Al2O3 Grain Boundary Segregation in a Thermal Barrier Coating on a Ni-Based Superalloy.

The segregation of reactive elements (REs) along thermally grown oxide (TGO) grain boundaries has been associated to slower oxide growth kinetics and improved creep properties. However, the incorporation and diffusion of these elements into the TGO during oxidation of Ni alloys remains an open question. In this work, electron backscatter diffraction in transmission mode (t-EBSD) was used to investigate the microstructure of TGO within the thermal barrier coating on a Ni-based superalloy, and atom probe tomography (APT) was used to quantify the segregation behavior of REs to α-Al2O3 grain boundaries. Integrating the two techniques enables a higher level of site-specific analysis compared to the routine focused ion beam lift-out sample preparation method without t-EBSD. Needle-shaped APT specimens readily meet the thickness criterion for electron diffraction analysis. Transmission EBSD provides an immediate feedback on grain orientation and grain boundary location within the APT specimens to help target grain boundaries in the TGO. Segregation behavior of REs is discussed in terms of the grain boundary character and relative location in TGO.

Sulfur Assimilation Alters Flagellar Function and Modulates the Gene Expression Landscape of Serratia marcescens.

Sulfur is an essential nutrient that contributes to cellular redox homeostasis, transcriptional regulation, and translation initiation when incorporated into different biomolecules. Transport and reduction of extracellular sulfate followed by cysteine biosynthesis is a major pathway of bacterial sulfur assimilation. For the opportunistic pathogen Serratia marcescens, function of the cysteine biosynthesis pathway is required for extracellular phospholipase activity and flagellum-mediated surface motility, but little else is known about the influence of sulfur assimilation on the physiology of this organism. In this work, it was determined that an S. marcescens cysteine auxotroph fails to differentiate into hyperflagellated and elongated swarmer cells and that cysteine, but not other organic sulfur molecules, restores swarming motility to these bacteria. The S. marcescens cysteine auxotroph further exhibits reduced transcription of phospholipase, hemolysin, and flagellin genes, each of which is subject to transcriptional control by the flagellar regulatory system. Based on these data and the central role of cysteine in sulfur assimilation, it was reasoned that environmental sulfur availability may contribute to the regulation of these functions in S. marcescens Indeed, bacteria that are starved for sulfate exhibit substantially reduced transcription of the genes for hemolysin, phospholipase, and the FlhD flagellar master regulator. A global transcriptomic analysis further defined a large set of S. marcescens genes that are responsive to extracellular sulfate availability, including genes that encode membrane transport, nutrient utilization, and metabolism functions. Finally, sulfate availability was demonstrated to alter S. marcescens cytolytic activity, suggesting that sulfate assimilation may impact the virulence of this organism.IMPORTANCE Serratia marcescens is a versatile bacterial species that inhabits diverse environmental niches and is capable of pathogenic interactions with host organisms ranging from insects to humans. This report demonstrates for the first time the extensive impacts that environmental sulfate availability and cysteine biosynthesis have on the transcriptome of S. marcescens The finding that greater than 1,000 S. marcescens genes are differentially expressed depending on sulfate availability suggests that sulfur abundance is a crucial factor that controls the physiology of this organism. Furthermore, the high relative expression levels for the putative virulence factors flagella, phospholipase, and hemolysin in the presence of sulfate suggests that a sulfur-rich host environment could contribute to the transcription of these genes during infection.

Beam broadening in transmission and conventional EBSD.

Transmission electron backscatter diffraction (t-EBSD) has become a routine technique for crystal orientation mapping when ultrahigh resolution is needed and has demonstrated advantages in the characterization of nanoscale and micron-sized samples (Babinsky et al., 2015). In this work, we use experimental measurements and simulations to compare the resolution of the transmission and conventional reflection EBSD techniques across a range of sample volumes and characterization conditions. Monte Carlo simulations of electron trajectories provide the opportunity to estimate beam size and effective resolution, as well as electron flux, as a function of sample thickness or incident beam energy in t-EBSD. Increasing incident beam energy is shown to negatively impact beam diameter in some cases, and the effect of thinning a sample for conventional EBSD is shown to improve characterization resolution but dramatically decrease the number of high-loss electrons backscattered to the detector. In addition to considering spatial resolution when implementing EBSD techniques, it is found that maintaining a high yield of diffracted electrons to the detector is also of critical importance, which is supported by experimental results. Consequently, this work provides key insights into the nature of electron scattering and probe volume for the practical implementation of both transmission and reflection EBSD techniques.

