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This work presents mathematical and computational approaches to cover various aspects of metabolic network modelling, especially regarding the limited availability of detailed kinetic knowledge on reaction rates. It is shown that precise mathematical formulations of problems are needed i) to find appropriate and, if possible, efficient algorithms to solve them, and ii) to determine the quality of the found approximate solutions. Furthermore, some means are introduced to gain insights on dynamic properties of metabolic networks either directly from the network structure or by additionally incorporating steady-state information. Finally, an approach to identify key reactions in a metabolic networks is introduced, which helps to develop simple yet useful kinetic models. The rise of novel techniques renders genome sequencing increasingly fast and cheap. In the near future, this will allow to analyze biological networks not only for species but also for individuals. Hence, automatic reconstruction of metabolic networks provides itself as a means for evaluating this huge amount of experimental data. A mathematical formulation as an optimization problem is presented, taking into account existing knowledge and experimental data as well as the probabilistic predictions of various bioinformatical methods. The reconstructed networks are optimized for having large connected components of high accuracy, hence avoiding fragmentation into small isolated subnetworks. The usefulness of this formalism is exemplified on the reconstruction of the sucrose biosynthesis pathway in Chlamydomonas reinhardtii. The problem is shown to be computationally demanding and therefore necessitates efficient approximation algorithms. The problem of minimal nutrient requirements for genome-scale metabolic networks is analyzed. Given a metabolic network and a set of target metabolites, the inverse scope problem has as it objective determining a minimal set of metabolites that have to be provided in order to produce the target metabolites. These target metabolites might stem from experimental measurements and therefore are known to be produced by the metabolic network under study, or are given as the desired end-products of a biotechological application. The inverse scope problem is shown to be computationally hard to solve. However, I assume that the complexity strongly depends on the number of directed cycles within the metabolic network. This might guide the development of efficient approximation algorithms. Assuming mass-action kinetics, chemical reaction network theory (CRNT) allows for eliciting conclusions about multistability directly from the structure of metabolic networks. Although CRNT is based on mass-action kinetics originally, it is shown how to incorporate further reaction schemes by emulating molecular enzyme mechanisms. CRNT is used to compare several models of the Calvin cycle, which differ in size and level of abstraction. Definite results are obtained for small models, but the available set of theorems and algorithms provided by CRNT can not be applied to larger models due to the computational limitations of the currently available implementations of the provided algorithms. Given the stoichiometry of a metabolic network together with steady-state fluxes and concentrations, structural kinetic modelling allows to analyze the dynamic behavior of the metabolic network, even if the explicit rate equations are not known. In particular, this sampling approach is used to study the stabilizing effects of allosteric regulation in a model of human erythrocytes. Furthermore, the reactions of that model can be ranked according to their impact on stability of the steady state. The most important reactions in that respect are identified as hexokinase, phosphofructokinase and pyruvate kinase, which are known to be highly regulated and almost irreversible. Kinetic modelling approaches using standard rate equations are compared and evaluated against reference models for erythrocytes and hepatocytes. The results from this simplified kinetic models can simulate acceptably the temporal behavior for small changes around a given steady state, but fail to capture important characteristics for larger changes. The aforementioned approach to rank reactions according to their influence on stability is used to identify a small number of key reactions. These reactions are modelled in detail, including knowledge about allosteric regulation, while all other reactions were still described by simplified reaction rates. These so-called hybrid models can capture the characteristics of the reference models significantly better than the simplified models alone. The resulting hybrid models might serve as a good starting point for kinetic modelling of genome-scale metabolic networks, as they provide reasonable results in the absence of experimental data, regarding, for instance, allosteric regulations, for a vast majority of enzymatic reactions.
The development of rural areas concerning food security, sustainability and social-economic stability is key issue to the globalized community. Regarding the current state of climatic change, especially semi-arid regions in uenced by monsoon or El Niño are prone to extreme weather events. Droughts, ooding, erosion, degradation of soils and water quality and deserti cation are some of the common impacts. State of the art in hydrologic environmental modeling is generally operating under a reductionist paradigm (Sivapalan 2005). Even an enormous quantity of process-oriented models exists, we fail in due reproduction of complexly interacting processes in their effective scale in the space-time-continuum, as they are described through deterministic small-scale process theories (e.g. Beven 2002). Yet large amounts of parameters - with partly doubtful physical expression - and input data are needed. In contradiction to that most soft information about patterns and organizing principles cannot be employed (Seibert and McDonnell 2002). For an analysis of possible strategies on the one hand towards integrated hydrologic modeling as decision support and on the other hand for sustainable land use development the 512 km2 large catchment of the Mod river in Jhabua, Madhya Pradesh, India has been chosen. It is characterized by a setting of common problems of peripheral rural semi-arid human-eco-systems with intensive agriculture, deforestation, droughts and general hardship for the people. Scarce data and missing gauges are adding to the requirements of data acquisition and process description. The study at hand presents a methodical framework to combine eld scale data analysis and remote sensing for the setup of a database focusing plausibility over strict data accuracy. The catena-based hydrologic model WASA (Güntner 2002) employes this database. It is expanded by a routine for crop development simulation after the de Wit approach (e.g. in Bouman et al. 1996). For its application as decision support system an agentbased land use algorithm is developed which decides on base of site speci cations and certain constraints (like maximum pro t or best local adaptation) about the cropping. The new model is employed to analyze (some) land use strategies. Not anticipated and a priori de ned scenarios will account for the realization of the model but the interactions within the system. This study points out possible approaches to enhance the situation in the catchment. It also approaches central questions of ways towards due integrated hydrological modeling on catchment scale for ungauged conditions and to overcome current paradigms.
