Syftet med detta arbete är att förbättra ett verktyg för strängsprutning (extrudering). Arbetet består av tre faser (konstruktion, tillverkning och statistiska analyser). Omkonstruktionen sker med hänsyn till en del områden som har potential för optimering. Man börjar med en förstudie för att lära sig mer om verktyget och produktionscykeln och för att få en bättre helhetsbild. Innan arbetets start fastläggs en del avgränsningar, så att studenterna får en ram att jobba inom. Idéer i konstruktionsfasen utvecklas till tänkbara förslag, som sedan verkställs grafiskt i en datorstyrd programvara. Vidare tillverkas förslagen utifrån ritningar till riktiga detaljer med hjälp av bland annat metoder för skärande bearbetning. Slutligen monteras och mäts komponenterna och sedan provkörs verktyget för att se faktiska förbättringar.

Les ataxies cérébelleuses héréditaires sont des pathologies neuro-dégénératives rares, hétérogènes, complexes affectant le cervelet et parfois la moelle épinière et/ou les nerfs périphériques. Elles se transmettent sur le mode autosomique récessif (ARCA), dominant (SCA) ou lié à l’X. Les objectifs de cette thèse de sciences étaient la description phénotypique d’ataxies cérébelleuses héréditaires, la mise en évidence de corrélations du génotype au phénotype et la description de stratégies diagnostiques pour mettre en évidence ces pathologies rares.Grâce à nos résultats, nous avons pu élargir le spectre phénotypique clinique, biologique, radiologique d’ataxies cérébelleuses héréditaires connues : Fragile X Tremor Ataxia Syndrome (FXTAS), ataxie récessive lentement progressive liée au gène PEX 10 impliqué dans la biogénèse du peroxysome, ataxie avec apraxie oculomotrice de type 1 (AOA1). Nous avons pu mettre en évidence des corrélations du génotype au phénotype dans AOA1 et montré que l’âge moyen de début était plus élevé et que la pathologie était moins sévère chez les patients avec au moins un faux sens (p <0,01) par rapport aux patients avec deux mutations tronquantes. Nous avons réussi également à établir un algorithme pour faciliter le diagnostic des ataxies cérébelleuses autosomiques récessives et aider à l’interprétation du séquençage à haut débit. Il est important dans ce type de pathologies rares de pouvoir établir au maximum un diagnostic moléculaire afin de guider le conseil génétique et mettre en évidence les ataxies accessibles à une thérapeutique. / Hereditary cerebellar ataxias are a group of rare and heterogeneous neurodegenerative diseases. The transmission mode is recessive, dominant or X-linked. Our objectives were to better describe the phenotype of some inherited ataxias, to provide genotype-phenotype correlations and to improve the diagnostic strategies for these rare diseases. We enlarged the clinical, biological, radiological phenotype of Fragile X Tremor Ataxia Syndrome (FXTAS), recessive ataxia due to PEX10 related peroxisomal biogenesis disorders, ataxia with oculomotor apraxia type 1 (AOA1). We showed genotype-phenotype correlations in AOA1 patients: mean age at onset was higher with at least one missense mutation. A ranking algorithm has been created to predicting the molecular diagnoses of recessive cerebellar ataxia in order to guide the diagnosis and facilitate interpretation of next generation sequencing. The establishment of a molecular diagnosis is important in this type of rare pathologies to guide the genetic counseling and to diagnosis the ataxias accessible to a treatment.

One possibility to automate more of software testing is to have developers write more general test cases. Given a general (parameterized test case), that holds in many situations, software can generate many different test instances and execute them automatically. Thus, even though the developers write fewer and smaller tests they can test more. However, it is not clear what other effects the use of generalized test cases has. One hypothesis is that “More general test cases are harder to understand than concrete ones and thus would lead to overall tests that are harder to understand”. Software understandability can be defined as the system that is written by one person is easy to read and understand by another person easily without any resistance. However, software understandability is hard to measure because understandability depends on the cognitive behavior of human. Software understandability assists in software reusability and software maintainability.

