Inverse models for ice-induced propeller moments on a polar vessel.

Thesis (PhD)--Stellenbosch University, 2021.ENGLISH ABSTRACT: It is necessary to quantify the loads experienced by the propellers of ice-going vessels.Knowledge of these loads will serve to improve propulsion design specifications and maintenance strategies for polar class ships. Recent developments include the inverse solutions of the external ice-induced propeller moments from indirect measurements on the propulsion shaft. These inverse solutions are performed using models that account for the dynamic influence of the shaft. Although torsional vibration calculations are required by design rules there is little information on the methodology external propeller moments as their use, in this context, is still relatively new. Full-scale propulsion shaft measurements were conducted on board the S.A. Agulhas II, in which the torque and angular velocity were captured, to be trans-formed into external propeller moments. Two inverse models of the propulsion shaft were investigated. The first is an existing model which represents the shaft as a combination of lumped masses. The inverse problem in this case is ill-posed and requires regularization. It was found that the assumptions made in the derivation of this model, that both the hydrodynamic and motor torques were constant, and its computational expense made it ill-suited for use in the inverse estimation of propeller moments. The second inverse model is newly developed and based on the superposition of the shaft modes, resulting in a well-posed problem. This model accounts for the modal inertia in the flexible modes of the shaft, as full-scale data indicated that this was important, and has increased accuracy and efficiency. To the author’s knowledge, this is the first model that has been efficiently applied to determine the inverse propeller moments from full-scale measurements for a complete voyage. The derivation of the corresponding estimated propeller load profiles is presented. The new model is suitable for the real-time monitoring of propeller loads, which can assist in ship operation.AFRIKAANSE OPSOMMING: Dit is nodig om die laste te kwantifiseer waaraan die skroewe van skepe onderhewig is ty-dens ysvaart. Kennis van hierdie laste dien om die spesifikasies en instandhoudingstrategieëvan aandrywingstelsels van ys-klas skepe toe te lig. Onlangse verwikkelinge sluit inverseoplossings van die eksterne in ys-geënduseerde skroefmomente in deur gebruik te maak vanindirekte metings op die dryfas. Hierdie inverse oplossings word uitgevoer met behulp vanmodelle wat die dinamiese invloed van die as in ag neem. Hoewel torsionele vibrasiebe-rekening deur ontwerpsreëls vereis word, is daar min inligting oor metodologie om inverseskroefmomente te bepaal, aangesien werk in die konteks nog relatief nuut is. Volskaalsedryfasmetings van wringkrag en hoeksnelheid is op die S.A. Agulhas II uitgevoer met diedoel om skroefmomente van hier af te bereken. Twee inverse modelle van die SA AghulhasII dryfas is ondersoek. Die eerste model is ’n bestaande model, wat die skag voorstel as’n kombinasie van gekonsentreerde massas. Die inverse probleem in hierdie geval is swakgestel en vereis regularisering. Verder word daar aangeneem dat beide die hidrodinamiese-en die motorwringkrag konstant is. Die berekeningsvereistes maak dit ongeskik vir gebruikin die inverse beraming van skroefmomente. ’n Tweede inverse model is nuut ontwikkel engebaseer op die superposisie van die modusse van die dryfas. Dit is meer akkuraat en doel-treffend en lei tot ’n volledig gestelde probleem. Dit sluit die modale traagheid van die as in,aangesien volskaalse data aandui dat dit belangrik is. Volgens die outeur is hierdie die eersteinverse model wat effektief aangewend is om invers-berekende skroefmomente vanaf volskaalmeetings te beraam vir ’n volledige vaart. Die afleiding van geskatte skroef lasprofiele wordaangebied. Die nuwe model is geskik vir intydse monitering van operasionele skroeflaste.Doctora

Spaceflight modulates gene expression in the whole blood of astronauts

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a first-of-its-kind pilot study to assess spaceflight-related gene-expression changes in the whole blood of astronauts. Using an array comprised of 234 well-characterized stress-response genes, we profiled transcriptomic changes in six astronauts (four men and two women) from blood preserved before and immediately following the spaceflight. Differentially regulated transcripts included those important for DNA repair, oxidative stress, and protein folding/degradation, including HSP90AB1, HSP27, GPX1, XRCC1, BAG-1, HHR23A, FAP48, and C-FOS. No gender-specific differences or relationship to number of missions flown was observed. This study provides a first assessment of transcriptomic changes occurring in the whole blood of astronauts in response to spaceflight

