine kinase 1, interleukin 1 receptor antagonise, progressive ankylosis, vascular endothelial growth factor c and dipepetidase 2 mRNA in response to elevated extracellular calcium, suggesting the potential roles of these genes in this unique niche. GNF Symatlas microarray and quantitative PCR demonstrated the expression of macrophage-restricted genes throughout a 21-day primary osteoblast differentiation time course, suggesting co-isolation of OsteoMacs with primary osteoblasts. Flow cytometry analysis confirmed that over all 15.9% of the digested primary calvarial cell preparations were OsteoMacs. Immunocytochemistry demonstrated that OsteoMacs persisted and expanded in standard 21-day osteoblast differentiation assays. Contrary to previous studies, we demonstrated it was the OsteoMacs, and not osteoblasts, within calvarial preparations that selectively detected patho-physiological concentrations of the bacterial product lipopolysaccharide (LPS). A protocol was developed to deplete OsteoMacs from calvarial digests to determine if their presence within these cultures facilitates osteoblast differentiation or function. OsteoMac removal did not affect expression of the early osteoblast differentiation marker genes collagen type I or alkaline phosphatase. However, OsteoMac removal significantly decreased gene expression of the osteoblast mineralisation marker osteocalcin and mineralisation function, assessed by von Kossa staining. Microarray gene expression profiling demonstrated that osteoblast enrichment had a broad impact on transcription within the culture, identifying both candidate OsteoMac marker genes as well as osteoblast expressed genes that are regulated by OsteoMacs. Potential OsteoMac-enriched candidate genes insulin-like growth factor a, dipepetidase 2, glycoprotein NMB, and macrophage expressed gene 1 as well as osteoblast-specific genes bone sialoprotein and thrombospondin 1 were selected based on their potential involvement in osteoblast function. In a transwell co-culture system of enriched osteoblasts and macrophages, it was demonstrated that macrophages were required for osteoblast mineralisation in response to the physiologic remodelling stimulus, elevated extracellular calcium. A blocking soluble receptor strategy provided evidence that this is mediated in a BMP-2 and -4 independent manner. To investigate the relevance of OsteoMacs to bone formation in vivo, immunohistochemistry staining for the mature tissue macrophage marker F4/80 was performed in long bone sections from rapidly growing mice. OsteoMacs were closely associated with areas of bone formation in situ, forming a distinctive canopy structure over mature cuboidal osteoblasts (collagen type I+, osteocalcin+) on endosteal cortical surfaces. Using adapted histomorphometic analysis, we determined that 77 ± 2.1% (n = 7) of the endosteal mature osteoblast surface was covered by the F4/80+ OsteoMac canopy. This observation suggested that OsteoMacs are optimally located to regulate osteoblast function in vivo. In summary, we have demonstrated that OsteoMacs are an integral component of bone lining tissues and play a novel role in bone dynamics through regulating osteoblast function. These observations implicate OsteoMacs, in addition to osteoclasts and osteoblasts, as principal participants in bone dynamics. Further delineation of OsteoMac functions is likely to provide new avenues for treating bone disease and assisting bone repair.

Hohenheim, Univ., Diss., 2007.

Magister Scientiae - MSc (Earth Science) / The complexity of the Platreef stratigraphy and the generic position of the Ni-Cu-PGE mineralisation is a challenge to prospecting and mining companies in the Northern Limb of the Bushveld Complex, partially, as a result of various floor rock interactions with the reef. Therefore, this study evaluated the effects of contact metasomatic fluids on the nature and style of PGE mineralisation as the main event leading to the complexity of the Platreef stratigraphy from the contact zone near the floor rock. Fifty samples from boreholes MO009 and MO019 drilled at Moordkopje 813 LR farm for Akanani Project by Lonmin Plc were used for this study. The mineralogy and geochemistry of the Platreef samples were studied and associated with their mineralisation occurrences. Major, minor and trace element contents were analysed by XRF analysis using fused beads, and PGE contents (Pt, Pd) in 11 samples were determined by Fire Assay.

This thesis deals with the areal survey of water resources in the area of Priessnitz baths, to search for natural medicinal sources and advanced data collection for evaluation radiohydrogeochemical situation of the area. The area of interest is situated in the Hrubý Jeseník mountains. Hydrogeologically it is a hard rock, which consists mainly of metamorphic rocks of the Bohemian Massif, the Moravian-Silesian region, presented as the methamorfic envelope of the desen group of Silenics. Altogether, 83 objects were recorded and many of them were visited repeatedly. Physical parameters (temperature, pH, Eh, conductivity), activity 222Rn and flow rate were measured. In addition, the chemical composition and tritium contents were determined on selected sources. Conductometry, thermometry, and probes for peloids were conducted. There was no source of water (or peloid) that would reach the criteria of a natural healing source (according to the Czech spa law). However, the overall hydrogeological and hydrochemical situation is quite complicated. Both the genesis of water and its chemical composition is highly heterogeneous and influenced by the heterogenical geological structure. Generally, we have distinguished three types of water according to the chemical composition. We also divided the water sources...

