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  • Public defence: 2019-11-28 10:00 KB.E3.01 (Lilla hörsalen), Umeå
    Lakehal, Abdellah
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    A molecular network mediating adventitious root initiation in Arabidopsis thaliana2019Doctoral thesis, comprehensive summary (Other academic)
    The full text will be freely available from 2020-11-08 07:00
  • Public defence: 2019-11-29 09:00 Stora hörsalen, målpunkt P, byggnad 5B, plan 6, Umeå
    Späth, Cornelia
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    The impact of nutrition on growth, biomarkers, and health outcomes in preterm infants2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: Nutrients play a crucial role for growth and brain development after preterm birth. Meeting the nutritional needs of preterm infants is challenging. Particularly, the most immature infants have a high risk of malnutrition and poor growth during hospital care. To meet recommended energy and nutrient intakes during early postnatal life, a concentrated parenteral nutrition (PN) regimen was implemented in clinical use in 2012 at the neonatal intensive care unit at Umeå University Hospital (Umeå, Sweden). However, electrolyte homeostasis is labile after preterm birth and infants require an electrolyte supply that corresponds to their energy and protein intakes to avoid electrolyte disturbances. Although sodium imbalances such as hyper- and hyponatremia are common in the most immature preterm infants, there is limited knowledge to what extent these imbalances are affected by fluid volume and sodium supply. Furthermore, it is unclear whether the early high sodium concentrations lead to any adverse effects, including intraventricular hemorrhage, or simply reflect immediate adaptive processes after preterm birth.

    Aim: This thesis investigates the impact of nutrition on growth, nutritional biomarkers, and health outcomes in preterm infants born with a birth weight below 1500 g.

    Methods: We used data from two study populations. First, we collected data for all very low birth weight infants (< 1500 g) born between 2010 and 2013 and treated at Umeå University Hospital (Umeå, Sweden; n = 134). Second, we used data from the EXtremly PREterm infants in Sweden Study (EXPRESS). We included all infants born before 27 gestational weeks in Sweden between 2004 and 2007 who survived the first 24 h (n = 602). Data collection for both study populations included a) intakes of all parenteral and enteral nutritional products and other fluids during the first 28 postnatal days, b) all anthropometric measurements during hospital stay, c) perinatal data, and d) neonatal morbidity.

    Results: The concentrated PN regimen improved early energy and macronutrient intakes in very low birth weight infants. Furthermore, weight and length growth from postnatal week two to a postmenstrual age of 36 weeks improved in very low birth weight infants who received the concentrated PN regimen compared with infants who received the previous original PN regimen (Paper I). Increased parenteral energy and protein intakes provided by the concentrated PN regimen, did not induce a higher occurrence of electrolyte imbalances as electrolytes were supplied according to the current recommendations (Paper II). In the EXPRESS cohort, the majority of extremely preterm infants had hypernatremia during the first and hyponatremia during the second postnatal week. Gestational age and supply of sodium, rather than fluid volume, were the major factors determining the risks of hyper- and hyponatremia (Paper III). High total supply of sodium was significantly correlated with severe intraventricular hemorrhage if mostly mediated by blood product transfusions (Paper IV).

    Conclusions: Our results suggest that in very immature preterm infants a concentrated PN regimen improves early nutrient intakes and postnatal growth without causing electrolyte disturbances. Hyper- and hyponatremia are common and the supply of sodium is a major predictor. The impact of sodium on severe intraventricular hemorrhage needs further investigation.

  • Public defence: 2019-11-29 09:00 Hörsal 933, byggnad 3, Umeå
    Adjeiwaah, Mary
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Quality assurance for magnetic resonance imaging (MRI) in radiotherapy2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The use of Magnetic Resonance Imaging (MRI) in the radiotherapy (RT) treatment planning workflow is increasing. MRI offers superior soft-tissue contrast compared to Computed Tomography (CT) and therefore improves the accuracy in target volume definitions. There are, however concerns with inherent geometric distortions from system- (gradient nonlinearities and main magnetic field inhomogeneities) and patient-related sources (magnetic susceptibility effect and chemical shift). The lack of clearly defined quality assurance (QA) procedures has also raised questions on the ability of current QA protocols to detect common image quality degradations under radiotherapy settings. To fully implement and take advantage of the benefits of MRI in radiotherapy, these concerns need to be addressed.