The Andes are a ~7000 km long N-S trending mountain range developed along the South American western continental margin. Driven by the subduction of the oceanic Nazca plate beneath the continental South American plate, the formation of the northern and central parts of the orogen is a type case for a non-collisional orogeny. In the southern Central Andes (SCA, 29°S-39°S), the oceanic plate changes the subduction angle between 33°S and 35°S from almost horizontal (< 5° dip) in the north to a steeper angle (~30° dip) in the south. This sector of the Andes also displays remarkable along- and across- strike variations of the tectonic deformation patterns. These include a systematic decrease of topographic elevation, of crustal shortening and foreland and orogenic width, as well as an alternation of the foreland deformation style between thick-skinned and thin-skinned recorded along- and across the strike of the subduction zone. Moreover, the SCA are a very seismically active region. The continental plate is characterized by a relatively shallow seismicity (< 30 km depth) which is mainly focussed at the transition from the orogen to the lowland areas of the foreland and the forearc; in contrast, deeper seismicity occurs below the interiors of the northern foreland. Additionally, frequent seismicity is also recorded in the shallow parts of the oceanic plate and in a sector of the flat slab segment between 31°S and 33°S. The observed spatial heterogeneity in tectonic and seismic deformation in the SCA has been attributed to multiple causes, including variations in sediment thickness, the presence of inherited structures and changes in the subduction angle of the oceanic slab. However, there is no study that inquired the relationship between the long-term rheological configuration of the SCA and the spatial deformation patterns. Moreover, the effects of the density and thickness configuration of the continental plate and of variations in the slab dip angle in the rheological state of the lithosphere have been not thoroughly investigated yet. Since rheology depends on composition, pressure and temperature, a detailed characterization of the compositional, structural and thermal fields of the lithosphere is needed. Therefore, by using multiple geophysical approaches and data sources, I constructed the following 3D models of the SCA lithosphere: (i) a seismically-constrained structural and density model that was tested against the gravity field; (ii) a thermal model integrating the conversion of mantle shear-wave velocities to temperature with steady-state conductive calculations in the uppermost lithosphere (< 50 km depth), validated by temperature and heat-flow measurements; and (iii) a rheological model of the long-term lithospheric strength using as input the previously-generated models.
The results of this dissertation indicate that the present-day thermal and rheological fields of the SCA are controlled by different mechanisms at different depths. At shallow depths (< 50 km), the thermomechanical field is modulated by the heterogeneous composition of the continental lithosphere. The overprint of the oceanic slab is detectable where the oceanic plate is shallow (< 85 km depth) and the radiogenic crust is thin, resulting in overall lower temperatures and higher strength compared to regions where the slab is steep and the radiogenic crust is thick. At depths > 50 km, largest temperatures variations occur where the descending slab is detected, which implies that the deep thermal field is mainly affected by the slab dip geometry.
The outcomes of this thesis suggests that long-term thermomechanical state of the lithosphere influences the spatial distribution of seismic deformation. Most of the seismicity within the continental plate occurs above the modelled transition from brittle to ductile conditions. Additionally, there is a spatial correlation between the location of these events and the transition from the mechanically strong domains of the forearc and foreland to the weak domain of the orogen. In contrast, seismicity within the oceanic plate is also detected where long-term ductile conditions are expected. I therefore analysed the possible influence of additional mechanisms triggering these earthquakes, including the compaction of sediments in the subduction interface and dehydration reactions in the slab. To that aim, I carried out a qualitative analysis of the state of hydration in the mantle using the ratio between compressional- and shear-wave velocity (vp/vs ratio) from a previous seismic tomography. The results from this analysis indicate that the majority of the seismicity spatially correlates with hydrated areas of the slab and overlying continental mantle, with the exception of the cluster within the flat slab segment. In this region, earthquakes are likely triggered by flexural processes where the slab changes from a flat to a steep subduction angle.
First-order variations in the observed tectonic patterns also seem to be influenced by the thermomechanical configuration of the lithosphere. The mechanically strong domains of the forearc and foreland, due to their resistance to deformation, display smaller amounts of shortening than the relatively weak orogenic domain. In addition, the structural and thermomechanical characteristics modelled in this dissertation confirm previous analyses from geodynamic models pointing to the control of the observed heterogeneities in the orogen and foreland deformation style. These characteristics include the lithospheric and crustal thickness, the presence of weak sediments and the variations in gravitational potential energy.
Specific conditions occur in the cold and strong northern foreland, which is characterized by active seismicity and thick-skinned structures, although the modelled crustal strength exceeds the typical values of externally-applied tectonic stresses. The additional mechanisms that could explain the strain localization in a region that should resist deformation are: (i) increased tectonic forces coming from the steepening of the slab and (ii) enhanced weakening along inherited structures from pre-Andean deformation events. Finally, the thermomechanical conditions of this sector of the foreland could be a key factor influencing the preservation of the flat subduction angle at these latitudes of the SCA.
A huge number of applications require coherent radiation in the visible spectral range. Since diode lasers are very compact and efficient light sources, there exists a great interest to cover these applications with diode laser emission. Despite modern band gap engineering not all wavelengths can be accessed with diode laser radiation. Especially in the visible spectral range between 480 nm and 630 nm no emission from diode lasers is available, yet. Nonlinear frequency conversion of near-infrared radiation is a common way to generate coherent emission in the visible spectral range. However, radiation with extraordinary spatial temporal and spectral quality is required to pump frequency conversion. Broad area (BA) diode lasers are reliable high power light sources in the near-infrared spectral range. They belong to the most efficient coherent light sources with electro-optical efficiencies of more than 70%. Standard BA lasers are not suitable as pump lasers for frequency conversion because of their poor beam quality and spectral properties. For this purpose, tapered lasers and diode lasers with Bragg gratings are utilized. However, these new diode laser structures demand for additional manufacturing and assembling steps that makes their processing challenging and expensive. An alternative to BA diode lasers is the stripe-array architecture. The emitting area of a stripe-array diode laser is comparable to a BA device and the manufacturing of these arrays requires only one additional process step. Such a stripe-array consists of several narrow striped emitters realized with close proximity. Due to the overlap of the fields of neighboring emitters or the presence of leaky waves, a strong coupling between the emitters exists. As a consequence, the emission of such an array is characterized by a so called supermode. However, for the free running stripe-array mode competition between several supermodes occurs because of the lack of wavelength stabilization. This leads to power fluctuations, spectral instabilities and poor beam quality. Thus, it was necessary to study the emission properties of those stripe-arrays to find new concepts to realize an external synchronization of the emitters. The aim was to achieve stable longitudinal and transversal single mode operation with high output powers giving a brightness sufficient for efficient nonlinear frequency conversion. For this purpose a comprehensive analysis of the stripe-array devices was done here. The physical effects that are the origin of the emission characteristics were investigated theoretically and experimentally. In this context numerical models could be verified and extended. A good agreement between simulation and experiment was observed. One way to stabilize a specific supermode of an array is to operate it in an external cavity. Based on mathematical simulations and experimental work, it was possible to design novel external cavities to select a specific supermode and stabilize all emitters of the array at the same wavelength. This resulted in stable emission with 1 W output power, a narrow bandwidth in the range of 2 MHz and a very good beam quality with M²<1.5. This is a new level of brightness and brilliance compared to other BA and stripe-array diode laser systems. The emission from this external cavity diode laser (ECDL) satisfied the requirements for nonlinear frequency conversion. Furthermore, a huge improvement to existing concepts was made. In the next step newly available periodically poled crystals were used for second harmonic generation (SHG) in single pass setups. With the stripe-array ECDL as pump source, more than 140 mW of coherent radiation at 488 nm could be generated with a very high opto-optical conversion efficiency. The generated blue light had very good transversal and longitudinal properties and could be used to generate biphotons by parametric down-conversion. This was feasible because of the improvement made with the infrared stripe-array diode lasers due to the development of new physical concepts.
