The process of drug discovery is very slow and expensive. There is a need for reliable in silico methods; however the performance of these methods differs. This work presents a targeted study on how the drug discovery methods used in OpenEye’s tools ROCS, EON and FRED perform on targets with small ligands. It was examined if 12 compounds (markers) somewhat similar to AMP could be detected by ROCS in a random data set comprised of 1000 compounds. It was also examined if EON could find any electrostatic similarities between the queries and the markers. The performance of FRED with respect to re-generation of bound ligand modes was examined on ten different protein/ligand complexes from the Brookhaven Protein Data Bank. It was also examined if FRED is suitable as a screening tool since several other docking methods are used in such a way. Finally it was also examined if it was possible to reduce the time requirements of ROCS when running multiconformer queries by using a combination of single conformer queries coupled with multiconformer queries. The conclusions that could be drawn from this project were that FRED is not a good screening tool, but ROCS performs well as such. It was also found that the scoring functions are the weak spots of FRED. EON is probably very sensitive to the conformers used but can in some cases strengthen the results from ROCS. A novel and simple way to reduce the time complexity with multiconformer queries to ROCS was discovered and was shown to work well.

<p>The process of drug discovery is very slow and expensive. There is a need for reliable in silico methods; however the performance of these methods differs.</p><p>This work presents a targeted study on how the drug discovery methods used in OpenEye’s tools ROCS, EON and FRED perform on targets with small ligands. It was examined if 12 compounds (markers) somewhat similar to AMP could be detected by ROCS in a random data set comprised of 1000 compounds. It was also examined if EON could find any electrostatic similarities between the queries and the markers. The performance of FRED with respect to re-generation of bound ligand modes was examined on ten different protein/ligand complexes from the Brookhaven Protein Data Bank. It was also examined if FRED is suitable as a screening tool since several other docking methods are used in such a way. Finally it was also examined if it was possible to reduce the time requirements of ROCS when running multiconformer queries by using a combination of single conformer queries coupled with multiconformer queries.</p><p>The conclusions that could be drawn from this project were that FRED is not a good screening tool, but ROCS performs well as such. It was also found that the scoring functions are the weak spots of FRED. EON is probably very sensitive to the conformers used but can in some cases strengthen the results from ROCS. A novel and simple way to reduce the time complexity with multiconformer queries to ROCS was discovered and was shown to work well.</p>

In this research, we consider the impact of spectrum fragmentation in optical single-/multi-path routing transmission on the efficiency of the elastic optical networks. O-OFDM multicarrier transmission is a promising technique that makes it possible to choose just an adequate portion of available spectrum to satisfy the requested capacity. This involves focusing on the work to reduce the fragmentation effects by dynamically updating and controlling the minimum bandwidth allocation granularity. that serves the light path requests over multipath networks. We adopt linear and nonlinear dynamic mechanisms, which are denoted as LDAɡ and NLDAɡ that are proportional to the optical link/path bandwidth fragmentation status. Simulation results show that the minimum bandwidth granularity dynamic adaptation based on the optical path fragmentation status offers improved performance over fixed minimum bandwidth allocation granularity with respect to the bandwidth blocking probability, the throughput, the network bandwidth utilization and the number of path splitting.

