Demonstration and Control of "Spoof-Plasmon" Scattering from 3D Spherical Metaparticles.

Geometries that replicate the behavior of metal nanostructures at much lower frequencies via texturing surfaces so they will support a surface wave have been a central pillar of metamaterials research. However, previous work has focused largely on geometries that can be reduced to symmetries in one or two dimensions, such as strips, flat planes, and cylinders. Shapes with isotropic responses in three dimensions are important for applications, such as radar scattering and the replication of certain nanoscale behaviors. This work presents a detailed exploration of the scattering behavior of 3D spherical "spoof plasmonic" metaparticles, based on the platonic solids. Their behavior is compared to an effective medium model through simulation and experiment, and the vast range of behaviors that can be produced from a metal sphere of a given radius via tuning its internal structure is explored in detail.

Dark Mode Excitation in Three-Dimensional Interlaced Metallic Meshes.

Interlaced metallic meshes form a class of three-dimensional metamaterials that exhibit nondispersive, broadband modes at low frequencies, without the low frequency cutoff typical of generic wire grid geometries. However, the experimental observation of these modes has remained an open challenge, both due to the difficulties in fabricating such complex structures and also because the broadband mode is longitudinal and does not couple to free-space radiation (dark mode). Here we report the first experimental observation of the low frequency modes in a block of interlaced meshes fabricated through 3D printing. We demonstrate how the addition of monopole antennas to opposing faces of one of the meshes enables coupling of a plane wave to the low frequency "dark mode" and use this to obtain the dispersion of the mode. In addition, we utilize orthogonal antennas on opposite faces to achieve polarization rotation as well as phase shifting of radiation passing through the structure. Our work paves the way toward further experimental study into interlaced meshes and other complex 3D metamaterials.

Organohalide-Respiring Bacteria at the Heart of Anaerobic Metabolism in Arctic Wet Tundra Soils.

Recent work revealed an active biological chlorine cycle in coastal Arctic tundra of northern Alaska. This raised the question of whether chlorine cycling was restricted to coastal areas or if these processes extended to inland tundra. The anaerobic process of organohalide respiration, carried out by specialized bacteria like Dehalococcoides, consumes hydrogen gas and acetate using halogenated organic compounds as terminal electron acceptors, potentially competing with methanogens that produce the greenhouse gas methane. We measured microbial community composition and soil chemistry along an ∼262-km coastal-inland transect to test for the potential of organohalide respiration across the Arctic Coastal Plain and studied the microbial community associated with Dehalococcoides to explore the ecology of this group and its potential to impact C cycling in the Arctic. Concentrations of brominated organic compounds declined sharply with distance from the coast, but the decrease in organic chlorine pools was more subtle. The relative abundances of Dehalococcoides were similar across the transect, except for being lower at the most inland site. Dehalococcoides correlated with other strictly anaerobic genera, plus some facultative ones, that had the genetic potential to provide essential resources (hydrogen, acetate, corrinoids, or organic chlorine). This community included iron reducers, sulfate reducers, syntrophic bacteria, acetogens, and methanogens, some of which might also compete with Dehalococcoides for hydrogen and acetate. Throughout the Arctic Coastal Plain, Dehalococcoides is associated with the dominant anaerobes that control fluxes of hydrogen, acetate, methane, and carbon dioxide. Depending on seasonal electron acceptor availability, organohalide-respiring bacteria could impact carbon cycling in Arctic wet tundra soils.IMPORTANCE Once considered relevant only in contaminated sites, it is now recognized that biological chlorine cycling is widespread in natural environments. However, linkages between chlorine cycling and other ecosystem processes are not well established. Species in the genus Dehalococcoides are highly specialized, using hydrogen, acetate, vitamin B12-like compounds, and organic chlorine produced by the surrounding community. We studied which neighbors might produce these essential resources for Dehalococcoides species. We found that Dehalococcoides species are ubiquitous across the Arctic Coastal Plain and are closely associated with a network of microbes that produce or consume hydrogen or acetate, including the most abundant anaerobic bacteria and methanogenic archaea. We also found organic chlorine and microbes that can produce these compounds throughout the study area. Therefore, Dehalococcoides could control the balance between carbon dioxide and methane (a more potent greenhouse gas) when suitable organic chlorine compounds are available to drive hydrogen and acetate uptake.

On-Demand Activation of Photochromic Nanoheaters for High Color Purity 3D Printing.