Structuring process models
(2012)
One can fairly adopt the ideas of Donald E. Knuth to conclude that process modeling is both a science and an art. Process modeling does have an aesthetic sense. Similar to composing an opera or writing a novel, process modeling is carried out by humans who undergo creative practices when engineering a process model. Therefore, the very same process can be modeled in a myriad number of ways. Once modeled, processes can be analyzed by employing scientific methods. Usually, process models are formalized as directed graphs, with nodes representing tasks and decisions, and directed arcs describing temporal constraints between the nodes. Common process definition languages, such as Business Process Model and Notation (BPMN) and Event-driven Process Chain (EPC) allow process analysts to define models with arbitrary complex topologies. The absence of structural constraints supports creativity and productivity, as there is no need to force ideas into a limited amount of available structural patterns. Nevertheless, it is often preferable that models follow certain structural rules. A well-known structural property of process models is (well-)structuredness. A process model is (well-)structured if and only if every node with multiple outgoing arcs (a split) has a corresponding node with multiple incoming arcs (a join), and vice versa, such that the set of nodes between the split and the join induces a single-entry-single-exit (SESE) region; otherwise the process model is unstructured. The motivations for well-structured process models are manifold: (i) Well-structured process models are easier to layout for visual representation as their formalizations are planar graphs. (ii) Well-structured process models are easier to comprehend by humans. (iii) Well-structured process models tend to have fewer errors than unstructured ones and it is less probable to introduce new errors when modifying a well-structured process model. (iv) Well-structured process models are better suited for analysis with many existing formal techniques applicable only for well-structured process models. (v) Well-structured process models are better suited for efficient execution and optimization, e.g., when discovering independent regions of a process model that can be executed concurrently. Consequently, there are process modeling languages that encourage well-structured modeling, e.g., Business Process Execution Language (BPEL) and ADEPT. However, the well-structured process modeling implies some limitations: (i) There exist processes that cannot be formalized as well-structured process models. (ii) There exist processes that when formalized as well-structured process models require a considerable duplication of modeling constructs. Rather than expecting well-structured modeling from start, we advocate for the absence of structural constraints when modeling. Afterwards, automated methods can suggest, upon request and whenever possible, alternative formalizations that are "better" structured, preferably well-structured. In this thesis, we study the problem of automatically transforming process models into equivalent well-structured models. The developed transformations are performed under a strong notion of behavioral equivalence which preserves concurrency. The findings are implemented in a tool, which is publicly available.
The deformation style of mountain belts is greatly influenced by the upper plate architecture created during preceding deformation phases. The Mesozoic Salta Rift extensional phase has created a dominant structural and lithological framework that controls Cenozoic deformation and exhumation patterns in the Central Andes. Studying the nature of these pre-existing anisotropies is a key to understanding the spatiotemporal distribution of exhumation and its controlling factors. The Eastern Cordillera in particular, has a structural grain that is in part controlled by Salta Rift structures and their orientation relative to Andean shortening. As a result, there are areas in which Andean deformation prevails and areas where the influence of the Salta Rift is the main control on deformation patterns.
Between 23 and 24°S, lithological and structural heterogeneities imposed by the Lomas de Olmedo sub-basin (Salta Rift basin) affect the development of the Eastern Cordillera fold-and-thrust belt. The inverted northern margin of the sub-basin now forms the southern boundary of the intermontane Cianzo basin. The former western margin of the sub-basin is located at the confluence of the Subandean Zone, the Santa Barbara System and the Eastern Cordillera. Here, the Salta Rift basin architecture is responsible for the distribution of these morphotectonic provinces. In this study we use a multi-method approach consisting of low-temperature (U-Th-Sm)/He and apatite fission track thermochronology, detrital geochronology, structural and sedimentological analyses to investigate the Mesozoic structural inheritance of the Lomas de Olmedo sub-basin and Cenozoic exhumation patterns.
Characterization of the extension-related Tacurú Group as an intermediate succession between Paleozoic basement and the syn-rift infill of the Lomas de Olmedo sub-basin reveals a Jurassic maximum depositional age. Zircon (U-Th-Sm)/He cooling ages record a pre-Cretaceous onset of exhumation for the rift shoulders in the northern part of the sub-basin, whereas the western shoulder shows a more recent onset (140–115 Ma). Variations in the sedimentary thickness of syn- and post-rift strata document the evolution of accommodation space in the sub-basin. While the thickness of syn-rift strata increases rapidly toward the northern basin margin, the post-rift strata thickness decreases toward the margin and forms a condensed section on the rift shoulder.
Inversion of Salta Rift structures commenced between the late Oligocene and Miocene (24–15 Ma) in the ranges surrounding the Cianzo basin. The eastern and western limbs of the Cianzo syncline, located in the hanging wall of the basin-bounding Hornocal fault, show diachronous exhumation. At the same time, western fault blocks of Tilcara Range, south of the Cianzo basin, began exhuming in the late Oligocene to early Miocene (26–16 Ma). Eastward propagation to the frontal thrust and to the Paleozoic strata east of the Tilcara Range occurred in the middle Miocene (22–10 Ma) and the late Miocene–early Pliocene (10–4 Ma), respectively.
Predator-prey interactions provide central links in food webs. These interaction are directly or indirectly impacted by a number of factors. These factors range from physiological characteristics of individual organisms, over specifics of their interaction to impacts of the environment. They may generate the potential for the application of different strategies by predators and prey. Within this thesis, I modelled predator-prey interactions and investigated a broad range of different factors driving the application of certain strategies, that affect the individuals or their populations. In doing so, I focused on phytoplankton-zooplankton systems as established model systems of predator-prey interactions.
At the level of predator physiology I proposed, and partly confirmed, adaptations to fluctuating availability of co-limiting nutrients as beneficial strategies. These may allow to store ingested nutrients or to regulate the effort put into nutrient assimilation. We found that these two strategies are beneficial at different fluctuation frequencies of the nutrients, but may positively interact at intermediate frequencies. The corresponding experiments supported our model results. We found that the temporal structure of nutrient fluctuations indeed has strong effects on the juvenile somatic growth rate of {\itshape Daphnia}.
