Vessel operations in relation to new types of offshore aquaculture facilities, and weather windows in exposed areas

The marine aquaculture industry is expanding the production into new sea areas. The technology is advancing, and offshore aquaculture facilities are being developed. The offshore developments can offer significant benefits that applies to the economy, optimization of operations and production, as well as minimizing the impact on the coastal areas. Structural and operation procedures need to be adapted as a result of transitioning from traditional production sites. Offshore aquaculture facilities are large rigid structures which leads to new challenges due to environmental parameters and dimensions. The field is rather unexplored compared to offshore wind or oil and gas industry. A dynamic analysis is conducted to study the response of the conceptual aquaculture facility ØyMerd. A 3D model of the structure is modeled, in order to further calculate the hydrostatic and hydrodynamic properties. The mesh of the structure is imported into a boundary element method code which provide option for hydrostatic computation, and solves the hydrostatic equilibrium for the given mass and center of gravity. Further, the hydrostatic data, mass distribution matrix, and hydrostatic restoring matrix is given as input for HAMS solver. ØyMerd is then modeled in the dynamic analysis software with the hydrodynamic data obtained from the potential theory software HAMS. The simulations in OrcaFlex contains a model of ØyMerd moored and service vessel, in order to analyze vessel operations in relation to the structure and wave parameters. Significant wave heigh and wave period data is analyzed for a potential production location. A weather window analysis is performed in order to identify the accessibility of the structure in relation to vessel operations. Vessel operations in relation to new types of offshore aquaculture facilities are facing new challenges which effects the safety and accessibility. It is important to avoid operations when the sea condition is close to either the aquaculture facility or the vessel natural frequency. Even though a structure like ØyMerd is stable in waves, sea conditions can lead to great response. For future work, wave disturbance and shielding effect benefits could be addressed

Effect of the rider on the horse's movement

Denne oppgaven er en systematisk litteraturstudie skrevet for å sammenfatte resultater fra relevante studier. Målet med oppgaven var å samle tilgjengelig informasjon fra studier som inkluderer både hest, rytter og halthet, og vurdere resultatene på en kritisk måte. Vi ønsker å finne ut hvilken effekt rytter, og faktorer ved rytteren, har på hesten og dens bevegelsesmønster. Da dette er en multifaktoriell interaksjon, som består av faktorer som er mer eller mindre umulig å standardisere, vil resultatene fra denne typen studier være vanskelige å tolke og sammenligne, og det finnes få konklusive svar. Det er noen resultater som er gjennomgående i flere av studiene. Salens påvirkning på hestens asymmetri og atferd er av betydning i studiene vi har evaluert. Lateral bevegelse av salen kan brukes for å oppdage bakbeinshaltheter. Det er også vist at ulike sitstyper har innvirkning på symmetrien i hestens gangarter. En rytter med tyngre vekt antas å ha en potensiell negativ effekt på hestens prestasjon, både når det gjelder atferd og halthet, men mengden data på dette området er sparsom. I tillegg til funnene på interaksjonen mellom hest og rytter, fant vi også noen interessante faktorer involvert i halthetsundersøkelse av hest. Det er store forskjeller mellom observatører ved subjektive halthetsundersøkelser når det kommer til å vurdere hvilket bein hesten er halt på, og å gradere haltheten. Bruken av objektive målemetoder kan være av stor nytte for å tolke vanskelige kasus som har asymmetrier som er vanskelige å oppdage med det blotte øye. For å få en helhetsforståelse av halthet hos ridehester, bør hesten alltid evalueres under rytter. Vi håper at funnene i denne litteraturstudien vil være nyttige for både ryttere, veterinærer og veterinærstudenter

