| 1. |
- Bresell, Anders, 1978-
(författare)
-
Characterization of protein families, sequence patterns, and functional annotations in large data sets
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bioinformatics involves storing, analyzing and making predictions on massive amounts of protein and nucleotide sequence data. The thesis consists of six papers and is focused on proteins. It describes the utilization of bioinformatics techniques to characterize protein families and to detect patterns in gene expression and in polypeptide occurrences. Two protein families were bioinformatically characterized - the membrane associated proteins in eicosanoid and glutathione metabolism (MAPEG) and the Tripartite motif (TRIM) protein families.In the study of the MAPEG super-family, application of different bioinformatic methods made it possible to characterize many new members leading to a doubling of the family size. Furthermore, the MAPEG members were subdivided into families. Remarkably, in six families with previously predominantly mammalian members, fish representatives were also now detected, which dated the origin of these families back to the Cambrium ”species explosion”, thus earlier than previously anticipated. Sequence comparisons made it possible to define diagnostic sequence patterns that can be used in genome annotations. Upon publication of several MAPEG structures, these patterns were confirmed to be part of the active sites.In the TRIM study, the bioinformatic analyses made it possible to subdivide the proteins into three subtypes and to characterize a large number of members. In addition, the analyses showed crucial structural dependencies between the RING and the B-box domains of the TRIM memberRo52. The linker region between the two domains, denoted RBL, is knownto be disease associated. Now, an amphipathic helix was found to be acharacteristic feature of the RBL region, which also was used to divide the family into three subtypes.The ontology annotation treebrowser (OAT) tool was developed to detect functional similarities or common concepts in long lists of proteins or genes, typically generated from proteomics or microarray experiments. OAT was the first annotation browser to include both Gene Ontology (GO) and Medical Subject Headings (MeSH) into the same framework. The complementarity of these two ontologies was demonstrated. OAT was used in the TRIM study to detect differences in functional annotations between the subtypes.In the oligopeptide study, we investigated pentapeptide patterns that were over- or under-represented in the current de facto standard database of protein knowledge and a set of completed genomes, compared to what could be expected from amino acid compositions. We found three predominant categories of patterns: (i) patterns originating from frequently occurring families, e.g. respiratory chain-associated proteins and translation machinery proteins; (ii) proteins with structurally and/or functionally favored patterns; (iii) multicopy species-specific retrotransposons, only found in the genome set. Such patterns may influence amino acid residue based prediction algorithms. These findings in the oligopeptide study were utilized for development of a new method that detects translated introns in unverified protein predictions, which are available in great numbers due to the many completed and ongoing genome projects.A new comprehensive database of protein sequences from completed genomes was developed, denoted genomeLKPG. This database was of central importance in the MAPEG, TRIM and oligopeptide studies. The new sequence database has also been proven useful in several other studies.
|
|
| 2. |
- Goldin, Stephen, 1948-
(författare)
-
Living in the present with the past : mental health of Bosnian refugee children in Sweden
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The negative impact of war on child mental health has been repeatedly documented. Still, the majority of children exposed to ethnic and political violence show no signs of clinical disorder. In Western countries of exile, these findings have prompted a variety of attempts to evaluate refugee children, in the hope of identifying and offering support to those children “at risk”. This study critically examines one such attempt. The aims are fourfold: 1. to describe the range and pattern of child trauma-stress exposure and mental health reactions as captured on clinician semi-structured interview; 2. to critically compare clinician assessment with independent parent, child and teacher reports; 3. to identify factors of potential risk or protective import for child mental health; 4. to draw clinical implications: from whom and by what means can children at risk be reasonably identified? The target of our study was the entire population of Bosnian-Serbian-Croatian speaking child refugee families assigned to Umeå and surrounding municipalities during 1994-95. Fifty families, containing 90 children aged one month to 20 