    In Papers I and II, the dosimetric impact of MR distortions was investigated. Patient CTs (CT) were deformed with MR distortion vector fields (from the residual system distortions after correcting for gradient nonlinearities and patient-induced susceptibility distortions) to create distorted CT (dCT) images. Field parameters from volumetric modulated arc therapy (VMAT) treatment plans initially optimized on dCT data sets were transferred to CT data to compute new treatment plans. Data from 19 prostate and 21 head and neck patients were used for the treatment planning. The dCT and CT treatment plans were compared to determine the impact of distortions on dose distributions. No clinically relevant dose differences between distorted CT and original CT treatment plans were found. Mean dose differences were < 1.0% and < 0.5% at the planning target volume (PTV) for the head and neck, and prostate treatment plans, respectively. 

    Strategies to reduce geometric distortions were also evaluated in Papers I and II. Using the vendor-supplied gradient non-linearity correction algorithm reduced overall distortions to less than half of the original value. A high acquisition bandwidth of 488 Hz/pixel (Paper I) and 488 Hz/mm (Paper II) kept the mean geometric distortions at the delineated structures below 1 mm. Furthermore, a patient-specific active shimming method implemented in Paper II significantly reduced the number of voxels with distortion shifts > 2 mm from 15.4% to 2.0%.

    B0 maps from patient-induced magnetic field inhomogeneities obtained through direct measurements and by simulations that used MR-generated synthetic CT (sCT) data were compared in Paper III. The validation showed excellent agreement between the simulated and measured B0 maps.

    In Paper IV, the ability of current QA methods to detect common MR image quality degradations under radiotherapy settings were investigated. By evaluating key image quality parameters, the QA protocols were found to be sensitive to some of the introduced degradations. However, image quality issues such as those caused by RF coil failures could not be adequately detected.

    In conclusion, this work has shown the feasibility of using MRI data for radiotherapy treatment planning as distortions resulted in a dose difference of less than 1% between distorted and undistorted images. The simulation software can be used to produce accurate B0 maps, which could then be used as the basis for the effective correction of patient-induced field inhomogeneity distortions and for the QA verification of sCT data. Furthermore, the analysis of the strengths and weaknesses in current QA tools for MRI in RT contribute to finding better methods to efficiently identify image quality errors.

  • Public defence: 2019-11-29 13:00 Major groove_J0, Umeå
    Aripaka, Karthik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Studies on the biological functions of interaction between components in Wnt, TGF-β and HIF pathways for cancer progression2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cancer is a disease that involves aggressive changes in the genome and aberrant signals between the living cells. Signalling pathways such as TGF-β (Transforming growth factor-β), Wnt, EGF (epidermal growth factor) and HIF (Hypoxia-inducible factor) evolved to regulate growth and development in mammals. These factors are also implicated for tumorigenesis due to failure or aberrant expression of components in these pathways. Cancer progression is a multistep process, and these steps reflect genetic alterations driving the progressive transformation of healthy human cells into highly malignant derivatives. Many types of cancers are diagnosed in the human population, such as head & neck, cervical, brain, liver, colon, prostate, uterine, breast, and renal cell cancer.

    Prostate cancer is the second most common cancer and one of the foremost leading cancer-related deaths in men in the world. Aberrant Wnt3a signals promote cancer progression through the accumulation of β-Catenin. In the first paper, we have elucidated intriguing functions for Tumour necrosis factor receptor-associated factor 6 (TRAF6) as a coregulatory factor for the expression of Wnt-target genes which was confirmed in vivo by using CRISPR/Cas9 genomic editing, in zebrafish. Our data suggest that Wnt3a promotes TRAF6 interaction with Wnt components, and TRAF6 is required for gene expression of β-Catenin as well as for the Wnt-ligand co-receptor LRP5. From the in vivo studies, we elucidated positive regulation of TRAF6, which is crucial for survival and development of zebrafish. This study identifies TRAF6 as an evolutionary conserved co-regulatory protein in the Wnt pathway that also promotes the progression of prostate and colorectal cancer due to its positive effects on Wnt3a signalling.

