A quasi-2D integrated experimental–numerical approach to high-fidelity mechanical analysis of metallic microstructures

Integrated experimental–numerical testing on bulk metal alloys with fine, complex microstructures is known to be highly challenging, since measurements are restricted to the sample surface, thereby failing to capture the effects of the 3D subsurface microstructure. Consequently, a quantitative comparison of deformation fields between experiments and simulations is hardly possible. To overcome this, we propose a novel ‘quasi-2D’ integrated experimental–numerical testing methodology that hinges on the fabrication of μm-thin specimens with practically through-thickness microstructures over large regions of &gt;100 μm. The specimens are fully characterized from both surfaces and tested in-situ to retrieve microstructure-resolved deformation fields. Simultaneously, the full microstructure is discretized in 3D and simulated. This allows for a detailed, one-to-one quantitative comparison of deformation fields between experiments and simulations, with negligible uncertainty in the subsurface microstructure. Consequently, a degree of agreement between experiments and simulations is attained which we believe to be unprecedented at this scale. We demonstrate the capabilities of the framework on polycrystalline ferritic steel and dual-phase ferritic–martensitic steel specimens. At the mesoscale, the methodology enables quantitative comparisons of the interaction between multiple grains, while, at the microscale, it enables advancement of numerical models by direct confrontation with detailed experimental observations. Specifically, it is revealed that the individual slip system activity maps, identified with SSLIP, near a grain boundary can only be reasonably predicted by enhancing the adopted crystal plasticity simulations with a discrete slip plane model. Additionally, the experimentally observed strong anisotropic plasticity of martensite can only be captured with a substructure-enriched crystal plasticity model.</p

satFRET: estimation of Forster resonance energy transfer by acceptor saturation

We demonstrate theoretically and experimentally the quantification of Förster resonance energy transfer (FRET) by direct and systematic saturation of the excited state of acceptor molecules. This version of acceptor depletion methods for FRET estimation, denoted as “satFRET” is reversible and suitable for time-resolved measurements. The technique was investigated theoretically using the steady-state solution of the differential equation system of donor and acceptor molecular states. The influence of acceptor photobleaching during measurement was included in the model. Experimental verification was achieved with the FRET-pair Alexa 546- Alexa 633 loaded on particles in different stoichiometries and measured in a confocal microscope. Estimates of energy transfer efficiency by excited state saturation were compared to those obtained by measurements of sensitised emission and acceptor photobleaching. The results lead to a protocol that allows time-resolved FRET measurements of fixed and living cells on a conventional confocal microscope. This procedure was applied to fixed Chinese hamster ovary cells containing a cyan fluorescent protein and yellow fluorescent protein pair. The time resolution of the technique was demonstrated in a live T cell activation assay comparing the FRET efficiencies measured using a genetically encoded green and red fluorescent protein biosensor for GTP/GDP turnover to those measured by acceptor photobleaching of fixed cells

Nocturnal dissolved organic matter release by turf algae and its role in the microbialization of reefs

The increased release of dissolved organic matter (DOM) by algae has been associated with the fast but inefficient growth of opportunistic microbial pathogens and the ongoing degradation of coral reefs. Turf algae (consortia of microalgae and macroalgae commonly including cyanobacteria) dominate benthic communities on many reefs worldwide. Opposite to other reef algae that predominantly release DOM during the day, turf algae containing cyanobacteria may additionally release large amounts of DOM at night. However, this night-DOM release and its potential contribution to the microbialization of reefs remains to be investigated. We first tested the occurrence of hypoxic conditions at the turf algae-water interface, as a lack of oxygen will facilitate the production and release of fermentation intermediates as night-time DOM. Second, the dissolved organic carbon (DOC) release by turf algae was quantified during day time and nighttime, and the quality of day and night exudates as food for bacterioplankton was tested. Finally, DOC release rates of turf algae were combined with estimates of DOC release based on benthic community composition in 1973 and 2013 to explore how changes in benthic community composition affected the contribution of night-DOC to the reef-wide DOC production. A rapid shift from supersaturated to hypoxic conditions at the turf algae-water interface occurred immediately after the onset of darkness, resulting in night-DOC release rates similar to those during daytime. Bioassays revealed major differences in the quality between day and night exudates: Night-DOC was utilized by bacterioplankton two times faster than day-DOC, but yielded a four times lower growth efficiency. Changes in benthic community composition were estimated to have resulted in a doubling of DOC release since 1973, due to an increasing abundance of benthic cyanobacterial mats (BCMs), with night-DOC release by BCMs and turf algae accounting for >50% of the total release over a diurnal cycle. Night-DOC released by BCMs and turf algae is likely an important driver in the microbialization of reefs by stimulating microbial respiration at the expense of energy and nutrient transfer to higher trophic levels via the microbial loop, thereby threatening the productivity and biodiversity of these unique ecosystems. Read the free Plain Language Summary for this article on the Journal blog

