Change of dominant material properties in laser perforation process with high-energy lasers up to 120 kilowatt.

In laser materials processing, energy losses due to reflection, heat conduction and thermal radiation play an important role. In this publication, we show that with increasing laser intensity, the energy lost within the sample becomes less important for metal perforation processes. We compare the laser-matter interaction of aluminum and steel plates. Material parameters such as density, melting point and especially thermal conductivity differ strongly, leading to much longer perforation times for aluminum in comparison to steel at laser powers of 20 kW. However, this behavior changes at laser powers of more than 80 kW where the perforation times of aluminum become shorter than the corresponding times for steel. By comparing experimental data and simulations, we conclude that thermal conduction is the dominant factor of energy loss at low powers, but is reduced at high laser powers.

Measuring the Cooling Behavior of Melt Pools in L-PBF by Pyrometry.

This study aims to measure the cooling rates or, more precisely, the cooling durations of single laser tracks by pyrometry within the laser powder bed fusion (L-PBF) process. Two-color, as well as one-color pyrometers are tested within this work. Regarding the second, the emissivity of the investigated 30CrMoNb5-2 alloy is determined in-situ within the L-PBF system in order to measure temperature instead of arbitrary units. This is done by heating up printed samples and verifying the measured pyrometer signal by comparing it to values obtained by thermocouples attached to the samples. In addition, the precision of two-color pyrometry is verified for the given setup. Following the verification experiments, single laser track experiments are conducted. The obtained signals prove to be partially distorted mainly due to by-products such as smoke and weld beads arising from the melt pool. To encounter this problem, a new fitting method is presented and experimentally validated. Melt pools resulting from different cooling durations are analyzed by EBSD. These measurements show areas of extreme deformation or potential amorphization correlating with the cooling durations. The obtained cooling duration can be used for the validation of simulations as well as for the correlation of corresponding microstructure and process parameters.

Minerals and Trace Elements in 990 Beverages and Their Contribution to Dietary Reference Values for German Consumers.

Beverages are an integral part of human nutrition, yet little is known about their contribution to daily intakes of minerals and trace elements in German consumers. Using inductively coupled plasma-mass spectrometry, we determined the concentration of five minerals and six trace elements in beverage samples (n = 990, assigned to different beverage groups) collected throughout Germany. For a calculation of their relative contribution to the mineral supply, available beverage consumption data was combined with our quantitative analysis to calculate the average contribution of beverage groups to meet the respective dietary reference values currently used in Germany, Austria and Switzerland (D-A-CH region). Based on their presence in beverages and their consumption, the top three minerals are phosphorous, calcium and magnesium, and they, therefore, may reasonably contribute to the reference values. Among the trace elements, beverages mostly contributed to the manganese supply, whereas at the same time, concentrations of iron, cobalt and copper were low across all tested groups. Our study provides an overview of the assumed mineral and trace element intake via beverages in Germany and may, thus, serve as a foundation for a mineral and trace element database of beverages that needs to be expanded in the future.

2D and 3D Triangulation Are Suitable In Situ Measurement Tools for High-Power Large Spot Laser Penetration Processes to Visualize Depressions and Protrusions before Perforating.

During laser penetration, the irradiated samples form a melt pool before perforation. Knowledge of the dynamics of this melt pool is of interest for the correct physical description of the process and leads to improved simulations. However, a direct investigation, especially at the location of high-power laser interaction with large spot diameters in the centimeter range is missing until now. Here, the applicability of 2D triangulation for surface topology observations is demonstrated. With the designed bidirectional 2D triangulation setup, the material cross-section is measured by profile detection at the front and back side. This allows a comprehensive description of the penetration process to be established, which is important for a detailed explanation of the process. Specific steps such as surface melting, indentations, protrusions during melt pool development and their dynamics, and the perforation are visualized, which were unknown until now. Furthermore, a scanning 3D triangulation setup is developed to obtain more information about the entire melt pool at the front side, and not just a single intersection line. The measurements exhibit a mirror-symmetric melt pool and the possibility to extrapolate from the central profile to the outer regions in most cases.

Bridging Fidelities to Predict Nanoindentation Tip Radii Using Interpretable Deep Learning Models.

