Analysis of aerodynamic stability of the MetNet entry and descent vehicle with FINFLO simulations

This Master's Thesis investigates the aerodynamic stability of the MetNet Mars atmospheric entry and descent vehicle, developed in cooperation between the Finnish Meteorological Institute (FMI) and the Lavochin Association (LA). The purpose of the study is performing Computational Fluid Dynamics (CFD) simulations and obtaining the pertinent aerodynamic coefficients for the vehicle in the landing phase to Mars. The results are compared with the values obtained by LA, the most important feature being the aerodynamic stability of the vehicle. In this work, only the static stability is assessed. The simulations were performed with an inhouse FINFLO software. Before the simulations, an atmospheric model of Mars was created. Some initial trajectory calculations were made in order to have approximate values for the combinations of the Reynolds and Mach numbers that the vehicle will experience during the landing. These initial trajectory calculations also provided a condition for the mesh creation. A coarse and a dense calculation meshes were created with 1.4 and 7 million cells, respectively. The SST k-ω turbulence model was used and the results were tabulated in a form of dimensionless coeffcients. Apart from the lift coeffcient, the values differ to some extent from the LA's results. However, the general trends lead to the same conclusions: the drag coeffcient is more than suffcient to ensure the designed landing speed and the negative slope of the pitching moment coeffcient indicates static stability for the vehicle. Some heat load analyses were also carried out. Unfortunately, the simulations converged only up to Ma = 1,9 and no results were obtained at larger velocities. The thermal analyses show that heating of the vehicle is highly dependent on the Mach number, and for these reasons it would be advisable to perform more simulations for the vehicle.Tässä diplomityössä tutkitaan Ilmatieteen Laitoksen ja Lavochin Associationin (LA) kehittämän Mars MetNet-laskeutujan aerodynaamista vakavuutta käyttäen laskennallista virtausmekaniikkaa. Tavoitteena on ratkaista relevantit aerodynaamiset kertoimet laskeutumisvaiheen aikana Marsiin. Tuloksia verrataan LA:n saamiin arvoihin ja tärkeimpänä tutkittavana ominaisuutena on aerodynaaminen vakavuus. Työssä tutkitaan vain staattista aerodynaamista stabiiliutta. Laskentaan käytettiin FINFLO-ohjelmaa. Marsin kaasukehästä luotiin malli ennen simulaatioita. Lisäksi tehtiin ratalaskelmia laskeutujan laskeutumisvaiheen aikana kokemien Reynoldsin luvun ja Machin luvun arvojen saamiseksi. Ratalaskelmat tuottivat myös ehdon, joka auttoi laskentaverkon luomisessa. Laskentaa varten luotiin harva ja tiheä laskentaverkko, joissa oli 1,4 ja 7 miljoonaa laskentakoppia. Turbulenssin kuvaukseen käytettiin SST k-ω-mallia ja tulokset taulukoitiin dimensiottomassa kerroinmuodossa. Nostovoimakerrointa lukuun ottamatta tulokset erosivat jonkin verran LA:n saamista arvoista. Tuloksista voidaan kuitenkin tehdä sama päätelmä: laskeutujan vastuskerroin on enemmän kuin riittävä suunniteltuun laskeutumisnopeuteen nähden ja pituusmomenttikertoimen negatiivinen kulmakerroin osoittaa laskeutujan olevan staattisesti stabiili. Laskenta ei kuitenkaan konvergoitunut suuremmilla Machin luvuilla kuin Ma = 1,9 eikä tuloksia saatu tätä suuremmilla nopeuksilla. Lämpötarkastelut osoittivat lisäksi laskeutujan pintalämpötilan olevan voimakkaasti riippuvainen Machin luvusta ja näistä syistä laskeutujalle suositellaan suoritettavan lisää simulaatioita

The MetNet vehicle : a lander to deploy environmental stations for local and global investigations of Mars

Investigations of global and related local phenomena on Mars such as atmospheric circulation patterns, boundary layer phenomena, water, dust and climatological cycles and investigations of the planetary interior would benefit from simultaneous, distributed in situ measurements. Practically, such an observation network would require low-mass landers, with a high packing density, so a large number of landers could be delivered to Mars with the minimum number of launchers. The Mars Network Lander (MetNet Lander; MNL), a small semi-hard lander/penetrator design with a payload mass fraction of approximately 17 %, has been developed, tested and prototyped. The MNL features an innovative Entry, Descent and Landing System (EDLS) that is based on inflatable structures. The EDLS is capable of decelerating the lander from interplanetary transfer trajectories down to a surface impact speed of 50-70 ms(-1) with a deceleration of <500 g for <20 ms. The total mass of the prototype design is approximate to 24 kg, with approximate to 4 kg of mass available for the payload. The EDLS is designed to orient the penetrator for a vertical impact. As the payload bay will be embedded in the surface materials, the bay's temperature excursions will be much less than if it were fully exposed on the Martian surface, allowing a reduction in the amount of thermal insulation and savings on mass. The MNL is well suited for delivering meteorological and atmospheric instruments to the Martian surface. The payload concept also enables the use of other environmental instruments. The small size and low mass of a MNL makes it ideally suited for piggy-backing on larger spacecraft. MNLs are designed primarily for use as surface networks but could also be used as pathfinders for high-value landed missions.Peer reviewe