years, were included in the study. Assessment occurred in two phases. First, a semi-structured interview was conducted that inquired broadly as to the child’s family background, trauma-stress exposure, emotional-behavioral problems, patterns of family functioning, and future hopes. Second, standardized self-report questionnaires were administered, separately to parent and child, to provide alternative appraisal of the child’s war exposure, mental health symptoms, coping strategies, and social network. Teacher evaluation of child cognitive-social functioning as well as emotional-behavioral problems was also obtained. Clinician semi-structured interview revealed the child’s pre-war period as preponderantly good, and provided richly detailed narratives of child exposure during war and resettlement that clustered into a limited number of type-stories. Independent parent assessment captured the same broad strokes of child war exposure; but both approaches – fixed questionnaire and semi-structured interview – showed specific areas of blindness. Teenage self-report offered a disparate but equally rich account of war exposure, while that of primary school child was significantly less detailed. Nearly half of the study children (48%) were identified on clinician interview with one or more mental health problem “demanding further attention”. Depressiveness was the single most prevalent symptom (31%), followed by posttraumatic reactions (23%) and anxiety-regressiveness (15%). Independent symptom appraisal by parent and primary school child was largely concordant with that of clinician, while teenagers made similar assessment as to who was in distress, but defined the nature of that distress differently. Teacher report stood apart, identifying fewer inward emotional problems and asserting the cognitive-social competence of the vast majority of study children. Trauma-stress exposure during both war and resettlement presented as an unequivocal risk to mental health, but accounted for only part of outcome variance. Additional factors of strong import related broadly to “living in the present”. Parent impairment of daily routines, child dissatisfaction with school and an ongoing quarrelsome relationship presented as risk factors. Protection was associated with parent maintenance of a warm family climate and of concrete physical-emotional caring, child social ties to physically present others, including teacher; and above all, a family sense of hope for the future. Results support the general robustness of our semi-structured approach. Exploring the child’s present well-being in narrative relation to past and future, our assessment captured and gave meaning to the complexity of child exposure and behavior. At the same time, independent parent and child appraisals provided an additional richness to the retelling and evaluation of child experience. Particularly the apartness of teacher report underscores the need to incorporate an outside-world vantage point in the process of risk assessment.
|
|
| 3. |
- Johansson, Anders, 1968-
(författare)
-
Search for Biomarkers in ALS and Parkinson's Disease : Positron Emission Tomography and Cerebrospinal Fluid Studies
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- New biomarkers are needed to improve knowledge about pathophysiology, in order to provide earlier correct diagnosis and to follow disease progression of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). The aim of this thesis was to find new biomarkers for these diseases. First, increased serum levels and unchanged levels in postmortal spinal cord of vascular endothelial growth factor (VEGF) were demonstrated. VEGF was not detected in cerebrospinal fluid (CSF) in ALS. Second, increased levels of fibroblast growth factor 2 were found in the CSF and serum of ALS patients. Both studies used enzyme-linked immunoassays. Third, a proteomics method for CSF analysis was explored, based on tryptic digestion and subsequent separation and detection of the peptides by on-line liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry. ALS-specific patterns were observed. Four out of five samples were correctly assigned, but no single protein biomarker could be identified. Fourth, [11C](L)-deprenyl-D2 (DED) positron emission tomography (PET) demonstrated increased retention in the pons and white matter in ALS. DED binds to monoamino oxidase B, which in the brain is primarily located in astrocytes. Thus evidence was provided that astrocytosis may be detected in vivo in ALS. Fifth, normal [11C]-PIB binding in five nondemented patients with PD was reported, in contrast to previous findings of increased retention in Alzheimer's disease reflecting amyloid aggregation. Finally, the combined use of fluorodeoxyglucose and L-[β 11C]-DOPA PET for the differential diagnosis of parkinsonian syndromes was evaluated. PET provided support for the clinical diagnosis in 62 out of 75 patients, and served to exclude suspected diagnoses in another five patients.