As the need for miniaturized structural and functional materials has increased, the need for precise materials characterizaton has also expanded. Nanoindentation is a popular method that can be used to measure material mechanical behavior which enables high-throughput experiments and, in some cases, can also provide images of the indented area through scanning. Both indenting and scanning can cause tip wear that can influence the measurements. Therefore, precise characterization of tip radii is needed to improve data evaluation. A data fusion method is introduced which uses finite element simulations and experimental data to estimate the tip radius in situ in a meaningful way using an interpretable multi-fidelity deep learning approach. By interpreting the machine learning models, it is shown that the approaches are able to accurately capture physical indentation phenomena.

Continuous wave high-power laser propagation in water is affected by strong thermal lensing and thermal blooming already at short distances.

When laser beams propagate through media with non-vanishing absorption, the media is heated resulting in a change of the refractive index, which can lead to thermal lensing and thermal blooming. However, experimental details about both phenomena for propagations in water are lacking, especially for high-power lasers in the kilowatt range. We show that significant thermal lensing occurs only for high input powers before the onset of convective flow, while for low input powers, no strong thermal lens arises. After the onset of water flow, thermal blooming occurs at low input powers comparable to that known for propagations over kilometres in the air. However, for high input powers a thermal blooming on a qualitatively higher level is shown. By wavefront sensing, the change of refractive index distribution in water is investigated. This clearly shows the fast development of a strong thermal lens for high input powers and the onset of convection. Furthermore, a qualitatively good agreement of the accompanying simulations is observed. It is found that the absorption coefficient is linear with a value of [Formula: see text] at least up to 7.5 kW, i.e. 8 [Formula: see text]. However, the directed transmission into an aperture is only constant before any thermal lensing of blooming occurs.

Variability in APOE genotype status in human-derived cell lines: a cause for concern in cell culture studies?

Although cell culture studies have provided landmark discoveries in the basic and applied life sciences, it is often under-appreciated that cells grown in culture are prone to generating artifacts. Here, we introduce the genotype status (exemplified by apolipoprotein E) of human-derived cells as a further important parameter that requires attention in cell culture experiments. Epidemiological and clinical studies indicate that variations from the main apolipoprotein E3/E3 genotype might alter the risk of developing chronic diseases, especially neurodegeneration, cardiovascular disease, and cancer. Whereas the apolipoprotein E allele distribution in human populations is well characterized, the apolipoprotein E genotype of human-derived cell lines is only rarely considered in interpreting cell culture data. However, we find that primary and immortalized human cell lines show substantial variation in their apolipoprotein E genotype status. We argue that the apolipoprotein E genotype status and corresponding gene expression level of human-derived cell lines should be considered to better avoid (or at least account for) inconsistencies in cell culture studies when different cell lines of the same tissue or organ are used and before extrapolating cell culture data to human physiology in health and disease.

Mitochondria-targeted antioxidants and metabolic modulators as pharmacological interventions to slow ageing.

Populations in many nations today are rapidly ageing. This unprecedented demographic change represents one of the main challenges of our time. A defining property of the ageing process is a marked increase in the risk of mortality and morbidity with age. The incidence of cancer, cardiovascular and neurodegenerative diseases increases non-linearly, sometimes exponentially with age. One of the most important tasks in biogerontology is to develop interventions leading to an increase in healthy lifespan (health span), and a better understanding of basic mechanisms underlying the ageing process itself may lead to interventions able to delay or prevent many or even all age-dependent conditions. One of the putative basic mechanisms of ageing is age-dependent mitochondrial deterioration, closely associated with damage mediated by reactive oxygen species (ROS). Given the central role that mitochondria and mitochondrial dysfunction play not only in ageing but also in apoptosis, cancer, neurodegeneration and other age-related diseases there is great interest in approaches to protect mitochondria from ROS-mediated damage. In this review, we explore strategies of targeting mitochondria to reduce mitochondrial oxidative damage with the aim of preventing or delaying age-dependent decline in mitochondrial function and some of the resulting pathologies. We discuss mitochondria-targeted and -localized antioxidants (e.g.: MitoQ, SkQ, ergothioneine), mitochondrial metabolic modulators (e.g. dichloroacetic acid), and uncouplers (e.g.: uncoupling proteins, dinitrophenol) as well as some alternative future approaches for targeting compounds to the mitochondria, including advances from nanotechnology.

