| 1. |
- Geli Rolfhamre, Patricia, 1979-
(författare)
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From Penicillin Binding Proteins to Community Interventions : Mathematical and Statistical Models Related to Antibiotic Resistance
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibiotic resistance has become a major public health concern and mathematical models are important analytical tools for the understanding, evaluation and prediction of the resistance problem and related control strategies.The risk of emerging antibiotic resistance and selection has rarely been a concern in the design of antibiotic drug dosing regimens. In the first paper, a selection of antibiotic resistant subpopulations for different antibiotic dosing regimens was studied in vitro. The demonstrated complex relationship was influenced by both the rise of new mutants and a postantibiotic effect (PAE) (continued inhibition of bacterial growth after removal of the antibiotic drug). By constructing a mathematical model that incorporated biologically relevant parameters, we were able to assess the risks of resistance development under different dosing strategies.In the second paper, the model for PAEs is further developed to determine the implications for different dosing regimens. The result challenges the conventional notion that long PAEs promote extended drug dosing intervals and it allows new hypotheses to be tested experimentally based on the findings from the theoretical framework.Since PAE experiments often are time-consuming and laborious, very few studies have been reporting variation for this phenomenon. In the third paper, an extension to capture the stochastic behavior of bacterial population growth under drug exposure is made. The stochastic nature of the model is also an important complement to the existing deterministic models on drug dose drug effect relationships.The last paper describes a controlled clinical intervention study aiming at determining whether the frequency of trimethoprim resistance in E. coli can be decreased by a sudden and drastic reduction in trimethoprim use. In addition to evaluating the intervention effect, the model, given estimated parameters, is also used for predicting other interesting outcomes.
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| 2. |
- Keller, Marek, 1983-
(författare)
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Konkurs och process
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Civil actions are a regular occurrence during the course of bankruptcy proceedings and may have wide-ranging and significant social impacts, not least due to the fact that they can pertain to assets of considerable value or affect a large number of individuals and various types of economic interests. These lawsuits also raise a number of legal issues regarding the delimitation of procedural rights of various bankruptcy actors, such as the bankruptcy trustee, the bankruptcy debtor and individual creditors.The mentioned competence issues are complex and have over the years generated relatively extensive case law. Additionally, they are of great importance in a bankruptcy, as they have a major impact on the outcome of bankruptcy proceedings and on the furthering of the efficacy of the policies underlying bankruptcy law.This thesis aims at systematizing and evaluating the rules regarding the bankruptcy actors' competence in civil proceedings to directly or indirectly dispose of assets and liabilities that are subject to a process by way of litigation. It is further intended to investigate how these rules affect the impact of the policy aims behind the substantive competence rules of bankruptcy law and the main purpose of the bankruptcy, and whether the regulation constitutes acceptable coordination between substantive bankruptcy law and procedural law.The investigation covers a very large number of legal issues at the intersection of substantive bankruptcy law and general procedural rules governing civil proceedings, for example: Who may be a party or intervener in actions regarding assets or debts in the bankruptcy? What are the legal implications of the estate substituting the debtor as a party to an action? What prospects does a bankruptcy estate have to avoid being drawn into the bankruptcy debtor's actions? To what extent are judgments in the debtor’s actions binding in bankruptcy proceedings?The inquiry shows that the relationship between the substantive and procedural rights of the individual bankruptcy actors is complex. In a number of situations, individual bankruptcy actors have a more wide-ranging procedural right of disposal regarding assets or liabilities than a substantive one. This gives rise to a risk that these rights will be used in ways that limit the impact for the policy aims of bankruptcy law, for example, by circumventing rules to protect third parties. However, it is argued that a more wide-ranging procedural right of disposal can, in certain instances, further the policies underlying bankruptcy law, provided that the relevant procedural rights are adequately set out. The thesis also discusses various solutions regarding the delimitation of the individual bankruptcy actors' procedural rights.