Predator colimitation by energy and essential biochemical nutrients gave rise to another physiological strategy. High-quality prey species may render themselves indispensable in a scenario of predator-mediated coexistence by being the only source of essential biochemical nutrients, such as cholesterol. Thereby, the high-quality prey may even compensate for a lacking defense and ensure its persistence in competition with other more defended prey species.
We found a similar effect in a model where algae and bacteria compete for nutrients. Now, being the only source of a compound that is required by the competitor (bacteria) prevented the competitive exclusion of the algae. In this case, the essential compounds were the organic carbon provided by the algae. Here again, being indispensable served as a prey strategy that ensured its coexistence.
The latter scenario also gave rise to the application of the two metabolic strategies of autotrophy and heterotrophy by algae and bacteria, respectively. We found that their coexistence allowed the recycling of resources in a microbial loop that would otherwise be lost. Instead, these resources were made available to higher trophic levels, increasing the trophic transfer efficiency in food webs.
The predation process comprises the next higher level of factors shaping the predator-prey interaction, besides these factors that originated from the functioning or composition of individuals. Here, I focused on defensive mechanisms and investigated multiple scenarios of static or adaptive combinations of prey defense and predator offense. I confirmed and extended earlier reports on the coexistence-promoting effects of partially lower palatability of the prey community. When bacteria and algae are coexisting, a higher palatability of bacteria may increase the average predator biomass, with the side effect of making the population dynamics more regular. This may facilitate experimental investigations and interpretations. If defense and offense are adaptive, this allows organisms to maximize their growth rate. Besides this fitness-enhancing effect, I found that co-adaptation may provide the predator-prey system with the flexibility to buffer external perturbations.
On top of these rather internal factors, environmental drivers also affect predator-prey interactions. I showed that environmental nutrient fluctuations may create a spatio-temporal resource heterogeneity that selects for different predator strategies. I hypothesized that this might favour either storage or acclimation specialists, depending on the frequency of the environmental fluctuations.
We found that many of these factors promote the coexistence of different strategies and may therefore support and sustain biodiversity. Thus, they might be relevant for the maintenance of crucial ecosystem functions that also affect us humans. Besides this, the richness of factors that impact predator-prey interactions might explain why so many species, especially in the planktonic regime, are able to coexist.
At present, carbon sequestration in terrestrial ecosystems slows the growth rate of atmospheric CO2 concentrations, and thereby reduces the impact of anthropogenic fossil fuel emissions on the climate system. Changes in climate and land use affect terrestrial biosphere structure and functioning at present, and will likely impact on the terrestrial carbon balance during the coming decades - potentially providing a positive feedback to the climate system due to soil carbon releases under a warmer climate. Quantifying changes, and the associated uncertainties, in regional terrestrial carbon budgets resulting from these effects is relevant for the scientific understanding of the Earth system and for long-term climate mitigation strategies. A model describing the relevant processes that govern the terrestrial carbon cycle is a necessary tool to project regional carbon budgets into the future. This study (1) provides an extensive evaluation of the parameter-based uncertainty in model results of a leading terrestrial biosphere model, the Lund-Potsdam-Jena Dynamic Global Vegetation Model (LPJ-DGVM), against a range of observations and under climate change, thereby complementing existing studies on other aspects of model uncertainty; (2) evaluates different hypotheses to explain the age-related decline in forest growth, both from theoretical and experimental evidence, and introduces the most promising hypothesis into the model; (3) demonstrates how forest statistics can be successfully integrated with process-based modelling to provide long-term constraints on regional-scale forest carbon budget estimates for a European forest case-study; and (4) elucidates the combined effects of land-use and climate changes on the present-day and future terrestrial carbon balance over Europe for four illustrative scenarios - implemented by four general circulation models - using a comprehensive description of different land-use types within the framework of LPJ-DGVM. This study presents a way to assess and reduce uncertainty in process-based terrestrial carbon estimates on a regional scale. The results of this study demonstrate that simulated present-day land-atmosphere carbon fluxes are relatively well constrained, despite considerable uncertainty in modelled net primary production. Process-based terrestrial modelling and forest statistics are successfully combined to improve model-based estimates of vegetation carbon stocks and their change over time. Application of the advanced model for 77 European provinces shows that model-based estimates of biomass development with stand age compare favourably with forest inventory-based estimates for different tree species. Driven by historic changes in climate, atmospheric CO2 concentration, forest area and wood demand between 1948 and 2000, the model predicts European-scale, present-day age structure of forests, ratio of biomass removals to increment, and vegetation carbon sequestration rates that are consistent with inventory-based estimates. Alternative scenarios of climate and land-use change in the 21<sup>st century suggest carbon sequestration in the European terrestrial biosphere during the coming decades will likely be on magnitudes relevant to climate mitigation strategies. However, the uptake rates are small in comparison to the European emissions from fossil fuel combustion, and will likely decline towards the end of the century. Uncertainty in climate change projections is a key driver for uncertainty in simulated land-atmosphere carbon fluxes and needs to be accounted for in mitigation studies of the terrestrial biosphere.
Monoclonal antibodies (mAbs) are an innovative group of drugs with increasing clinical importance in oncology, combining high specificity with generally low toxicity. There are, however, numerous challenges associated with the development of mAbs as therapeutics. Mechanistic understanding of factors that govern the pharmacokinetics (PK) of mAbs is critical for drug development and the optimisation of effective therapies; in particular, adequate dosing strategies can improve patient quality life and lower drug cost. Physiologically-based PK (PBPK) models offer a physiological and mechanistic framework, which is of advantage in the context of animal to human extrapolation. Unlike for small molecule drugs, however, there is no consensus on how to model mAb disposition in a PBPK context. Current PBPK models for mAb PK hugely vary in their representation of physiology and parameterisation. Their complexity poses a challenge for their applications, e.g., translating knowledge from animal species to humans.
In this thesis, we developed and validated a consensus PBPK model for mAb disposition taking into account recent insights into mAb distribution (antibody biodistribution coefficients and interstitial immunoglobulin G (IgG) pharmacokinetics) to predict tissue PK across several pre-clinical species and humans based on plasma data only. The model allows to a priori predict target-independent (unspecific) mAb disposition processes as well as mAb disposition in concentration ranges, for which the unspecific clearance (CL) dominates target-mediated CL processes. This is often the case for mAb therapies at steady state dosing.
The consensus PBPK model was then used and refined to address two important problems:
1) Immunodeficient mice are crucial models to evaluate mAb efficacy in cancer therapy. Protection from elimination by binding to the neonatal Fc receptor is known to be a major pathway influencing the unspecific CL of both, endogenous and therapeutic IgG. The concentration of endogenous IgG, however, is reduced in immunodeficient mouse models, and this effect on unspecific mAb CL is unknown, yet of great importance for the extrapolation to human in the context of mAb cancer therapy.