Effects of polyphenols on brain ageing and Alzheimer's disease: focus on mitochondria.

The global trend of the phenomenon of population ageing has dramatic consequences on public health and the incidence of neurodegenerative diseases. Physiological changes that occur during normal ageing of the brain may exacerbate and initiate pathological processes that may lead to neurodegenerative disorders, especially Alzheimer's disease (AD). Hence, the risk of AD rises exponentially with age. While there is no cure currently available, sufficient intake of certain micronutrients and secondary plant metabolites may prevent disease onset. Polyphenols are highly abundant in the human diet, and several experimental and epidemiological evidences indicate that these secondary plant products have beneficial effects on AD risks. This study reviews current knowledge on the potential of polyphenols and selected polyphenol-rich diets on memory and cognition in human subjects, focusing on recent data showing in vivo efficacy of polyphenols in preventing neurodegenerative events during brain ageing and in dementia. Concentrations of polyphenols in animal brains following oral administration have been consistently reported to be very low, thus eliciting controversial discussion on their neuroprotective effects and potential mechanisms. Whether polyphenols exert any direct antioxidant effects in the brain or rather act by evoking alterations in regulatory systems of the brain or even the body periphery is still unclear. To understand the mechanisms behind the protective abilities of polyphenol-rich foods, an overall understanding of the biotransformation of polyphenols and identification of the various metabolites arising in the human body is also urgently needed.

Do polyphenols enter the brain and does it matter? Some theoretical and practical considerations.

Although several epidemiological and intervention studies suggest that polyphenols (PPs) and PP-rich foods may improve memory and cognition in animals and humans, PPs' mode of action is only poorly understood. To help distinguish between the different modes of action that have been proposed for PPs, it is obviously important to know how much PPs can accumulate in the brain, if any at all. However, reliable data on PP uptake into the brain of animals are limited as many studies failed to report important control procedures during data acquisition. In this paper, we summarize published data on the penetration of PPs into animal brain and review some hypotheses to explain the biological basis of potentially health-beneficial effects of PPs to the brain. Finally, we highlight promising new approaches, especially those of a hormetic dose-response and gut microbiota-brain interaction, which may allow a better understanding of PPs' mode of action in animals and humans.

Mitochondrial changes in ageing Caenorhabditis elegans--what do we learn from superoxide dismutase knockouts?

One of the most popular damage accumulation theories of ageing is the mitochondrial free radical theory of ageing (mFRTA). The mFRTA proposes that ageing is due to the accumulation of unrepaired oxidative damage, in particular damage to mitochondrial DNA (mtDNA). Within the mFRTA, the "vicious cycle" theory further proposes that reactive oxygen species (ROS) promote mtDNA mutations, which then lead to a further increase in ROS production. Recently, data have been published on Caenorhabditis elegans mutants deficient in one or both forms of mitochondrial superoxide dismutase (SOD). Surprisingly, even double mutants, lacking both mitochondrial forms of SOD, show no reduction in lifespan. This has been interpreted as evidence against the mFRTA because it is assumed that these mutants suffer from significantly elevated oxidative damage to their mitochondria. Here, using a novel mtDNA damage assay in conjunction with related, well established damage and metabolic markers, we first investigate the age-dependent mitochondrial decline in a cohort of ageing wild-type nematodes, in particular testing the plausibility of the "vicious cycle" theory. We then apply the methods and insights gained from this investigation to a mutant strain for C. elegans that lacks both forms of mitochondrial SOD. While we show a clear age-dependent, linear increase in oxidative damage in WT nematodes, we find no evidence for autocatalytic damage amplification as proposed by the "vicious cycle" theory. Comparing the SOD mutants with wild-type animals, we further show that oxidative damage levels in the mtDNA of SOD mutants are not significantly different from those in wild-type animals, i.e. even the total loss of mitochondrial SOD did not significantly increase oxidative damage to mtDNA. Possible reasons for this unexpected result and some implications for the mFRTA are discussed.

Cytoprotective effects of olive mill wastewater extract and its main constituent hydroxytyrosol in PC12 cells.

