Activating extrinsic and intrinsic toughening mechanisms in polycrystalline ceramics and their composites via microstructural engineering

Ferroelastic toughening is one of a limited number of intrinsic toughening mechanisms available for ceramics, yet rarely is it effectively implemented due to a limited understanding of the activation mechanisms within a polycrystalline framework. In the earliest descriptions of ferroelastic toughening, terms such as the transformation strain, coercive stress and process zone parameters were included following other (extrinsic) crack tip shielding models. In the years that have followed, constitutive models have become more sophisticated, incorporating crystal orientation, rate behaviors, and several other factors. However, further development of these models has been limited by the paucity of experimental observations linking ferroelastic switching with critical, yet common, microstructural variations (i.e. grain size, nearest neighbor orientations, secondary/grain boundary phases, etc.). Here we present a multi-scale experimental approach to explore the role of stress concentration, stress transfer and localized constraint in ferroelastic domain nucleation, motion and subsequent toughening. In situ TEM nanopillar and ex situ micropillar compression on single crystal specimens extracted from a polycrystalline ceramic have been used to correlate crystallographic orientation with coercive stresses for domain nucleation and motion. The comparison between these two length scales also highlights the importance of boundary conditions on the nucleation of ferroelastic domains and sheds light on the grain size dependence of domain nucleation probability extracted from Vicker’s indentation of polycrystalline ceramics of the same composition. This insight will ultimately be coupled with grain orientation, elastic anisotropy data and quantified stress distributions during deformation to establish the early foundations of a microstructural design framework for ferroelastically toughened ceramics. Please click Additional Files below to see the full abstract

Social media divide: Characteristics of emerging adults who do not use social network websites

Public opinion has embraced social media as a vital tool to reach U.S. emerging adults, but this generation has not universally adopted social media technologies. Using indepth interviews, this study examined the characteristics of 20 emerging adults (18 to 23 years old) who were non-adopters of social media. Compared to social media users, non-adopters had less economic stability, more fractured educational trajectories, and weaker support from parents and friends. Non-adopters did not use social media because they lacked access or leisure time, were not socialized into their use, lacked skills, or did not want to maintain social contacts via social media technologies. If social media are increasingly used in attempts to improve young people’s lives, practitioners must understand who is left behind in the wake of these technologies

Capacity building efforts and perceptions for wildlife surveillance to detect zoonotic pathogens: comparing stakeholder perspectives.

BackgroundThe capacity to conduct zoonotic pathogen surveillance in wildlife is critical for the recognition and identification of emerging health threats. The PREDICT project, a component of United States Agency for International Development's Emerging Pandemic Threats program, has introduced capacity building efforts to increase zoonotic pathogen surveillance in wildlife in global 'hot spot' regions where zoonotic disease emergence is likely to occur. Understanding priorities, challenges, and opportunities from the perspectives of the stakeholders is a key component of any successful capacity building program.MethodsA survey was administered to wildlife officials and to PREDICT-implementing in-country project scientists in 16 participating countries in order to identify similarities and differences in perspectives between the groups regarding capacity needs for zoonotic pathogen surveillance in wildlife.ResultsBoth stakeholder groups identified some human-animal interfaces (i.e. areas of high contact between wildlife and humans with the potential risk for disease transmission), such as hunting and markets, as important for ongoing targeting of wildlife surveillance. Similarly, findings regarding challenges across stakeholder groups showed some agreement in that a lack of sustainable funding across regions was the greatest challenge for conducting wildlife surveillance for zoonotic pathogens (wildlife officials: 96% and project scientists: 81%). However, the opportunity for improving zoonotic pathogen surveillance capacity identified most frequently by wildlife officials as important was increasing communication or coordination among agencies, sectors, or regions (100% of wildlife officials), whereas the most frequent opportunities identified as important by project scientists were increasing human capacity, increasing laboratory capacity, and the growing interest or awareness regarding wildlife disease or surveillance programs (all identified by 69% of project scientists).ConclusionsA One Health approach to capacity building applied at local and global scales will have the greatest impact on improving zoonotic pathogen surveillance in wildlife. This approach will involve increasing communication and cooperation across ministries and sectors so that experts and stakeholders work together to identify and mitigate surveillance gaps. Over time, this transdisciplinary approach to capacity building will help overcome existing challenges and promote efficient targeting of high risk interfaces for zoonotic pathogen transmission