Reprint of "Biological motion perception links diverse facets of theory of mind during middle childhood".

Two cornerstones of social development-social perception and theory of mind-undergo brain and behavioral changes during middle childhood, but the link between these developing domains is unclear. One theoretical perspective argues that these skills represent domain-specific areas of social development, whereas other perspectives suggest that both skills may reflect a more integrated social system. Given recent evidence from adults that these superficially different domains may be related, the current study examined the developmental relation between these social processes in 52 children aged 7 to 12years. Controlling for age and IQ, social perception (perception of biological motion in noise) was significantly correlated with two measures of theory of mind: one in which children made mental state inferences based on photographs of the eye region of the face and another in which children made mental state inferences based on stories. Social perception, however, was not correlated with children's ability to make physical inferences from stories about people. Furthermore, the mental state inference tasks were not correlated with each other, suggesting a role for social perception in linking various facets of theory of mind.

Perceived live interaction modulates the developing social brain.

Although children's social development is embedded in social interaction, most developmental neuroscience studies have examined responses to non-interactive social stimuli (e.g. photographs of faces). The neural mechanisms of real-world social behavior are of special interest during middle childhood (roughly ages 7-13), a time of increased social complexity and competence coinciding with structural and functional social brain development. Evidence from adult neuroscience studies suggests that social interaction may alter neural processing, but no neuroimaging studies in children have directly examined the effects of live social-interactive context on social cognition. In the current study of middle childhood, we compare the processing of two types of speech: speech that children believed was presented over a real-time audio-feed by a social partner and speech that they believed was recorded. Although in reality all speech was prerecorded, perceived live speech resulted in significantly greater neural activation in regions associated with social cognitive processing. These findings underscore the importance of using ecologically-valid and interactive methods to understand the developing social brain.

Implementing Transmission Electron Backscatter Diffraction for Atom Probe Tomography.

There are advantages to performing transmission electron backscattering diffraction (tEBSD) in conjunction with focused ion beam-based specimen preparation for atom probe tomography (APT). Although tEBSD allows users to identify the position and character of grain boundaries, which can then be combined with APT to provide full chemical and orientation characterization of grain boundaries, tEBSD can also provide imaging information that improves the APT specimen preparation process by insuring proper placement of the targeted grain boundary within an APT specimen. In this report we discuss sample tilt angles, ion beam milling energies, and other considerations to optimize Kikuchi diffraction pattern quality for the APT specimen geometry. Coordinated specimen preparation and analysis of a grain boundary in a Ni-based Inconel 600 alloy is used to illustrate the approach revealing a 50° misorientation and trace element segregation to the grain boundary.

Biological motion perception links diverse facets of theory of mind during middle childhood.

Two cornerstones of social development--social perception and theory of mind--undergo brain and behavioral changes during middle childhood, but the link between these developing domains is unclear. One theoretical perspective argues that these skills represent domain-specific areas of social development, whereas other perspectives suggest that both skills may reflect a more integrated social system. Given recent evidence from adults that these superficially different domains may be related, the current study examined the developmental relation between these social processes in 52 children aged 7 to 12 years. Controlling for age and IQ, social perception (perception of biological motion in noise) was significantly correlated with two measures of theory of mind: one in which children made mental state inferences based on photographs of the eye region of the face and another in which children made mental state inferences based on stories. Social perception, however, was not correlated with children's ability to make physical inferences from stories about people. Furthermore, the mental state inference tasks were not correlated with each other, suggesting a role for social perception in linking various facets of theory of mind.

Interaction matters: A perceived social partner alters the neural processing of human speech.

Mounting evidence suggests that social interaction changes how communicative behaviors (e.g., spoken language, gaze) are processed, but the precise neural bases by which social-interactive context may alter communication remain unknown. Various perspectives suggest that live interactions are more rewarding, more attention-grabbing, or require increased mentalizing-thinking about the thoughts of others. Dissociating between these possibilities is difficult because most extant neuroimaging paradigms examining social interaction have not directly compared live paradigms to conventional "offline" (or recorded) paradigms. We developed a novel fMRI paradigm to assess whether and how an interactive context changes the processing of speech matched in content and vocal characteristics. Participants listened to short vignettes--which contained no reference to people or mental states--believing that some vignettes were prerecorded and that others were presented over a real-time audio-feed by a live social partner. In actuality, all speech was prerecorded. Simply believing that speech was live increased activation in each participant's own mentalizing regions, defined using a functional localizer. Contrasting live to recorded speech did not reveal significant differences in attention or reward regions. Further, higher levels of autistic-like traits were associated with altered neural specialization for live interaction. These results suggest that humans engage in ongoing mentalizing about social partners, even when such mentalizing is not explicitly required, illustrating how social context shapes social cognition. Understanding communication in social context has important implications for typical and atypical social processing, especially for disorders like autism where social difficulties are more acute in live interaction.

Developmental Differences in Relations Between Episodic Memory and Hippocampal Subregion Volume During Early Childhood.

Episodic memory shows striking improvement during early childhood. However, neural contributions to these behavioral changes are not well understood. This study examined associations between episodic memory and volume of subregions (head, body, and tail) of the hippocampus-a structure known to support episodic memory in school-aged children and adults-during early childhood (n = 45). Results revealed significant positive relations between episodic memory and volume of the hippocampal head in both the left and right hemispheres for 6- but not 4-year-old children, suggesting brain-behavior relations vary across development. These findings add new information regarding neural mechanisms of change in memory development during early childhood and suggest that developmental differences in hippocampal subregions may contribute to age-related differences in episodic memory ability.

Tracking the Neurodevelopmental Correlates of Mental State Inference in Early Childhood.

Between ages 4 and 6, children become better at inferring what others are thinking and feeling. However, the neural correlates of these advances are understudied. The current study investigated the relation between performance on a face-based mental state inference task and white matter characteristics. Two tracts of interest, the uncinate fasciculus (UF) and inferior longitudinal fasciculus, were analyzed due to their involvement in social-emotional and face processing, respectively. Findings demonstrate a significant relation between fractional anisotropy in the UF and task performance in 4- but not 6-year-old children. Findings have implications for typical and atypical populations.

Spontaneous mentalizing captures variability in the cortical thickness of social brain regions.

Theory of mind (ToM)--or thinking about the mental states of others--is a cornerstone of successful everyday social interaction. However, the brain bases of ToM are most frequently measured via explicit laboratory tasks that pose direct questions about mental states (e.g. "In this story, what does Steve think Julia believes?"). Neuroanatomical measures may provide a way to explore the brain bases of individual differences in more naturalistic everyday mentalizing. In the current study, we examined the relation between cortical thickness and spontaneous ToM using the novel Spontaneous Theory of Mind Protocol (STOMP), which measures participants' spontaneous descriptions of the beliefs, emotions and goals of characters in naturalistic videos. We administered standard ToM tasks and the STOMP to young adults (aged 18-26 years) and collected structural magnetic resonance imaging data from a subset of these participants. The STOMP produced robust individual variability and was correlated with performance on traditional ToM tasks. Further, unlike the traditional ToM tasks, STOMP performance was related to cortical thickness for a set of brain regions that have been functionally linked to ToM processing. These findings offer novel insight into the brain bases of variability in naturalistic mentalizing performance, with implications for both typical and atypical populations.

Amygdala volume linked to individual differences in mental state inference in early childhood and adulthood.

We investigated the role of the amygdala in mental state inference in a sample of adults and in a sample of children aged 4 and 6 years. This period in early childhood represents a time when mentalizing abilities undergo dramatic changes. Both children and adults inferred mental states from pictures of others' eyes, and children also inferred the mental states of others from stories (e.g., a false belief task). We also collected structural MRI data from these participants, to determine whether larger amygdala volumes (controlling for age and total gray matter volume) were related to better face-based and story-based mentalizing. For children, larger amygdala volumes were related to better face-based, but not story-based, mentalizing. In contrast, in adults, amygdala volume was not related to face-based mentalizing. We next divided the face-based items into two subscales: cognitive (e.g., thinking, not believing) versus affective (e.g., friendly, kind) items. For children, performance on cognitive items was positively correlated with amygdala volume, but for adults, only performance on affective items was positively correlated with amygdala volume. These results indicate that the amygdala's role in mentalizing may be specific to face-based tasks and that the nature of its involvement may change over development.

Interaction versus observation: a finer look at this distinction and its importance to autism.

Although a second-person neuroscience has high ecological validity, the extent to which a second- versus third-person neuroscience approach fundamentally alters neural patterns of activation requires more careful investigation. Nonetheless, we are hopeful that this new avenue will prove fruitful in significantly advancing our understanding of typical and atypical social cognition.

Seed-mediated growth of shape-controlled wurtzite CdSe nanocrystals: platelets, cubes, and rods.

Prior investigations into the synthesis of colloidal CdSe nanocrystals with a wurtzite crystal structure (wz-CdSe) have given rise to well-developed methods for producing particles with anisotropic shapes such as rods, tetrapods, and wires; however, the synthesis of other shapes has proved challenging. Here we present a seed-mediated approach for the growth of colloidal, shape-controlled wz-CdSe nanoparticles with previously unobserved morphologies. The synthesis, which makes use of small (2-3 nm) wz-CdSe nanocrystals as nucleation sites for subsequent growth, can be tuned to selectively yield colloidal wz-CdSe nanocubes and hexagonal nanoplatelets in addition to nanorod and bullet-shaped particles. We thoroughly characterize the morphology and crystal structures of these new shapes, as well as discuss possible growth mechanisms in the context of control over surface chemistry and the nucleation stage.

Parsing heterogeneity in autism spectrum disorders: visual scanning of dynamic social scenes in school-aged children.

OBJECTIVE: To examine patterns of variability in social visual engagement and their relationship to standardized measures of social disability in a heterogeneous sample of school-aged children with autism spectrum disorders (ASD). METHOD: Eye-tracking measures of visual fixation during free-viewing of dynamic social scenes were obtained for 109 children with ASD (mean age, 10.2 ± 3.2 years), 37 of whom were matched with 26 typically-developing (TD) children (mean age, 9.5 ± 2.2 years) on gender, age, and IQ. The smaller subset allowed between-group comparisons, whereas the larger group was used for within-group examinations of ASD heterogeneity. RESULTS: Between-group comparisons revealed significantly attenuated orientation to socially salient aspects of the scenes, with the largest effect size (Cohen's d = 1.5) obtained for reduced fixation on faces. Within-group analyses revealed a robust association between higher fixation on the inanimate environment and greater social disability. However, the associations between fixation on the eyes and mouth and social adaptation varied greatly, even reversing, when comparing different cognitive profile subgroups. CONCLUSIONS: Although patterns of social visual engagement with naturalistic social stimuli are profoundly altered in children with ASD, the social adaptivity of these behaviors varies for different groups of children. This variation likely represents different patterns of adaptation and maladaptation that should be traced longitudinally to the first years of life, before complex interactions between early predispositions and compensatory learning take place. We propose that variability in these early mechanisms of socialization may serve as proximal behavioral manifestations of genetic vulnerabilities.

Diagnosis of fetal limb abnormalities before 15 weeks: cause for concern.

OBJECTIVES: The purposes of this study were (1) to identify cases of limb abnormalities identified before 15 weeks and correlate with outcomes and (2) to assess first-trimester nuchal translucency examinations to determine how frequently the upper and lower limbs were identified. METHODS: A retrospective review was conducted of sonographic studies up to 15 weeks' gestational age from 2003 to 2010 at our high-risk fetal center. Data were collected regarding fetal gestational age, limb abnormalities, associated anatomic abnormalities, pregnancy outcomes, karyotypes, autopsy results, and the utility of transabdominal sonography, transvaginal sonography, and 3-dimensional sonography. A retrospective analysis of 100 consecutive first-trimester examinations was also conducted to assess the sensitivity of transabdominal sonography in visualization of limb buds. RESULTS: A total of 15 cases were identified with a mean gestational age of 12 weeks 6 days. Club hand was the most common abnormality seen (8 cases), followed by absence of long bones (5 cases), a missing limb (5 cases), club foot (5 cases), shortening of long bones (2 cases), abnormal hands (2 cases), clenched hands (2 cases), and overlapping digits (1 case). Trisomy 18 was present in 9 cases. Transabdominal sonography allowed for detection of all limb buds in 100 consecutive nuchal translucency examinations and 9 of 15 cases of limb abnormalities. Four of the cases resulted in fetal death, and the remaining 11 cases were terminated. CONCLUSIONS: Fetal limb abnormalities can be detected on sonography before 15 weeks' gestational age and are often associated with serious congenital conditions, especially trisomy 18. Transabdominal sonography alone can show most of these abnormalities, although transvaginal and 3-dimensional sonography can provide additional information. Targeted evaluation of fetal limbs during sonography before 15 weeks should be considered in high-risk populations.