    Hypoxia is a condition due to O2 deprivation, and Hypoxia-inducible factors (HIF) transcription factors are responsible for the maintenance of oxygen homeostasis in living cells. Irregularities in these HIF transcription factors trigger pathological cellular responses for initiation and progression of malignant cancers. Renal cell carcinoma, malignant cancer arising in renal parenchyma and renal pelvis and, hypoxia plays a vital role in its progression. In the second paper, we have investigated the clinicopathological relevance of several hypoxic and TGF-β component proteins such as HIF-1α/2α/3α, TGF-β type 1 receptor (ALK5-FL) and the intracellular domain of ALK5 (ALK5-ICD), SNAI1 and PAI-1 with patient survival in clear cell renal cell carcinoma (ccRCC). We showed that HIF-2α associated with low cancer-specific survival. HIF-2α and SNAI1 positively correlated with ALK5-ICD, pSMAD2/3, PAI-1 and SNAI1 with HIF-2α; HIF-1α positively correlated with pSMAD2/3. Further, under normoxic conditions, our data suggest that ALK5 interacts with HIF-1α and HIF-2α, and promotes their expression and target genes such as GLUT1 and CA9, in a VHL dependent manner through its kinase activity. These findings shed light on the critical aspect of cross-talk between TGF-β signalling and hypoxia pathway, and also the novel finding of an interaction between ALK5 and HIF-α might provide a more in-depth understanding of mechanisms behind tumour progression

    In the third paper, an ongoing study, we investigated the role of HIF-3α in the progression of Renal cell carcinoma and its association with the components of TGF-β and HIF pathways. We have observed increased levels of HIF-3α in ccRCC and pRCC (papillary renal cell carcinoma) which are associated with advanced tumour stage, metastasis and larger tumours. Also, we found HIF-3α show a significant positive association with pro-invasive gene SNAI1, which is a crucial regulator of epithelial to mesenchymal transition. TRAF6 an E3 ligase known to be a prognostic marker in RCC and we observed HIF-3α associates with TRAF6.

  • Public defence: 2019-12-05 13:00 MA121, Umeå
    Ostovar, Ahmad
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Object Detection and Recognition in Unstructured Outdoor Environments2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Computer vision and machine learning based systems are often developed to replace humans in harsh, dangerous, or tedious situations, as well as to reduce the required time to accomplish a task. Another goal is to increase performance by introducing automation to tasks such as inspections in manufacturing applications, sorting timber during harvesting, surveillance, fruit grading, yield prediction, and harvesting operations.Depending on the task, a variety of object detection and recognition algorithms can be applied, including both conventional and deep learning based approaches. Moreover, within the process of developing image analysis algorithms, it is essential to consider environmental challenges, e.g. illumination changes, occlusion, shadows, and divergence in colour, shape, texture, and size of objects.

    The goal of this thesis is to address these challenges to support development of autonomous agricultural and forestry systems with enhanced performance and reduced need for human involvement.This thesis provides algorithms and techniques based on adaptive image segmentation for tree detection in forest environment and also yellow pepper recognition in greenhouses. For segmentation, seed point generation and a region growing method was used to detect trees. An algorithm based on reinforcement learning was developed to detect yellow peppers. RGB and depth data was integrated and used in classifiers to detect trees, bushes, stones, and humans in forest environments. Another part of the thesis describe deep learning based approaches to detect stumps and classify the level of rot based on images.

    Another major contribution of this thesis is a method using infrared images to detect humans in forest environments. To detect humans, one shape-dependent and one shape-independent method were proposed.

    Algorithms to recognize the intention of humans based on hand gestures were also developed. 3D hand gestures were recognized by first detecting and tracking hands in a sequence of depth images, and then utilizing optical flow constraint equations.

    The thesis also presents methods to answer human queries about objects and their spatial relation in images. The solution was developed by merging a deep learning based method for object detection and recognition with natural language processing techniques.