Pinpointed Stimulation of EphA2 Receptors via DNA-Templated Oligovalence

DNA nanostructures enable the attachment of functional molecules to nearly any unique location on their underlying structure. Due to their single-base-pair structural resolution, several ligands can be spatially arranged and closely controlled according to the geometry of their desired target, resulting in optimized binding and/or signaling interactions. Here, the efficacy of SWL, an ephrin-mimicking peptide that binds specifically to EphrinA2 (EphA2) receptors, increased by presenting up to three of these peptides on small DNA nanostructures in an oligovalent manner. Ephrin signaling pathways play crucial roles in tumor development and progression. Moreover, Eph receptors are potential targets in cancer diagnosis and treatment. Here, the quantitative impact of SWL valency on binding, phosphorylation (key player for activation) and phenotype regulation in EphA2-expressing prostate cancer cells was demonstrated. EphA2 phosphorylation was significantly increased by DNA trimers carrying three SWL peptides compared to monovalent SWL. In comparison to one of EphA2’s natural ligands ephrin-A1, which is known to bind promiscuously to multiple receptors, pinpointed targeting of EphA2 by oligovalent DNA-SWL constructs showed enhanced cell retraction. Overall, we show that DNA scaffolds can increase the potency of weak signaling peptides through oligovalent presentation and serve as potential tools for examination of complex signaling pathways

Spatial Distribution of Competing Ions around DNA in Solution

The competition of monovalent and divalent cations for proximity to negatively charged DNA is of biological importance and can provide strong constraints for theoretical treatments of polyelectrolytes. Resonant x-ray scattering experiments have allowed us to monitor the number and distribution of each cation in a mixed ion cloud around DNA. These measurements provide experimental evidence to support a general theoretical prediction: the normalized distribution of each ion around polyelectrolytes remains constant when ions are mixed at different ratios. In addition, the amplitudes of the scattering signals throughout the competition provide a measurement of the surface concentration parameter that predicts the competition behavior of these cations. The data suggest that ion size needs to be taken into account in applying Poisson-Boltzmann treatments to polyelectrolytes such as DNA

KRAB zinc finger protein diversification drives mammalian interindividual methylation variability.

Most transposable elements (TEs) in the mouse genome are heavily modified by DNA methylation and repressive histone modifications. However, a subset of TEs exhibit variable methylation levels in genetically identical individuals, and this is associated with epigenetically conferred phenotypic differences, environmental adaptability, and transgenerational epigenetic inheritance. The evolutionary origins and molecular mechanisms underlying interindividual epigenetic variability remain unknown. Using a repertoire of murine variably methylated intracisternal A-particle (VM-IAP) epialleles as a model, we demonstrate that variable DNA methylation states at TEs are highly susceptible to genetic background effects. Taking a classical genetics approach coupled with genome-wide analysis, we harness these effects and identify a cluster of KRAB zinc finger protein (KZFP) genes that modifies VM-IAPs in trans in a sequence-specific manner. Deletion of the cluster results in decreased DNA methylation levels and altered histone modifications at the targeted VM-IAPs. In some cases, these effects are accompanied by dysregulation of neighboring genes. We find that VM-IAPs cluster together phylogenetically and that this is linked to differential KZFP binding, suggestive of an ongoing evolutionary arms race between TEs and this large family of epigenetic regulators. These findings indicate that KZFP divergence and concomitant evolution of DNA binding capabilities are mechanistically linked to methylation variability in mammals, with implications for phenotypic variation and putative paradigms of mammalian epigenetic inheritance