2) The distribution of mAbs into solid tumours is of great interest. To comprehensively investigate mAb distribution within tumour tissue and its implications for therapeutic efficacy, we extended the consensus PBPK model by a detailed tumour distribution model incorporating a cell-level model for mAb-target interaction. We studied the impact of variations in tumour microenvironment on therapeutic efficacy and explored the plausibility of different mechanisms of action in mAb cancer therapy.
The mathematical findings and observed phenomena shed new light on therapeutic utility and dosing regimens in mAb cancer treatment.
This study presents the development of 1D and 2D Surface Evolution Codes (SECs) and their coupling to any lithospheric-scale (thermo-)mechanical code with a quadrilateral structured surface mesh.
Both SECs involve diffusion as approach for hillslope processes and the stream power law to reflect riverbed incision. The 1D SEC settles sediment that was produced by fluvial incision in the appropriate minimum, while the supply-limited 2D SEC DANSER uses a fast filling algorithm to model sedimantation. It is based on a cellular automaton. A slope-dependent factor in the sediment flux extends the diffusion equation to nonlinear diffusion. The discharge accumulation is achieved with the D8-algorithm and an improved drainage accumulation routine. Lateral incision enhances the incision's modelling. Following empirical laws, it incises channels of several cells width.
The coupling method enables different temporal and spatial resolutions of the SEC and the thermo-mechanical code. It transfers vertical as well as horizontal displacements to the surface model. A weighted smoothing of the 3D surface displacements is implemented. The smoothed displacement vectors transmit the deformation by bilinear interpolation to the surface model. These interpolation methods ensure mass conservation in both directions and prevent the two surfaces from drifting apart.
The presented applications refer to the evolution of the Pamir orogen. A calibration of DANSER's parameters with geomorphological data and a DEM as initial topography highlights the advantage of lateral incision. Preserving the channel width and reflecting incision peaks in narrow channels, this closes the huge gap between current orogen-scale incision models and observed topographies.
River capturing models in a system of fault-bounded block rotations reaffirm the importance of the lateral incision routine for capturing events with channel initiation. The models show a low probability of river capturings with large deflection angles. While the probability of river capturing is directly depending on the uplift rate, the erodibility inside of a dip-slip fault speeds up headward erosion along the fault: The model's capturing speed increases within a fault.
Coupling DANSER with the thermo-mechanical code SLIM 3D emphasizes the versatility of the SEC. While DANSER has minor influence on the lithospheric evolution of an indenter model, the brittle surface deformation is strongly affected by its sedimentation, widening a basin in between two forming orogens and also the southern part of the southern orogen to south, east and west.
Chemical transformations and hydraulic processes in soil and groundwater often lead to an apparent retention of nitrate in lowland catchments. Models are needed to evaluate the interaction of these processes in space and time. The objectives of this study are i) to develop a specific modelling approach by combining selected modelling tools simulating N-transport and turnover in soils and groundwater of lowland catchments, ii) to study interactions between catchment properties and nitrogen transport. Special attention was paid to potential N-loads to surface waters. The modelling approach combines various submodels for water flow and solute transport in soil and groundwater: The soil-water- and nitrogen-model mRISK-N, the groundwater flow model MODFLOW and the solute transport model RT3D. In order to investigate interactions of N-transport and catchment characteristics, the distribution and availability of reaction partners have to be taken into account. Therefore, a special reaction-module is developed, which simulates various chemical processes in groundwater, such as the degradation of organic matter by oxygen, nitrate, sulphate or pyrite oxidation by oxygen and nitrate. The model approach is applied to different simulation, focussing on specific submodels. All simulation studies are based on field data from the Schaugraben catchment, a pleistocene catchment of approximately 25 km², close to Osterburg(Altmark) in the North of Saxony-Anhalt. The following modelling studies have been carried out: i) evaluation of the soil-water- and nitrogen-model based on lysimeter data, ii) modelling of a field scale tracer experiment on nitrate transport and turnover in the groundwater as a first application of the reaction module, iii) evaluation of interactions between hydraulic and chemical aquifer properties in a two-dimensional groundwater transect, iv) modelling of distributed groundwater recharge and soil nitrogen leaching in the study area, to be used as input data for subsequent groundwater simulations, v) study of groundwater nitrate distribution and nitrate breakthrough to the surface water system in the Schaugraben catchment area and a subcatchment, using three-dimensional modelling of reactive groundwater transport. The various model applications prove the model to be capable of simulating interactions between transport, turnover and hydraulic and chemical catchment properties. The distribution of nitrate in the sediment and the resulting loads to surface waters are strongly affected by the amount of reactive substances and by the residence time within the aquifer. In the Schaugraben catchment simulations, it is found that a period of 70 years is needed to raise the average seepage concentrations of nitrate to a level corresponding to the given input situation, if no reactions are considered. Under reactive transport conditions, nitrate concentrations are reduced effectively. Simulation results show that groundwater exfiltration does not contribute considerably to the nitrate pollution of surface waters, as most nitrate entering soils and groundwater is lost by denitrification. Additional sources, such as direct inputs or tile drains have to be taken into account to explain surface water loads. The prognostic value of the models for the study site is limited by uncertainties of input data and estimation of model parameters. Nevertheless, the modelling approach is a useful aid for the identification of source and sink areas of nitrate pollution as well as the investigation of system response to management measures or landuse changes with scenario simulations. The modelling approach assists in the interpretation of observed data, as it allows to integrate local observations into a spatial and temporal framework.
Continental rift systems open up unique possibilities to study the geodynamic system of our planet: geodynamic localization processes are imprinted in the morphology of the rift by governing the time-dependent activity of faults, the topographic evolution of the rift or by controlling whether a rift is symmetric or asymmetric. Since lithospheric necking localizes strain towards the rift centre, deformation structures of previous rift phases are often well preserved and passive margins, the end product of continental rifting, retain key information about the tectonic history from rift inception to continental rupture.
Current understanding of continental rift evolution is based on combining observations from active rifts with data collected at rifted margins. Connecting these isolated data sets is often accomplished in a conceptual way and leaves room for subjective interpretation. Geodynamic forward models, however, have the potential to link individual data sets in a quantitative manner, using additional constraints from rock mechanics and rheology, which allows to transcend previous conceptual models of rift evolution. By quantifying geodynamic processes within continental rifts, numerical modelling allows key insight to tectonic processes that operate also in other plate boundary settings, such as mid ocean ridges, collisional mountain chains or subduction zones.