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| 3. |
- Andersson, Bengt-Åke
(författare)
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Circulating Biomarkers in Patients with Head and Neck Cancer and the Influence of Cigarette Smoking
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Head and neck cancer (HNC) is a collective name for heterogeneous tumors located in the head and neck regions for which smoking, alcohol and human papillomavirus (HPV) are documented risk factors. The survival of HNC patients has only improved marginally during the last decade. The most important prognostic factors are tumor size, local spread and distant metastases, tumor node metastasis (TNM) staging. Prognostic biomarkers are needed as a complement to TNM staging.The aim for this thesis was to investigate rapid and low cost blood based biomarkers which could indicate the risk of HNC, recurrence of the disease or the survival of HNC patients. Furthermore, the aim was to examine how cigarette smoking influences the levels of biomarkers.In paper I, a possible role of plasma cytokines or proteins associated with immune response or inflammation, as biomarkers for the survival of HNC patients was investigated. Higher levels of C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α) were detected in plasma of the patients compared with the levels in the controls. The elevated levels of these two biomarkers detected in patients were associated with decreased survival.In paper II, the influence of 45 single nucleotide polymorphisms (SNPs) located in 41 genes associated with cell cycle progression, cell death, DNA repair or immune response on cancer risk, tumor recurrence and survival in HNC patients were investigated. SNPs in immune response genes were associated with risk for HNC, an elevated risk for recurrence and a decreased survival in HNC patients.In paper III, the influence of cigarette smoking on levels of inflammatory cells, proteins or cytokines/chemokines, microRNAs (miRNAs) and SNPs was analysed in healthy smokers and non-smokers. Higher levels of total white blood cells (WBCs), neutrophils, monocytes, lymphocytes, neutrophil to lymphocyte ratio (NLR), CRP, monocyte chemoattractant protein- 1 (MCP-1) and interferon gamma (IFN-γ) were detected in smokers compared to non-smokers and indicate an inflammatory response. Also, a lower level of oncomiRNA miR-21was detected in smokers. This alteration, in combination with the elevated levels of IFN-γ in smokers could be a protective response to cigarette smoke. The higher levels of IFN-γ in smokers compared to non-smokers were however only detected in individuals with SNP rs2069705 genotype AG/GG. This indicates a genetic association of the levels of IFN-γ.In paper IV, the separate effects of cigarette smoking and HNC on inflammatory or immune biomarkers and the impact of high risk human papillomavirus, age and gender were investigated. Comparisons of circulating levels of WBCs and its subpopulations, plasma proteins or cytokines/chemokines between smoking and non-smoking patients, smoking and non-smoking controls and between the patient and control groups were analysed. Smoking had highest impact on elevated levels of WBCs, IFN-γ and MCP-1, and HNC had highest impact on elevated levels of neutrophils, monocytes, NLR, CRP, macrophage inflammatory protein 1 beta and TNF-α.In conclusion, host immune response associated parameters could be suitable as biomarkers for the risk of HNC, risk of recurrence or in predicting survival of HNC patients. This thesis show that HNC are associated with systemic inflammatory response and upregulated CRP and TNF-α is related to shorter survival in HNC patients. Additionally, SNPs in immune response genes such as rs1800629 in the TNF-α gene indicates a risk for HNC or an elevated risk for recurrence and a decreased survival in HNC patients. These rapid and low cost blood based biomarkers could be used in combination or as a supplement to established biomarkers in the clinic for a more personalized treatment modality.
