Capability of load-time history reconstruction and fatigue crack growth rate estimation for 2024-T3 aluminium alloy on the basis of fractographic analysis

The subject of the paper is the considerations of the capability of load-time history reconstruction for the component under variable amplitude loading and fatigue crack growth rate estimation for the 2024-T3 Alclad aluminium alloy on the basis of microfracture analysis. For this goal three variable amplitude (VA) load sequences with multiple overloads and differing from the level of load sequence complexity were applied. These loads are employed when simulating the fatigue behaviour of aeronautical alloys. To reveal the load sequence effect on crack growth behaviour the microfracture analysis were provided by means of TEM microscope

Fatigue research 2024-T3 aluminium alloy

В роботі представлено дослідження втомного руйнування листів алюмінієвого сплаву 2024-Т3 товщиною 3 мм при трьох видах блокового змінно амплітудного навантаження. Прикладене навантаження моделює реальний спектр навантажень нижньої частини крила літака. Метою дослідження було виявлення впливу спектру навантаження на формування втомних борозенок на поверхні руйнування та перевірка можливості відтворення історії навантаження на основі фрактографічного аналізу. Результати дослідження швидкості руйнування відносяться до довгих тріщин. Експериментально визначена швидкість руйнування була порівняна з швидкістю отриманою на основі аналізу відстані між втомними борозенками. Фрактографічний аналіз дозволяє отримати кількісний опис залежності між міжборозенковою відстанню на поверхні руйнування та швидкістю втомного руйнування в цілому діапазоні довжини тріщини.The subject of the paper is fatigue crack growth rate investigation for 2024-T3 3 mm thick Alclad aluminium alloy sheet under three variable amplitude load programs with multiple overloadsunderloads. These programs correspond to a flight simulation spectrum of a lower skin wing structure. The research was undertaken in order to learn an interaction between applied load and formation of fatigue striations on the specimen fracture surfaces as well as to check the capability for load-time history reconstruction on the basis of microfracture analysis. All considerations in the terms of fatigue crack growth behaviour refer mainly to long cracks. Experimentally determined crack growth rates were compared with the growth rates that were evaluated from the striations spacing. Quantitative fractography allowed to deliver the relation between surface crack and crack depth growth rates for whole range of crack growth.W pracy przedstawiono badania zmęczeniowego pękania 3 mm blachy ze stopu aluminium 2024-T3 pod wpływem trzech zmiennoamplitudowych programów obciążeń. Zastosowane obciążenia były związane z widmem obciążeń dolnego pokrycia skrzydła samolotu. Badania miały na celu określenie wpływu widma obciążeń na kształtowanie się prążków zmęczeniowych na powierzchni przełomu oraz sprawdzenie możliwości odtwarzania historii obciążenia na podstawie analizy fraktograficznej. Wyniki badań prędkości pękania dotyczyły długich pęknięć. Doświadczalnie wyznaczone prędkości zmęczeniowego pękania były porównywane z prędkościami wyznaczonymi na podstawie odległości międzyprążkowych. Analiza fraktograficzna pozwala na określenie ilościowych relacji między odległościami międzyprążkowymi na powierzchni przełomu a prędkością zmęczeniowego pękania w całym zakresie długości pęknięcia

Case report: C-reactive protein apheresis in cardiogenic shock: case series from the C-reactive protein apheresis in acute myocardial infarction-registry

C-reactive protein (CRP) apheresis may preserve myocardial tissue after acute myocardial infarction with delayed revascularization. Ten consecutive patients with cardiogenic shock were graded using the Society of Cardiovascular Angiography and Interventions shock classification and treated with CRP apheresis. All patients tolerated CRP apheresis well and were discharged in good clinical condition

Functional analysis of the C-reactive protein (CRP) gene -717A>G polymorphism associated with coronary heart disease

<p>Abstract</p> <p>Background</p> <p>Atherosclerosis underlies the major pathophysiological mechanisms of coronary heart disease (CHD), and inflammation contributes to all phases of atherosclerosis. C-reactive protein (CRP), a sensitive, but nonspecific marker of inflammation has been shown to play proatherogenic roles in the process of atherosclerosis. Our previous report showed that rs2794521 (-717A>G), located in the promoter of the CRP gene, was independently associated with CHD in Chinese subjects. In the present study, we tried to investigate the biological significance of this genetic variation <it>in vitro</it>.</p> <p>Methods</p> <p>The influence of G to A substitution at the site of rs2794521 on the transcriptional activity of the promoter of the CRP gene was assessed by luciferase reporter assay, and protein binding to the site of rs2794521 was detected by EMSA assay.</p> <p>Results</p> <p>The G to A exchange at the site of rs2794521 resulted in an increased transcriptional activity of the promoter of CRP gene, and glucocorticoid receptor (GR) protein factor bound drastically differently to the A and G alleles at the site of rs2794521.</p> <p>Conclusion</p> <p>These results provided functional evidence supporting the association of the SNP rs2794521 of the CRP gene with CHD probably through regulating the expression level of CRP by different variations of rs2794521.</p

CD55 Deficiency Protects against Atherosclerosis in ApoE-Deficient Mice via C3a Modulation of Lipid Metabolism