Located at an important intersect between orogenic Au deposits in Sweden’s Gold Line and volcanicmassive sulphide (VMS) deposits in the Skellefte Mining District, the Barsele area is of high interest.Currently, the Barsele deposit consists of the Norra VMS deposit and 3 intrusive-hosted orogenic Audeposits: Avan, Central, and Skiråsen which are hosted in a 1876 ± 10 Ma early orogenic granodiorite(Thomas, et al., 2019). The aim of this thesis is to create a structural and geological model of the Barsele area whilst improvingthe understanding of the structural controls on VMS and intrusive-hosted Au mineralisation in thearea. Furthermore, this thesis aims to highlight prospective areas for future study and targeting inhopes to aid mineral exploration in the region. Geological mapping has been carried out in an area ofaround 440km2, with emphasis on structural measurements. 381 outcrop observations and more than4200 structural features were recorded using a combination of traditional and digital mappingmethods, including the use of Field Move by Petroleum Experts. The area was chosen as part of AgnicoEagle, Sweden’s mineral exploration project. The region has been affected by two dominant, syn-metamorphic cleavage forming events. The eventsdefine the main phase of the Svecofennian Orogeny which has produced ubiquitous slaty cleavage, Ndirected thrusts, and steeply inclined axial surfaces throughout the region. The region is characterisedby important N-S displacements with sinistral movement along major N-S trending transfer faults. Theabsence of strike-slip shearing in D1 structures indicates that D1 deformation was dominantly coaxialin nature and developed due to SW-NE crustal shortening. Along with this, a major ESE-WNW-strikingshear zone is identified with an inferred syn-extensional (D1) origin. D2 involved fault inversion and reactivation of syn-extensional faults as reverse shear zones. E-Wtrending lineations along more brittle SSW-NNE striking shear zones inferred to indicate an E-Worientation for crustal shortening during D2. D3 caused reactivation of the N-S-striking high-strain zones with reverse kinematics. This reactivationof trending shear zones resulted in strain partitioning into N-S zones. D3 is manifested by broad, open,N-NE trending upright folds of bedding and S2 foliation. 1st, 2nd, and 3rd order D3 structures have beencharacterised and illustrated by combining a range of data including outcrop observations, regionalStereonets, magnetic anomaly maps, and other geophysical maps.

Per- and polyfluoroalkyl substances (PFAS) are a rising topic in the field of contaminated sites around the world, with destruction of these being an area in dire need of innovation. Previous experiments of destructive character have been proven efficient using boron doped diamond electrodes (BDD) in small scale electrochemical cells. Further need for experimentation on actual site conditions is needed to further evaluate the use of this method, as well as research on alternative electrode materials to reduce the cost of remediation.  In this study, four cells containing contaminated soil were used: one with BDD electrodes, one with iron electrodes and two control cells. The iron electrodes were used to investigate if a less costly electrode material could achieve any degree of PFAS degradation. For the experiment a soil from a previous firefighting training site where firefighting foam containing high amounts of PFAS (620                     g/kg soil concentration) was used. During the first phase of the experiment a constant flow of deionized water was added to the cells containing the soil, and porewater was sampled at the in- and outflow along with the soil porewater, on a weekly basis, to evaluate the distribution of PFAS to provide information about possible degradation taking place. The extent of degradation was not quantified. However, due to differences in the molecular composition of the analysed PFAS a trend where short-chain PFAS increase throughout the experiment in the BDD cell indicated that short-chain PFAS were generated, which is an expected by-product in electrochemical oxidation of PFAS. No short-chain PFAS generation was seen in the iron electrode cell, nor was there a high amount present in the control cell leachate.  Further, leaching of PFAS was more efficient in the control cells, while PFAS in the BDD and iron electrode cell were retained or leaching was slowed down, most likely due to the electrode interaction with PFAS in porewater.Additionally a second phase where water flow through was halted and the cells were run in a batch mode was conducted to see PFAS degradation in stagnant conditions over time. In the stagnant cell in the second phase, only low PFAS concentrations in porewater were recorded while no degradation was established.  Further, fluoride analysis recorded F- concentrations in the range of    M, where the limit of detection was   M, which limited the confirmation of PFAS mineralisation in soil.  From this study insight of the difficulties with soil treatment of PFAS using electrokinetic method was highlighted, with sampling being a key factor in the accuracy of the result. For a more accurate establishment of the degradation experiments in a closed cell, with more extensive sampling throughout the entire column would be necessary. This is needed to generate a clearer picture of changes in PFAS concentration in the soil from the presumed degradation, coupled with a mass balance to provide the fate of PFAS in this type of setup.