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| 4. |
- Andersson, Johan, 1971-
(författare)
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Summation formulae and zeta functions
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis in analytic number theory consists of 3 parts and 13 individual papers.In the first part we prove some results in Turán power sum theory. We solve a problem of Paul Erdös and disprove conjectures of Paul Turán and K. Ramachandra that would have implied important results on the Riemann zeta function.In the second part we prove some new results on moments of the Hurwitz and Lerch zeta functions (generalized versions of the Riemann zeta function) on the critical line.In the third and final part we consider the following question: What is the natural generalization of the classical Poisson summation formula from the Fourier analysis of the real line to the matrix group SL(2,R)? There are candidates in the literature such as the pre-trace formula and the Selberg trace formula.We develop a new summation formula for sums over the matrix group SL(2,Z) which we propose as a candidate for the title "The Poisson summation formula for SL(2,Z)". The summation formula allows us to express a sum over SL(2,Z) of smooth functions f on SL(2,R) with compact support, in terms of spectral theory coming from the full modular group, such as Maass wave forms, holomorphic cusp forms and the Eisenstein series. In contrast, the pre-trace formula allows us to get such a result only if we assume that f is also SO(2) bi-invariant.We indicate the summation formula's relationship with additive divisor problems and the fourth power moment of the Riemann zeta function as given by Motohashi. We prove some identities on Kloosterman sums, and generalize our main summation formula to a summation formula over integer matrices of fixed determinant D. We then deduce some consequences, such as the Kuznetsov summation formula, the Eichler-Selberg trace formula and the classical Selberg trace formula.
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| 5. |
- Andersson, Mikael, 1979-
(författare)
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Assessing Physical Activity and Physical Capacity in Subjects with Chronic Obstructive Pulmonary Disease
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to assess measurement properties of methods suitable for screening or monitoring of physical capacity and physical activity in subjects with chronic obstructive pulmonary disease (COPD), and to explore factors associated with physical activity levels.Methods: Four observational studies were conducted. Participants in studies I-III (sample sizes) (n=49, n=15, n=73) were recruited from specialist clinics, and in study IV from a population-based cohort (COPD n=470 and Non-COPD n=659). Psychometric properties of methods assessing physical capacity (study I) and physical activity (study II) were investigated in laboratory settings. Daily physical activity and clinical characteristics were assessed with objective methods (study III) and with subjective methods (study IV).Results: Physical capacity as measured by walking speed during a 30-metre walk test displayed high test-retest correlations (ICC>0.87) and small measurement error. The accuracy for step count and body positions differed between activity monitors and direct observations. In study III 92% of subjects had an activity level below what is recommended in guidelines. Forty five percent of subjects’ activity could be accounted for by clinical characteristics with lung function (22.5%), walking speed (10.1%), quadriceps strength (7.0%) and fat-free mass index (3.0%) being significant predictors. In study IV, low physical activity was significantly more prevalent in COPD subjects from GOLD grade ≥II than among Non-COPD subjects (22.4 vs. 14.6%, p = 0.016). The strongest factors associated with low activity in COPD subjects were a history of heart disease, OR (CI 95%) 2.11 (1.10-4.08) and fatigue, OR 2.33 (1.31-4.13) while obesity was the only significant factor in Non-COPD subjects, OR 2.26 (1.17-4.35).Conclusion: The 30 meter walk test and activity monitors are useful when assessing physical capacity and physical activity, respectively in patients with COPD. Impaired physical activity in severe COPD is related to low lung function, low walking speed, low muscle strength and altered body composition, whereas comorbidities and fatigue are linked to insufficient physical activity in patients with moderately severe COPD.