|
|
| 4. |
- Lesser, Alice, 1977-
(författare)
-
Optimal and Hereditarily Optimal Realizations of Metric Spaces
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This PhD thesis, consisting of an introduction, four papers, and some supplementary results, studies the problem of finding an optimal realization of a given finite metric space: a weighted graph which preserves the metric's distances and has minimal total edge weight. This problem is known to be NP-hard, and solutions are not necessarily unique.It has been conjectured that extremally weighted optimal realizations may be found as subgraphs of the hereditarily optimal realization Γd, a graph which in general has a higher total edge weight than the optimal realization but has the advantages of being unique, and possible to construct explicitly via the tight span of the metric.In Paper I, we prove that the graph Γd is equivalent to the 1-skeleton of the tight span precisely when the metric considered is totally split-decomposable. For the subset of totally split-decomposable metrics known as consistent metrics this implies that Γd is isomorphic to the easily constructed Buneman graph.In Paper II, we show that for any metric on at most five points, any optimal realization can be found as a subgraph of Γd.In Paper III we provide a series of counterexamples; metrics for which there exist extremally weighted optimal realizations which are not subgraphs of Γd. However, for these examples there also exists at least one optimal realization which is a subgraph.Finally, Paper IV examines a weakened conjecture suggested by the above counterexamples: can we always find some optimal realization as a subgraph in Γd? Defining extremal optimal realizations as those having the maximum possible number of shortest paths, we prove that any embedding of the vertices of an extremal optimal realization into Γd is injective. Moreover, we prove that this weakened conjecture holds for the subset of consistent metrics which have a 2-dimensional tight span
|
|
| 5. |
- Persson, Anders J, 1959-
(författare)
-
Workplace Ethics : Some practical and foundational problems
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the present thesis is twofold: first, to analyse some practical ethical problems that stem from the workplace and the working environment and to offer guidelines concerning how such problems can be solved; second, to illuminate how the specific nature of work and the working environment is intimately connected to the relation between the employee and the employing entity, as set forth in an employment contract, and how the form and content of such contracts are, among other things, determined by culturally and socially established ideas. The normative question to be addressed is thus: which of these ideas should be maintained? This can be seen as a second-order, or more fundamental, ethical question whose answer depends on determining which normative principles are right. An additional aim of this thesis is thus to illuminate that the contract relation has relevance to practical ethical problems in the workplace context in this second-order mode. The thesis consists of an Introduction and five papers. In Paper I (written together with Sven Ove Hansson) we argue that employees have a prima facie right to privacy, but that this right can be overridden by competing moral principles that follow, explicitly or implicitly, from the contract of employment. A set of ethical criteria is developed and summarized in the form of a guideline for determining the moral status of infringements into workplace privacy. In Paper II these criteria are applied to three broad classes of privacy-intrusive workplace practices: (1) monitoring and surveillance, (2) genetic testing, and (3) drug testing. In relation to some scenarios on these themes, it is shown that it is possible to handle such practical ethical problems systematically by way of the proposed guideline. Paper III deals with the fact that employees are protected by health and safety standards that are less protective than those that apply to the general public. Emphasis is put on the distinction between exposure and risk, and this distinction is claimed to be a key determinant for the relevance of arguments put forward in support of such double standards. In Paper IV the nature of the contract of employment is explored from an ethical point of view. An argument is developed against the claim that (a) the individual’s freedom of decision and (b) the practice of institutional arrangements are sufficient to justify a contract of employment. Paper V questions the standpoint that the voluntariness of the contracting parties in an employment relationship has substantial value. One overarching issue concerns the meaning of voluntariness in the employment context, another, its normative importance. It is argued that it is indeterminate exactly where the line should be drawn between voluntary and non–voluntary agreements in this context. Concerning the latter issue, it is claimed that even if we were able to draw such a line, this fact does not tell us anything about the normative importance of the voluntariness condition, nor how much normative weight we should assign to the fulfilment of its conditions in the workplace context.