Titanium alloys are frequently used in the medical field as bone implant materials due to their excellent biocompatibility and corrosion resistance. Yet, their elastic modulus is usually significantly higher than the one of bone, which can lead to a reduction of bone tissue at the implant site. The current research is therefore focused on the development of highly porous implants, which promise a low elastic modulus close to that of bone, an enhanced bone ingrowth and an improved vascularization. However, the appropriate pore size for an optimal osseointegration still remains unclear. To that end, a transparent tubular microsystem is developed to mimic such a porous microenvironment in order to study single bone cell behavior and early bone formation processes. The system is fabricated out of an implant material (β-stabilized Ti-45Nb (wt%)). It is demonstrated that the bulk material composition, which is consisting of a high Nb content, can be closely transferred to transparent thin films by using reactive sputtering. These films then self-assemble into tubular microscaffolds (TS) with a diameter range between 10-42 μm. Biological studies are subsequently performed to investigate the response (e.g. cell adhesion, migration, osteogenic differentiation) of human Mesenchymal Stem Cells (MSC) to the TS. It is shown that cells form fewer, more diffuse focal adhesion points inside the TS compared to a planar surface and the spatial confinement causes a switch in between amoeboid and mesenchymal migration modes. In addition, it is demonstrated that cells can survive inside the TS for at least 12 days during osteogenic differentiation and partly mineralize the TS interior. The observed mineralization process is furthermore linked to the formation of hydroxyapatite crystals inside dead cells bodies, which leads to a crystallization over time. All in all, the TS platform offers an easy way to identify key factors of bone cell-implant interactions that can be used to improve the biocompatibility of the bone-implant interface in the future.

No description available.

Dental enamel is an excellent example of a highly mineralised tissue, composed of hierarchically organised apatite mineral. This unique organisation gives enamel superior mechanical properties. However, when mature, enamel becomes acellular and unable to repair itself during traumatic or carious damage. The lack of self-repair requires dental intervention, where the common treatment of decayed enamel is to remove the affected and healthy tissue, and replace with restorative materials. The restorative materials, currently used, can cause further complications in the form of secondary caries or failure due to thermal and mechanical property mismatch with enamel. Problems associated with current restorative materials have driven researchers to explore biomimetic enamel treatment routes. To mimic the natural enamel formation, we can explore how proteins can guide mineral growth, in order to form enamel-like ordered mineral structures. In this thesis, the use of a synthetic, recombinant protein called an elastin-like protein (ELP) containing the analogue of the N-terminal of statherin (STNA15) was under investigation. Statherin is a protein present in saliva that is said to aid in the remineralisation of enamel. ELP with STNA15 (STNA15-ELP) has already shown promise in biomimetic mineralisation. This thesis investigated how conformation and structure of STNA15-ELP can be affected and manipulated by different chemical environments, surface constraint and crosslinking. The STNA15-ELP characteristics were related to formation of fluorapatite. STNA15-ELP conformation changed due to presence if salts in solution and whether or not it was constrained. We linked the conformational changes within STNA15-ELP, in solution versus on the surface, to two different routes of mineral formation. FAp formed in an uncontrolled manner with free STNA15-ELP. Ordered FAp formed via a precursor when STNA15-ELP was constrained on a surface. This work leads to an understanding of biomimetic mineralisation using STNA15-ELP. This information can aid in the design of novel biomimetic, enamel-like therapeutics.

