217 research outputs found

    The role of Kindlin-2 for early events in integrin activation and signaling

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    Effects of force load, muscle fatigue and extremely low frequency magnetic stimulation on EEG signals during side arm lateral raise task

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    Objective: This study was to quantitatively investigate the effects of force load, muscle fatigue and extremely low frequency (ELF) magnetic stimulation on electroencephalography (EEG) signal features during side arm lateral raise task. Approach: EEG signals were recorded by a BIOSEMI Active Two system with Pin-Type active-electrodes from 18 healthy subjects when they performed the right arm side lateral raise task (90° away from the body) with three different loads (0 kg, 1 kg and 3 kg; their order was randomized among the subjects) on the forearm. The arm maintained the loads until the subject felt exhausted. The first 10 s recording for each load was regarded as non-fatigue status and the last 10 s before the subject was exhausted as fatigue status. The subject was then given a 5 min resting between different loads. Two days later, the same experiment was performed on each subject except that ELF magnetic stimulation was applied to the subject's deltoid muscle during the 5 min resting period. EEG features from C3 and C4 electrodes including the power of alpha, beta and gamma and sample entropy were analyzed and compared between different loads, non-fatigue/fatigue status, and with/without ELF magnetic stimulation. Main results: The key results were associated with the change of the power of alpha band. From both C3-EEG and C4-EEG, with 1 kg and 3 kg force loads, the power of alpha band was significantly smaller than that from 0 kg for both non-fatigue and fatigue periods (all p    0.05 for all the force loads except C4-EEG with ELF simulation). The power of alpha band at fatigue status was significantly increased for both C3-EEG and C4-EEG when compared with the non-fatigue status (p    0.05, except between non-fatigue and fatigue with magnetic stimulation in gamma band of C3-EEG at 1 kg, and in the SampEn at 1 kg and 3 kg force loads from C4-EEG). Significance: Our study comprehensively quantified the effects of force, fatigue and the ELF magnetic stimulation on EEG features with difference forces, fatigue status and ELF magnetic stimulation

    State diagrams of the heart – a new approach to describing cardiac mechanics

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    <p>Abstract</p> <p>Background</p> <p>Cardiac time intervals have been described as a measure of cardiac performance, where prolongation, shortening and delay of the different time intervals have been evaluated as markers of cardiac dysfunction. A relatively recently developed method with improved ability to measure cardiac events is Tissue Doppler Imaging (TDI), allowing accurate measurement of myocardial movements.</p> <p>Methods</p> <p>We propose the state diagram of the heart as a new visualization tool for cardiac time intervals, presenting comparative, normalized data of systolic and diastolic performance, providing a more complete overview of cardiac function. This study aimed to test the feasibility of the state diagram method by presenting examples demonstrating its potential use in the clinical setting and by performing a clinical study, which included a comparison of the state diagram method with established echocardiography methods (E/E' ratio, LVEF and WMSI). The population in the clinical study consisted of seven patients with non ST-elevation myocardial infarction (NSTEMI) and seven control subjects, individually matched according to age and gender. The state diagram of the heart was generated from TDI curves from seven positions in the myocardium, visualizing the inter- and intraventricular function of the heart by displaying the cardiac phases.</p> <p>Results</p> <p>The clinical examples demonstrated that the state diagram allows for an intuitive visualization of pathological patterns as ischemia and dyssynchrony. Further, significant differences in percentage duration between the control group and the NSTEMI group were found in eight of the totally twenty phases (10 phases for each ventricle), e.g. in the transition phases (Pre-Ejection and Post-Ejection). These phases were significantly longer (> 2.18%) for the NSTEMI group than for the control group (p < 0.05). No significant differences between the groups were found for the established echocardiography methods.</p> <p>Conclusion</p> <p>The test results clearly indicate that the state diagram has potential to be an efficient tool for visualization of cardiac dysfunction and for detection of NSTEMI.</p