  • Public defence: 2019-12-06 09:00 933, Unod B 9, Umeå
    Farag, Salah I.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University.
    Biogenesis, function and regulation of the type III secretion translocon of Yersinia pseudotuberculosis2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Many Gram negative bacteria use type III secretion systems to cross-talk with eukaryotic cells. Type III secretion system assembly and function is tightly regulated. It initiates with assembly of a basal body-like structure, and is followed by a cytoplasmic-located substrate sorting and export platform that first engages with early substrates required for needle assembly. At the needle tip, a translocon is formed upon eukaryotic cell contact to allow the translocation of effector proteins to the host cell. The focus of this thesis is on understanding aspects of biogenesis, regulation and function of the translocon and its interaction with the host cell. Research questions are addressed in enteropathogenic Yersinia pseudotuberculosis model.

    Prioritising the secretion of translocon components before effector proteins is a task given partly to the InvE/MxiC/HrpJ family of proteins. In Yersinia, homology to this protein family is partitioned over two proteins; YopN and TyeA. Certain Yersinia strains naturally produce a single YopN/TyeA polypeptide hybrid. To understand the implications of hybrid formation towards type III secretion control, a series of mutants were engineered to produce only a single hybrid peptide. Using in vitro assays revealed no difference in substrate secretion profiles between parent and mutants. Moreover, no obvious prioritisation of secretion between translocator and effector substrates was observed. Although these in vitro studies indicate that the YopN-TyeA single polypeptide is fully functionally competent, these mutants were attenuated in the mouse infection model. Hence, natural production of YopN and TyeA as a single polypeptide alone is unlikely to confer a fitness advantage to the infecting bacteria and is unlikely to orchestrate hierarchal substrate secretion.

    The YopB and YopD translocon components form a pore in the host cell plasma membrane to deliver the effectors into the host cell. To better understand how YopD contributes to the biogenesis, function and regulation of the translocon pore, a series of mutants were constructed to disrupt two predicted α-helix motifs, one lying at the N-terminus and the other at the C-terminus. Based upon phenotypes associated with environmental control of Yop synthesis and secretion, effector translocation, evasion of phagocytosis, killing of immune cells and virulence in a mouse infection model, the mutants were grouped into three phenotypic classes. A particularly interesting mutant class maintained full T3SS function in vitro, but were attenuated for virulence in a murine oral-infection model. To better understand the molecular basis for these phenotypic differences, the effectiveness of RAW 264.7 cells to respond to infection by these mutants was scrutinised. Sixteen individual cytokines were profiled with mouse cytokine screen multiplex analysis. Signature cytokine profiles were observed that could again separate the different YopD mutants into distinct categories. The activation and supression of certain cytokines that function as central innate immune response modulators correlated well with the ability of mutant bacteria to modulate programmed cell death and antiphagocytosis pathways. Hence, the biogenesis of sub-optimal translocon pores alters host cell responsiveness and limits the ability of Yersinia to fortify against attack by both early and late arms of the host innate immune response.

    The amount of bacteria now resistant to multiple antibiotics is alarming. By providing insights into a common virulence process, this work may ultimately facilitate the design of novel broad-acting inhibitors of type III secretion, and thereby be useful to treat an array of bacterial infections.

  • Public defence: 2019-12-06 13:00 Hörsal B, Unod T9, Umeå
    Holmgren, Klas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Permanent stoma after anterior resection for rectal cancer: prevalence and mechanisms2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    While sphincter-saving surgery constitutes standard treatment for rectal cancer, anterior resection still harbours a significant risk of a permanent stoma in the long run. Although anastomotic leakage plays a major role in this surgical dilemma, the exact mechanisms are not known, while surveys indicate a stoma-free outcome is essential for a majority of patients. To address this issue, the overall aim of the present thesis was to investigate the permanent stoma prevalence in patients undergoing anterior resection for rectal cancer in Sweden, and to identify plausible mechanisms that impede prospects of a stoma-free outcome.

    In a population-based cohort, chart review of patients who had anterior resection for rectal cancer in the Northern healthcare region in Sweden between 2007 and 2013 showed that 75 out of 316 (24%) patients ended up with a permanent stoma. Of 274 patients (87%) primarily defunctioned with a stoma, 229 underwent stoma closure, 21 (9%) of whom suffered major complications that required return to theatre or worse. A permanent stoma was shown to be more common among patients with anastomotic leakage and an advanced tumour stage.