Evidence from epidemiological studies indicates that adherence to diets rich in secondary plant metabolites, such as polyphenols and phenolic acids, possibly reduces the risk of age-dependent neurodegeneration and subsequent cognitive decline. Olive mill wastewater is particularly rich in the ortho-diphenol hydroxytyrosol (HT) that can be recovered with ad hoc techniques. In a previous study, we showed that hydroxytyrosol-rich olive mill wastewater extract protects dissociated brain cells not only in vitro but also ex vivo after subchronic oral administration of the extract to mice. As plant extracts often contain constituents with potentially confounding activities, our present study aimed to test in vitro whether HT at concentrations present in olive mill wastewater extract is able to protect PC12 cells with similar efficiency. Following a short-term exposure (30min) to the compounds of interest, cells were subjected to oxidative or nitrosative stress by adding either ferrous iron or sodium nitroprusside to the cell culture medium for 18h, respectively. Cytotoxicity was assessed by measuring MTT reduction, cellular ATP levels and mitochondrial membrane potential in the absence and presence of HT or HT-rich olive mill wastewater extract. The results we obtained mainly confirm our previous observation of promising cytoprotection of brain cells by HT-rich olive mill wastewater extract in different stressor paradigms. Furthermore, correlation analyses revealed that the observed cytoprotective effects in PC12 cells are likely due to HT present in the extract.

Caenorhabditis elegans life span studies: the challenge of maintaining synchronous cohorts.

Due to its many advantages, the nematode worm Caenorhabditis elegans (C. elegans) is commonly employed as a convenient model for aging studies as well as for testing life span effects of chemical compounds. However, some challenges exist in the context of such life span studies, particularly in relation to generation and maintenance of synchronized cohorts, and these challenges are not always fully appreciated. Here we discuss the impact of incomplete control of nematode proliferation on life span studies and suggest some solutions to minimize these artefacts.

Ageing in nematodes: do antioxidants extend lifespan in Caenorhabditis elegans?

Antioxidants are often investigated as a promising strategy for extending lifespan. Accordingly, there is significant interest in novel antioxidant compounds derived from natural sources such as plant extracts. However, because lifespan studies are laborious and expensive to conduct, candidate compounds are frequently selected based simply on their in vitro antioxidant efficacy, with the implicit assumption that in vitro antioxidants are also in vivo antioxidants, and that in vivo antioxidants will decrease functionally relevant oxidative damage and thereby extend lifespan. We investigated the validity of these assumptions in the model organism, Caenorhabditis elegans. Nematodes were exposed to 6 plant extracts, selected out of a total of 34 based on a simple in vitro antioxidant assay. We found no correlation between in vitro and in vivo antioxidant capacities. Antioxidant efficacies were also not predictive of lifespan benefits. Further studies into those extracts that produced significant lifespan extension indicated that a direct antioxidant effect is unlikely to be the main factor responsible for the modulation of nematode lifespan.

The mitochondrial free radical theory of ageing--where do we stand?

Understanding the molecular mechanisms underlying the ageing process may provide the best strategy for addressing the challenges posed by ageing populations worldwide. One theory proposing such molecular mechanisms was formulated 50 years ago. Harman et al. suggested that ageing might be mediated by macromolecular damage through reactions involving reactive oxygen species (ROS). Today, a version of the free radical theory of ageing, focusing on mitochondria as source as well as target of ROS, is one of the most popular theories of ageing. Here we critically review the status of key principles and concepts on which this theory is based. We find that the evidence to date shows that many of the original assumptions are questionable, while on some critical issues further refinements in techniques are required. Even so, it is becoming evident that mitochondria and mtDNA integrity may indeed be crucial determinants of organismal ageing. Implications for the prospect of successful interventions as well as evidence for and against efficacy of current therapeutic approaches are discussed.

Apolipoprotein E genotype and alpha-tocopherol modulate amyloid precursor protein metabolism and cell cycle regulation.