Revisiting the martensite/ferrite interface damage initiation mechanism:The key role of substructure boundary sliding

Martensite/ferrite (M/F) interface damage plays a critical role in controlling failure of dual-phase (DP) steels and is commonly understood to originate from the large phase contrast between martensite and ferrite. This however conflicts with a few, recent observations, showing that considerable M/F interface damage initiation is often accompanied by apparent martensite island plasticity and weak M/F strain partitioning. In fact, martensite has a complex hierarchical structure which induces a strongly heterogeneous and orientation-dependent plastic response. Depending on the local stress state, (lath) martensite is presumed to be hard to deform based on common understanding. However, when favourably oriented, substructure boundary sliding can be triggered at a resolved shear stress which is comparable to that of ferrite. Moreover, careful measurements of the M/F interface structure indicate the occurrence of sharp martensite wedges protruding into the ferrite and clear steps in correspondence with lath boundaries, constituting a jagged M/F interfacial morphology that may have a large effect on the M/F interface behaviour. By taking into account the substructure and morphology features, which are usually overlooked in the literature, this contribution re-examines the M/F interface damage initiation mechanism. A systematic study is performed, which accounts for different loading conditions, phase contrasts, residual stresses/strains resulting from the preceding martensitic phase transformation, as well as the possible M/F interfacial morphologies. Crystal plasticity simulations are conducted to include inter-lath retained austenite (RA) films enabling the substructure boundary sliding. The results show that the substructure boundary sliding, which is the most favourable plastic deformation mode of lath martensite, can trigger M/F interface damage and hence control the failure behaviour of DP steels. The present finding may change the way in which M/F interface damage initiation is understood as a critical failure mechanism in DP steels

Immunological and Clinical Effects of Vaccines Targeting p53-Overexpressing Malignancies

Approximately 50% of human malignancies carry p53 mutations, which makes it a potential antigenic target for cancer immunotherapy. Adoptive transfer with p53-specific cytotoxic T-lymphocytes (CTL) and CD4+ T-helper cells eradicates p53-overexpressing tumors in mice. Furthermore, p53 antibodies and p53-specific CTLs can be detected in cancer patients, indicating that p53 is immunogenic. Based on these results, clinical trials were initiated. In this paper, we review immunological and clinical responses observed in cancer patients vaccinated with p53 targeting vaccines. In most trials, p53-specific vaccine-induced immunological responses were observed. Unfortunately, no clinical responses with significant reduction of tumor-burden have occurred. We will elaborate on possible explanations for this lack of clinical effectiveness. In the second part of this paper, we summarize several immunopotentiating combination strategies suitable for clinical use. In our opinion, future p53-vaccine studies should focus on addition of these immunopotentiating regimens to achieve clinically effective therapeutic vaccination strategies for cancer patients

Kempfarm vleesvarkensstal: milieu-emissies en investeringskosten = Kempfarm housing system for growing-finishing pigs : environmental emissions and investment costs

De milieu-emissies en de kosten zijn bepaald van een innovatieve stal voor vleesvarkens: de Kempfarm-sta