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| 6. |
- Andersson, Mikael, 1964-
(författare)
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Characterisation of Chromatography Media Aimed for Purification of Biomolecules
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chromatography media (resins) are very important for and widely used by the biopharma industry in large scale production of biopharmaceuticals, e.g. monoclonal antibodies. Today there are several hundred biopharmaceuticals released globally on the healthcare market. This thesis discusses various strategies and methods for the characterisation of chemical and functional stability of chromatography media. In addition, various analytical techniques used in these areas were evaluated and applied. Further, more specific physical and chemical characterisation methods were evaluated and applied to explore different properties of various chromatography media.In Papers I-III, established methodologies for performing chemical and functional stability studies were used. Mainly agarose-based chromatography media were investigated. For fast screening of the chemical stability, the total organic carbon analysis technique was evaluated and applied. This technique that measures the carbon leakage from the chromatography media at different conditions, proved to be very suitable and robust. For detection and/or identification of leakage compounds responsible for or for part of the measured carbon leakage, different methods such as (high performance) liquid chromatography and gas chromatography mass spectrometry were used.In Papers IV-VII, different properties (i.e. functional performance, ligand content and surface chemistry) were evaluated for different agarose-based chromatography media. Standard chromatographic methods (ion exchange chromatography) and spectroscopic methods (e.g. Fourier transform infrared spectroscopy and time-of-flight secondary ion mass spectrometry) were evaluated and applied. Chemometric methods were used for efficient evaluation of data.Information of chemical, functional and leakage data of chromatography media are valuable and important for the biopharmaceutical companies to be able to fulfil the regulatory requirements of biopharmaceuticals. In addition, information of various chemical, functional and physical properties of chromatography media is likewise important during development and set up of new biopharmaceutical processes.
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| 7. |
- Andersson, Mattias, 1980-
(författare)
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Coding and Transmission Strategies for Secrecy
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis we consider several problems relating to information theoretic security. The wiretap channel is the simplest information theoretic setting which takes security into account, and in the first chapters of the thesis we design some practical coding schemes for this channel model.First we consider the design of two edge type low density parity check (LDPC) codes for the binary erasure wiretap channel (BEC-WT). For the scenario when the main channel is error free and the wiretapper's channel is a binary erasure channel (BEC) we find secrecy capacity achieving code sequences based on standard LDPC code sequences for the BEC. However, this construction does not work when there are also erasures on the main channel. For this case we develop a method based on linear programming to optimize two edge type degree distributions. Using this method we find code ensembles that perform close to the secrecy capacity of the BEC-WT. We generalize a method of Méasson, Montanari, and Urbanke in order to compute the conditional entropy of the message at the wiretapper. We apply this method to relatively simple ensembles and find very good secrecy performance.We then show that Arikan's polar codes can be used to achieve the whole capacity-equivocation region of for any degraded symmetric binary input wiretap channel. We also design capacity achieving polar codes for the decode-and-forward scheme for the physically degraded relay channel, and for the bidirectional broadcast channel with common and confidential messages.In the subsequent chapter we consider a Gaussian system model. We show that sparse regression codes (SPARCS) as introduced by Joseph and Barron achieve the secrecy capacity of the additive white Gaussian noise (AWGN) wiretap channel, and can be used to implement the decode-and-forward scheme for the Gaussian relay channel. We also consider secret key agreement using correlated Gaussian random variables and a rate-limited public channel. We show that SPARCs attain the capacity region also for this problem.Finally we consider secret key agreement over reciprocal fading channels. We first consider a multiple-antenna setup in the high signal-to-noise-ratio (SNR) regime and propose a scheme based on training and randomness sharing. We then consider a single antenna setup in the low SNR regime, where one of the terminals is only allowed to transmit pilot signals. We propose a bursty transmission scheme based on training and opportunistic transmission using a wiretap channel code, and show that this scheme is optimal.