    A registry-based method to estimate nationwide stoma outcome after anterior resection for rectal cancer was developed, using data from the Swedish Colorectal Cancer Registry and the National Patient Registry. With a chart-reviewed cohort as reference, stoma outcome was assessed with a positive predictive value of 85.1%, and a negative predictive value of 100.0%. In patients operated in Sweden between 2007 and 2013, the registry-based method determined that 942 out of 4768 (19.8%) had a permanent stoma, while stoma rates varied substantially between different healthcare regions.

    In a 1:1 matched case-control study of 82 patients who had curative resection for non-disseminated colorectal cancer, a subgroup analysis of 34 patients with rectal cancer displayed biomarker aberrations in serum measured preoperatively in those with anastomotic leakage. Compared to complication-free controls, 15 proteins related to inflammation were elevated, of which two (C-X-C motif chemokine 6, and C-C motif chemokine 11) remained significant after adjustment for multiple testing.

    Based on a cohort of 4529 patients who had anterior resection, tumour height served as a proxy to determine the extent of mesorectal excision, while long-term stoma outcome was classified using a previously validated registry-based method. Defunctioning stomas significantly decreased chances of a stoma-free outcome, especially in patients undergoing partial mesorectal excision; for these patients, faecal diversion was also least beneficial in terms of reducing anastomotic leakage.

    In conclusion, every fifth patient undergoing anterior resection for rectal cancer in Sweden eventually ends up with a permanent stoma. Although construction of a defunctioning stoma decreases the risk of symptomatic anastomotic leakage, subsequent takedown surgery carries a substantial risk of major complications, while chances of a long-term stoma-free outcome become significantly reduced. To facilitate selective use of faecal diversion, novel markers to identify high-risk anastomoses prior to surgery have been identified, but require validation in larger prospective settings. Anterior resection without a defunctioning stoma should be considered in appropriately informed patients for whom a stoma-free outcome is of importance. In particular, this holds true for patients eligible for partial mesorectal excision, where anastomotic dehiscence is less frequent and the advantageous effects of a defunctioning stoma are limited.

  • Public defence: 2019-12-11 09:00 N460
    Rebbling, Anders
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Application of fuel design to mitigate ash-related problemsduring combustion of biomass2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The energy supply of today is, through the use of fossil energy carriers,contributing to increased net emissions of greenhouse gases. This hasseveral negative effects on our environment and our climate. In order toreduce the impact of this, and possibly to reverse some of the effects, allrenewable energy sources must be used. Biomass is the renewable energycarrier that has the greatest potential to reduce net greenhouse gasemissions, but the transition from fossil fuels to biofuels is challenging.The combustion of biomass is associated with various technical andenvironmental problems such as slagging, corrosion, and emissions ofparticles, soot, or harmful chemical compounds. Most of these problemsare linked to ash chemical reactions involving alkali metals. Therefore, toreduce the risk of operational and environmental problems, it is importantto understand and control the ash transformation reactions involvingalkali metals.The research presented in this thesis has focused on the development oftools, such as models and indices, for predicting the behaviour of variousbiofuels during combustion, and on the development of the concept of fueldesign and implementation of the same during industrial combustion ofbiomass. The development of easy-to-use tools for predicting problematicash behaviour is crucial in order to make it possible to increase the use ofbiomass as an alternative to fossil fuels. The tools presented here are basedon theoretical and empirical knowledge and can be used to predictchallenges concerning the fuel ash composition and to propose relevantfuel design measures.The purpose of fuel design, as used here, is to broaden the fuel feedstockand to increase the usability of biomass in the global energy system. Thisis achieved through measures to change the ash chemical composition inorder to enhance beneficial properties, or reduce problematic properties,via the use of additives or blending of two or more different fuels.The present thesis extends the foundation of knowledge regarding fuel ashtransformation reactions and their implications for operational problemsthrough in-depth laboratory studies and analyses. Furthermore, thefeasibility of applying this extended knowledge in the medium and largescaleindustrial combustion of biomass is demonstrated and validated. More specifically, a slagging index has been developed using the results ofseveral years of combustion experiments. Fuel designs based on the indexwas demonstrated during normal operation in local and district heatingplants. Furthermore, a model was developed for predicting slaggingproblems that take into account both the chemical composition of the fueland the burner technology.Several studies have also been performed on different fuel designs basedon the same foundation as the index and the model. Additives to supply forexample calcium and sulphur, as well as the clay kaolin, have been used toreduce both technical and environmental problems.The conclusion is that fuel design, based on ash chemistry, is a possiblepath for increased fuel flexibility and a broader feedstock for bioenergy.