The creation of white and multicoloured 3D-printed objects with high color fidelity via powder sintering processes is currently limited by discolouration from thermal sensitizers used in the printing process. Here, we circumvent this problem by using switchable, photochromic tungsten oxide nanoparticles, which are colorless even at high concentrations. Upon ultraviolet illumination, the tungsten oxide nanoparticles can be reversibly activated, making them highly absorbing in the infrared. Their strong infrared absorption upon activation renders them efficient photothermal sensitizers that can act as fusing agents for polymer powders in sintering-based 3D printing. The WO3 nanoparticles show fast activation times, and when mixed with polyamide powders, they exhibit a heating-to-color-change ratio greatly exceeding other sensitizers in the literature. Upon mixing with colored inks, powders containing WO3 display identical coloration to a pristine powder. This demonstrates the potential of WO3, and photochromic nanoparticles in general as a new class of material for advanced manufacturing.

Assessing the Wider Implementation of the SHARP Principles: Increasing Physical Activity in Primary Physical Education.

To assess the wider application of the SHARP (Stretching whilst moving, High repetition of skills, Accessibility, Reducing sitting and standing, and Promotion of physical activity) Principles intervention on children's moderate to vigorous physical activity (MVPA) in physical education (PE), when applied by teachers and coaches. A quasi-experimental intervention was employed in nine primary schools (experimental, n = 6: control, n = 3) including teachers (n = 10), coaches (n = 4), and children (aged 5 to 11 years, n = 84) in the West Midlands, UK. Practitioners applied the SHARP Principles to PE lessons, guided by an innovative behaviour change model. The System for Observing Fitness and Instruction Time (SOFIT) was used to measure children's MVPA in 111 lessons at pre- (n = 60) and post-intervention (n = 51). Seven interviews were conducted post-intervention to explore practitioners' perceptions. Two-way ANOVA (Analysis of Variance) revealed that teachers increased children's MVPA by 27.7%. No statistically significant change in children's MVPA was observed when taught by the coaches. The qualitative results for teachers were 'children's engagement', a 'pedagogical paradigm shift', and 'relatedness'; and for coaches 'organisational culture' and 'insufficient support and motivation'. The SHARP Principles intervention is the most effective teaching strategy at increasing MVPA in primary PE when taught by school based staff (rather than outsourced coaches), evidencing increases almost double that of any previously published study internationally and demonstrating the capacity to influence educational policy and practice internationally.

Evaluation of a Walking-Track Intervention to Increase Children's Physical Activity during Primary School Break Times.

Despite the known benefits of engaging in daily moderate to vigorous physical activity (MVPA), only 22% of children in England are meeting the recommended guidelines. School break times have been advocated as a key part of children's daily routines in which their MVPA can be increased. The main aim of this study was to evaluate the effect of installing a walking-track on children's MVPA during school break times. A mixed method design was employed which allowed for the quantitative measurement of children's PA at three time points (baseline, mid-intervention (1⁻5 weeks) and follow-up (6⁻9 weeks)), using pedometers (n = 81, 5⁻9 years) and systematic observation (n = 23, 7⁻9 years). A semi-structured interview (n = 1) was also conducted at 10 weeks' follow-up. The installation of the walking-track was grounded in a unique set of theoretical constructs to aid the behaviour change of the teachers. Short term positive increases in girls' and boys' MVPA and longer term increases in boys' vigorous PA (VPA) were found. Qualitative data highlighted that boys dominated the walking-track and the inconsistent behaviour of school staff negatively impacted upon children's MVPA. A set of principles to guide the installment of walking-tracks in school playgrounds are recommended.

White and Brightly Colored 3D Printing Based on Resonant Photothermal Sensitizers.

The use of photothermal sensitizers to facilitate the sintering of polymer powders is rapidly becoming a pivotal additive manufacturing technology, impacting multiple sectors of industry. However, conventional carbon-based sensitizers can only produce black or gray objects. To create white or colorful prints with this method, visibly transparent equivalents are needed. Here, we address this problem by designing resonant photothermal sensitizers made of plasmonic nanoparticles that strongly absorb in the near-infrared, while only minimally interacting with visible light. Gold nanorods were coated with silica before being mixed with polyamide powders to create stable colorful nanocomposite powders. At resonance, these composites showed greatly improved light-to-heat conversion compared with equivalent composites using the industry standard carbon black as a sensitizer and could be sintered using low-power light sources. Furthermore, they appear much whiter and can produce brightly colored 3D objects when mixed with dyes. Our results open a new route to utilize plasmonic nanoparticles to produce colorful and functional 3D-printed objects.

Developing Mental Toughness: Lessons from Paralympians.