Indiana University-Purdue University Indianapolis (IUPUI) / Introduction: One of the challenges of non-surgical root canal treatment (NSRCT) is determining the working length of the canal which indicates the exact end point of root canal preparation and obturation. The development of the Electronic Apex Locator (EAL) has helped the clinician to determine the location of the apical foramen, and hence the working length, when performing NSRCT. Objective: The objective of this in vitro study was to determine the accuracy of a new EAL, the E-PEX (Changzhou Eighteeth Medical Technology Co., China), and compare it to a commonly used EAL, the Root ZX II (J. Morita Corp, Kyoto, Japan), for determining the location of the apical foramen. Materials and Methods: Twenty extracted single rooted teeth were used in this study. The crowns were removed and the distance from a coronal reference point to the apical foramen was measured utilizing a k-file and direct visualization under magnification. Teeth were then mounted in alginate and measurements for the apical foramen were made using the Root ZX II and the E-PEX. The difference between the actual canal length and the electronic length was then calculated and compared. Results: The mean true difference was -0.20, and -0.19 for the E-PEX and Root ZX II respectively. The mean absolute difference was 0.28, and 0.26 for the E-PEX and Root ZX II respectively. Paired t-tests done separately for true differences (p = 0.45) and absolute differences (p = 0.21) showed no significant difference among EALs. The percentage of measurements falling within 0.5 mm of the actual canal lengths for each EAL were 95% and 90% for the E-PEX and Root ZX II respectively. McNemar’s test was used to compare between the two test methods for the percentage within 0.5 mm and revealed no significant difference (p = 0.32). Conclusion: The Root ZX II had an average measurement that was slightly closer to the actual length of the canal when compared to the E-PEX, while the E-PEX had a higher percentage of measurement within 0.5 mm of the apical foramen. However, these differences were not statistically significant.

The peroxisome is a subcellular organelle that carries out a diverse range of metabolic functions, including the b-oxidation of very long chain fatty acids, the breakdown of peroxide and the a-oxidation of fatty acids. Disruption of peroxisome metabolic functions leads to severe disease in humans. These diseases can be broadly grouped into two categories: those in which a single enzyme is defective, and those known as the peroxisome biogenesis disorders (PBDs), which result from a generalised failure to import peroxisomal matrix proteins (and consequently result in disruption of multiple metabolic pathways). The PBDs result from mutations in PEX genes, which encode protein products called peroxins, required for the normal biogenesis of the peroxisome. PEX1 encodes an AAA ATPase that is essential for peroxisome biogenesis, and mutations in PEX1 are the most common cause of PBDs worldwide. This study focused on the identification of mutations in PEX1 in an Australasian cohort of PBD patients, and the impact of these mutations on PEX1 function. As a result of the studies presented in this thesis, twelve mutations in PEX1 were identified in the Australasian cohort of patients. The identified mutations can be broadly grouped into three categories: missense mutations, mutations directly introducing a premature termination codon (PTC) and mutations that interrupt the reading frame of PEX1. The missense mutations that were identified were R798G, G843D, I989T and R998Q; all of these mutations affect amino acid residues located in the AAA domains of the PEX1 protein. Two mutations that directly introduce PTCs into the PEX1 transcript (R790X and R998X), and four frameshift mutations (A302fs, I370fs, I700fs and S797fs) were identified. There was also one mutation found in an intronic region (IVS22-19A>G) that is presumed to affect splicing of the PEX1 mRNA. Three of these mutations, G843D, I700fs and G973fs, were found at high frequency in this patient cohort. At the commencement of these studies, it was hypothesised that missense mutations would result in attenuation of PEX1 function, but mutations that introduced PTCs, either directly or indirectly, would have a deleterious effect on PEX1 function. Mutations introducing PTCs are thought to cause mRNA to be degraded by the nonsense-mediated decay of mRNA (NMD) pathway, and thus result in a decrease in PEX1 protein levels. The studies on the cellular impact of the identified PEX1 mutations were consistent with these hypotheses. Missense mutations were found to reduce peroxisomal protein import and PEX1 protein levels, but a residual level of function remained. PTC-generating mutations were found to have a major impact on PEX1 function, with PEX1 mRNA and protein levels being drastically reduced, and peroxisomal