    Constructing a new understanding of the environment under postsocialism

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    This paper introduces a special grouping of papers on the theme of the environment and postsocialism. After the collapse of state socialism in Europe between 1989 and 1991, many immediate approaches to environmental reconstruction assumed that economic liberalisation and democratisation would alleviate problems. Since then, critics have argued that these proposed solutions were themselves problematic, and too closely reflected Western European and North American conceptions of environmental quality and democracy. The result has been a counterreaction focusing on detail and specificity at national levels and below. In this paper, we summarise debates about the environment and postsocialism since the period 1989 - 91. In particular, we examine whether an essentialistic link can be made between state socialism and environmental problems, and how far civil society -- or environmentalism -- may result in an improvement in perceived environmental quality. Finally, we consider the possibility for developing an approach to the environment and postsocialism that lies between crude generalisation and microscale studies

    Tumour cells expressing single VEGF isoforms display distinct growth, survival and migration characteristics

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    Vascular endothelial growth factor-A (VEGF) is produced by most cancer cells as multiple isoforms, which display distinct biological activities. VEGF plays an undisputed role in tumour growth, vascularisation and metastasis; nevertheless the functions of individual isoforms in these processes remain poorly understood. We investigated the effects of three main murine isoforms (VEGF188, 164 and 120) on tumour cell behaviour, using a panel of fibrosarcoma cells we developed that express them individually under endogenous promoter control. Fibrosarcomas expressing only VEGF188 (fs188) or wild type controls (fswt) were typically mesenchymal, formed ruffles and displayed strong matrix-binding activity. VEGF164- and VEGF120-producing cells (fs164 and fs120 respectively) were less typically mesenchymal, lacked ruffles but formed abundant cell-cell contacts. On 3D collagen, fs188 cells remained mesenchymal while fs164 and fs120 cells adopted rounded/amoeboid and a mix of rounded and elongated morphologies respectively. Consistent with their mesenchymal characteristics, fs188 cells migrated significantly faster than fs164 or fs120 cells on 2D surfaces while contractility inhibitors accelerated fs164 and fs120 cell migration. VEGF164/VEGF120 expression correlated with faster proliferation rates and lower levels of spontaneous apoptosis than VEGF188 expression. Nevertheless, VEGF188 was associated with constitutively active/phosphorylated AKT, ERK1/2 and Stat3 proteins. Differences in proliferation rates and apoptosis could be explained by defective signalling downstream of pAKT to FOXO and GSK3 in fs188 and fswt cells, which also correlated with p27/p21 cyclin-dependent kinase inhibitor over-expression. All cells expressed tyrosine kinase VEGF receptors, but these were not active/activatable suggesting that inherent differences between the cell lines are governed by endogenous VEGF isoform expression through complex interactions that are independent of tyrosine kinase receptor activation. VEGF isoforms are emerging as potential biomarkers for anti-VEGF therapies. Our results reveal novel roles of individual isoforms associated with cancer growth and metastasis and highlight the importance of understanding their diverse actions

    Principles of genetic circuit design

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    Cells navigate environments, communicate and build complex patterns by initiating gene expression in response to specific signals. Engineers seek to harness this capability to program cells to perform tasks or create chemicals and materials that match the complexity seen in nature. This Review describes new tools that aid the construction of genetic circuits. Circuit dynamics can be influenced by the choice of regulators and changed with expression 'tuning knobs'. We collate the failure modes encountered when assembling circuits, quantify their impact on performance and review mitigation efforts. Finally, we discuss the constraints that arise from circuits having to operate within a living cell. Collectively, better tools, well-characterized parts and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials.National Institute of General Medical Sciences (U.S.) (Grant P50 GM098792)National Institute of General Medical Sciences (U.S.) (Grant R01 GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (EEC0540879)Life Technologies, Inc. (A114510)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant 4500000552

    The 'ebb and flow' of transatlantic regulatory cooperation in banking

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    Do financial crises promote or hamper transatlantic regulatory cooperation in banking? This article argues that financial crises have an impact upon the alignment of regulatory preferences of the United States (US) and the European Union (EU), causing an 'ebb and flow' in transatlantic cooperation. When EU-US preferences are broadly aligned in periods of financial stability, transatlantic regulatory cooperation is intense. It is relatively easy for the EU and US to agree on market-friendly regulation promoted by banks. When preferences are different, especially in the context and aftermath of the exogenous shock of financial crises, transatlantic cooperation is more problematic because crises re-assert the importance of nationally embedded patterns of market organisation

    Synthetic biology approaches in drug discovery and pharmaceutical biotechnology

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    Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology
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