The timescale of chemical reactions in solid-state systems greatly exceeds what may be modeled by direct integration of Newton's equation of motion. This limitation spawned the development of many different methods such as (adaptive) kinetic Monte Carlo (A)KMC, (harmonic) transition state theory (H)TST, parallel replica dynamics (PRD), hyperdynamics (HD), and temperature accelerated dynamics. The focus of this thesis was to (1) implement many of these methods in a single open-source software package (2) develop standard benchmarks to compare their accuracy and computational cost and (3) develop new long timescale methods. The lack of a open-source package that implements long timescale methods makes it difficult to directly evaluate the quality of different approaches. It also impedes the development of new techniques. Due to these concerns we developed Eon, a program that implements several long timescale methods including PRD, HD, and AKMC as well as global optimization algorithms basin hopping, and minima hopping. Standard benchmarks to evaluate the performance of local geometry optimization; global optimization; and single-ended and double-ended saddle point searches were created. Using Eon and several other well known programs, the accuracy and performance of different algorithms was compared. Important to this work is a website where anyone may download the code to repeat any of the numerical experiments. A new method for long timescale simulations is also introduced: molecular dynamics saddle search adaptive kinetic Monte Carlo (AKMC-MDSS). AKMC-MDSS improves upon AKMC by using short high-temperature MD trajectories to locate the important low-temperature reaction mechanisms of interest. Most importantly, the use of MD enables the development of a proper stopping criterion for the AKMC simulation that ensures that the relevant reaction mechanisms at the low temperature have been found. Important to the simulation of any material is knowledge of the experimental structure. Extended x-ray absorption fine structure (EXAFS) is a technique often used to determine local atomic structure. We propose a technique to quantitatively measure the accuracy of the commonly used fitting models. This technique reveals that the fitting models interpreted nanoparticles as being significantly more ordered and of much shorter bond length than they really are. / text

E.ON har satt som mål att leverera 100% förnybar och återvunnen energi år 2025. På E.ON:s kraftvärmeverk Händelö i Norrköping måste då den koldrivna Panna 12, men även den biodrivna Panna 11 ersättas med en ny typ av förnybar och återvunnen lösning som ska producera värme. En lösning som diskuteras på E.ON är att ersätta dessa två pannor med en biohetvattenpanna, Panna 16. I Händelöområdet finns dock en del verksamheter med restflöden i form av överskottsvärme som i nuläget inte tas vara på. Genom utnyttjande av överskottsvärme kan växthuseffekten minskas och det nationella energisystemet effektiviseras. En ytterligare lösning skulle därför kunna vara att ersätta pannorna med en energilösning som utnyttjar överskottsvärme och med hjälp av värmepump producerar värme. Syftet med det här projektet har därför varit att undersöka möjligheterna för en framtida energilösning med värmepump och hur den kan användas i samverkan med Händelöverket för att minska investerings-och marginalkostnaderna för värmeproduktionen till Norrköpings fjärrvärmenät. Målet med projektet har därför varit att ta fram en modell i modelleringsverktyget reMind och VBA Excel som kan beräkna lönsamheten för den framtida värmepumpslösningen gentemot den nya Panna 16 med olika scenarier för elpriser. Under projektet har en dimensionering av en kompressordriven värmepump utförts för att ta reda på de tekniska och driftmässiga förutsättningarna för en värmepump. Sedan har olika modeller gjorts i reMind och VBA Excel för en kompressordriven värmepump och en absorptionsvärmepump. Absorptionsvärmepumpen har inte dimensionerats under projektet, utan där har olika värden relaterade till de tekniska-och driftmässiga förutsättningarna erhållits från en värmepumpsleverantör. Resultatet visar att en energilösning med absorptionsvärmepump är betydligt mer lönsam än en lösning med enbart Panna 16. Absorptionsvärmepumpen blev 30 – 42 MSEK billigare i investering gentemot Panna 16. Dessutom blev absorptionsvärmepumpen 79 – 102 MSEK mer lönsam med en ekonomisk livslängd på 20 för de olika elprisscenarierna. Totalt sett blev det en lönsamhet på ca 110 – 140 MSEK gentemot Panna 16. Den kompressordrivna värmepumpen blev å andra sidan inte lönsam i jämförelse med Panna 16. Investeringskostnaden för den kompressordrivna värmepumpen blev 14 – 24 MSEK dyrare än Panna 16:s motsvarande investeringskostnad och skillnaden i marginalkostnad hamnade endast i intervallet 0 – 5 MSEK med olika elprisscenarion. Slutsatsen blev att E.ON ska fortsätta att utreda möjligheterna med att eventuellt investera i en absorptionsvärmepump. För den kompressordrivna värmepumpen anses det dock inte vara värt att undersöka vidare. / E.ON has set a goal to deliver 100% renewable and recycled energy year 2025. To achieve this goal at E.ON’s combined heat-and power plant, Händelö in Norrköping, the coal driven Boiler 12 and the biofuel driven Boiler 11 must be replaced with a new renewable and recycled solution to