High protein flexibility and reduced hydration water dynamics are key pressure adaptive strategies in prokaryotes

Water and protein dynamics on a nanometer scale were measured by quasi-elastic neutron scattering in the piezophile archaeon Thermococcus barophilus and the closely related pressure-sensitive Thermococcus kodakarensis, at 0.1 and 40 MPa. We show that cells of the pressure sensitive organism exhibit higher intrinsic stability. Both the hydration water dynamics and the fast protein and lipid dynamics are reduced under pressure. In contrast, the proteome of T. barophilus is more pressure sensitive than that of T. kodakarensis. The diffusion coefficient of hydration water is reduced, while the fast protein and lipid dynamics are slightly enhanced with increasing pressure. These findings show that the coupling between hydration water and cellular constituents might not be simply a master-slave relationship. We propose that the high flexibility of the T. barophilus proteome associated with reduced hydration water may be the keys to the molecular adaptation of the cells to high hydrostatic pressure.

Metabolic and hormonal response to intermittent high-intensity and continuous moderate intensity exercise in individuals with type 1 diabetes: a randomised crossover study.

AIMS/HYPOTHESIS To investigate exercise-related fuel metabolism in intermittent high-intensity (IHE) and continuous moderate intensity (CONT) exercise in individuals with type 1 diabetes mellitus. METHODS In a prospective randomised open-label cross-over trial twelve male individuals with well-controlled type 1 diabetes underwent a 90 min iso-energetic cycling session at 50% maximal oxygen consumption ([Formula: see text]), with (IHE) or without (CONT) interspersed 10 s sprints every 10 min without insulin adaptation. Euglycaemia was maintained using oral (13)C-labelled glucose. (13)C Magnetic resonance spectroscopy (MRS) served to quantify hepatocellular and intramyocellular glycogen. Measurements of glucose kinetics (stable isotopes), hormones and metabolites complemented the investigation. RESULTS Glucose and insulin levels were comparable between interventions. Exogenous glucose requirements during the last 30 min of exercise were significantly lower in IHE (p = 0.02). Hepatic glucose output did not differ significantly between interventions, but glucose disposal was significantly lower in IHE (p < 0.05). There was no significant difference in glycogen consumption. Growth hormone, catecholamine and lactate levels were significantly higher in IHE (p < 0.05). CONCLUSIONS/INTERPRETATION IHE in individuals with type 1 diabetes without insulin adaptation reduced exogenous glucose requirements compared with CONT. The difference was not related to increased hepatic glucose output, nor to enhanced muscle glycogen utilisation, but to decreased glucose uptake. The lower glucose disposal in IHE implies a shift towards consumption of alternative substrates. These findings indicate a high flexibility of exercise-related fuel metabolism in type 1 diabetes, and point towards a novel and potentially beneficial role of IHE in these individuals. TRIAL REGISTRATION ClinicalTrials.gov NCT02068638 FUNDING: Swiss National Science Foundation (grant number 320030_149321/) and R&A Scherbarth Foundation (Switzerland).

Simultaneous high-resolution pH and spectrophotometric recordings of oxygen binding in native blood microvolumes, link to supplementary material

Oxygen equilibrium curves have been widely used to understand oxygen transport in numerous organisms. A major challenge has been to monitor oxygen binding characteristics and concomitant pH changes as they occur in vivo, in limited sample volumes. Here we report a technique allowing highly resolved and simultaneous monitoring of pH and blood pigment saturation in minute blood volumes. We equipped a gas diffusion chamber with a broad range fibre optic spectrophotometer and a micro-pH optode and recorded changes of pigment oxygenation along PO2 and pH gradients to test the setup. Oxygen binding parameters derived from measurements in only 15 µl of haemolymph from the cephalopod Octopus vulgaris showed low instrumental error (0.93%) and good agreement with published data. Broad range spectra, each resolving 2048 data points, provided detailed insight into the complex absorbance characteristics of diverse blood types. After consideration of photobleaching and intrinsic fluorescence, pH optodes yielded accurate recordings and resolved a sigmoidal shift of 0.03 pH units in response to changing PO2 from 0-21 kPa. Highly resolved continuous recordings along pH gradients conformed to stepwise measurements at low rates of pH changes. In this study we showed that a diffusion chamber upgraded with a broad range spectrophotometer and an optical pH sensor accurately characterizes oxygen binding with minimal sample consumption and manipulation. We conclude that the modified diffusion chamber is highly suitable for experimental biologists who demand high flexibility, detailed insight into oxygen binding as well as experimental and biological accuracy combined in a single set up.