Merkekonseptets betydning for merkeutvidelser

For å skape vekst hos en merkevare blir det ofte benyttet en vekstrategi med merkeutvidelser. En merkeutvidelse vil i de fleste tilfeller plassere merkevaren inn i en ny produktkategori. Det vi har sett på i denne oppgaven er om det å plassere en merkevare inn i en ny fjern produktkategori har en sammenheng med valgt merkekonsept. Er det lettere for et av de tre konseptene: symbolsk, funksjonelt eller opplevelsesbasert å komme med nye merkeutvidelser i fjerntliggende produktkategorier? Dette testet vi ved å se om det var en forskjell mellom å kun presentere et merke innen et av merkekonseptene og en utvidelse, versus merket sammen med merkevarestrategien sekvensiell merkeutvidelse. Problemstillingen til oppgaven lyder derfor som følger: “Hvilken effekt har et merkekonsept på merkets mulighet til å utvide til fjerne produktkategorier?”. For å besvare forskningsspørsmålet er studien delt i to deler med tilhørende hypoteser. For innsamling av data benyttet vi oss av kvantitativ metode med et eksperimentelt design på studiet. Første del baseres på en spørreundersøkelse, hvor vi ser på hvilket konsept som gjør det dårligst med den fjerne merkeutvidelsen. Dette konseptet ble tatt med videre i del to for å se om vi kunne endre holdningen til samme nivå som det beste konseptet. I del to har vi testet hypotesen med et eksperiment. En av gruppene ble utsatt for en “historie” med sekvensielle utvidelser fra mormerket før den fjerne merkeutvidelse vi egentlig ser på. I den andre gruppen ble de kun presentert for mormerket med den fjerne merkeutvidelsen. Resultatene fra undersøkelsene viser mange interessante funn. I del én viste resultatene at det symbolske konseptet sin fjerne utvidelse gjorde det dårligst, og det opplevelsesbaserte konseptet best. Dette var motsatt av hva teorien tilsier og vi fikk ikke støtte for hypotesen i første del. Vi tok med oss den symbolske fjerne utvidelsen videre til del to og benyttet strategien sekvensiell merkeutvidelse for å minske gapet mellom mormerket og utvidelsen. Dette utgjorde en betydelig forskjell i resultatene. Basert på denne manipulasjonen endret holdningen respondentene hadde til den fjerne utvidelsen seg såpass at den overgikk holdningen for det opplevelsesbaserte konseptet i del én. I tillegg viste funnene med sekvensiell merkeutvidelse at omdømmet til mormerket ikke lenger har en påvirkning på holdningen til utvidelsen slik som tidligere. Et generelt funn for alle konsepter og utvidelser er at innovativitetsgraden til respondentene ikke har en signifikant påvirkning på holdningen. Om dette er tilfelle eller et resultat av dårlig operasjonalisering stiller vi oss kritiske til

Comparing the mitochondrial signatures in ESCs and iPSCs and their neural derivations

Under embargo until: 2023-07-10Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have distinct origins: ESCs are derived from pre-implanted embryos while iPSCs are reprogrammed somatic cells. Both have their own characteristics and lineage specificity, and both are valuable tools for studying human neurological development and disease. Thus far, few studies have analyzed how differences between stem cell types influence mitochondrial function and mitochondrial DNA (mtDNA) homeostasis during differentiation into neural and glial lineages. In this study, we compared mitochondrial function and mtDNA replication in human ESCs and iPSCs at three different stages − pluripotent, neural progenitor and astrocyte. We found that while ESCs and iPSCs have a similar mitochondrial signature, neural and astrocyte derivations manifested differences. At the neural stem cell (NSC) stage, iPSC-NSCs displayed decreased ATP production and a reduction in mitochondrial respiratory chain (MRC) complex IV expression compared to ESC-NSCs. IPSC-astrocytes showed increased mitochondrial activity including elevated ATP production, MRC complex IV expression, mtDNA copy number and mitochondrial biogenesis relative to those derived from ESCs. These findings show that while ESCs and iPSCs are similar at the pluripotent stage, differences in mitochondrial function may develop during differentiation and must be taken into account when extrapolating results from different cell types.acceptedVersio