produce heat. A solution that is being discussed at E.ON is replacing these two boilers with a single heat water boiler, Boiler 16 which will be producing heat. In the Händelö area there are some enterprises with residual flows in form of excess heat that is not being used today. By using the excess heat, the greenhouse emissions can be reduced and the national energy system can become more efficient. Another solution is therefore replacing the boilers with an energy solution that uses the excess heat and with the help of a heat pump producing heat. The aim of this project has been to investigate the possibilities of a future energy solution with heat pump and how it can be used in cooperation with the Händelö plant to decrease the investment-and marginal costs of the heat production to the district heating network of Norrköping. The objective of this project has therefore been, creating a model in the modelling tool remind and VBA Excel that can calculate the profitability of the future heat pump solution in comparison to the new Boiler 16 with different scenarios of the electricity price. A dimensioning of a compressor heat pump has been performed to investigate the technical-and operation qualifications for a heat pump. Furthermore, different models have been created in remind and VBA Excel for a compressor heat pump and an absorptions heat pump. The absorption heat pump has not been dimensioned, a heat pump supplier has provided different values based on the technical- and operating qualifications. The result shows that an energy solution with an absorption heat pump is considerably more profitable than a solution consisting of a single Boiler 16. The investment cost of an absorption heat pump became 30 – 42 MSEK cheaper than the corresponding investment cost for the Boiler 16. In addition, the marginal cost of the absorption heat pump became 79 -102 MSEK more profitable than Boiler 16’s marginal cost considering an economical life span of 20 years and different electricity price scenarios. The total profitability of the absorption heat pump became 110 – 140 MSEK. The compressor heat pump did not become profitable in comparison to Boiler 16. The investment cost for the compressor heat pump became 14 – 24 MSEK more expensive than the corresponding investment cost of Boiler 16 and the marginal cost was only 0 – 5 MSEK less expensive than considering different electricity price scenarios. The conclusion of the project is that E.ON should continue investigating the possibilities of investing in an absorption heat pump. The compressor heat pump is not considered being worth investigating further.

La planificación de la producción en plantas de proceso discontinuo es uno de los problemas más complejos e importantes para una amplia variedad de procesos industriales. A pesar de esta importancia la planificación de la producción es habitualmente un proceso manual que puede conducir a un exceso de inventario, una utilización ineficiente del capital y aumento en costes de producción.Este problema ha sido el sujeto de un importante esfuerzo investigador en los últimos años, especialmente desde principios de los 80 hasta la actualidad, aunque la industria se ha mostrado interesada en el problema desde los años 40. Durante este tiempo se ha realizado mucha investigación al respecto, pero la naturaleza compleja de problema hace que todavía no exista una solución aceptada ampliamente en la industria.Esta tesis describe un entorno genérico para la planificación de la producción en plantas de proceso discontinuo. Se han desarrollado diferentes componentes: un modelo de datos, un modelo de temporización, estrategias de asignación y secuenciación y diferentes alternativas de optimización.Uno de los aspectos más importantes del entorno presentado es su modularidad. El hecho de dividir el problema de planificación de la producción en diferentes módulos que comparten un modelo de datos común facilita la reutilización y la adaptación a escenarios industriales de las diferentes técnicas desarrolladas escogiendo la mejor alternativa para cada uno de ellos.El modelo de información orientado a objetos que se presenta en esta tesis permite la organización sistemática de la información de planta, permitiendo una representación detallada de las restricciones presentes en la industria.Por otra parte, el modelo de temporización de operaciones (EON) desarrollado en la presente tesis es la capacidad de representar restricciones temporales complejas presentes en la industria utilizando componentes sencillos. Se ha desarrollado una metodología para generar modelos EON a partir del modelo de información utilizado incluyendo restricciones de depósitos y restricciones temporales entre operaciones. Adicionalmente, un método iterativo permite tener en cuenta otros recursos limitantes dependientes de calendario, como mano de obra, electricidad, etc.En relación a las decisiones de nivel superior, se han desarrollado también reglas de balance de materiales, asignación y secuenciación que permiten obtener de una forma rápida y sencilla planes factibles a partir de un conjunto de demandas. Estas reglas se pueden aplicar tanto a planes de producción vacíos en situaciones de puesta en marcha de la planta, como a planes parcialmente llenos con la información de lotes que se están ejecutando en planta, lo que permite la