In this thesis, I combine numerical, plate-tectonic, analytical, and analogue modelling approaches, whereas numerical thermomechanical modelling constitutes the primary tool. This method advanced rapidly during the last two decades owing to dedicated software development and the availability of massively parallel computer facilities. Nevertheless, only recently the geodynamical modelling community was able to capture 3D lithospheric-scale rift dynamics from onset of extension to final continental rupture.
The first chapter of this thesis provides a broad introduction to continental rifting, a summary of the applied rift modelling methods and a short overview of previews studies. The following chapters, which constitute the main part of this thesis feature studies on plate boundary dynamics in two and three dimension followed by global scale analyses (Fig. 1).
Chapter II focuses on 2D geodynamic modelling of rifted margin formation. It highlights the formation of wide areas of hyperextended crustal slivers via rift migration as a key process that affected many rifted margins worldwide. This chapter also contains a study of rift velocity evolution, showing that rift strength loss and extension velocity are linked through a dynamic feed-back. This process results in abrupt accelerations of the involved plates during rifting illustrating for the first time that rift dynamics plays a role in changing global-scale plate motions. Since rift velocity affects key processes like faulting, melting and lower crustal flow, this study also implies that the slow-fast velocity evolution should be imprinted in rifted margin structures.
Chapter III relies on 3D Cartesian rift models in order to investigate various aspects of rift obliquity. Oblique rifting occurs if the extension direction is not orthogonal to the rift trend. Using 3D lithospheric-scale models from rift initialisation to breakup I could isolate a characteristic evolution of dominant fault orientations. Further work in Chapter III addresses the impact of rift obliquity on the strength of the rift system. We illustrate that oblique rifting is mechanically preferred over orthogonal rifting, because the brittle yielding requires a lower tectonic force. This mechanism elucidates rift competition during South Atlantic rifting, where the more oblique Equatorial Atlantic Rift proceeded to breakup while the simultaneously active but less oblique West African rift system became a failed rift. Finally this Chapter also investigates the impact of a previous rift phase on current tectonic activity in the linkage area of the Kenyan with Ethiopian rift. We show that the along strike changes in rift style are not caused by changes in crustal rheology. Instead the rift linkage pattern in this area can be explained when accounting for the thinned crust and lithosphere of a Mesozoic rift event.
Chapter IV investigates rifting from the global perspective. A first study extends the oblique rift topic of the previous chapter to global scale by investigating the frequency of oblique rifting during the last 230 million years. We find that approximately 70% of all ocean-forming rift segments involved an oblique component of extension where obliquities exceed 20°. This highlights the relevance of 3D approaches in modelling, surveying, and interpretation of many rifted margins. In a final study, we propose a link between continental rift activity, diffuse CO2 degassing and Mesozoic/Cenozoic climate changes. We used recent CO2 flux measurements in continental rifts to estimate worldwide rift-related CO2 release, which we based on the global extent of rifts through time. The first-order correlation to paleo-atmospheric CO2 proxy data suggests that rifts constitute a major element of the global carbon cycle.
This thesis discusses theoretical and practical aspects of modelling of light propagation in non-aged and aged step-index polymer optical fibres (POFs). Special attention has been paid in describing optical characteristics of non-ideal fibres, scattering and attenuation, and in combining application-oriented and theoretical approaches. The precedence has been given to practical issues, but much effort has been also spent on the theoretical analysis of basic mechanisms governing light propagation in cylindrical waveguides.As a result a practically usable general POF model based on the raytracing approach has been developed and implemented. A systematic numerical optimisation of its parameters has been performed to obtain the best fit between simulated and measured optical characteristics of numerous non-aged and aged fibre samples. The model was verified by providing good agreement, especially for the non-aged fibres. The relations found between aging time and optimal values of model parameters contribute to a better understanding of the aging mechanisms of POFs.
Modelling and simulation of light propagation in non-aged and aged step-index polymer optical fibres
(2004)
This thesis discusses theoretical and practical aspects of modelling of light propagation in non-aged and aged step-index polymer optical fibres (POFs). Special attention has been paid in describing optical characteristics of non-ideal fibres, scattering and attenuation, and in combining application-oriented and theoretical approaches. The precedence has been given to practical issues, but much effort has been also spent on the theoretical analysis of basic mechanisms governing light propagation in cylindrical waveguides. As a result a practically usable general POF model based on the raytracing approach has been developed and implemented. A systematic numerical optimisation of its parameters has been performed to obtain the best fit between simulated and measured optical characteristics of numerous non-aged and aged fibre samples. The model was verified by providing good agreement, especially for the non-aged fibres. The relations found between aging time and optimal values of model parameters contribute to a better understanding of the aging mechanisms of POFs.
An increasing demand on functionality and flexibility leads to an integration of beforehand isolated system solutions building a so-called System of Systems (SoS). Furthermore, the overall SoS should be adaptive to react on changing requirements and environmental conditions. Due SoS are composed of different independent systems that may join or leave the overall SoS at arbitrary point in times, the SoS structure varies during the systems lifetime and the overall SoS behavior emerges from the capabilities of the contained subsystems. In such complex system ensembles new demands of understanding the interaction among subsystems, the coupling of shared system knowledge and the influence of local adaptation strategies to the overall resulting system behavior arise. In this report, we formulate research questions with the focus of modeling interactions between system parts inside a SoS. Furthermore, we define our notion of important system types and terms by retrieving the current state of the art from literature. Having a common understanding of SoS, we discuss a set of typical SoS characteristics and derive general requirements for a collaboration modeling language. Additionally, we retrieve a broad spectrum of real scenarios and frameworks from literature and discuss how these scenarios cope with different characteristics of SoS. Finally, we discuss the state of the art for existing modeling languages that cope with collaborations for different system types such as SoS.
The service-oriented architecture supports the dynamic assembly and runtime reconfiguration of complex open IT landscapes by means of runtime binding of service contracts, launching of new components and termination of outdated ones. Furthermore, the evolution of these IT landscapes is not restricted to exchanging components with other ones using the same service contracts, as new services contracts can be added as well. However, current approaches for modeling and verification of service-oriented architectures do not support these important capabilities to their full extend.In this report we present an extension of the current OMG proposal for service modeling with UML - SoaML - which overcomes these limitations. It permits modeling services and their service contracts at different levels of abstraction, provides a formal semantics for all modeling concepts, and enables verifying critical properties. Our compositional and incremental verification approach allows for complex properties including communication parameters and time and covers besides the dynamic binding of service contracts and the replacement of components also the evolution of the systems by means of new service contracts. The modeling as well as verification capabilities of the presented approach are demonstrated by means of a supply chain example and the verification results of a first prototype are shown.