L'altération hydrothermale du manteau lithosphérique dans les dorsales médio-océaniques fournit un mécanisme de transfert de chaleur et de masse entre la terre profonde et l'océan recouvrant. Le manteau lithosphérique est constituée de roches ultramafiques, également appelées péridotites. Ils comprennent plus de 70% d'olivine, de pyroxènes associés et de phases minérales mineures. La percolation de l'eau de mer dans le socle ultramafique produit l'altération de l'olivine et des pyroxènes en serpentine par le processus de serpentinisation et il est associé à des réactions d'oxydation et de carbonatation (lorsque le CO2 est présent dans le fluide). Le processus de serpentinisation présente un intérêt particulier pour la production de H2, le stockage du CO2, le développement de la vie et la production de gisements de minerai économiquement intéressants concentrés dans les fumeroles hydrothermaux. La durabilité et l'efficacité des réactions nécessitent la pénétration et le renouvellement des fluides à l'interface fluide-minéral. Les failles et les fractures des détachements océaniques sont les zones hautement perméables qui permettent à l'eau de mer de pénétrer profondément dans le manteau lithosphérique. Cependant, le processus de serpentinisation conduit à la précipitation de minéraux de faible densité qui peuvent remplir le réseau poreux, colmatant les chemins d'écoulement qui peuvent modifier les propriétés hydrodynamiques et la réactivité des roches réagi.Ces travaux de thèse visent à améliorer la compréhension des effets en retour des réactions sur les propriétés hydrodynamique du milieu dans les zones hautement perméables au cours des premières étapes de l'altération du socle ultramafique. Il se concentre en particulier sur les changements de texture et les réactions chimiques des roches ultramafiques en évaluant les effets du (i) débit et (ii) des fluides salins riches en CO2. Deux séries d'expériences de percolation réactive ont été réalisées à T = 170-190°C et P = 25MPa. La première série d'expériences consistait à injecter de l'eau de mer dans des échantillonnes de poudre d'olivine compressé sur une large gamme de débits constants. La tomographie par rayons X de haute résolution a été acquise avant et après l'expérience avec des débits élevés; afin d'évaluer les changements dans la microstructure de la roche lors de la réaction de serpentinisation. La deuxième série d'expériences consistait à injecter des fluides salins riches en CO2 dans des échantillonnes de péridotite fracturés mécaniquement.Les résultats ont permis de différencier: (1) un contrôle du débit du flux à l'échelle du pore peut contrôler la composition du fluide local et le développement de différents chemins de réaction à l'échelle de l'échantillon. (2) Le développement de différentes chemins réactifs et les changements de texture dans la roche dépend de la concentration de CO2 dissous dans la solution. (3) La formation de minéraux carbonatés (MgCO3) peut stocker du CO2 sous forme stable de minéral à long terme. (4) Un contrôle de la concentration de CO2 dissous dans le fluide et du réseau de fractures peut améliorer / limiter l'efficacité du stockage de CO2 dans les réservoirs de péridotite fracturés.Ces nouvelles données suggèrent un contrôle complexe de la structure des roches ultramafiques dans le processus de serpentinisation et fournissent de nouvelles perspectives pour le stockage potentiel du CO2 dans les réservoirs fracturés à la péridotite. / The hydrothermal alteration of the mantle lithosphere at mid-ocean ridges provides a mechanism for transferring heat and mass between the deep Earth and the overlaying ocean. The mantle lithosphere is constituted by ultramafic rocks, also called Peridotites. They comprise more than 70% of olivine, associated pyroxenes and minor mineral phases. The percolation of seawater into the ultramafic basement produces the alteration of olivine and pyroxenes to serpentine through the so-called serpentinization process and is associated to oxidation and carbonation reactions, the later when CO2 is present. The serpentinization process has special interest on H2 production, CO2 storage, development of life, and the production of economically valuable ore-deposits concentrated at hydrothermal vents. The sustainability and efficiency of the reactions requires penetration and renewal of fluids at the mineral-fluid interface. Oceanic detachment faults and fractures are the highly permeable zones allowing seawater derived fluids to penetrate deeply into the mantle lithosphere. However, the serpentinization process lead to the precipitation of low density minerals that can fill the porous network, clogging flow paths efficiently that may in turn modify the hydrodynamic properties and the reactivity of the reacted rocks.This PhD thesis aims at better understanding the feedback effects of chemical reactions on the hydrodynamic rock properties occurred on highly permeable zones during the earliest stages of alteration of the ultramafic basement. It focuses in particular on the changes in texture and chemical reaction paths of ultramafic rocks by assessing the effects of (i) flow rate and (ii) CO2-rich saline fluids. Two suite of reactive percolation experiments were performed at T=170-190°C and P=25MPa. The first suite of experiments consisted in injecting artificial seawater into porous compressed olivine powder cores over a wide range of constant flow rates. X-Ray µ-tomography of high resolution was acquired before and after the experiment run with high flow rates; in order to evaluate the micro-structural changes of the rock occurred during the serpentinization reaction. The second suite of experiments consisted in injecting CO2-rich saline fluids into peridotite cores mechanically fractured.The results allowed us to differentiate: (1) That, a control of flow infiltration rate at the pore-scale can control the local fluid compositions and the development of different reaction paths at the sample-scale. (2) The development of different reaction paths and textural changes in the rock depends on the concentration of CO2 dissolved in solution. (3) The formation of carbonate minerals (MgCO3) can store CO2 in a form of stable mineral at long-term. (4) A control of the concentration of dissolved CO2(g) and the fracture network can enhance/limit the efficiency of CO2-storage in peridotite fractured reservoirs.These new supporting data suggest a complex control of the structure of the ultramafic rocks in serpentinization process and provides new insights for the potential CO2-storage in peridotite fractured reservoirs.