Design and implementation of a virtual world training simulation of ICU first hour handover processes

Nursing training for an Intensive Care Unit (ICU) is a resource intensive process. High demands are made on staff, students and physical resources. Interactive, 3D computer simulations, known as virtual worlds, are increasingly being used to supplement training regimes in the health sciences; especially in areas such as complex hospital ward processes. Such worlds have been found to be very useful in maximising the utilisation of training resources. Our aim is to design and develop a novel virtual world application for teaching and training Intensive Care nurses in the approach and method for shift handover, to provide an independent, but rigorous approach to teaching these important skills. In this paper we present a virtual world simulator for students to practice key steps in handing over the 24/7 care requirements of intensive care patients during the commencing first hour of a shift. We describe the modelling process to provide a convincing interactive simulation of the handover steps involved. The virtual world provides a practice tool for students to test their analytical skills with scenarios previously provided by simple physical simulations, and live on the job training. Additional educational benefits include facilitation of remote learning, high flexibility in study hours and the automatic recording of a reviewable log from the session. To the best of our knowledge, we believe this is a novel and original application of virtual worlds to an ICU handover process. The major outcome of the work was a virtual world environment for training nurses in the shift handover process, designed and developed for use by postgraduate nurses in training.

Influence of plate bending stiffness on mechanical properties of healing fracture, mouse femora

Mechanically well-defined stabilization systems have only recently become available, providing standardized conditions for studying the role of the mechanical environment on mouse bone fracture healing. The aim of this study was to characterize the time course of strength recovery and callus development of mouse femoral osteotomies stabilized with either low or high flexibility (in bending and torsion) internal fixation plates. Animals were euthanized and femora excised at 14, 21, and 28 days post-osteotomy for microCT analysis and torsional strength testing. While a larger mineralized callus was observed in osteotomies under more flexible conditions at all time points, the earlier bridging of the mineralized callus under less flexible conditions by 1 week resulted in an earlier recovery of torsional strength in mice stabilized with low flexibility fixation. Ultimate torque values for these bones were significantly higher at 14 and 21 days post-osteotomy compared to bones with the more flexible stabilization. Our study confirms the high reproducibility of the results that are achieved with this new implant system, therefore making it ideal for studying the influence of the mechanical environment on murine fracture healing under highly standardized conditions.

Architecture of a polymorphic ASIC for interoperability across multi-mode H.264 decoders

Run-time interoperability between different applications based on H.264/AVC is an emerging need in networked infotainment, where media delivery must match the desired resolution and quality of the end terminals. In this paper, we describe the architecture and design of a polymorphic ASIC to support this. The H.264 decoding flow is partitioned into modules, such that the polymorphic ASIC meets the design goals of low-power, low-area, high flexibility, high throughput and fast interoperability between different profiles and levels of H.264. We demonstrate the idea with a multi-mode decoder that can decode baseline, main and high profile H.264 streams and can interoperate at run.time across these profiles. The decoder is capable of processing frame sizes of up to 1024 times 768 at 30 fps. The design synthesized with UMC 0.13 mum technology, occupies 250 k gates and runs at 100 MHz.