The development of self-adaptive software requires the engineering of an adaptation engine that controls and adapts the underlying adaptable software by means of feedback loops. The adaptation engine often describes the adaptation by using runtime models representing relevant aspects of the adaptable software and particular activities such as analysis and planning that operate on these runtime models. To systematically address the interplay between runtime models and adaptation activities in adaptation engines, runtime megamodels have been proposed for self-adaptive software. A runtime megamodel is a specific runtime model whose elements are runtime models and adaptation activities. Thus, a megamodel captures the interplay between multiple models and between models and activities as well as the activation of the activities. In this article, we go one step further and present a modeling language for ExecUtable RuntimE MegAmodels (EUREMA) that considerably eases the development of adaptation engines by following a model-driven engineering approach. We provide a domain-specific modeling language and a runtime interpreter for adaptation engines, in particular for feedback loops. Megamodels are kept explicit and alive at runtime and by interpreting them, they are directly executed to run feedback loops. Additionally, they can be dynamically adjusted to adapt feedback loops. Thus, EUREMA supports development by making feedback loops, their runtime models, and adaptation activities explicit at a higher level of abstraction. Moreover, it enables complex solutions where multiple feedback loops interact or even operate on top of each other. Finally, it leverages the co-existence of self-adaptation and off-line adaptation for evolution.
Migration and development in Senegal : a system dynamics analysis of the feedback relationships
(2011)
This thesis investigates the reciprocal relationship between migration and development in Senegal. Therewith, it contributes to the debate as to whether migration in developing countries enhances or rather impedes the development process. Even though extensive and controversial discussions can be found in the scientific literature regarding the impact of migration on development, research has scarcely examined the feedback relationships between migration and development. Science however agrees with both the fact that migration affects development as well as that the level of development in a country determines migration behaviour. Thus, both variables are neither dependent nor independent, but endogenous variables influencing each other and producing behavioural pattern that cannot be investigated using a static and unidirectional approach. On account of this, the thesis studies the feedback mechanisms existing between migration and development and the behavioural pattern generated by the high interdependence in order to be able to draw conclusions concerning the impact of changes in migration behaviour on the development process. To explore these research questions, the study applies the computer simulation method ‘System Dynamics’ and amplifies the simulation model for national development planning called ‘Threshold 21’ (T21), representing development processes endogenously and integrating economic, social and environmental aspects, using a structure that portrays the reasons and consequences of migration. The model has been customised to Senegal, being an appropriate representative of the theoretical interesting universe of cases. The comparison of the model generated scenarios - in which the intensity of emigration, the loss and gain of education, the remittances or the level of dependence changes - facilitates the analysis. The present study produces two important results. The first outcome is the development of an integrative framework representing migration and development in an endogenous way and incorporating several aspects of different theories. This model can be used as a starting point for further discussions and improvements and it is a fairly relevant and useful result against the background that migration is not integrated into most of the development planning tools despite its significant impact. The second outcome is the gained insights concerning the feedback relations between migration and development and the impact of changes in migration on development. To give two examples: It could be found that migration impacts development positively, indicated by HDI, but that the dominant behaviour of migration and development is a counteracting behaviour. That means that an increase in emigration leads to an improvement in development, while this in turn causes a decline in emigration, counterbalancing the initial increase. Another insight concerns the discovery that migration causes a decline in education in the short term, but leads to an increase in the long term, after approximately 25 years - a typical worse-before-better behaviour. From these and further observations, important policy implications can be derived for the sending and receiving countries. Hence, by overcoming the unidirectional perspective, this study contributes to an improved understanding of the highly complex relationship between migration and development and their feedback relations.
Water shortage is a serious threat for many societies worldwide. In drylands, water management measures like the construction of reservoirs are affected by eroded sediments transported in the rivers. Thus, the capability of assessing water and sediment fluxes at the river basin scale is of vital importance to support management decisions and policy making. This subject was addressed by the DFG-funded SESAM-project (Sediment Export from large Semi-Arid catchments: Measurements and Modelling). As a part of this project, this thesis focuses on (1) the development and implementation of an erosion module for a meso-scale catchment model, (2) the development of upscaling and generalization methods for the parameterization of such model, (3) the execution of measurements to obtain data required for the modelling and (4) the application of the model to different study areas and its evaluation. The research was carried out in two meso-scale dryland catchments in NE-Spain: Ribera Salada (200 km²) and Isábena (450 km²). Adressing objective 1, WASA-SED, a spatially semi-distributed model for water and sediment transport at the meso-scale was developed. The model simulates runoff and erosion processes at the hillslope scale, transport processes of suspended and bedload fluxes in the river reaches, and retention and remobilisation processes of sediments in reservoirs. This thesis introduces the model concept, presents current model applications and discusses its capabilities and limitations. Modelling at larger scales faces the dilemma of describing relevant processes while maintaining a manageable demand for input data and computation time. WASA-SED addresses this challenge by employing an innovative catena-based upscaling approach: the landscape is represented by characteristic toposequences. For deriving these toposequences with regard to multiple attributes (eg. topography, soils, vegetation) the LUMP-algorithm (Landscape Unit Mapping Program) was developed and related to objective 2. It incorporates an algorithm to retrieve representative catenas and their attributes, based on a Digital Elevation Model and supplemental spatial data. These catenas are classified to provide the discretization for the WASA-SED model. For objective 3, water and sediment fluxes were monitored at the catchment outlet of the Isábena and some of its sub-catchments. For sediment yield estimation, the intermittent measurements of suspended sediment concentration (SSC) had to be interpolated. This thesis presents a comparison of traditional sediment rating curves (SRCs), generalized linear models (GLMs) and non-parametric regression using Random Forests (RF) and Quantile Regression Forests (QRF). The observed SSCs are highly variable and range over six orders of magnitude. For these data, traditional SRCs performed poorly, as did GLMs, despite including other relevant process variables (e.g. rainfall intensities, discharge characteristics). RF and QRF proved to be very robust and performed favourably for reproducing sediment dynamics. QRF additionally excels in providing estimates on the accuracy of the predictions. Subsequent analysis showed that most of the sediment was exported during intense storms of late summer. Later floods yielded successively less sediment. Comparing sediment generation to yield at the outlet suggested considerable storage effects within the river channel. Addressing objective 4, the WASA-SED model was parameterized for the two study areas in NE Spain and applied with different foci. For Ribera Salada, the uncalibrated model yielded reasonable results for runoff and sediment. It provided quantitative measures of the change in runoff and sediment yield for different land-uses. Additional land management scenarios were presented and compared to impacts caused by climate change projections. In contrast, the application for the Isábena focussed on exploring the full potential of the model's predictive capabilities. The calibrated model achieved an acceptable performance for the validation period in terms of water and sediment fluxes. The inadequate representation of the lower sub-catchments inflicted considerable reductions on model performance, while results for the headwater catchments showed good agreement despite stark contrasts in sediment yield. In summary, the application of WASA-SED to three catchments proved the model framework to be a practicable multi-scale approach. It successfully links the hillslope to the catchment scale and integrates the three components hillslope, river and reservoir in one model. Thus, it provides a feasible approach for tackling issues of water and sediment yield at the meso-scale. The crucial role of processes like transmission losses and sediment storage in the river has been identified. Further advances can be expected when the representation of connectivity of water and sediment fluxes (intra-hillslope, hillslope-river, intra-river) is refined and input data improves.