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| 8. |
- Andersson, Mikael, 1986
(författare)
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Control Rod Homogenization in Heterogeneous Sodium-Cooled Fast Reactors
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The sodium-cooled fast reactor is one of the candidates for a sustainable nuclearreactor system. In particular, the French ASTRID project employs an axiallyheterogeneous design, proposed in the so-called CFV (low sodium effect) core, toenhance the inherent safety features of the reactor.This thesis focuses on the accurate modeling of the control rods, through thehomogenization method. The control rods in a sodium-cooled fast reactor are usedfor reactivity compensation during the cycle, power shaping, and to shutdownthe reactor. In previous control rod homogenization procedures, only a radialdescription of the geometry was implemented, hence the axially heterogeneousfeatures of the CFV core could not be taken into account. This thesis investigatesthe different axial variations the control rod experiences in a CFV core, to determinethe impact that these axial environments have on the control rod modeling.The methodology used in this work is based on previous homogenizationprocedures, the so-called equivalence procedure. The procedure was newly implementedin the PARIS code system in order to be able to use 3D geometries, andthereby be take axial effects into account.The thesis is divided into three parts. The first part investigates the impactof different neutron spectra on the homogeneous control-rod cross sections. Thesecond part investigates the cases where the traditional radial control-rod homogenizationprocedure is no longer applicable in the CFV core, which was found tobe 5-10 cm away from any material interface.In the third part, based on the results from the second part, a 3D model of thecontrol rod is used to calculate homogenized control-rod cross sections. In a fullcore model, a study is made to investigate the impact these axial effects have oncontrol rod-related core parameters, such as the control rod worth, the capturerates in the control rod, and the power in the adjacent fuel assemblies. All resultswere compared to a Monte Carlo-based model which served as the reference.It was demonstrated that the treatment of the radial environment, surroundingthe control rod, has a small impact on the core parameters, and the traditionalradial homogenization procedure yields reliable results. For axial interfaces withinthe control rod itself, the traditional radial homogenization procedure could nolonger capture the large environmental impact, hence 3D modeling is recommended.
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| 9. |
- Andersson, Mikael
(författare)
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Hur kan akademi organisera samverkan för tillväxt? : Deliberativ Organiserad Samverkan, DOS, en ny styrningsmodell
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Within research and education policies of later decades, a clear trend can be seen in expanded attempts to stimulate growth-concentrated cooperation between government, academia and industry. With economic financing, channelled to academia through different kinds of research and development councils, follows a responsibility to operationally organize the actors' cooperation. This task is rather complex. The cooperative process is expected to be equal, provided that the participating actors have different professional identities, belong to different organizations, have different values and ideas of norms, and satisfy different interests. With present research and education policies, follows the idea of academia acting as a potential growth engine that should be directly used to develop society's innovation system, production system and markets. In connection with this, discussions regarding academic capitalism, commercialisation of research results, incubation processes, etc., are being conducted. The traditional role of academia as a research university has also been complemented by the roles of organizer for growth-concentrated cooperation and entrepreneur.Pursuing independent research, being an organizer for similar cooperation, and satisfying their personal interests all at the same time is contradictory. A way for academia to prevent their own interests from getting out of hand during cooperation is to avoid all forms of external management, and instead focus on stimulating the participating actors to evaluate, develop and manage their cooperation themselves. Conventional education, research and project models are developed for purposes other than this. Desipte this, their usage with the cooperative task is rather widespred. For cooperative actors to understand and handle their activities in an aware, collective and flexible manner, they need to use some form of management model that allows for communicative coordination, evaluation and development of organizational action. As an alternative to those conventional models, a new management model has been developed in this thesis, called Deliberative Organized Cooperation, DOC. The model is developed with inspiration from deliberative theory. Simply put, the actors' cooperation is expected to occur through repeated dialectic movements between deliberative phases (management process), where actors produce valid action alternatives and legitimate interpersonal and systematic relations, and systematic phases (operational activities), where the actors transform the gained validity and legitimacy in systematic action and resulting factuality. While the deliberative phase corresponds to evaluation and development orientated logic with open rationality conditions, the systematic phase corresponds to production orientated logic with closed rationality conditions.The primary empirical results of the thesis are collected from activities that have been driven or are driven within or closely connected to two competence centres located at Luleå Univeristy of Technology. The first competence centre, the Polhem Laboratory, is presently being phased out and replaced by the Faste Laboratory. Both operations can be described with help from the Triple Helix model. Simply stated, the government contributes with direct economic funding for R&D as well as the overall rules of the game regarding the actors' cooperation, the industry with supplementary economic funding and direct turnover of the developed knowledge. The economic funding also goes to academia with an organizing of the cooperation process, knowledge development and commercialisation of interesting spin-off knowledge. An essential element in the operations of the Polhem and Faste Laboratories constitutes the so-called Sirius Project, an industrially oriented product development project conducted by fourth year students in the mechanical engineering program. This project is primarily conducted in cooperation between academia and large companies. Closely connected to this activity, Arena innovative technology and business, organizes multi-science undergraduate studies. An important part of this education is to cooperate in so-called greenhouse projects. Here, students from various study years and majors, meets researchers/teachers from different subject fields, and actors from different companies and development firms. The over-all aim of the projects is to stimulate entrepreneurship and starting of new robust companies. DOC comprises an attempt to solve management problem identified in connection to the above activities.The activities have been investigated through participating observations. Individual events have been worked upon and weaved together into a cohesive and anonymous scenario that is told by giving voices to a variety of the participating actors. In the theoretically oriented chapter of the thesis, events are problematised from the scenario through analytical and pragmatic reflections. With help of these reflections, the DOC model is successively built up.