Genetic and Epigenetic Characteristics of Inflammatory Bowel Disease–Associated Colorectal Cancer

doi: 10.1053/j.gastro.2021.04.042Background & Aims Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs. Methods Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue samples of tumor and corresponding normal tissues from 31 patients with IBD-CRC. Results Transcriptome-based tumor subtyping revealed the complete absence of canonical epithelial tumor subtype associated with WNT signaling in IBD-CRCs, dominated instead by mesenchymal stroma-rich subtype. Negative WNT regulators AXIN2 and RNF43 were strongly down-regulated in IBD-CRCs and chromosomal gains at HNF4A, a negative regulator of WNT-induced epithelial–mesenchymal transition (EMT), were less frequent compared to sCRCs. Enrichment of hypomethylation at HNF4α binding sites was detected solely in sCRC genomes. PIGR and OSMR involved in mucosal immunity were dysregulated via epigenetic modifications in IBD-CRCs. Genome-wide analysis showed significant enrichment of noncoding mutations to 5′untranslated region of TP53 in IBD-CRCs. As reported previously, somatic mutations in APC and KRAS were less frequent in IBD-CRCs compared to sCRCs. Conclusions Distinct mechanisms of WNT pathway dysregulation skew IBD-CRCs toward mesenchymal tumor subtype, which may affect prognosis and treatment options. Increased OSMR signaling may favor the establishment of mesenchymal tumors in patients with IBD.BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs. METHODS: Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue samples of tumor and corresponding normal tissues from 31 patients with IBD-CRC. RESULTS: Transcriptome-based tumor subtyping revealed the complete absence of canonical epithelial tumor subtype associated with WNT signaling in IBD-CRCs, dominated instead by mesenchymal stroma-rich subtype. Negative WNT regulators AXIN2 and RNF43 were strongly down-regulated in IBD-CRCs and chromosomal gains at HNF4A, a negative regulator of WNTinduced epithelial-mesenchymal transition (EMT), were less frequent compared to sCRCs. Enrichment of hypomethylation at HNF4 alpha binding sites was detected solely in sCRC genomes. PIGR and OSMR involved in mucosal immunity were dysregulated via epigenetic modifications in IBD-CRCs. Genome-wide analysis showed significant enrichment of noncoding mutations to 50 untranslated region of TP53 in IBD-CRCs. As reported previously, somatic mutations in APC and KRAS were less frequent in IBD-CRCs compared to sCRCs. CONCLUSIONS: Distinct mechanisms of WNT pathway dysregulation skew IBD-CRCs toward mesenchymal tumor subtype, which may affect prognosis and treatment options. Increased OSMR signaling may favor the establishment of mesenchymal tumors in patients with IBD.Peer reviewe

Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data

Abstract: Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers

Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata

Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.Peer reviewe

Genetic architecture of human plasma lipidome and its link to cardiovascular disease

Abstract Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P &lt;5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate&lt;0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD

Sleep apnoea is a risk factor for severe COVID-19

Background Obstructive sleep apnoea (OSA) is associated with higher body mass index (BMI), diabetes, older age and male gender, which are all risk factors for severe COVID-19.We aimed to study if OSA is an independent risk factor for COVID-19 infection or for severe COVID-19.Methods OSA diagnosis and COVID-19 infection were extracted from the hospital discharge, causes of death and infectious diseases registries in individuals who participated in the FinnGen study (n=260 405). Severe COVID-19 was defined as COVID-19 requiring hospitalisation. Multivariate logistic regression model was used to examine association. Comorbidities for either COVID-19 or OSA were selected as covariates. We performed a meta-analysis with previous studies.Results We identified 445 individuals with COVID-19, and 38 (8.5%) of them with OSA of whom 19 out of 91 (20.9%) were hospitalised. OSA associated with COVID-19 hospitalisation independent from age, sex, BMI and comorbidities (p-unadjusted=5.13×10−5, OR-adjusted=2.93 (95% CI 1.02 to 8.39), p-adjusted=0.045). OSA was not associated with the risk of contracting COVID-19 (p=0.25). A meta-analysis of OSA and severe COVID-19 showed association across 15 835 COVID-19 positive controls, and n=1294 patients with OSA with severe COVID-19 (OR=2.37 (95% 1.14 to 4.95), p=0.021).Conclusion Risk for contracting COVID-19 was the same for patients with OSA and those without OSA. In contrast, among COVID-19 positive patients, OSA was associated with higher risk for hospitalisation. Our findings are in line with earlier works and suggest OSA as an independent risk factor for severe COVID-19