Magmatic-hydrothermal systems form a variety of ore deposits at different proximities to upper-crustal hydrous magma chambers, ranging from greisenization in the roof zone of the intrusion, porphyry mineralization at intermediate depths to epithermal vein deposits near the surface. The physical transport processes and chemical precipitation mechanisms vary between deposit types and are often still debated.
The majority of magmatic-hydrothermal ore deposits are located along the Pacific Ring of Fire, whose eastern part is characterized by the Mesozoic to Cenozoic orogenic belts of the western North and South Americas, namely the American Cordillera. Major magmatic-hydrothermal ore deposits along the American Cordillera include (i) porphyry Cu(-Mo-Au) deposits (along the western cordilleras of Mexico, the western U.S., Canada, Chile, Peru, and Argentina); (ii) Climax- (and sub−) type Mo deposits (Colorado Mineral Belt and northern New Mexico); and (iii) porphyry and IS-type epithermal Sn(-W-Ag) deposits of the Central Andean Tin Belt (Bolivia, Peru and northern Argentina).
The individual studies presented in this thesis primarily focus on the formation of different styles of mineralization located at different proximities to the intrusion in magmatic-hydrothermal systems along the American Cordillera. This includes (i) two individual geochemical studies on the Sweet Home Mine in the Colorado Mineral Belt (potential endmember of peripheral Climax-type mineralization); (ii) one numerical modeling study setup in a generic porphyry Cu-environment; and (iii) a numerical modeling study on the Central Andean Tin Belt-type Pirquitas Mine in NW Argentina.
Microthermometric data of fluid inclusions trapped in greisen quartz and fluorite from the Sweet Home Mine (Detroit City Portal) suggest that the early-stage mineralization precipitated from low- to medium-salinity (1.5-11.5 wt.% equiv. NaCl), CO2-bearing fluids at temperatures between 360 and 415°C and at depths of at least 3.5 km. Stable isotope and noble gas isotope data indicate that greisen formation and base metal mineralization at the Sweet Home Mine was related to fluids of different origins. Early magmatic fluids were the principal source for mantle-derived volatiles (CO2, H2S/SO2, noble gases), which subsequently mixed with significant amounts of heated meteoric water. Mixing of magmatic fluids with meteoric water is constrained by δ2Hw-δ18Ow relationships of fluid inclusions. The deep hydrothermal mineralization at the Sweet Home Mine shows features similar to deep hydrothermal vein mineralization at Climax-type Mo deposits or on their periphery. This suggests that fluid migration and the deposition of ore and gangue minerals in the Sweet Home Mine was triggered by a deep-seated magmatic intrusion.
The second study on the Sweet Home Mine presents Re-Os molybdenite ages of 65.86±0.30 Ma from a Mo-mineralized major normal fault, namely the Contact Structure, and multimineral Rb-Sr isochron ages of 26.26±0.38 Ma and 25.3±3.0 Ma from gangue minerals in greisen assemblages. The age data imply that mineralization at the Sweet Home Mine formed in two separate events: Late Cretaceous (Laramide-related) and Oligocene (Rio Grande Rift-related). Thus, the age of Mo mineralization at the Sweet Home Mine clearly predates that of the Oligocene Climax-type deposits elsewhere in the Colorado Mineral Belt. The Re-Os and Rb-Sr ages also constrain the age of the latest deformation along the Contact Structure to between 62.77±0.50 Ma and 26.26±0.38 Ma, which was employed and/or crosscut by Late Cretaceous and Oligocene fluids. Along the Contact Structure Late Cretaceous molybdenite is spatially associated with Oligocene minerals in the same vein system, a feature that precludes molybdenite recrystallization or reprecipitation by Oligocene ore fluids.
Ore precipitation in porphyry copper systems is generally characterized by metal zoning (Cu-Mo to Zn-Pb-Ag), which is suggested to be variably related to solubility decreases during fluid cooling, fluid-rock interactions, partitioning during fluid phase separation and mixing with external fluids. The numerical modeling study setup in a generic porphyry Cu-environment presents new advances of a numerical process model by considering published constraints on the temperature- and salinity-dependent solubility of Cu, Pb and Zn in the ore fluid. This study investigates the roles of vapor-brine separation, halite saturation, initial metal contents, fluid mixing, and remobilization as first-order controls of the physical hydrology on ore formation. The results show that the magmatic vapor and brine phases ascend with different residence times but as miscible fluid mixtures, with salinity increases generating metal-undersaturated bulk fluids. The release rates of magmatic fluids affect the location of the thermohaline fronts, leading to contrasting mechanisms for ore precipitation: higher rates result in halite saturation without significant metal zoning, lower rates produce zoned ore shells due to mixing with meteoric water. Varying metal contents can affect the order of the final metal precipitation sequence. Redissolution of precipitated metals results in zoned ore shell patterns in more peripheral locations and also decouples halite saturation from ore precipitation.
The epithermal Pirquitas Sn-Ag-Pb-Zn mine in NW Argentina is hosted in a domain of metamorphosed sediments without geological evidence for volcanic activity within a distance of about 10 km from the deposit. However, recent geochemical studies of ore-stage fluid inclusions indicate a significant contribution of magmatic volatiles. This study tested different formation models by applying an existing numerical process model for porphyry-epithermal systems with a magmatic intrusion located either at a distance of about 10 km underneath the nearest active volcano or hidden underneath the deposit. The results show that the migration of the ore fluid over a 10-km distance results in metal precipitation by cooling before the deposit site is reached. In contrast, simulations with a hidden magmatic intrusion beneath the Pirquitas deposit are in line with field observations, which include mineralized hydrothermal breccias in the deposit area.