POLG genotype influences degree of mitochondrial dysfunction in iPSC derived neural progenitors, but not the parent iPSC or derived glia

Diseases caused by POLG mutations are the most common form of mitochondrial diseases and associated with phenotypes of varying severity. Clinical studies have shown that patients with compound heterozygous POLG mutations have a lower survival rate than patients with homozygous mutations, but the molecular mechanisms behind this remain unexplored. Using an induced pluripotent stem cell (iPSC) model, we investigate differences between homozygous and compound heterozygous genotypes in different cell types, including patient-specific fibroblasts, iPSCs, and iPSC-derived neural stem cells (NSCs) and astrocytes. We found that compound heterozygous lines exhibited greater impairment of mitochondrial function in NSCs than homozygous NSCs, but not in fibroblasts, iPSCs, or astrocytes. Compared with homozygous NSCs, compound heterozygous NSCs exhibited more severe functional defects, including reduced ATP production, loss of mitochondrial DNA (mtDNA) copy number and complex I expression, disturbance of NAD+ metabolism, and higher ROS levels, which further led to cellular senescence and activation of mitophagy. RNA sequencing analysis revealed greater downregulation of mitochondrial and metabolic pathways, including the citric acid cycle and oxidative phosphorylation, in compound heterozygous NSCs. Our iPSC-based disease model can be widely used to understand the genotype-phenotype relationship of affected brain cells in mitochondrial diseases, and further drug discovery applications.publishedVersio

OXR1A, a Coactivator of PRMT5 Regulating Histone Arginine Methylation

Oxidation resistance gene 1 (OXR1) protects cells against oxidative stress. We find that male mice with brain-specific isoform A knockout (Oxr1A−/−) develop fatty liver. RNA sequencing of male Oxr1A−/− liver indicates decreased growth hormone (GH) signaling, which is known to affect liver metabolism. Indeed, Gh expression is reduced in male mice Oxr1A−/− pituitary gland and in rat Oxr1A−/− pituitary adenoma cell-line GH3. Oxr1A−/− male mice show reduced fasting-blood GH levels. Pull-down and proximity ligation assays reveal that OXR1A is associated with arginine methyl transferase PRMT5. OXR1A-depleted GH3 cells show reduced symmetrical dimethylation of histone H3 arginine 2 (H3R2me2s), a product of PRMT5 catalyzed methylation, and chromatin immunoprecipitation (ChIP) of H3R2me2s shows reduced Gh promoter enrichment. Finally, we demonstrate with purified proteins that OXR1A stimulates PRMT5/MEP50-catalyzed H3R2me2s. Our data suggest that OXR1A is a coactivator of PRMT5, regulating histone arginine methylation and thereby GH production within the pituitary gland.publishedVersio

Frontotemporal dementia and its subtypes: a genome-wide association study

SummaryBackground Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes—MAPT, GRN, and C9orf72—have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with {FTD} and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with {FTD} and 4308 controls), we did separate association analyses for each {FTD} subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and {FTD} overlapping with motor neuron disease FTD-MND), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10−8) single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10−8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, \{HLA\} locus (immune system), for rs9268877 (p=1·05 × 10−8; odds ratio=1·204 95% \{CI\} 1·11–1·30), rs9268856 (p=5·51 × 10−9; 0·809 0·76–0·86) and rs1980493 (p value=1·57 × 10−8, 0·775 0·69–0·86) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural \{FTD\} subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10−7; 0·814 0·71–0·92). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center

Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis

Funder: QingLan Research Project of Jiangsu for Outstanding Young TeachersFunder: Project funded by Postdoctoral Science Foundation of Xuzhou Medical UniversityFunder: Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) for Xuzhou Medical UniversityAbstract: We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population

Effects of eight neuropsychiatric copy number variants on human brain structure

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions