53 research outputs found
Post processing of additively manufactured metal parts by using pulse electrochemical machining
In response of the growing demand for higher product requirements concerning quality, durability and efficiency by simultaneously decreasing product life cycles, the product development has to consider suitable production technologies at an early stage of the development process. This implicates also the choice of new manufacturing or technology approaches. Additively manufactured parts can be produced with a high geometrical complexity. To produce such geometrically complex parts from metal, the so called selective laser melting (SLM) technology is often the method of choice. In order to produce SLM-parts, support structures have to be used. They have several functions, such as connecting the component to a building platform, supporting overhanging and tilted areas but they also dissipate the heat of fusion. However, those support structures have to be removed for the use of the component, which often involves numerous time- consuming and difficult to automatize operation steps. A promising alternative can be pulse electrochemical machining (PECM) as there is no contact between tool and workpiece. This allows the adaption of the tool to complex geometries and the improvement of the workpiece surface quality in one machining step. Therefore, a fundamental study of the electrochemical dissolution behavior and machinability aspects of the support structures is performed
Histamine can be Formed and Degraded in the Human and Mouse Heart
Histamine is metabolized by several enzymes in vitro and in vivo. The relevance of this
metabolism in the mammalian heart in vivo is unclear. However, histamine can exert
positive inotropic effects (PIE) and positive chronotropic effects (PCE) in humans via H2-
histamine receptors. In transgenic mice (H2-TG) that overexpress the human H2 receptor in
cardiomyocytes but not in wild-type littermate mice (WT), histamine induced PIE and PCE
in isolated left or right atrial preparations. These H2-TG were used to investigate the
putative relevance of histamine degrading enzymes in the mammalian heart. Histidine, the
precursor of histamine, increased force of contraction (FOC) in human atrial preparations.
Moreover, histamine increased the phosphorylation state of phospholamban in human
atrium. Here, we could detect histidine decarboxylase (HDC) and histamine itself in
cardiomyocytes of mouse hearts. Moreover, our data indicate that histamine is subject
to degradation in the mammalian heart. Inhibition of the histamine metabolizing enzymes
diamine oxidase (DAO) and monoamine oxidase (MAO) shifted the concentration response
curves for the PIE in H2-TG atria to the left. Moreover, activity of histamine metabolizing
enzymes was present in mouse cardiac samples as well as in human atrial samples. Thus,
drugs used for other indication (e.g. antidepressants) can alter histamine levels in the heart.
Our results deepen our understanding of the physiological role of histamine in the mouse
and human heart. Our findings might be clinically relevant because we show enzyme
targets for drugs to modify the beating rate and force of the human heart
Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism
Although the immunomodulatory and cytoprotective properties of itaconate have been studied extensively, it is not known whether its naturally occurring isomers mesaconate and citraconate have similar properties. Here, we show that itaconate is partially converted to mesaconate intracellularly and that mesaconate accumulation in macrophage activation depends on prior itaconate synthesis. When added to human cells in supraphysiological concentrations, all three isomers reduce lactate levels, whereas itaconate is the strongest succinate dehydrogenase (SDH) inhibitor. In cells infected with influenza A virus (IAV), all three isomers profoundly alter amino acid metabolism, modulate cytokine/chemokine release and reduce interferon signalling, oxidative stress and the release of viral particles. Of the three isomers, citraconate is the strongest electrophile and nuclear factor-erythroid 2-related factor 2 (NRF2) agonist. Only citraconate inhibits catalysis of itaconate by cis-aconitate decarboxylase (ACOD1), probably by competitive binding to the substrate-binding site. These results reveal mesaconate and citraconate as immunomodulatory, anti-oxidative and antiviral compounds, and citraconate as the first naturally occurring ACOD1 inhibitor. [Image: see text
Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism
Although the immunomodulatory and cytoprotective properties of itaconate have been studied extensively, it is not known
whether its naturally occurring isomers mesaconate and citraconate have similar properties. Here, we show that itaconate
is partially converted to mesaconate intracellularly and that
mesaconate accumulation in macrophage activation depends
on prior itaconate synthesis. When added to human cells in
supraphysiological concentrations, all three isomers reduce
lactate levels, whereas itaconate is the strongest succinate
dehydrogenase (SDH) inhibitor. In cells infected with influenza A virus (IAV), all three isomers profoundly alter amino
acid metabolism, modulate cytokine/chemokine release and
reduce interferon signalling, oxidative stress and the release
of viral particles. Of the three isomers, citraconate is the
strongest electrophile and nuclear factor-erythroid 2-related
factor 2 (NRF2) agonist. Only citraconate inhibits catalysis of
itaconate by cis-aconitate decarboxylase (ACOD1), probably
by competitive binding to the substrate-binding site. These
results reveal mesaconate and citraconate as immunomodulatory, anti-oxidative and antiviral compounds, and citraconate
as the first naturally occurring ACOD1 inhibitor
Just compensation? The price of death and injury after the Rana Plaza garment factory collapse
The 2013 collapse of the Rana Plaza factory building in Dhaka, Bangladesh was the most deadly disaster in garment manufacturing history, with at least 1,134 people killed and hundreds injured. In 2015, injured workers and the families of those killed received compensation from global apparel brands through a $30 million voluntary initiative known as the Rana Plaza Arrangement. Overseen by the International Labour Organization (ILO), the Rana Plaza Arrangement awarded payments to survivors using a pricing formula developed by a diverse team of âstakeholdersâ that included labour groups, multinational apparel companies, representatives of the Bangladesh government and local employers, and ILO actuaries. This article draws from anthropological scholarship on the âjust priceâ to explore how a formula for pricing death and injury became both the means and form of a fragile political settlement in the wake of a shocking and widely publicised industrial disaster. By unpacking the complicated âethics of a formulaâ (Ballestero 2015), I demonstrate how the project of creating a just price involves not two sets of values (ethical and financial) but rather multiple, competing values. This article argues for recognition of the persistence and power of these competing values, showing how they variously strengthen and undermine the claim that justice was served by the Rana Plaza Arrangement. This analysis reveals the deficiencies of counterposing âmoralityâ and âeconomyâ in the study of price by reflecting upon all elements of price as situated within political economy and history
A novel approach to roundness generation analysis in centerless throughfeed grinding in consider of decisive parameters of grinding gap by use of 3D kinematic simulation
Grinding gap geometry based on setup conditions and its effect on roundness generation is a complex phenomenon in through-feed centerless grinding process. The objective of this paper is to introduce a suitable solution for the use of simulation in through-feed centerless grinding, to assist in the selection of acceptable set-up conditions for centerless grinding and their effect on roundness quality. A qualitative assessment of geometrical influence parameters is carried out by means of a kinematics simulation based on a non-linear 3-dimensional model of the centerless grinding process. The novel aspect of the model analysis is the determination of the grinding gap with two new decisive parameters in centerless through-feed grinding and their effect on geometrical rounding stability. The ratio of the finishing to roughing length and ratio of the finishing to roughing material removal rate are crucial to minimize roundness errors
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