Weakly Nonlinear Analysis of Electroconvection in a Suspended Fluid Film

It has been experimentally observed that weakly conducting suspended films of smectic liquid crystals undergo electroconvection when subjected to a large enough potential difference. The resulting counter-rotating vortices form a very simple convection pattern and exhibit a variety of interesting nonlinear effects. The linear stability problem for this system has recently been solved. The convection mechanism, which involves charge separation at the free surfaces of the film, is applicable to any sufficiently two-dimensional fluid. In this paper, we derive an amplitude equation which describes the weakly nonlinear regime, by starting from the basic electrohydrodynamic equations. This regime has been the subject of several recent experimental studies. The lowest order amplitude equation we derive is of the Ginzburg-Landau form, and describes a forward bifurcation as is observed experimentally. The coefficients of the amplitude equation are calculated and compared with the values independently deduced from the linear stability calculation.Comment: 26 pages, 2 included eps figures, submitted to Phys Rev E. For more information, see http://mobydick.physics.utoronto.c

Wnt16 Elicits a Protective Effect Against Fractures and Supports Bone Repair in Zebrafish

Bone homeostasis is a dynamic, multicellular process which is required throughout life to maintain bone integrity, prevent fracture and respond to skeletal damage. WNT16 has been linked to bone fragility and osteoporosis in human genome wide association studies, as well as the functional haematopoiesis of leukocytes in vivo. However, the mechanisms by which WNT16 promotes bone health and repair are not fully understood. We used CRISPR-Cas9 to generate mutant zebrafish lacking Wnt16 (wnt16-/-) to study its effect on bone dynamically. wnt16 mutants displayed variable tissue mineral density and were susceptible to spontaneous fractures and the accumulation of bone calluses at an early age. Fractures were induced in the lepidotrichia of the caudal fins of wnt16-/- and wild type (WT) zebrafish; this model was used to probe the mechanisms by which Wnt16 regulates skeletal and immune cell-dynamics in vivo. In WT fins, wnt16 expression increased significantly during the early stages for bone repair. Mineralization of bone during fracture repair was significantly delayed in wnt16 mutants compared to WT zebrafish. Surprisingly, we found no evidence that the recruitment of innate immune cells to fractures or soft callus formation was altered in wnt16 mutants. However, osteoblast recruitment was significantly delayed in wnt16 mutants post-fracture, coinciding with precocious activation of the canonical Wnt signalling pathway. In situ hybridization suggests that canonical Wnt-responsive cells within fractures are osteoblast progenitors, and that osteoblast differentiation during bone repair is coordinated by the dynamic expression of runx2a and wnt16. This study highlights zebrafish as an emerging model for functionally validating osteoporosis-associated genes and investigating fracture repair dynamically in vivo. Using this model, we demonstrate that Wnt16 protects against fracture and supports bone repair, likely by modulating canonical Wnt activity, via runx2a, to facilitate osteoblast differentiation and bone matrix deposition

Prediction of landing gear loads using machine learning techniques

This article investigates the feasibility of using machine learning algorithms to predict the loads experienced by a landing gear during landing. For this purpose, the results on drop test data and flight test data will be examined. This article will focus on the use of Gaussian process regression for the prediction of loads on the components of a landing gear. For the learning task, comprehensive measurement data from drop tests are available. These include measurements of strains at key locations, such as on the side-stay and torque link, as well as acceleration measurements of the drop carriage and the gear itself, measurements of shock absorber travel, tyre closure, shock absorber pressure and wheel speed. Ground-to-tyre loads are also available through measurements made with a drop test ground reaction platform. The aim is to train the Gaussian process to predict load at a particular location from other available measurements, such as accelerations, or measurements of the shock absorber. If models can be successfully trained, then future load patterns may be predicted using only these measurements. The ultimate aim is to produce an accurate model that can predict the load at a number of locations across the landing gear using measurements that are readily available or may be measured more easily than directly measuring strain on the gear itself (for example, these may be measurements already available on the aircraft, or from a small number of sensors attached to the gear). The drop test data models provide a positive feasibility test which is the basis for moving on to the critical task of prediction on flight test data. For this, a wide range of available flight test measurements are considered for potential model inputs (excluding strain measurements themselves), before attempting to refine the model or use a smaller number of measurements for the prediction

Efficacy of the Aussie Optimism Program: Promoting pro-social behavior and preventing suicidality in primary school students. A randomised-controlled trial

The efficacy of an enhanced version of the Aussie Optimism Program (AOP) was investigated in a cluster randomized controlled trial. Grade 6 students aged 10–11 years of age (N = 2288) from 63 government primary schools in Perth, Western Australia, participated in the pre, post, and follow-up study. Schools were randomly assigned to one of three conditions: Aussie Optimism with teacher training, Aussie Optimism with teacher training plus coaching, or a usual care condition that received the regular Western Australian Health Education Curriculum. Students in the Aussie Optimism conditions received 20, 1-h lessons relating to social and interpersonal skills and optimistic thinking skills over the last 2 years of primary school. Parents in the active conditions received a parent information booklet each year, plus a self-directed program in Grade 7. Students and parents completed the Extended Strengths and Difficulties Questionnaire. Students who scored in the clinical range on the Emotional Symptoms Scale were given The Diagnostic Interview for Children and Adolescents IV, to assess suicidal ideation and behavior, and depressive and anxiety disorders. Results indicated that Aussie Optimism with teacher training plus coaching was associated with the best outcomes: a significant increase in student-reported pro-social behavior from pre-test to post-test 1 (maintained at post-test 2) and significantly lower incidence rates from suicidal ideation at post-test 2 and follow-up. No significant intervention effects on anxiety and depressive disorders, and total difficulties were reported. These findings suggest that the AOP with teacher training along with coaching may have the potential to positively impact on suicidality and pro-social behavior in the pre-adolescent years

