Analysis of Sequence Divergence in Mammalian ABCGs Predicts a Structural Network of Residues That Underlies Functional Divergence

The five members of the mammalian G subfamily of ATP-binding cassette transporters differ greatly in their substrate specificity. Four members of the subfamily are important in lipid transport and the wide substrate specificity of one of the members, ABCG2, is of significance due to its role in multidrug resistance. To explore the origin of substrate selectivity in members 1, 2, 4, 5 and 8 of this subfamily, we have analysed the differences in conservation between members in a multiple sequence alignment of ABCG sequences from mammals. Mapping sets of residues with similar patterns of conservation onto the resolved 3D structure of ABCG2 reveals possible explanations for differences in function, via a connected network of residues from the cytoplasmic to transmembrane domains. In ABCG2, this network of residues may confer extra conformational flexibility, enabling it to transport a wider array of substrates.     

The Role of Innate and Adaptive Immune Cells in Skeletal Muscle Regeneration

Skeletal muscle regeneration is highly dependent on the inflammatory response. A wide variety of innate and adaptive immune cells orchestrate the complex process of muscle repair. This review provides information about the various types of immune cells and biomolecules that have been shown to mediate muscle regeneration following injury and degenerative diseases. Recently developed cell and drug-based immunomodulatory strategies are highlighted. An improved understanding of the immune response to injured and diseased skeletal muscle will be essential for the development of therapeutic strategies.     

Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression

TP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53.     

Micron-Scale Soft Actuators Fabricated from Multi-Shell Polystyrene Particle-Gold Nanoparticle Nanohybrids

Actuators made of soft matter are needed for a variety of fields ranging from biomedical devices to soft robotics to microelectromechanical systems. While there are a variety of excellent methods of soft actuation known, the field is still an area of intense research activity as new niches and needs emerge with new technology development. Here, a soft actuation system is described, based on a core-multi-shell particle, which moves via photothermal expansion. The system consists of a novel polystyrene-based thermally expandable microsphere, with a secondary shell of a silicate-silane graft copolymer, to which gold nanoparticles are covalently linked. The gold nanoparticles act as photothermal nano-transducers, converting light energy into the thermal energy necessary for microsphere expansion, which in turn results in material movement. Actuation is shown in isolated particles in thermal and photothermal regimes using metal ceramic heaters or 520 nm laser illumination, respectively. Macroscale actuation is demonstrated by making a composite material of particles suspended in the transparent elastomer polydimethylsiloxane. The sample demonstrates an inchworm-like movement by starting from an arched geometry. Overall, this work describes a new particle-based actuation method for soft materials, and demonstrates its utility in driving the movement of a composite elastomer.     

Predicting and interpreting identification errors in military vehicle training using multidimensional scaling

We compared methods for predicting and understanding the source of confusion errors during military vehicle identification training. Participants completed training to identify main battle tanks. They also completed card-sorting and similarity-rating tasks to express their mental representation of resemblance across the set of training items. We expected participants to selectively attend to a subset of vehicle features during these tasks, and we hypothesised that we could predict identification confusion errors based on the outcomes of the card-sort and similarity-rating tasks. Based on card-sorting results, we were able to predict about 45% of observed identification confusions. Based on multidimensional scaling of the similarity-rating data, we could predict more than 80% of identification confusions. These methods also enabled us to infer the dimensions receiving significant attention from each participant. This understanding of mental representation may be crucial in creating personalised training that directs attention to features that are critical for accurate identification.

Practitioner Summary: Participants completed military vehicle identification training and testing, along with card-sorting and similarity-rating tasks. The data enabled us to predict up to 84% of identification confusion errors and to understand the mental representation underlying these errors. These methods have potential to improve training and reduce identification errors leading to fratricide.     

Learning perceptually grounded word meanings from unaligned parallel data

In order for robots to effectively understand natural language commands, they must be able to acquire meaning representations that can be mapped to perceptual features in the external world. Previous approaches to learning these grounded meaning representations require detailed annotations at training time. In this paper, we present an approach to grounded language acquisition which is capable of jointly learning a policy for following natural language commands such as “Pick up the tire pallet,” as well as a mapping between specific phrases in the language and aspects of the external world; for example the mapping between the words “the tire pallet” and a specific object in the environment. Our approach assumes a parametric form for the policy that the robot uses to choose actions in response to a natural language command that factors based on the structure of the language. We use a gradient method to optimize model parameters. Our evaluation demonstrates the effectiveness of the model on a corpus of commands given to a robotic forklift by untrained users.     

CeO2−CoO Phase Diagram

Phase equilibria in the CeO₂−CoO system at temperatures above 1500°C were investigated. The microstructures and the phase compositions of the DTA (differential thermal analysis) samples and the quenched solid pellets were analyzed using SEM (scanning electron microscope), EDX (energy dispersive X-ray), and WDX (wavelength dispersive X-ray). A eutectic reaction was found at 1645 ± 5°C. The eutectic point was calculated to be at 82 ± 1.5 mol% CoO. The eutectic phases were the CeO₂-rich phase (containing <5 mol% CoO) and the CoO-rich phase (containing ∼0.5 mol% CeO₂). At 1580°C, the solubility of CoO in CeO₂ was ∼3 mol%.     

Thermogenic Effect from Nutritionally Enriched Coffee Consumption

Background  

The purpose of this study was to examine the effect of nutritionally enriched JavaFit™ (JF) coffee (450 mg of caffeine, 1200 mg of garcinia cambogia, 360 mg of citrus aurantium extract, and 225 mcg of chromium polynicotinate) on resting oxygen uptake (VO₂), respiratory exchange ratio (RER), heart rate (HR), and blood pressure (BP) in healthy and physically active individuals.     

Monodisperse nanoparticles of poly(ethylene glycol) macromers and N‐isopropyl acrylamide for biomedical applications

Poly(ethylene glycol)‐based nanoparticles have received significant attention in the field of biomedicine. When they are copolymerized with pH‐ or temperature‐sensitive comonomers, their small size allows them to respond very quickly to changes in the environment, including changes in the pH, ionic strength, and temperature. In addition, the high surface‐to‐volume ratio makes them highly functionalized. In this work, nanoparticles composed of temperature‐sensitive poly(N‐isopropylacrylamide), poly(ethylene glycol) 400 dimethacrylate, and poly(ethylene glycol) 1000 methacrylate were prepared by a thermally initiated, free‐radical dispersion polymerization method. The temperature‐responsive behavior of the hydrogel nanoparticles was characterized by the study of their particle size with photon correlation spectroscopy. The size of the nanoparticles varied from 200 to 1100 nm and was a strong function of the temperature of the system, from 5 to 40°C. The thermal, structural, and morphological characteristics were also investigated. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1678–1684, 2003     

Public Displays of Play: Studying Online Games in Physical Settings

As research on virtual worlds gains increasing attention in educational, commercial, and military domains, a consideration of how player populations are ‘reassembled’ through social scientific data is a timely matter for communication scholars. This paper describes a large‐scale study of virtual worlds in which participants were recruited at public gaming events, as opposed to through online means, and explores the dynamic relationships between players and contexts of play that this approach makes visible. Challenging conventional approaches to quantitatively driven virtual worlds research, which categorizes players based on their involvement in an online game at a particular point in time, this account demonstrates how players' networked gaming activities are contingent on who they are playing with, where, and when.