protein import capability abolished. Patients with two missense mutations showed the least impact on PEX1 function, patients with two PTC-generating mutations had a severe defect in PEX1 function, and patients carrying a combination of a missense mutation and a PTC-generating mutation showed levels of PEX1 function that were intermediate between these extremes. Thus, a correlation between PEX1 genotype and phenotype was defined for the Australasian cohort of patients investigated in these studies. For a number of patients, mutations in the coding sequence of one PEX1 allele could not be identified. Analysis of the 5' UTR of this gene was therefore pursued for potential novel mutations. The initial analyses demonstrated that the 5' end of PEX1 extended further than previously reported. Two co-segregating polymorphisms were also identified, termed –137 T>C and –53C>G. The -137T>C polymorphism resided in an upstream, in-frame ATG (termed ATG1), and the possibility that the additional sequence represented PEX1 coding sequence was examined. While both ATGs were found to be functional by virtue of in vitro and in vivo expression investigations, Western blot analysis of the PEX1 protein in patient and control cell extracts indicated that physiological translation of PEX1 was from the second ATG only. Using a luciferase reporter approach, the additional sequence was found to exhibit promoter activity. When examined alone the -137T>C polymorphism exerted a detrimental effect on PEX1 promoter activity, reducing activity to half that of wild-type levels, and the -53C>G polymorphism increased PEX1 promoter activity by 25%. When co-expressed (mimicking the physiological condition) these polymorphisms compensated for each other to bring PEX1 promoter activity to near wild-type levels. The PEX1 mutations identified in this study have been utilised by collaborators at the National Referral Laboratory for Lysosomal, Peroxisomal and Related Genetic Disorders (based at the Women's and Children's Hospital, Adelaide), in prenatal diagnosis of the PBDs. In addition, the identification of three common mutations in Australasian PBD patients has led to the implementation of screening for these mutations in newly referred patients, often enabling a precise diagnosis of a PBD to be made. Finally, the strong correlation between genotype and phenotype for the patient cohort investigated as part of these studies has generated a basis for the assessment of newly identified mutations in PEX1.

Pseudoexfoliation (PEX) syndrome is an age-related condition characterized by the production and accumulation of extracellular fibrillary material in the anterior segment of the eye. PEX predisposes for several pathological conditions, such as glaucoma and complications during and after cataract surgery. The pathogenesis of PEX is not yet fully understood. It is multifactorial with genetics and ageing as contributing factors. We aimed to study the proteome in aqueous humor (AH) in PEX in order to increase the knowledge about its pathophysiology. Therefore, we developed sampling techniques and evaluated separation methods necessary for analyzing small sample volumes. Other objectives were to study the lens capsule in eyes with PEX regarding small molecules, and to investigate the association between PEX and cataract surgery in a population-based 30-year follow-up study. Samples of AH from eyes with PEX and control eyes were collected during cataract surgery. In pooled, and individual samples, various liquid based separation techniques and high resolution mass spectrometry were utilized. For quantitation, various methods for labeling, and label free techniques were applied. Lens capsules were collected from some of the patients, and analysed by imaging mass spectrometry. A cohort of 1,471 elderly individuals underwent a comprehensive ophthalmological examination at baseline. Medical information was obtained by questionnaires, and from medical records. Incident cases of cataract surgery were identified by review of medical records. In the initial study, several techniques were explored for protein detection, and a number of proteins were identified as differentially expressed. In the individually labelled samples, changes in the proteome were observed. Eyes with PEX contained higher levels of proteins involved in inflammation, oxidative stress, and coagulation, suggesting that these mechanisms are involved in the pathogenesis in PEX. The levels of β/γ-crystallins were significantly increased in PEX, which is a novel finding. In the lens capsules from individuals with PEX, changes in the lipid composition was observed with time-of-flight secondary ion mass spectrometry. These changes remain to be elucidated. By multivariate analysis, lens opacities were the first, and PEX the second most important predictor for cataract surgery, the later accounting for a 2.38-fold increased risk for cataract surgery.