Apolipoprotein E4 (apoE4) genotype is associated with an increased risk for Alzheimer's disease (AD). This is thought to be in part attributable to an impact of apoE genotype on the processing of the transmembrane amyloid precursor protein (APP) thereby contributing to amyloid beta peptide formation in apoE4 carriers, which is a primary patho-physiological feature of AD. As apoE and alpha-tocopherol (alpha-toc) have been shown to modulate membrane bilayer properties and hippocampal gene expression, we studied the effect of apoE genotype on APP metabolism and cell cycle regulation in response to dietary alpha-toc. ApoE3 and apoE4 transgenic mice were fed a diet low (VE) or high (+VE) in vitamin E (3 and 235 mg alpha-toc/kg diet, respectively) for 12 weeks. Cholesterol levels and membrane fluidity were not different in synaptosomal plasma membranes isolated from brains of apoE3 and apoE4 mice (-VE and +VE). Non-amyloidogenic alpha-secretase mRNA concentration and activity were significantly higher in brains of apoE3 relative to apoE4 mice irrespective of the dietary alpha-toc supply, while amyloidogenic beta-secretase and gamma-secretase remained unchanged. Relative mRNA concentration of cell cycle related proteins were modulated differentially by dietary alpha-toc supplementation in apoE3 and apoE4 mice, suggesting genotype-dependent signalling effects on cell cycle regulation.

Novel photoswitchable rotaxanes.

A photoresponsive rotaxane based on the photoheterolysis of an acridane unit which is at the same time a bulky end group has been developed.

Hydroxytyrosol-rich olive mill wastewater extract protects brain cells in vitro and ex vivo.

UNLABELLED: Elevated oxidative and nitrosative stress both impair the integrity and functioning of brain tissue, especially in aging. As long-term intake of plant foods rich in antioxidant phenolics, such as extra virgin olive oil, positively modulates surrogate markers of many human pathological alterations, the interest in cheap and abundant sources of such phenolics is rapidly growing. Olive mill wastewater is particularly rich in hydroxytyrosol, an o-diphenol with powerful antioxidant, anti-inflammatory, and antithrombotic activities. Due to the deleterious effect of oxidative stress on brain cell survival, the efficacy of a hydroxytyrosol-rich extract to attenuate Fe2+- and nitric oxide (NO)-induced cytotoxicity in murine-dissociated brain cells was investigated. The addition of either Fe2+ or SNP (an NO donor) caused both a severe loss of cellular ATP and a markedly depolarized mitochondrial membrane potential. Preincubation with hydroxytyrosol significantly attenuated the cytotoxic effect of both stressors, although with different efficiencies. Mice feeding studies were performed to assess the brain bioactivity of hydroxytyrosol ex vivo. Subchronic, but not acute, administration of 100 mg of hydroxytyrosol per kilogram body weight for 12 days enhanced resistance of dissociated brain cells to oxidative stress, as shown by reduced basal and stress-induced lipid peroxidation. Also, basal mitochondrial membrane potential was moderately hyperpolarized (P < 0.05), an effect suggestive of cytoprotection. In synthesis, the ex vivo data provide the first evidence of neuroprotective effects of oral hydroxytyrosol intake. KEYWORDS: Hydroxytyrosol; olive mill wastewater; dissociated brain cells; oxidative stress; brain; Mediterranean diet.

Tocotrienols: constitutional effects in aging and disease.

Tocotrienols, a class of vitamin E analogs, modulate several mechanisms associated with the aging process and aging-related diseases. Most studies compare the activities of tocotrienols with those of tocopherols ("classical vitamin E"). However, some biological effects were found to be unique for tocotrienols. Although the absorption mechanisms are essentially the same for all vitamin E analogs, tocotrienols are degraded to a greater extent than tocopherols. The levels of tocotrienols in the plasma of animals and humans were estimated to reach low micromolar concentrations. One hallmark in the origin of disease and aging is the overproduction of reactive oxygen species (ROS). Tocotrienols possess excellent antioxidant activity in vitro and have been suggested to suppress ROS production more efficiently than tocopherols. In addition, tocotrienols show promising nonantioxidant activities in various in vitro and in vivo models. Most notable are the interactions of tocotrienols with the mevalonate pathway leading to the lowering of cholesterol levels, the prevention of cell adhesion to endothelial cells, and the suppression of tumor cell growth. Furthermore, glutamate-induced neurotoxicity is suppressed in the presence of tocotrienols. This review summarizes the main antioxidant and nonantioxidant effects of tocotrienols and assesses their potential as health-maintaining compounds.