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Contains fulltext : 232514.pdf (Publisher’s version ) (Open Access) BACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema. OBJECTIVE: We sought to identify DNA methylation profiles associated with childhood allergy. METHODS: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discovery study included 219 case patients and 417 controls at age 4 years and 228 case patients and 593 controls at age 8 years from 3 birth cohorts, with replication analyses in 325 case patients and 1111 controls. We performed additional analyses on 21 replicated sites in 785 case patients and 2124 controls by allergic symptoms only from 8 cohorts, 3 of which were not previously included in analyses. RESULTS: We identified 80 differentially methylated CpG sites that showed a 1% to 3% methylation difference in the discovery phase, of which 21 (including 5 novel CpG sites) passed genome-wide significance after meta-analysis. All 21 CpG sites were also significantly differentially methylated with allergic symptoms and shared between asthma, rhinitis, and eczema. The 21 CpG sites mapped to relevant genes, including ACOT7, LMAN3, and CLDN23. All 21 CpG sties were differently methylated in asthma in isolated eosinophils, and 10 were replicated in respiratory epithelium. CONCLUSION: Reduced whole blood DNA methylation at 21 CpG sites was significantly associated with childhood allergy. The findings provide novel insights into the shared molecular mechanisms underlying asthma, rhinitis, and eczema.

Denne bacheloroppgaven dokumenterer utviklingen av et overaktuert robotben med fire frihetsgrader. Dette omfatter design, konstruksjon, det matematiske rammeverket, regulering og simulering. Målet med prosjektet er å muliggjøre framtidig forskning på biomimetisk robotbevegelse og skape en fysisk modell for bruk i undervisning innen robotikk. Robotbenet består av fire aktuatorer hvor tre er plassert i samme plan for å etterligne hofte, kne og ankel til en vanlig huskatt. Dette gjør roboten overaktuert hvis den blir sett på i to dimensjoner. 3D-printede deler utgjør de fleste delene som kobler aktuatorene sammen. En enkel anatomisk analyse ble utført for å finne korrekte proporsjoner for hver lenke. Robotbenet er festet til et stativ med kulehjul for å muliggjøre bevegelse. En matematisk modell for kinematikken til roboten ble implementert i Matlab. Dette muliggjorde planlegging av baner mellom viapunkter funnet i en gangeanalyse av katter. Matlab modellen for roboten ble aldri implementert på den fysiske modellen, men er inkludert som grunnlaget for integrasjon mellom Matlab og ROS i framtidig arbeid. En mer komplett matematisk modell og optimal regulerings løsning er også presentert. Det integrerte elektroniske systemet består av fire likestrøms børstemotorer kontrollert av en Arduino Mega som kjører individuell PID-regulator for hvert ledd. Doble motordrivere brukes for å konvertere PID-regulatorens pådragssignal til aktuatorhastighet. Vinkelposisjonen til leddene er målt med inkrementelle enkodere, hvor signalene blir lest og posisjonen lagret av en Arduino Nano for hver aktuator. Kommunikasjonen mellom enhetene er gjort ved hjelp av I2C protokollen, mens mellom Megaen og ROS benyttes seriell USB. Til slutt fungerte det integrerte elektroniske systemet som planlagt med unntak av motorene som viste seg å være for svake for roboten under bruk. Ved å eksportere informasjon fra designfilene ble det laget en robotmodell som kunne brukes i blant annet ROS. Denne muliggjør simulering av bevegelse og ganglag før testing på den fysiske modellen. Baner ble generert ved å sette start og stopp posisjoner for robotbenet. ROS er satt opp til å sende settpunkter til motor regulatorene slik at den fysiske roboten vil følge den planlagte banen. En modell med fire ben er også laget og simulert i ROS. De fleste aspektene ved roboten fungerte til slutt som planlagt, med unntak av aktuatorene som var for svake. Før de sviktet ble det vist at ROS sendte settpunkter til regulatorene og at ønskede posisjoner ble oppnådd. Gitt mer tid eller større budsjett er gruppemedlemmene sikre på at full funksjonalitet ville blitt oppnådd. For å gjøre framtidig arbeid enklere er mye av diskusjonen funnet i denne oppgaven fokusert på framtidig arbeid og mulige forbedringer. This thesis documents the development of an over-actuated robot leg with four degrees of freedom. The thesis covers design, fabrication, assembly, mathematical framework, control, and simulation. The thesis aims to enable future research on biomimetic robot movement and create a physical model for educational purposes in robotics. The robot leg consists of four actuators where three are placed in the same plane to emulate the hip, knee, and ankle of a domestic cat's hind leg. This makes the robot over-actuated when viewed as a planar robot. 3D-printed parts make up the majority of parts connecting the actuators together. A simple anatomical analysis was undertaken to find correct proportions for each link. The robot leg is fastened to a stand with caster wheels to emulate locomotion. A mathematical model for the kinematics of the robot leg was created and implemented in Matlab. This enabled planning trajectories between waypoints found in a gait analysis on cats. The Matlab model for the robot was never implemented on the physical model but is included as a foundation for integrating Matlab with ROS in future work. A more complete modeling scheme and more optimal controllers for the robot are also discussed. The embedded system consists of four brushed DC motors controlled by an Arduino Mega running independent joint PID control for each actuator. Dual motor drivers are used for translating the PID control signals into actuator speeds. The angular position of the joints is recorded using incremental encoders connected to an Arduino Nano operating as an incremental encoder interface. The communication between the units is done using the I2C protocol and between the Mega and ROS using serial USB. In the end, the physical model worked as intended, but the actuators were undersized and could not handle the gravitational forces acting on the upper joints. A robot model for use in ROS was created by exporting design files. The robot model enables simulating movements and gaits before implementing it on the physical model. Trajectories were generated by setting a start and stop pose for the robot leg. ROS transmits setpoints to the embedded motor controllers that track the planned trajectory. Finally, a model including four legs was created and simulated with the use of ROS. In the end, most aspects of the robot worked as intended. The actuators were too weak, but in the short time before failure ROS was able to send setpoints to the controllers, and the correct poses were achieved. Given more time or a larger budget, the group is confident that the robot would be completely operational. To make future work on the robot easier, a lot of the discussions found in this thesis are focused on future work and possible improvements.

Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4–5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4–16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2–56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1–79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting. Findings: 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p