A new adaptive marine policy toolbox to support ecosystem-based approach to management

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Local chain motions in a dilute solution of phenolphthalein poly(ether sulfone)

C-13 and H-1 relaxation times were measured as a function of temperature in two magnetic fields for dilute solutions of phenolphthalein poly(ether sulfone) (PES-C) in deuterated chloroform. The spin-lattice relaxation times were interpreted in terms of segmental motion characterized by the sharp cutoff model of Jones and Stockmayer (J. S. model). The phenyl group rotation is treated as a stochastic diffusion by the J. S. model. The restricted butterfly motion of the phenyl group attached to the cardo ring in PES-C is mentioned but is not discussed in detail in this work. Correlation times for the segmental motion are in the picosecond range which indicates the high flexibility of PES-C chains. The correlation time for the phenyl group internal rotation is similar to that of the segmental motion. The temperature dependence of these motions is weak. The apparent activation energy of the motions considered is less than 10 kJ/mol. The simulating results for PES are also reasonable considering the differences in structure compared with PES-C. The correlation times and the apparent activation energy obtained using the J. S. model for the main chain motion of PES-C are the same as those obtained using the damped orientational diffusion model and the conformational jump model.

NMR Spectra of polyimides: Interpretation and local chain motion study

Three kinds of high-performance polyimides 1 (poly(ketone-imide) PKI), 2 (poly(ether-imide) PEI) and 3 (poly(oxy-imide) POI) were studied using nuclear magnetic resonance (NMR). The NMR spectra of the polyimides were assigned according to the comprehensive consideration of the substitution effect of different substituting groups, viz. distortionless enhancement by polarization transfer (DEPT), no nuclear Overhauser effect (NNE), analysis of relaxation time, and two-dimensional correlated spectroscopy (COSY) techniques. The structural units of these three polyimides were determined. Carbon-13 and proton relaxation times for PEI and PKI were interpreted in terms of segmental motion characterized by the sharp cutoff model of Jones and Stockmayer (JS model) and anisotropic group rotation such as phenyl group rotation and methyl group rotation. Correlation times for the main-chain motion are in the tens of picosecond range which indicates the high flexibility of polyimide chains. Correlation times for phenyl group and methyl group rotations are more than 1 order of magnitude lower and approximately 1 order of magnitude higher than that of the main chain, respectively.

碳纳米管探针的制作方法研究

碳纳米管的小直径、高纵横比、高强度和高弹性、优良的耐磨损性能以及独特的电学和化学特性,使其成为高分辨率原子力显微镜的理想探针针尖。本文根据制作工艺的特点,综述现有碳纳米管探针的代表性研究和制作方法:组装式和生长式。组装式是通过手工、电场或磁场的方式将制备好的碳纳米管粘附到常规硅探针的末端;而生长式是在常规硅探针末端或悬臂梁上定点催化生长出一定直径和长度的CNT。最后指出这些方法目前存在的主要问题。

基于加速度传感器反馈控制的谐波驱动系统的研究

在机器人驱动中经常采用谐波传动。但谐波减速器的柔性、非线性摩擦、随速度波动、低阻尼等因素会给负载端带来振动 ,导致工作端的轨迹跟踪精度不高。为了抑制其振动 ,实现高精度轨迹跟踪控制 ,提出利用加速度传感器反馈控制来抑制负载端的振动、力矩干扰和动力学效应 ,提高其响应性能。理论分析和实验结果证实了提出方法的可行性。

谐波驱动系统的特性及控制策略研究

谐波传动有很多优点，在机器人驱动中经常被使用．但谐波传动也有一些缺点，如柔性等因素影响负载端轨迹跟踪精度．本文系统地分析了谐波传动系统的动力学特性，建立了包括电机转子惯量在内的动力学模型，疽对系统进行全面实验研究的基础上总结出谐波传动系统中存在的问题，采用相应的基于传感器的控制策略克服存在的问题，提高系统的响应性能．从理论分析和实验结果证实了提出方法的可行性。

金属粉末激光成形系统的研究

为了实现功能零件金属粉末激光快速成形的制备,研究开发了一套金属粉末激光成形系统。系统基于模块化设计思想,主要包括5个组成部分。每个模块既具备各自的特定功能,又相互协调来统一完成功能零件快速成形制备,而且系统具备高度柔性和自动控制的特点,使得操作与运转简单易行。