  • Public defence: 2019-12-12 13:00 Hörsal E, Umeå
    Dahlkvist, Mattias
    Umeå University, Faculty of Arts, Department of historical, philosophical and religious studies.
    The politics of Islam, non-violence, and peace: the thought of Maulana Wahiduddin Khan in context2019Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This is a study of the multifaceted thought of Maulana Wahiduddin Khan (b.1925–), Indian writer, public intellectual, and Muslim religious leader. Khan has been a prolific writer since at least the 1970s and is also an ālim, a Muslim scholar learned in religion. His reputation is based on his public presentation of Islam, non-violence, and peace – a position he has defended in his monthly journal, al-Risāla (Eng. version: Spirit of Islam), a large number of published books and pamphlets, and recently also through use of the internet and social media. Furthermore, as a religious leader and debater Khan has been active as a commentator in Indian national media and through religious dialogue meetings, for which he has received national awards and honours. Khan’s religious thought may be summarised as a thorough attempt at presenting Islam, the Quran, and the example of the Prophet Muhammad as a systematic message of peace. Islam is described as a divine message calling for individual commitment and knowledge. Hence, Islam requires a setting of freedom, peace, and stability so that believers can choose its message without restriction. The Quran is regarded as highlighting non-violent patience as the most significant virtue and peace is both a divine quality as well as a requirement for salvation. The religious ideal of the Prophet Muhammad is not his political achievements. Instead, the Prophet’s message is understood as peaceful negotiation and success through turning conflict into friendship as the ultimate path to end hatred, violence, and persecution. The concept of jihad is seen as essential to this type of peace-building struggle; spreading Islam only through preaching, as well as overcoming the hurdles of the self and ego, for instance anger and violent impulses. By situating Khan’s thought in a context of historical and contemporary debate on the meaning of Islam, this study argues that he continues and develops the nineteenth century Indian Islamic Modernist tradition of presenting Islam, non-violence, and peace in relation to issues of the modern state and the minority situation of Indian Muslims. This type of religious position became nationally prominent from the 1920s during the Indian independence movement. In the contemporary Indian political and social situation however, Hindu nationalist and anti-Muslim rhetoric is being followed by large-scale violence. Khan’s thinking aims to dissociate the rhetorical connection between Islam and violence, while supporting the democratic, pluralist, and secular trappings of the state. The analysis of Khan’s thought considers Islamic Modernism and unmarked reform Sufi Islam, alongside the secularism, democratic liberalism, and reform socialism of the Indian constitution. However, these thematic and discursive structures of thought are formulated by Khan with regard to a certain historical situation, and address particular political and social issues. Studying the various connections between Khan’s thought, the ideological and religious debates, and the historical context of Indian and global society, the final analysis of this study takes on the theoretical issue of whether contemporary and globalised religion can be a force for the development of more democratic and peaceful societies.

  • Public defence: 2019-12-13 10:00 KB.E3.01 (Lilla hörsalen), Umeå
    Phal, Sereilakhena
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Development of electrochemical sensor and biosensor platforms: detection of therapeutic drugs and heavy metal ions2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Electrochemical sensors and biosensors combine the sensitivity of electroanalytical methods with the selectivity of a sensor or biosensor surface. The chemical or biochemical component (receptor) in the sensor recognizes an analyte and produces an electrical signal which is proportional to the analyte concentration. Some of these sensors are routinely used in clinical applications and are known for their simplicity, portability, cost-effective, and miniaturization. The glucose sensor used in the management of diabetes is a good example of such biosensors.

    This thesis deals with the development of electrochemical biosensor and sensor platforms for the detection of therapeutic drugs, demonstrated using methotrexate (MTX) which is the most common drug used for the treatment of cancer patients, and heavy metal ions (Pb2+ and Cd2+).