Mental toughness (MT) is a key psychological variable related to perseverance and success in performance domains. MT and its development has been explored across a range of contexts and across different sports, but no research to date has examined MT in relation to Paralympic athletes. We sought to understand the lived-experiences of mentally tough Paralympians, aiming to conceptualize MT in a Paralympic context and investigate its development. Ten Paralympic athletes were interviewed using in-depth, semi-structured interviews. The verbatim transcripts of the interviews served as the data for an interpretative phenomenological analysis. Three broad themes and several subthemes emerged in conceptualizing Paralympian MT: characteristics (determination, defiance, pragmatic, optimistic, resilient, self-belief and independence and autonomy), cognitions (normalization, sense of escape, non-acceptance of constraints, influence perception and connection) and cognitive strategies (rational thinking, goal setting, pain management and control). In understanding MT development, two broad themes and several subthemes emerged: formative experiences (challenge, classification, setbacks, critical incident, trauma and recovery, sustained commitment, development of mind-set and perspective during challenge, failure, and acceptance), and support and coping resources (social support and significant others, external shaping, social support, overcoming problems, social comparison and reflective practice). The findings suggest that Paralympians benefited from exposure to highly demanding situations in a supportive environment and this helped develop mentally tough characteristics and behaviors and individualized cognitive coping strategies. Our findings highlight the association between the adaptive development of personal characteristics by overcoming physical and mental setbacks over a sustained time period. Overall, the findings suggest that to develop mentally tough characteristics and behaviors, athletes in general could benefit from exposure to highly demanding situations in a supportive environment.

Reproducibility and interobserver variability of systolic blood flow velocity and 3D wall shear stress derived from 4D flow MRI in the healthy aorta.

PURPOSE: To investigate the reproducibility and interobserver variability of 3D aortic velocity vector fields and wall shear stress (WSS) averaged over five systolic timeframes derived from noncontrast 4D flow magnetic resonance imaging (MRI). MATERIALS AND METHODS: Fourteen controls underwent test-retest 4D flow MRI examinations separated by 16 ± 3 days (resolution = 3.0-3.6 × 2.3-2.6 × 2.5-2.7 mm(3) ; TE/TR/FA = 2.5/4.9 msec/7°; Venc = 150 cm/s). Two observers segmented the aorta, and WSS was calculated for both series of scans and both segmentations. Test-retest and interobserver velocity and WSS vectors were compared on a voxel-by-voxel basis in the aorta and on a regional basis by subdividing the aortas in six segments. RESULTS: Test-retest: voxel-by-voxel Bland-Altman analysis revealed small differences (-0.03/-0.02 m/s/Pa), limits of agreement (LOA) of 0.25 m/s/0.29 Pa, and coefficients of variation (CV) of 20% for velocity/WSS. Voxel-by-voxel orthogonal regression analysis showed moderate agreement (slope: 1.14/1.16, intraclass correlation coefficient [ICC]: 0.76/0.67 for velocity/WSS). The regional analysis revealed a CV of 9%/8% and ICC of 0.9/0.9 for velocity/WSS. Interobserver: voxel-by-voxel difference for WSS was 0, LOA: 0.17/0.19 Pa, CV: 12/13%, slope: 1.01/1.09, ICC: 0.87/0.85 for test/retest. The CV/ICC for WSS in the regional analysis was 4%/1.0 for test and 3%/1.0 for retest. CONCLUSION: Systolic velocity and WSS derived from 4D flow MRI are reproducible between consecutive visits, with low interobserver variability in healthy volunteers.

A Novel Small Molecule Inhibitor of Candida albicans Biofilm Formation, Filamentation and Virulence with Low Potential for the Development of Resistance.

BACKGROUND/OBJECTIVES: Candida albicans is the principal causative agent of candidiasis, the most common fungal infection in humans. Candidiasis represents the third-to-fourth most frequent nosocomial infection worldwide, as this normal commensal of humans causes opportunistic infections in an expanding population of immune- and medically-compromised patients. These infections are frequently associated with biofilm formation, which complicates treatment and contributes to unacceptably high mortality rates. METHODS: To address the pressing need for new antifungals we have performed a high content screen of 20,000 small molecules in a chemical library (NOVACore™) to identify compounds that inhibit C. albicans biofilm formation, and conducted a series of follow-up studies to examine the in vitro and in vivo activity of the identified compounds. RESULTS: The screen identified a novel series of diazaspiro-decane structural analogs which were largely represented among the bioactive compounds. Characterization of the leading compound from this series indicated that it inhibits processes associated with C. albicans virulence, most notably biofilm formation and filamentation, without having an effect on overall growth or eliciting resistance. This compound demonstrated in vivo activity in clinically-relevant murine models of both invasive and oral candidiasis and as such represents a promising lead for antifungal drug development. Furthermore, these results provide proof of concept for the implementation of anti-virulence approaches against C. albicans and other fungal infections that would be less likely to foster the emergence of resistance.

Identification of a BRCA1-mRNA splicing complex required for efficient DNA repair and maintenance of genomic stability.

Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage.