replanificación en linea en caso de ser necesario.También se han aplicado diferentes técnicas de optimización a fin de mejorar planes de producción. Se han probado tanto métodos heurísticos como modelización matemática.En lo referente a los métodos heurísticos, se ha desarrollado un nuevo método de optimización (MSES) que mejora algunos aspectos referentes al algoritmo estándar de recocido simulado. Los algoritmos genéticos han sido también objeto de estudio, incorporando un algoritmo que transforma los individuos infactibles en factibles. Todos estos métodos han sido adaptados al entorno desarrollado permitiendo cambios de secuencia y asignación.En lo que respecta a la modelización matemática, se ha desarrollado un nuevo modelo MILP basado en una extensión del EON introduciendo variables de decisión de secuencia y asignación así como restricciones asociadas a almacenamientos intermedios.El entorno desarrollado en esta tesis ha sido aplicado a diferentes entornos industriales, proporcionando una validación de las tecnologías y modelos desarrollados. En todos los casos estudiados se han podido obtener planes de producción que cumplen con las restricciones presentes en planta, lo que permite establecer la validez de las metodologías desarrolladas para la planificación de la producción en plantas químicas de proceso discontinuo. / The scheduling of batch processes is one of the most complex and important problems faced by a wide variety of processing industries. In spite of this importance, scheduling is often a manual procedure, which leads to operation characterized by high inventories, inefficient capital utilization and increased operation costs. There are also reported complains about the lack of powerful, easy-to-use, PC based tools able to solve detailed operational problems, as well as perform high level analysis across the supply chain.This problem has been the focus of an important amount of research work in the recent years, especially from the early 1980's to nowadays, although the industry has been interested in effective ways of solving the scheduling problem since the early 1940's. An extensive work has been done but the complex nature of the scheduling problem results on the lack of a unique solution widely accepted in the industry.This thesis describes a global generic framework for planning and scheduling of batch chemical plants. Different components have been studied: a data model, a timing model, heuristic sequencing and assignment strategies and optimization procedures.One of the strongest points of the framework presented is its modularity. The fact of having the different components of planning and scheduling as separate modules sharing a common data model allows an easy use and adaptation of different techniques that can help solving the scheduling and planning problem in specific cases. This modular approach has been useful when applying the techniques presented to industrial scenarios. Adaptation to specific scenarios choosing the best alternative for each one is not only possible but also easy.The key point for achieving this is to share the common data and timing model (the EON model). The extensible object oriented data model presented in this thesis allows an organized and systematic information management dealing with the detailed representation of batch processes in the chemical industry. The main strength of the EON model is the capability of representation of complex time constraints between operations in the same schedule using simple components. EON model is presented and developed in detail. A methodology for the representation of storage constraints as time constraints as EON constraints is also presented. An iterative procedure allows also to take into account of limited resources as manpower, electricity, etc.Dispatching-like rules have been developed for the calculation of the material balances, the unit assignment and the batch sequencing. The strength of this approach is based in the easy implementation and adaptation to a batch oriented framework. These rules can be applied to empty schedules or to schedules that already contain frozen batches, which represents the actual situation in the plant. This last aspect allows the use of this kind of rules when performing on-line scheduling.Different optimization techniques have been used in this thesis to solve the scheduling approach presented. Stochastic and mathematical methods have been used and tested.Regarding to the stochastic methods, a new optimization algorithm (MSES) has been introduced that improves the performance of the SA standard algorithm. A modified GA algorithm has also been proposed that transforms the infeasible sequences commonly generated into feasible ones. All the stochastic methods used were adapted to batch processing structures involving batch sequencing and rule driven unit assignment.Regarding to the mathematical approach, the mathematical formulation presented in the EON timing model has been extended by introducing sequence and assignment variables as well as storage constraints.The framework developed in this thesis has been successfully applied to different industrial scenarios that are shown. The proposed solutions have been able to represent all the complexity of the test cases studied providing a powerful tool for planning and scheduling of the different plants.