Detta examensarbete utfördes vid Bodens Energi Nät AB under våren 2017 och behandlar mätmetoder och olika tester som kan utföras på markförlagd kabel för kontroll av tillståndet på exempelvis isolation, mantel och skarvar. Bakgrunden till arbetet är att man inom Bodens Energi Nät har ett flertal kilometer kabel på mellanspänningsnivå 20 kV. En stor del av kablarna är isolerade med tvärbunden polyeten, PEX och härstammar från 1970 och 1980-talet. Dessa kablar har i efterhand visat sig ha problem med vattenträd, vilket kan beskrivas som trädliknande strukturer som uppstår i en kabels isolation på grund av fukt och orenheter när dessa blir utsatta för kraftigare elektriska fält. Problem med vattenträd i kablar leder efter en tid, ofrånkomligen till genomslag i isolationen med påföljande jordfel.  Syftet med denna rapport är att undersöka och kartlägga olika tillståndsbedömningsmetoder för kraftkabel avsedd för 12/24 kV-nät. Rapporten avser att vara en metodbeskrivning för de vanligaste diagnostiska mätmetoder samt redogör för dess för- och nackdelar. Följande frågeställningar ämnas besvaras: Vilka metoder finns tillgängliga för tillståndsbedömning av mellanspänningskabel och vilka egenskaper är mätbara? Vad har respektive mätmetod för svagheter och styrkor samt vilka begränsningar finns det? Finns det möjlighet att utföra mätningar på en kabel i drift eller måste den tilltänkta kabelsträckan frånskiljas den övriga anläggningen?Om mätningar kan utföras på en kabel i drift, vilka metoder gäller detta? Rapporten bygger till största del på en litteraturstudie där mycket av informationen är hämtad ifrån standarder, handböcker och guider. Rapporten behandlar dels allmän information om kraftkablar samt PEX-kabelns konstruktion vilket bör kännas till för att kunna tillgodogöra sig informationen på bästa sätt. Vidare avhandlas åldringsmekanismer för PEX-isolerad kabel. Metoderna som presenteras i rapporten omfattar bland annat; mantelprovning, hållprov med olika typer av spänning, mätning av den dielektriska förlustfaktorn tan delta samt mätning av partiella urladdningar, PD. I kapitel 5 presenteras mätresultat från ett antal olika tan delta-mätningar samt en mätning av partiella urladdningar, vidare ges en kortare förklaring till mätresultaten. Vid mätning av de dielektriska förlusterna fås information om isolationens totala skick. Mätning av partiella urladdningar (även kallat glimning) ger information om var eventuella ojämnheter och håligheter finns. Det är dock viktigt att komma ihåg att de metoder som finns måste anpassas till den kabel som avses mätas eftersom det inte går att identifiera alla typer av defekter och fel med hjälp av endast en metod. Metoderna bör användas som diagnostiska hjälpmedel som i sin tur ger fingervisningar om kabelanläggningens totala tillstånd. De är därmed inte att betrakta som en definitiv bekräftelse avseende funktionsdugligheten för kabeln. / The work in this bachelor’s thesis was conducted at Bodens Energi Nät AB during the spring of 2017. The report describes common methods available for testing and diagnostic measurements of electric power cables. Bodens Energi Nät manages a medium voltage power grid which consists of around 700 kilometers of power lines and about 200 kilometers of cables. A large part of these cables have an insulating layer consisting of cross-linked polyethylene (XLPE) and originates from the 1970s and the 1980s. These particular XLPE cables have a higher than normal tendency to develop problems with water trees. Water trees can be described as tree-shaped structures forming inside the insulating layer of the cable in the presence of an electrical field and water. Issues with water trees leads to local degradation of the dielectric material in the cable and usually ends with a phase-to-ground fault. The purpose of this thesis is to examine and describe different methods for diagnostic measurements of medium voltage cables. Through the use of a literature study the following questions will be answered: Which methods are available for diagnostic measurements and what properties can be measured? What are the strengths and weaknesses for each of these methods? Can measurements be performed on cables on-line or is it required to disconnect the cables from the grid before any measurements can be performed?In the case of on-line testing, which methods does this apply to?  The overall disposition of this thesis starts with a general description of power cables including XLPE cables, as well as aging mechanisms in extruded cables. Subsequent chapters describes testing methods such as cable sheath testing, hipot testing using different types of voltages, measurements of the dielectric dissipation factor tan , as well as partial discharge testing.  Chapter 5 discloses the results from some different tan  measurements including a partial discharge measurement. A short description and explanation is included with every figure.  Measuring the dielectric dissipation factor yields information about the total condition of the insulation. Partial discharge offers information regarding the location of irregularities, cavities and impurities within the insulation. It is important to have in mind that each of these methods on its own will not be able to identify all types of defects. Therefore it may be required to carry out several measurements using different types of methods in order to get a general idea of the condition of the cable. Methods for cable diagnostic measurements should be seen as a tool to get an estimate about the total condition of a power cable and is not considered a fail safe way to determine the operational ability.