Atherosclerosis, the leading cause of death in the Western world, is driven by chronic inflammation within the artery wall. Elements of the complement cascade are implicated in the pathogenesis, because complement proteins and their activation products are found in the atherosclerotic plaque. We examined the role of CD55, a membrane inhibitor of the complement component 3 (C3) convertase, which converts C3 into C3a and C3b, in atherosclerosis. CD55-deficient (CD55−/−) mice were crossed onto the atherosclerosis-prone apolipoprotein E (apoE)-deficient (apoE−/−) background. High fat–fed male apoE−/−/CD55−/− mice were strongly protected from developing atherosclerosis compared with apoE−/− controls. Lipid profiling showed significantly lower levels of triglycerides, nonesterified fatty acids, and cholesterol in apoE−/−/CD55−/− mice than that in controls after high-fat feeding, whereas body fat in apoE−/−/CD55−/− mice content was increased. Plasma levels of C3 fell, whereas concentrations of C3adesArg (alias acylation stimulating protein; ASP), produced by serum carboxypeptidase N–mediated desargination of C3a, increased in nonfasted high fat–fed apoE−/−/CD55−/− mice, indicating complement activation. Thus, complement dysregulation in the absence of CD55 provoked increased C3adesArg production that, in turn, caused altered lipid handling, resulting in atheroprotection and increased adiposity. Interventions that target complement activation in adipose tissue should be explored as lipid-decreasing strategies

Doxycycline Stabilizes Vulnerable Plaque via Inhibiting Matrix Metalloproteinases and Attenuating Inflammation in Rabbits

Enhanced matrix metalloproteinases (MMPs) activity is implicated in the process of atherosclerotic plaque instability. We hypothesized that doxycycline, a broad MMPs inhibitor, was as effective as simvastatin in reducing the incidence of plaque disruption. Thirty rabbits underwent aortic balloon injury and were fed a high-fat diet for 20 weeks. At the end of week 8, the rabbits were divided into three groups for 12-week treatment: a doxycycline-treated group that received oral doxycycline at a dose of 10 mg/kg/d, a simvastatin-treated group that received oral simvastatin at a dose of 5 mg/kg/d, and a control group that received no treatment. At the end of week 20, pharmacological triggering was performed to induce plaque rupture. Biochemical, ultrasonographic, pathologic, immunohistochemical and mRNA expression studies were performed. The results showed that oral administration of doxycycline resulted in a significant increase in the thickness of the fibrous cap of the aortic plaque whereas there was a substantial reduction of MMPs expression, local and systemic inflammation, and aortic plaque vulnerability. The incidence of plaque rupture with either treatment (0% for both) was significantly lower than that for controls (56.0%, P<0.05). There was no significant difference between doxycycline-treated group and simvastatin-treated group in any serological, ultrasonographic, pathologic, immunohistochemical and mRNA expression measurement except for the serum lipid levels that were higher with doxycycline than with simvastatin treatment. In conclusion, doxycycline at a common antimicrobial dose stabilizes atherosclerotic lesions via inhibiting matrix metalloproteinases and attenuating inflammation in a rabbit model of vulnerable plaque. These effects were similar to a large dose of simvastatin and independent of serum lipid levels

Biological foundation for periodontitis as a potential risk factor for atherosclerosis

Links between periodontal diseases and systemic diseases have been well documented by epidemiological studies. Recently, research has shifted to elucidating the biologic mechanism for a causal relationship. One focus of interest is atherosclerosis, the underlying event of cardiovascular diseases due to its serious health impact. However, it is still not clear whether periodontopathic pathogens are truly etiologic agents or ubiquitous bystanders. This article reviews the current understanding about the molecular biological interactions between periodontal disease and atherosclerosis and the biological plausibility of periodontitis as a potential risk factor for cardiovascular disease. Materials and methods:  The current literature regarding periodontal diseases and atherosclerosis and coronary vascular disease was searched using the Medline and PubMed databases. Results:  In vitro experiments and animal models are appropriate tools to investigate the biological interactions between periodontal disease and atherosclerosis at the cell molecular level. The concepts linking both pathologies refer to inflammatory response, immune responses, and hemostasis. In particular, Porphyromonas gingivalis appears to have unique, versatile pathogenic properties. Whether or not these findings from isolated cells or animal models are applicable in humans with genetic and environmental variations is yet to be determined. Likewise, the benefit from periodontal therapy on the development of atherosclerosis is unclear. Approaches targeting inflammatory and immune responses of periodontitis and atherosclerosis simultaneously are very intriguing. Conclusion:  An emerging concept suggests that a pathogenic burden from different sources might overcome an individual threshold culminating in clinical sequela. P. gingivalis contributes directly and indirectly to atherosclerosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66109/1/j.1600-0765.2004.00771.x.pd

Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age

<p>Abstract</p> <p>Background</p> <p>In <it>Plasmodium falciparum</it>-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults.</p> <p>Methods</p> <p>Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-β and IL-10, and ANA were determined by immunoassay.</p> <p>Results</p> <p>The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment.</p> <p>Conclusion</p> <p>The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed.</p