Hiding the squid:patterns in artificial cephalopod skin

Cephalopods employ their chromomorphic skins for rapid and versatile active camouflage and signalling effects. This is achieved using dense networks of pigmented, muscle-driven chromatophore cells which are neurally stimulated to actuate and affect local skin colouring. This allows cephalopods to adopt numerous dynamic and complex skin patterns, most commonly used to blend into the environment or to communicate with other animals. Our ultimate goal is to create an artificial skin that can mimic such pattern generation techniques, and that could produce a host of novel and compliant devices such as cloaking suits and dynamic illuminated clothing. This paper presents the design, mathematical modelling and analysis of a dynamic biomimetic pattern generation system using bioinspired artificial chromatophores. The artificial skin is made from electroactive dielectric elastomer: a soft, planar-actuating smart material that we show can be effective at mimicking the actuation of biological chromatophores. The proposed system achieves dynamic pattern generation by imposing simple local rules into the artificial chromatophore cells so that they can sense their surroundings in order to manipulate their actuation. By modelling sets of artificial chromatophores in linear arrays of cells, we explore the capability of the system to generate a variety of dynamic pattern types. We show that it is possible to mimic patterning seen in cephalopods, such as the passing cloud display, and other complex dynamic patterning

Semaphorin-Plexin Signaling Guides Patterning of the Developing Vasculature

AbstractMajor vessels of the vertebrate circulatory system display evolutionarily conserved and reproducible anatomy, but the cues guiding this stereotypic patterning remain obscure. In the nervous system, axonal pathways are shaped by repulsive cues provided by ligands of the semaphorin family that are sensed by migrating neuronal growth cones through plexin receptors. We show that proper blood vessel pathfinding requires the endothelial receptor PlexinD1 and semaphorin signals, and we identify mutations in plexinD1 in the zebrafish vascular patterning mutant out of bounds. These results reveal the fundamental conservation of repulsive patterning mechanisms between axonal migration in the central nervous system and vascular endothelium during angiogenesis

Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer’s disease-relevant murine model

Mitochondrial dysfunction is a hallmark of neurodegenerative diseases including Alzheimer’s disease (AD), with morphological and functional abnormalities limiting the electron transport chain and ATP production. A contributing factor of mitochondrial abnormalities is loss of nicotinamide adenine dinucleotide (NAD), an important cofactor in multiple metabolic reactions. Depletion of mitochondrial and consequently cellular NAD(H) levels by activated NAD glycohydrolases then culminates in bioenergetic failure and cell death. De Novo NAD+ synthesis from tryptophan requires a multi-step enzymatic reaction. Thus, an alternative strategy to maintain cellular NAD+ levels is to administer NAD+ precursors facilitating generation via a salvage pathway. We administered nicotinamide mononucleotide (NMN), an NAD+ precursor to APP(swe)/PS1(ΔE9) double transgenic (AD-Tg) mice to assess amelioration of mitochondrial respiratory deficits. In addition to mitochondrial respiratory function, we examined levels of full-length mutant APP, NAD+-dependent substrates (SIRT1 and CD38) in homogenates and fission/fusion proteins (DRP1, OPA1 and MFN2) in mitochondria isolated from brain. To examine changes in mitochondrial morphology, bigenic mice possessing a fluorescent protein targeted to neuronal mitochondria (CaMK2a-mito/eYFP), were administered NMN. Mitochondrial oxygen consumption rates were examined in N2A neuroblastoma cells and non-synaptic brain mitochondria isolated from mice (3 months). Western blotting was utilized to assess APP, SIRT1, CD38, DRP1, OPA1 and MFN2 in brain of transgenic and non-transgenic mice (3–12 months). Mitochondrial morphology was assessed with confocal microscopy. One-way or two-way analysis of variance (ANOVA) and post-hoc Holm-Sidak method were used for statistical analyses of data. Student t-test was used for direct comparison of two groups. We now demonstrate that mitochondrial respiratory function was restored in NMN-treated AD-Tg mice. Levels of SIRT1 and CD38 change with age and NMN treatment. Furthermore, we found a shift in dynamics from fission to fusion proteins in the NMN-treated mice. This is the first study to directly examine amelioration of NAD+ catabolism and changes in mitochondrial morphological dynamics in brain utilizing the immediate precursor NMN as a potential therapeutic compound. This might lead to well-defined physiologic abnormalities that can serve an important role in the validation of promising agents such as NMN that target NAD+ catabolism preserving mitochondrial function.https://doi.org/10.1186/s12883-015-0272-