Studying Host-Pathogen Interactions In 3-D: Organotypic Models For Infectious Disease And Drug Development

Representative, reproducible and high-throughput models of human cells and tissues are critical for a meaningful evaluation of host-pathogen interactions and are an essential component of the research developmental pipeline. The most informative infection models - animals, organ explants and human trials - are not suited for extensive evaluation of pathogenesis mechanisms and screening of candidate drugs. At the other extreme, more cost effective and accessible infection models such as conventional cell culture and static co-culture may not capture physiological and three-dimensional aspects of tissue biology that are important in assessing pathogenesis, and effectiveness and cytotoxicity of therapeutics. Our lab has used innovative bioengineering technology to establish biologically meaningful 3-D models of human tissues that recapitulate many aspects of the differentiated structure and function of the parental tissue in vivo, and we have applied these models to study infectious disease. We have established a variety of different 3-D models that are currently being used in infection studies - including small intestine, colon, lung, placenta, bladder, periodontal ligament, and neuronal models. Published work from our lab has shown that our 3-D models respond to infection with bacterial and viral pathogens in ways that reflect the infection process in vivo. By virtue of their physiological relevance, 3-D cell cultures may also hold significant potential as models to provide insight into the neuropathogenesis of HIV infection. Furthermore, the experimental flexibility, reproducibility, cost-efficiency, and high throughput platform afforded by these 3-D models may have important implications for the design and development of drugs with which to effectively treat neurological complications of HIV infection

Low Fluid Shear Culture of Staphylococcus Aureus Represses hfq Expression and Induces an Attachment-Independent Biofilm Phenotype

Background: The opportunistic pathogen, Staphylococcus aureus, experiences fluctuations in fluid shear during infection and colonization of a human host. Colonization frequently occurs at mucus membrane sites such as in the gastrointestinal tract where the bacterium may experience low levels of fluid shear. The response of S. aureus to low fluid shear remains unclear. Methods: S. aureus was cultured to stationary phase using Rotating-Wall Vessel (RWV) bioreactors which produce a physiologically relevant low fluid shear environment. The bacterial aggregates that developed in the RWV were evaluated by electron microscopy as well as for antibiotic resistance and other virulence-associated stressors. Genetic expression profiles for the low-shear cultured S. aureus were determined by microarray analysis and quantitative real-time PCR. Results: Planktonic S. aureus cultures in the low-shear environment formed aggregates completely encased in high amounts of extracellular polymeric substances. In addition, these aggregates demonstrated increased antibiotic resistance indicating attachment-independent biofilm formation. Carotenoid production in the low-shear cultured S. aureus was significantly decreased, and these cultures displayed an increased susceptibility to oxidative stress and killing by whole blood. The hfq gene, associated with low-shear growth in Gram negative organisms, was also found to be down-regulated in S. aureus. Conclusions: Collectively, this data suggests that S. aureus decreases virulence characteristics in favor of a biofilm-dwelling colonization phenotype in response to a low fluid shear environment. Furthermore, the identification of an Hfq response to low-shear culture in S. aureus, in addition to the previously reported responses in Gram negative organisms, strongly suggests an evolutionarily conserved response to mechanical stimuli among structurally diverse prokaryotes

Toll-like Receptor 7 and TLR9 Dictate Autoantibody Specificity and Have Opposing Inflammatory and Regulatory Roles in a Murine Model of Lupus

SummaryAntibodies (Abs) to RNA- and DNA-containing autoantigens are characteristic of systemic lupus erythematosus (SLE). We showed previously that Toll-like receptor (TLR) 9, recognizing DNA, is required for the spontaneous generation of DNA autoantibodies, but not for the development of lupus nephritis in susceptible mice. We report that lupus-prone mice deficient in TLR7, a receptor for ssRNA, failed to generate Abs to RNA-containing antigens (Ags) such as Smith (Sm) Ag. TLR9 and TLR7 also had dramatic effects on clinical disease in lupus-prone mice. In the absence of TLR9, autoimmune disease was exacerbated, lymphocytes and plasmacytoid DCs were more activated, and serum IgG and IFN-α were increased. In contrast, TLR7-deficient mice had ameliorated disease, decreased lymphocyte activation, and decreased serum IgG. These findings reveal opposing inflammatory and regulatory roles for TLR7 and TLR9, despite similar tissue expression and signaling pathways. These results have important implications for TLR-directed therapy of autoimmune disease