District heating is an environmentally friendly heating principle that is widely used in Sweden. A problem that has arisen is that while district heating dominates heating of apartment buildings, the district heating companies have difficulties competing in single-family houses. In Örebro, the 7th largest city in Sweden, this problem causes some worries because of the environmental benefits with district heating compared to electricity-based heating alternatives which are more commonly used. The goal of this study has been to calculate the life cycle costs for district heating in Örebro from the house owner’s perspective and to compare these with the life cycle costs for heating by geothermal heat pumps. The study also examines the potential of a few proposed solutions for improved economy for district heating in areas with single-family houses. The calculations estimate the life cycle costs during 30 years for district heating to 697 kkr and 562 kkr for geothermal heat pumps. High energy costs being the primary reason for the district heating’s expensive outcome. A possible solution to improve the situation for district heating is the development of low temperature distribution.This could decrease the heat losses and thereby make district heating less expensive. Another solution that will make district heating more profitable in the future is district heating powered machines such as washing machines, dryers and dishwashers. The use of these machines replaces electricity consumption with heating consumption. For the use of these machines in houses with conventional district heating a separate pipe is needed which makes them not profitable at the moment. In Västerås, a city comparable to Örebro, low temperature grids are being developed with district heated machines in areas with newly built low energy houses. This solution uses a secondary grid with only one pipe for heating, heating of water and the district heated machines. The life cycle costs for this solution is 653 kkr, much less expensive than the conventional district heating in Örebro. An introduction of a similar solution in Örebro could make district heating in one-family houses more profitable, for both producer and consumer.

Superheaters suffer large material loss during combustion of waste and biomass, causing a short life time for these expensive components. During combustion, corrosive ash particles are formed and erosion is caused by circulating bed material and sand particles, all contributing to the material loss. This study examines whether corrosion or erosion has the largest effect on this material loss by investigating two superheaters in loop seal during biomass and waste combustion of an 85 MW, Circulating Fluidized Bed (CFB) boiler in Händelö. The samples were investigated by SEM/EDX and XRD with regard to material loss and corrosion products. The superheaters have different thermal conditions since the material temperature in the first superheater that the steam passes is lower than in the one that comes after. In this report, a model to determine the tube temperature in steam boiler superheaters is also described due to the fact that the local tube temperature is of great importance of condensation of corrosive gases such as KCl and NaCl. Material loss was significantly greater on the cooler superheater compared with the warmer. The material temperatures on the outside of the tubes, were calculated to be about 574 °C for the cooler superheater and about 617°C for the warmer superheater. Overall, all analyzes showed low levels of corrosive substances, although there was a certain corrosion tendency, which indicates that material loss of the superheaters is caused by corrosion-assisted erosion. Lower material temperature of the superheater resulted in a higher degree of condensation of corrosive species such as alkali chlorides, which might have accelerated the erosion. The conclusion is that the dominant mechanism of material loss on the superheaters is erosion.