    The biosensor surfaces were generated by immobilization of antibody (anti-MTX) on chemically modified gold electrodes using different surface modification protocols. Self-assemble monolayer (SAM) using alkanethiol (cysteamine) or electrografting with diazonium salt (4- carboxybenzenediaonium tetrafluoroborate, 4-CBD) was used for surface modification. The surface modification was monitored and characterized using electrochemical immittance spectroscopy (EIS) and cyclic voltammetry (CV) along with other complementary technique such as X-ray photoelectron spectroscopy (XPS). The biosensing surfaces were used for the detection of MTX in an electrochemical flow cell (paper I) and in a batch system (paper II). The detection was based on non-faradaic electrochemical immittance spectroscopy (EIS) and singular value decomposition (SVD) for data evaluation. Both electrochemical biosensors provided the lowest limit of detection, LOD (at picomolar level) compared to earlier reports.

    The electrografting of 4-CBD on glassy carbon electrode (GCE) using CV and the parameters that influence the number of monolayers that can be grafted on the surface are demonstrated (paper III). The CVs obtained during grafting showed one or two reduction peaks, and this was found to be related to the number of monolayers deposited on the electrode. One can increase the number of monolayers by increasing the concentration of 4-CBD or decreasing the scan rate. The GCE, grafted using 4-CBD, was incorporated with Bi by an in situ electrodeposition of Bi3+ and used as an electrochemical sensor for detection of Pb2+ and Cd2+ using square wave anodic stripping voltammetry, SWASV (paper IV). The sensor resulted in LOD of 10 μg L-1 for Pb2+ and 25 μg L-1 for Cd2+. The applicability of the sensor was tested for detection of Pb2+ and Cd2+ in tap water and compared with ICP-OES. The results were comparable, demonstrating the potential of the sensor as an alternative to ICP-OES for the detection of metal ions in water samples.

  • Public defence: 2019-12-13 10:15 Hörsal S 213, Samhällsvetarhuset, Umeå
    Barnes, Philippa
    Umeå University, Faculty of Social Sciences, Department of Political Science.
    When processes collide: leadership, legitimacy and liberation in Palestine2019Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Palestinian national movement leadership has long been intertwined with thecontext of the national movement processes – liberation, peace and statebuilding. Over time, as these processes have not come to fruition, the numerousleadership groups have had to negotiate their relationships with these processesas both the groups and processes increasingly overlap, creating significantobservable points of tension within Palestinian politics. There are currentlymultiple levels of leadership across the national movement: two representativegoverning institutions – the Palestine Liberation Organisation and thePalestinian Authority; two dominant political movements – Fatah and Hamas;and numerous popular resistance initiatives such as the Boycott, Divestment andSanctions movement coalition that has different levels of endorsement (or lackof) by the other leaderships. This thesis seeks to map the Palestinian nationalliberation movement leadership, examining the inter-relations between themultiple leadership groups and internal (i.e. intra-Palestinian) legitimacies.Examining the internal legitimacies of the Palestinian leaderships results in anexpansion of how internal legitimacy can be conceptualised. For the historicalperiod (1958-2008) analysed, I found revolutionary, representative,oppositional, institutional, democratic and moral legitimacy types within thePalestinian case. Furthermore, these were all attributed to respective nationalmovement processes. Analysing the recent period (2016-2017) requires the useof a relational approach to further develop understandings of legitimacy. Thisapproach transforms legitimacy into a process of (de)legitimisation, whichinteracts with the national movement processes and helps us capture and analysethe complexities of the Palestinian case – that of concurrent, multiple andcontending perspectives. I found the continuation of the liberation and statebuilding processes as simultaneous bases of legitimisation to be a critical point oftension within the tandem legitimisation-delegitisimation process. Engaging arelational approach demonstrated the need for ongoing leadershipreconstruction. I conclude that, in order to negotiate the interactions andcontestations between the multiple and dynamic processes that underlielegitimacy, leaderships face an ultimatum of ‘reconstruct or delegitimise’. WherePalestinian leadership groups have stagnated and not engaged with a process ofreconstruction, we see processes of delegitimisation arising that can explain thecurrent leadership complexities within the Palestinian national movement.