974 research outputs found
A Solution to the Circular Restricted N Body Problem in Planetary Systems
This thesis is a brief look at a new solution to a problem that has been approached in many different ways in the past - the N body problem. By focusing on planetary systems, satellite dynamics can be modeled in a fashion similar to the Circular Restricted Three Body Problem (CR3BP) with the Circular Restricted N Body Problem (CRNBP). It was found that this new formulation of the dynamics can then utilize the tools created from all the research into the CR3BP to reassess the possibility of different complex trajectories in systems where there are more than just two large gravitational bodies affecting the dynamics, namely periodic and semi-periodic orbits, halo orbits, and low energy transfers It was also found that not only system dynamics, but models of the Jacobi constant could also be formulated similarly to the CR3BP. Validating the authenticity of these new sets of equations, the CRNBP dynamics are applied to a satellite in the Earth-Moon system and compared to a simulation of the CR3BP under identical circumstances. This test verified the dynamics of the CRNBP, showing that the two systems created almost identical results with relatively small deviations over time and with essentially identical path trends. In the Jovian system, it was found the mass ratio required to validated the assumptions required to integrate the equations of motion was around .1. Once the mass ratio grew past that limit, trajectories propagated with the CRNBP showed significant deviation from trajectories propagated with a higher fidelity model of Newtonian motion. The results from the derivation of the Jacobi constant are consistent with the 3 body system, but they are fairly standalone
Quantifying the relationship between mechanical loading and the skeletal response in pre- and early-pubertal girls
PURPOSEBefore exercise prescription for bone health can be recommended, the relationship between mechanical loading characteristics and the skeletal response need to be quantified. We asked i) does moderate impact exercise result in a greater gain in BMC than low impact exercise, ii) what are the loading characteristics associated with a moderate and low impact exercise program and does this differ from non-structured play?, and iii) does loading history affect the osteogenic response to a moderate or low impact program? METHODSSixty-eight pre- and early-pubertal girls (aged 8.9 +/- 0.2 yrs) were randomized to take part in a moderate or low impact exercise program 3 times/wk for 8.5 mnths. The number and type of loads associated with the exercise classes and non-structured play (recess) were assessed from video footage. The magnitude of load was assessed using a pedar in-sole mobile system. Hours of moderate and high impact organized sport were assessed from a physical activity questionnaire. RESULTSThe moderate and low impact exercise programs consisted of -400 impacts per class, but the jumping, hopping and dynamic activities performed during the moderate impact program produced forces ranging from 2 to 4 times body weight (BW) compared to -1 BW for the low impact program. Moderate impact exercise resulted in a 2.7% greater gain in BMC at the tibia compared to the low impact exercise. The moderate impact exercise program consisted of fewer low impacts (1-2 BW) and a higher number of moderate impacts (2-4BW) compared to those typically performed during non-structured play. There were greater gains in BMC in subjects participating in the moderate versus the low impact exercise programs who participated in 2 to 3 hours of moderate impact sports outside school (2.5% to 4.5%, p CONCLUSIONApproximately 400 impacts ranging 2-4 BW, 3 times/wk was enough stimuli to result in an osteogenic response in normally active girls; even in those actively involved in moderate impact sports outside school.<br /
Endothelial cells, endoplasmic reticulum stress and oxysterols
Oxysterols are bioactive lipids that act as regulators of lipid metabolism, inflammation, cell viability and are involved in several diseases, including atherosclerosis. Mounting evidence linked the atherosclerosis to endothelium dysfunction; in fact, the endothelium regulates the vascular system with roles in processes such as hemostasis, cell cholesterol, hormone trafficking, signal transduction and inflammation. Several papers shed light the ability of oxysterols to induce apoptosis in different cell lines including endothelial cells. Apoptotic endothelial cell and endothelial denudation may constitute a critical step in the transition to plaque erosion and vessel thrombosis, so preventing the endothelial damaged has garnered considerable attention as a novel means of treating atherosclerosis. Endoplasmic reticulum (ER) is the site where the proteins are synthetized and folded and is necessary for most cellular activity; perturbations of ER homeostasis leads to a condition known as endoplasmic reticulum stress. This condition evokes the unfolded protein response (UPR) an adaptive pathway that aims to restore ER homeostasis. Mounting evidence suggests that chronic activation of UPR leads to cell dysfunction and death and recently has been implicated in pathogenesis of endothelial dysfunction. Autophagy is an essential catabolic mechanism that delivers misfolded proteins and damaged organelles to the lysosome for degradation, maintaining basal levels of autophagic activity it is critical for cell survival. Several evidence suggests that persistent ER stress often results in stimulation of autophagic activities, likely as a compensatory mechanism to relieve ER stress and consequently cell death. In this review, we summarize evidence for the effect of oxysterols on endothelial cells, especially focusing on oxysterols-mediated induction of endoplasmic reticulum stress