A Glutathione-independent Glyoxalase of the DJ-1 Superfamily Plays an Important Role in Managing Metabolically Generated Methylglyoxal in \u3ci\u3eCandida albicans\u3c/i\u3e

Methylglyoxal is a cytotoxic reactive carbonyl compound produced by central metabolism. Dedicated glyoxalases convert methylglyoxal to D-lactate using multiple catalytic strategies. In this study, the DJ-1 superfamily member ORF 19.251/GLX3 from Candida albicans is shown to possess glyoxalase activity, making this the first demonstrated glutathione-independent glyoxalase in fungi. The crystal structure of Glx3p indicates that the protein is a monomer containing the catalytic triad Cys136- His137-Glu168. Purified Glx3p has an in vitro methylglyoxalase activity (Km = 5.5 mM andkcat = 7.8 s-1) that is significantly greater than that of more distantly related members of the DJ-1 superfamily. A close Glx3p homolog from Saccharomyces cerevisiae (YDR533C/Hsp31) also has glyoxalase activity, suggesting that fungal members of the Hsp31 clade of the DJ-1 superfamily are all probable glutathione-independent glyoxalases. A homozygous glx3 null mutant in C. albicans strain SC5314 displays greater sensitivity to millimolar levels of exogenous methylglyoxal, elevated levels of intracellular methylglyoxal, and carbon source-dependent growth defects, especially when grown on glycerol. These phenotypic defects are complemented by restoration of the wild-type GLX3 locus. The growth defect of Glx3-deficient cells in glycerol is also partially complemented by added inorganic phosphate, which is not observed for wild-type or glucose-grown cells. Therefore, C. albicans Glx3 and its fungal homologs are physiologically relevant glutathione- independent glyoxalases that are not redundant with the previously characterized glutathione-dependent GLO1/GLO2 system. In addition to its role in detoxifying glyoxals, Glx3 and its close homologs may have other important roles in stress response

Smooth muscle cell specific deletion of the PKGIα target RGS2 induces vascular dysfunction and hypertension

International audiencen.

Allele Frequency Matching Between SNPs Reveals an Excess of Linkage Disequilibrium in Genic Regions of the Human Genome

Significant interest has emerged in mapping genetic susceptibility for complex traits through whole-genome association studies. These studies rely on the extent of association, i.e., linkage disequilibrium (LD), between single nucleotide polymorphisms (SNPs) across the human genome. LD describes the nonrandom association between SNP pairs and can be used as a metric when designing maximally informative panels of SNPs for association studies in human populations. Using data from the 1.58 million SNPs genotyped by Perlegen, we explored the allele frequency dependence of the LD statistic r (2) both empirically and theoretically. We show that average r (2) values between SNPs unmatched for allele frequency are always limited to much less than 1 (theoretical [Image: see text] approximately 0.46 to 0.57 for this dataset). Frequency matching of SNP pairs provides a more sensitive measure for assessing the average decay of LD and generates average r (2) values across nearly the entire informative range (from 0 to 0.89 through 0.95). Additionally, we analyzed the extent of perfect LD (r (2) = 1.0) using frequency-matched SNPs and found significant differences in the extent of LD in genic regions versus intergenic regions. The SNP pairs exhibiting perfect LD showed a significant bias for derived, nonancestral alleles, providing evidence for positive natural selection in the human genome

ReelFramer: Co-creating News Reels on Social Media with Generative AI

Short videos on social media are a prime way many young people find and consume content. News outlets would like to reach audiences through news reels, but currently struggle to translate traditional journalistic formats into the short, entertaining videos that match the style of the platform. There are many ways to frame a reel-style narrative around a news story, and selecting one is a challenge. Different news stories call for different framings, and require a different trade-off between entertainment and information. We present a system called ReelFramer that uses text and image generation to help journalists explore multiple narrative framings for a story, then generate scripts, character boards and storyboards they can edit and iterate on. A user study of five graduate students in journalism-related fields found the system greatly eased the burden of transforming a written story into a reel, and that exploring framings to find the right one was a rewarding process