3-5岁幼儿认知灵活性的发展

To test preschoolers’ development of cognitive flexibility--an ability to solve a problem in one way and to then switch solution strategies, and the mechanism involved in the development, 3-5-year-olds are asked to perform switching tasks in which the experimenter manipulates the way the stimuli are presented: consecutive or simultaneous; the way the switching happens: between dimensions or within a dimension; the conceptual domains involved: shape, color, number and direction; the specific labels used. The main results of this work are presented below: (1) 3-5-year-olds’ cognitive flexibility develops with age, yet its development is not of the same speed in extra-dimensional switch tasks and inter-dimensional reversal tasks. 3-year-olds manifest some cognitive flexibility, but their performance is significantly worse than that of 4- and 5-year-olds. For the 3-year-olds, in reversal tasks, although 80% of the children passed the post-switch phrase in color task; less then 60% children passed the post-switch phrase in shape, number and direction tasks. In extra-dimensional tasks, 3-year-olds performance is worse than that in the reversal tasks. Less than 50% of the children passed the tasks. Children’s cognitive flexibility develops fast from 3-year-olds to 4-year-olds. Both 4-year-olds and 5-year-olds demonstrate high flexibility without significant difference between them. (2) Children’s flexibility in the conceptual domains of shape, color, number and direction follows different developing patterns. In inter-dimensional reversal tasks, 3-year-olds’ performance is not the same in the 4 conceptual domains, but the difference among the domains is insignificant in 4-and-5-year-olds. In extra-dimensional switching tasks, children’s performance on the 4 domain tasks is significantly different from one another in 3-, 4-, and 5-year-olds. (3) The way the stimuli are presented affects children’s development of cognitive flexibility. In inter-dimensional reversal tasks, 3-year-olds’ performance in consecutive presentation is significantly better than that in simultaneous presentation. 4- and 5-year-olds’ performance in the 2 presentations is not significantly different from each other. In extra-dimensional switch tasks, 3-, 4-, and 5-year-olds’ performance in the consecutive presentation is not significantly better than that in the simultaneous presentation (4) 3-, 4-, and 5-year-olds’ self-issued labeling aids their performance on the switching tasks. Children’ performance in the labeling condition is significantly better than that of no labeling. (5) 3-5-year-olds’ cognitive flexibility is highly correlated with their working memory and inhibition. Children’ development of cognitive flexibility is a process that involves activation of working memory and inhibition, in which the complexity of the task also plays a role.

Solid phase synthesis of Smac/DIABLO-derived peptides using a 'Safety-Catch' resin:Identification of potent XIAP BIR3 antagonists

The N-terminal sequence of the Smac/DIABLO protein is known to be involved in binding to the BIR3 domain of the anti-apoptotic proteins IAPs, antagonizing their action. Short peptides and peptide mimetics based on the first 4-residues of Smac/DIABLO have been demonstrated to re-sensitize resistant cancer cells, over-expressing IAPs, to apoptosis. Based on the well-defined structural basis for this interaction, a small focused library of C-terminal capped Smac/DIABLO-derived peptides was designed in silico using docking to the XIAP BIR3 domain. The top-ranked computational hits were conveniently synthesized employing Solid Phase Synthesis (SPS) on an alkane sulfonamide 'Safety-Catch' resin. This novel approach afforded the rapid synthesis of the target peptide library with high flexibility for the introduction of various C-terminal amide-capping groups. The library members were obtained in high yield (>65%) and purity (>85%), upon nucleophilic release from the activated resin by treatment with various amine nucleophiles. In vitro caspase-9 activity reconstitution assays of the peptides in the presence of the recombinant BIR3-domain of human XIAP (500nM) revealed N-methylalanyl-tertiarybutylglycinyl-4-(R)-phenoxyprolyl-N-biphenylmethyl carboxamide (11a) to be the most potent XIAP BIR3 antagonist of the series synthesized inducing 93% recovery of caspase-9 activity, when used at 1µM concentration. Compound (11a) also demonstrated moderate cytotoxicity against the breast cancer cell lines MDA-MB-231 and MCF-7, compared to the Smac/DIABLO-derived wild-type peptide sequences that were totally inactive in the same cell lines.