|
|
| 6. |
- Persson, Anders, 1953-
(författare)
-
Volume imaging of the abdomen : three-dimensional visualisation of tubular structures in the body with CT and MRI
- 2005
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overwhelming amount of image-based information in modem medicine makes it crucial to develop methods to handle and analyze images and make them comprehensible for users. The aim of this thesis was to study the radiological practice of three-dimensional (3D) visualization of tubular structures in the body with CT and MRI. All the studies cancern 3D imaging of tubular structures with camputed tomography (CT) and magnetic resonance imaging (MRI). The first three studies examine the abdominal aorta; the two later ones the, bile ducts.Study I compared measurements of aorta diameters taken from MR images presented using two visualization methods - maximum intensity projection (MlP) and volume rendering (VRT) - with invasive angiography (DSA) and CT as reference methods. Mean diameters of MR images were smaller than those from DSA and CT when MlP was used, but in general not when VRT was used.Study II evaluated the dependence on the observer and the choice of method and settings during rendering using the same material as in Study 1. In both MlP and VRT, the choice of settings had significant influence on the results. With DSA as the reference method, VRT gave larger measurement errors than MIP when the rendering parameters were set to fixed values, but not if the user was allowed to select the settings freely.Study III evaluated three new techniques for standardizing VRT protocols for MRA. Inter-reader variability and agreement with DSA were studied by comparing diameter measurements of the abdominal aorta obtained by the three new techniques, by VRT with freely chosen parameters and by MlP. All three new methods were significantly better than MlP and VRT with freely chosen parameters conceming inter-observer agreement. Agreement with DSA was significantly better for one of the methods. Standardized protocols seem to have a potential to make VRT a clinically useful alternative to MlP for MR angiography measurements.Study IV evaluated CT imaging of the bile ducts after drip intravenous infusion of the contrast medium iotroxate (CT cholangiography) in terms of adverse effects and visibility. With infusion time adjusted for individual variation in serum bilirubin concentration, a total side-effect frequency of less than 1% was found. A systematic review of previously published studies indicated a frequency of 2.3%. Good contrast excretion and visualization of bile ducts even in patients with elevated bilirubin levels were noted.Study V evaluated the diagnostic benefits of the same imaging method by comparing it with findings from surgery and endoscopic retrograde cholangiopancreatography (ERCP). The consensus sensitivity and specificity for diagnosing biliary stones was 88% and 94%, respectively. The use of VRT improved diagnostic certainty in 14% of the evaluatians, and the visualization of ductal stones was improved in 38% of the positive cases.In conclusion, volume rendering technique with standardized parameters may become a clinically useful tool in the clinical MRI environment. DIC-CT with bilirubin-governed infusion time and volume rendering post-processing produces detailed images of the biliary tree, resulting in good sensitivity and specificity. Moreover the safety is acceptable.
|
|
| 7. |
- Wilhelmsson, Dan, 1969-
(författare)
-
Aspects of offshore renewable energy and the alterations of marine habitats
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Several Western European countries are planning for a massive offshore renewable energy (i.e. wind and wave energy) development (ORED) along the European Atlantic coast and in the Baltic Sea. Acknowledging the scale of ORED, there is an increasing interest in the opportunities offered by the fishery closures and the addition of artificial hard substrata. This is in tandem with uncertainties on positive and negative effects on benthic assemblages and specific species of this large-scale deployment of artificial reefs. This thesis focuses on the artificial reef effects of ORED, dealing with benthic assemblages on and in the vicinity of wind- and wave power foundations. Field surveys within offshore wind- and wave farms as well as targeted field experiments were conducted. Results suggest that wind- and wave power foundations can positively affect local abundances and diversity of several species of fish and decapods. Reef profile up to 1 m above the seabed may enhance benthic fish numbers. Structural complexity in the form of single-entrance holes positively affected numbers of edible crab (Cancer pagurus), but no effect on fish was shown. Enhanced structural complexity may, moreover, adversely affect abundances of some species through an induced predation pressure. Micro-habitat use by fish and lobsters (Homarus gammarus) encountered was described, and preferences of the edible crab were shown. Filtrating organisms (i.e. blue mussels Mytilus spp. and barnacles Balanus spp.) seem to be particularly favoured by the conditions on offshore energy installations. The material and orientation of the substrate influenced colonisation patterns of epibiota. Moreover, wind turbines may alter the habitat composition on adjacent seabeds. ORED could induce local ecological changes and put areas and species of conservation interest at risk. If well planned and co-ordinated, on the other hand, ORED could even be beneficial to the subsurface marine environment in several aspects.
|
|