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| 10. |
- Andersson, Malin
(författare)
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Modelling, parameter identification and aging-sensitive management of lithium-ion batteries in heavy-duty electric vehicles
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The battery is a component with significant impact on both the cost and environmental footprint of a full electric vehicle (EV). Consequently, there is a strong motivation to maximize its degree of utilization. Usage limits are enforced by the battery management system (BMS) to ensure safe operation and limit battery degradation. The limits tend to be conservative to account for uncertainty in battery state estimation as well as changes in the battery's characteristics due to aging. To improve the utilization degree, aging-sensitive battery management is necessary. This refers to a management strategy that a) adjusts during the battery's life based on its state and b) balances the trade-off between utilization and degradation according to requirements from the specific application. In state-of-the-art battery installations, only three signals are measured; current, voltage and temperature. However, the battery's behaviour is governed by other states that must be estimated such as its state-of-charge (SOC) or local concentrations and potentials. The BMS therefore relies on models to estimate states and to perform control actions. In order to realize points a) and b), the models that are used for state estimation and control must be updated onboard. An updated model can also serve the purpose of diagnosing the battery since it reflects the changing properties of an aging battery. This thesis investigates identification of electrochemical and empirical battery models from operational EV data. In addition, it studies model-based strategies for optimal and adaptive fast charging. The work is divided into four main studies.1) Empirical linear-parameter-varying (LPV) dynamic models were identified on driving data. Model parameters were formulated as functions of the measured temperature, current magnitude and estimated open circuit voltage (OCV). To handle the time-scale differences in battery voltage response, continuous-time system identification was employed. We concluded that the proposed models had superior predictive abilities compared to discrete and time-invariant counterparts.2) A global sensitivity analysis was performed on the parameters of a high-order electrochemical model. Measured current profiles from real EVs were used as input and the parameters' impact on both modelled cell voltage and other internal states was assessed. The study revealed that in order to excite all model parameters, an input with high current rates, large SOC span and longer charge or discharge periods was required. This was only present in the data set from an electric truck with few battery packs. Data sets from vehicles with more packs (electric bus) and limited SOC operating window (plug-in hybrid truck) excited fewer model parameters.3) Instead of using driving data to parametrize models, we also investigated the possibility to design the charging current in order to increase its information content about model parameters. This was formulated as an optimal experiment design problem in frequency domain. An aging-sensitive fast-charge procedure was optimized based on equivalent circuit model (ECM) states. Finally, different methods for combining the optimal fast charge and the optimal experiment were evaluated with regard to the resulting charging time and model performance. 4) Finally, aging-adaptive fast charging of automotive lithium-ion cells was studied. An electrochemical model was identified at the beginning of life and an electrochemically constrained fast charge was designed. The model parameters were then periodically re-evaluated during a cycling study and the charging procedure was updated to account for cell degradation. The study showed that adaptation of charge protocols increased the cell utilization compared to static protocols, but that heterogeneous degradation reduced the validity of the model and the adherence to electrochemical constraints.
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