Modelling a dynamic magneto-agglutination bioassay

The process of developing an end-to-end model of a magneto-immunoassay is described which models the agglutination effect due to specific binding of bacteria to paramagnetic particles. After establishing the properties of the dose-specific agglutination through direct imaging, a microfluidic assay was used to demonstrate changes in the magnetophoretic transport dynamics of agglutinated clusters via transient inductive magentometer measurements. End-to-end mathematical modelling is used to establish the physical processes underlying the assay. First, a modification form of Becker–Döring nucleation kinetic equations is used to establish a relationship between analyte dose and average cluster size. Next, Stokes flow equations are used to establish a relationship between cluster size and speed of motion within the fluid chamber. This predicts a cluster-size dynamic profile of concentration of PMPs versus time when the magnetic field is switched between the two actuated magnets. Finally, inductive modelling is carried out to predict the response of the magnetometer circuit in response to this dynamics of magnetic clusters. The predictions of this model is shown to agree well with the results of experiments, and to predict the shape of the dose-response curve

The developmental dynamics of terrorist organizations

We identify robust statistical patterns in the frequency and severity of violent attacks by terrorist organizations as they grow and age. Using group-level static and dynamic analyses of terrorist events worldwide from 1968-2008 and a simulation model of organizational dynamics, we show that the production of violent events tends to accelerate with increasing size and experience. This coupling of frequency, experience and size arises from a fundamental positive feedback loop in which attacks lead to growth which leads to increased production of new attacks. In contrast, event severity is independent of both size and experience. Thus larger, more experienced organizations are more deadly because they attack more frequently, not because their attacks are more deadly, and large events are equally likely to come from large and small organizations. These results hold across political ideologies and time, suggesting that the frequency and severity of terrorism may be constrained by fundamental processes.Comment: 28 pages, 8 figures, 4 tables, supplementary materia

A Randomized Trial to Identify Accurate and Cost-Effective Fidelity Measurement Methods for Cognitive-Behavioral Therapy: Project FACTS Study Protocol

Background: This randomized trial will compare three methods of assessing fidelity to cognitive-behavioral therapy (CBT) for youth to identify the most accurate and cost-effective method. The three methods include self-report (i.e., therapist completes a self-report measure on the CBT interventions used in session while circumventing some of the typical barriers to self-report), chart-stimulated recall (i.e., therapist reports on the CBT interventions used in session via an interview with a trained rater, and with the chart to assist him/her) and behavioral rehearsal (i.e., therapist demonstrates the CBT interventions used in session via a role-play with a trained rater). Direct observation will be used as the gold-standard comparison for each of the three methods. Methods/design: This trial will recruit 135 therapists in approximately 12 community agencies in the City of Philadelphia. Therapists will be randomized to one of the three conditions. Each therapist will provide data from three unique sessions, for a total of 405 sessions. All sessions will be audio-recorded and coded using the Therapy Process Observational Coding System for Child Psychotherapy-Revised Strategies scale. This will enable comparison of each measurement approach to direct observation of therapist session behavior to determine which most accurately assesses fidelity. Cost data associated with each method will be gathered. To gather stakeholder perspectives of each measurement method, we will use purposive sampling to recruit 12 therapists from each condition (total of 36 therapists) and 12 supervisors to participate in semi-structured qualitative interviews. Discussion: Results will provide needed information on how to accurately and cost-effectively measure therapist fidelity to CBT for youth, as well as important information about stakeholder perspectives with regard to each measurement method. Findings will inform fidelity measurement practices in future implementation studies as well as in clinical practice. Trial registration: NCT02820623, June 3rd, 2016