Up-regulation of prostaglandin biosynthesis by leukotriene C4 in elicited mice peritoneal macrophages activated with lipopolysaccharide/interferon-gamma
Leukotrienes (LT) and prostaglandins (PG) are proinflammatory mediators generated by the conversion of arachidonic acid via 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways. It has long been proposed that the inhibition of the 5-LO could enhance the COX pathway leading to an increased PG generation. We have found that in in vitro models of inflammation, such as mice-elicited peritoneal macrophages activated with lipopolysaccharide (LPS)/interferon- Îł (IFN-Îł), the deletion of the gene encoding for 5-LO or the enzyme activity inhibition corresponded to a negative modulation of the COX pathway. Moreover, exogenously added LTC4, but not LTD4, LTE 4, and LTB4, was able to increase PG production in stimulated cells from 5-LO wild-type and knockout mice. LTC4 was not able to induce COX-2 expression by itself but rather potentiated the action of LPS/IFN-Îł through the extracellular signal-regulated kinase-1/2 activation, as demonstrated by the use of a specific mitogen-activated protein kinase (MAPK) kinase inhibitor. The LT-induced increase in PG generation, as well as MAPK activation, was dependent by a specific ligand-receptor interaction, as demonstrated by the use of a cys-LT1 receptor antagonist, although also a direct action of the antagonist used, on PG generation, cannot be excluded. Thus, the balance between COX and 5-LO metabolites could be of great importance in controlling macrophage functions and consequently, inflammation and tumor promotion
Performance assessment of a vibro-finishing technology for additively manufactured components
Metal components produced by Additive Manufacturing (AM) technologies usually exhibit a rough surface, that in certain applications can result
detrimental for the part’s functionality. Thus, it is of great interest to study the finishing processes that can be applied to the surfaces, both external
and internal, of AM components. The aim of this work is the evaluation of the capabilities of a vibro-finishing process in the treatment of samples
produced by Laser-Powder Bed Fusion (L-PBF) from AlSi10Mg powders. In this research, the abrasive media is identified, and the surface
quality improvement is analysed in terms of surface roughness and modifications induced by the finishing treatment (i.e., edge rounding, material
loss) against finishing duration. The cost of the treatment is also evaluated
Additive manufacturing for an urban vehicle prototype: re-design and sustainability implications
Additive Manufacturing (AM), allowing the layer-by-layer fabrication of products characterized by a shape complexity unobtainable with conventional manufacturing routes, has been widely recognized as a disruptive technology enabling the transition to the Industry 4.0. In this context, the design of a Portable Assisted Mobile Device (PAMD) prototype was considered as a case study. The best practices of the re-design for AM were applied to three of the main structural components, and the most sustainable manufacturing approach between AM processes and the conventional ones was identified with respect to cumulative energy demand, carbon dioxide emissions and costs. The paper aims to promote the debate concerning the correlation between design choices, process selection and sustainable product development
A novel ABCC6 variant causative of pseudoxanthoma elasticum
Pseudoxanthoma elasticum is an autosomal recessive heritable disorder caused by mutations in ABCC6. We describetwo siblings showing typical skin lesions and a clinical diagnosis of pseudoxanthoma elasticum. Genetic analysis ofABCC6 revealed a novel homozygous c.4041G > A variant located in the last position of exon 28 that compromises thesplicing donor site, resulting in a shorter messenger RNA. The deletion impairs the nucleotide-binding fold region,which is crucial for ABCC6 function
Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression
The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury
A novel splicing variant of col2a1 in a fetus with achondrogenesis type ii: Interpretation of pathogenicity of in-frame deletions
Achondrogenesis type II (ACG2) is a lethal skeletal dysplasia caused by dominant pathogenic variants in COL2A1. Most of the variants found in patients with ACG2 affect the glycine residue included in the Gly-X-Y tripeptide repeat that characterizes the type II collagen helix. In this study, we reported a case of a novel splicing variant of COL2A1 in a fetus with ACG2. An NGS analysis of fetal DNA revealed a heterozygous variant c.1267-2_1269del located in intron 20/exon 21. The variant occurred de novo since it was not detected in DNA from the blood samples of parents. We generated an appropriate minigene construct to study the effect of the variant detected. The minigene expression resulted in the synthesis of a COL2A1 messenger RNA lacking exon 21, which generated a predicted in-frame deleted protein. Usually, in-frame deletion variants of COL2A1 cause a phenotype such as Kniest dysplasia, which is milder than ACG2. Therefore, we propose that the size and position of an in-frame deletion in COL2A1 may be relevant in determining the phenotype of skeletal dysplasia
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