MEKK2 regulates the coordinate activation of ERK5 and JNK in response to FGF-2 in fibroblasts.

Mitogen-activated protein kinases (MAPKs) are regulated by MAPK kinases (MKKs), which are in turn regulated by MKK kinases (MKKKs). While a single MKKK can regulate several different MAPK family members, and several MKKKs can often activate the same MAPK, emerging evidence indicates a unique role for individual MKKKs in acting as signaling nodes to coordinately activate different subsets of MAPKs in response to specific cellular stimuli. Thus, while there is much apparent overlap in MAPK regulation by different MKKKs, each MKKK serves a specific purpose in regulation of unique cellular functions. The purpose of this study was to define the specific role of MEKK2, an MKKK, in MAPK regulation and cell function. MEKK2 coordinately activates the ERK5 and JNK pathways. Targeted disruption of MEKK2 expression causes loss of ERK5 and JNK activation in response to FGF-2 in mouse embryonic fibroblasts (MEFs). FGF-2 receptor signaling requires MEKK2 for induction of mRNA for c-Jun, Fra-1, and Fra-2, components of the AP-1 transcription complex. In FGF-2-stimulated MEKK2-/- fibroblasts, c-Jun phosphorylation is inhibited, consistent with a loss of JNK activation. Thus, MEKK2 regulates AP-1 activity at two levels, by regulating both expression of AP-1 components and c-Jun N-terminal phosphorylation. One function of the AP-1 transcription complex is to regulate cytokine gene expression. Expression of IL-1alpha, IL-1beta, IL-6, and TNFalpha is inhibited in MEKK2-/- fibroblasts. Bacterial lipopolysaccharide (LPS) and TNFalpha neither activate ERK5 nor require MEKK2 for JNK activation, demonstrating specificity of MEKK2 in FGF-2 receptor signaling and control of cytokine gene expression.

Colorectal cancer cells induce lymphocyte apoptosis by an endothelial monocyte-activating polypeptide-II-dependent mechanism.

Endothelial monocyte-activating polypeptide-II (EMAP-II) was first isolated from cell growth medium conditioned by tumor cells, and is closely related or identical with the p43 component of the mammalian multisynthase complex. In its secreted form, EMAP-II has multiple cytokine-like activities in vitro, inducing procoagulant activity on the surface of endothelial cells, increasing expression of E- and P-selectins and TNF-R1, and directing migration of monocytes and neutrophils. EMAP-II has also been shown to induce apoptosis in endothelial cells, leading to the suggestion that it is a proinflammatory polypeptide with antiangiogenic activity. The role of secreted EMAP-II in tumors remains poorly understood, and we hypothesized that EMAP-II may play a role in immune evasion by tumor cells. We investigated its effects on lymphocytes, using recombinant protein, or colorectal cancer cell lines, as a source of native EMAP-II. Recombinant EMAP-II inhibits DNA synthesis and cell division, and induces apoptosis in mitogen-activated lymphocytes in PBMC preparations, and in Jurkat T cells. Native EMAP-II, released by or expressed on the surface of colorectal carcinoma cells, also induces activation of caspase 8 and apoptosis of PBLs and Jurkat cells, which are partially blocked by addition of Abs against EMAP-II. Thus, activated lymphocytes, along with proliferating endothelial cells, are targets for the cytotoxic activity of EMAP-II. Membrane-bound and soluble EMAP-II appear to play multiple roles in the tumor microenvironment, one of which is to assist in immune evasion.