The Forms of Bullying Scale (FBS): Validity and reliability estimates for a measure of bullying victimization and perpetration in adolescence

The study of bullying behavior and its consequences for young people depends on valid and reliable measurement of bullying victimization and perpetration. Although numerous self-report bullying-related measures have been developed, robust evidence of their psychometric properties is scant, and several limitations inhibit their applicability. The Forms of Bullying Scale (FBS), with versions to measure bullying victimization (FBS-V) and perpetration (FBS-P), was developed on the basis of existing instruments, for use with 12-to 15-year-old adolescents to economically, yet comprehensively measure both bullying perpetration and victimization. Measurement properties were estimated. Scale validity was tested using data from 2 independent studies of 3,496 Grade 8 and 783 Grade 8-10 students, respectively. Construct validity of scores on the FBS was shown in confirmatory factor analysis. The factor structure was not invariant across gender. Strong associations between the FBS-V and FBS-P and separate single-item bullying items demonstrated adequate concurrent validity. Correlations, in directions as expected with social-emotional outcomes (i.e., depression, anxiety, conduct problems, and peer support), provided robust evidence of convergent and discriminant validity. Responses to the FBS items were found to be valid and concurrently reliable measures of self-reported frequency of bullying victimization and perpetration, as well as being useful to measure involvement in the different forms of bullying behaviors

Macrophage Reprogramming with Anti-miR223-Loaded Artificial Protocells Enhances In Vivo Cancer Therapeutic Potential

Several immune cell‐expressed miRNAs (miRs) are associated with altered prognostic outcome in cancer patients, suggesting that they may be potential targets for development of cancer therapies. Here, translucent zebrafish (Danio rerio) is utilized to demonstrate that genetic knockout or knockdown of one such miR, microRNA‐223 (miR223), globally or specifically in leukocytes, does indeed lead to reduced cancer progression. As a first step toward potential translation to a clinical therapy, a novel strategy is described for reprogramming neutrophils and macrophages utilizing miniature artificial protocells (PCs) to deliver anti‐miRs against the anti‐inflammatory miR223. Using genetic and live imaging approaches, it is shown that phagocytic uptake of anti‐miR223‐loaded PCs by leukocytes in zebrafish (and by human macrophages in vitro) effectively prolongs their pro‐inflammatory state by blocking the suppression of pro‐inflammatory cytokines, which, in turn, drives altered immune cell‐cancer cell interactions and ultimately leads to a reduced cancer burden by driving reduced proliferation and increased cell death of tumor cells. This PC cargo delivery strategy for reprogramming leukocytes toward beneficial phenotypes has implications also for treating other systemic or local immune‐mediated pathologies

Convective Fingering of an Autocatalytic Reaction Front

We report experimental observations of the convection-driven fingering instability of an iodate-arsenous acid chemical reaction front. The front propagated upward in a vertical slab; the thickness of the slab was varied to control the degree of instability. We observed the onset and subsequent nonlinear evolution of the fingers, which were made visible by a {\it p}H indicator. We measured the spacing of the fingers during their initial stages and compared this to the wavelength of the fastest growing linear mode predicted by the stability analysis of Huang {\it et. al.} [{\it Phys. Rev. E}, {\bf 48}, 4378 (1993), and unpublished]. We find agreement with the thickness dependence predicted by the theory.Comment: 11 pages, RevTex with 3 eps figures. To be published in Phys Rev E, [email protected], [email protected], [email protected]

Repurposed 3D Printer Allows Economical and Programmable Fraction Collection for Proteomics of Nanogram Scale Samples

In this work, we describe the construction and application of a repurposed 3D-printer as a fraction collector. We utilize a nano-LC to ensure minimal volumes and surfaces although any LC can be coupled. The setup operates as a high-pH fractionation system capable of effectively working with nanogram scales of lysate digests. The 2D RP–RP system demonstrated superior proteome coverage over single-shot data-dependent acquisition (DDA) analysis using only 5 ng of human cell lysate digest with performance increasing with increasing amounts of material. We found that the fractionation system allowed over 60% signal recovery at the peptide level and, more importantly, we observed improved protein level intensity coverage, which indicates the complexity reduction afforded by the system outweighs the sample losses endured. The application of data-independent acquisition (DIA) and wide window acquisition (WWA) to fractionated samples allowed nearly 8000 proteins to be identified from 50 ng of the material. The utility of the 2D system was further investigated for phosphoproteomics (>21 000 phosphosites from 50 μg starting material) and pull-down type experiments and showed substantial improvements over single-shot experiments. We show that the 2D RP–RP system is a highly versatile and powerful tool for many proteomics workflows

ENDO-Pore:high-throughput linked-end mapping of single DNA cleavage events using nanopore sequencing

Mapping the precise position of DNA cleavage events plays a key role in determining the mechanism and function of endonucleases. ENDO-Pore is a high-throughput nanopore-based method that allows the time resolved mapping single molecule DNA cleavage events in vitro. Following linearisation of a circular DNA substrate by the endonuclease, a resistance cassette is ligated recording the position of the cleavage event. A library of single cleavage events is constructed and subjected to rolling circle amplification to generate concatemers. These are sequenced and used to produce accurate consensus sequences. To identify the cleavage site(s), we developed CSI (Cleavage Site Investigator). CSI recognizes the ends of the cassette ligated into the cleaved substrate and triangulates the position of the dsDNA break. We firstly benchmarked ENDO-Pore using Type II restriction endonucleases. Secondly, we analysed the effect of crRNA length on the cleavage pattern of CRISPR Cas12a. Finally, we mapped the time-resolved DNA cleavage by the Type ISP restriction endonuclease LlaGI that introduces random double-strand breaks into its DNA substrates