BRCA1 deficiency exacerbates estrogen-induced DNA damage and genomic instability.

Germline mutations in BRCA1 predispose carriers to a high incidence of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through critical roles in DNA repair, cell-cycle arrest, and transcriptional control. A major question has been why BRCA1 loss or mutation leads to tumors mainly in estrogen-regulated tissues, given that BRCA1 has essential functions in all cell types. Here, we report that estrogen and estrogen metabolites can cause DNA double-strand breaks (DSB) in estrogen receptor-α-negative breast cells and that BRCA1 is required to repair these DSBs to prevent metabolite-induced genomic instability. We found that BRCA1 also regulates estrogen metabolism and metabolite-mediated DNA damage by repressing the transcription of estrogen-metabolizing enzymes, such as CYP1A1, in breast cells. Finally, we used a knock-in human cell model with a heterozygous BRCA1 pathogenic mutation to show how BRCA1 haploinsufficiency affects these processes. Our findings provide pivotal new insights into why BRCA1 mutation drives the formation of tumors in estrogen-regulated tissues, despite the general role of BRCA1 in DNA repair in all cell types.

Asynchronous expression of the homeodomain protein CUX1 in Sertoli cells and spermatids during spermatogenesis in mice.

The homeodomain CUX1 protein exists as multiple isoforms that arise from proteolytic processing of a 200-kDa protein or an alternate splicing or from the use of an alternate promoter. The 200-kDa CUX1 protein is highly expressed in the developing kidney, where it functions to regulate cell proliferation. Transgenic mice ectopically expressing the 200-kDa CUX1 protein develop renal hyperplasia associated with reduced expression of the cyclin kinase inhibitor p27. A 55-kDa CUX1 isoform is expressed exclusively in the testes. We determined the pattern and timing of CUX1 protein expression in developing testes. CUX1 expression was continuous in Sertoli cells from prepubertal testes but became cyclic when spermatids appeared. In testes from mature mice, CUX1 was highly expressed only in round spermatids at stages IV-V of spermatogenesis, in both spermatids and Sertoli cells at stages VI-X of spermatogenesis, and only in Sertoli cells at stage XI of spermatogenesis. While most of the seminiferous tubules in wild-type mice were between stages VI and X of spermatogenesis, there was a significant reduction in the percentage of seminiferous tubules between stages VI and X in Cux1 transgenic mice and a significant increase in the percentage of seminiferous tubules in stages IV-V and XI. Moreover, CUX1 was not expressed in proliferating cells in testes from either wild-type or transgenic mice. Thus, unlike the somatic form of CUX1, which has a role in cell proliferation, the testis-specific form of CUX1 is not involved in cell division and appears to play a role in signaling between Sertoli cells and spermatids.

From molecules to systems: the importance of looking both ways.

Although molecular biology has meant different things at different times, the term is often associated with a tendency to view cellular causation as conforming to simple linear schemas in which macro-scale effects are specified by micro-scale structures. The early achievements of molecular biologists were important for the formation of such an outlook, one to which the discovery of recombinant DNA techniques, and a number of other findings, gave new life even after the complexity of genotype-phenotype relations had become apparent. Against this background we outline how a range of scientific developments and conceptual considerations can be regarded as enabling and perhaps necessitating contemporary systems approaches. We suggest that philosophical ideas have a valuable part to play in making sense of complex scientific and disciplinary issues.

Knowledge-making distinctions in synthetic biology.

Synthetic biology is an increasingly high-profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA-based device construction, genome-driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie into two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge-making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems.

Disciplinary baptisms: a comparison of the naming stories of genetics, molecular biology, genomics, and systems biology.

Understanding how scientific activities use naming stories to achieve disciplinary status is important not only for insight into the past, but for evaluating current claims that new disciplines are emerging. In order to gain a historical understanding of how new disciplines develop in relation to these baptismal narratives, we compare two recently formed disciplines, systems biology and genomics, with two earlier related life sciences, genetics and molecular biology. These four disciplines span the twentieth century, a period in which the processes of disciplinary demarcation fundamentally changed from those characteristic of the nineteenth century. We outline how the establishment of each discipline relies upon an interplay of factors that include paradigmatic achievements, technological innovation, and social formations. Our focus, however, is the baptism stories that give the new discipline a founding narrative and articulate core problems, general approaches and constitutive methods. The highly plastic process of achieving disciplinary identity is further marked by the openness of disciplinary definition, tension between technological possibilities and the ways in which scientific issues are conceived and approached, synthesis of reductive and integrative strategies, and complex social interactions. The importance--albeit highly variable--of naming stories in these four cases indicates the scope for future studies that focus on failed disciplines or competing names. Further attention to disciplinary histories could, we suggest, give us richer insight into scientific development.