112 research outputs found
Drawing as transcription: how do graphical techniques inform interaction analysis?
This is an Open Access Article. It is published by Aarhus University Library under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/Drawing as a form of analytical inscription can provide researchers with highly flexible methods for exploring embodied interaction. Graphical techniques can combine spatial layouts, trajectories of action and anatomical detail, as well as rich descriptions of movement and temporal effects. This paper introduces some of the possibilities and challenges of adapting graphical techniques from life drawing and still life for interaction research. We demonstrate how many of these techniques are used in interaction research by illustrating the postural configurations and movements of participants in a ballet class. We then discuss a prototype software tool that is being developed to support interaction analysis specifically in the context of a collaborative data analysis session
Embodied Interactions with E-Textiles and the Internet of Sounds for Performing Arts
This paper presents initial steps towards the design of an embedded system for body-centric sonic performance. The proposed prototyping system allows performers to manipulate sounds through gestural interactions captured by textile wearable sensors. The e-textile sensor data control, in real-time, audio synthesis algorithms working with content from Audio Commons, a novel web-based ecosystem for repurposing crowd-sourced audio. The system enables creative embodied music interactions by combining seamless physical e-textiles with web-based digital audio technologies
Explaining the onset of cohabitation under semi-presidentialism
Semi-presidentialism – where the constitution provides for both a directly elected fixed-term president and a prime minister and cabinet collectively responsible to the legislature – is an increasingly common form of government. For many observers cohabitation is the Achilles heel of semi-presidentialism. This article aims to identify the conditions that are associated with the onset of cohabitation.We specify a number of hypotheses that predict the conditions under which cohabitation should occur.We then test our hypotheses on the basis of a new data set that records every case of cohabitation in all semi-presidential electoral democracies from 1989 to 2008 inclusive.We confirm that cohabi- tation is more likely to occur in countries with a premier-presidential form of semi-presidentialism and show that it is more likely to follow an election that occurs midway through a parliamentary or presidential term, and that when cohabitation follows a presidential election, it is likely to do so in a country where there is only a very weak president. Overall, we find that the conditions under which cohabitation is most likely to occur are also the ones where it is most easily managed. Thus, our findings imply that cohabitation is not likely to be as problematic as the existing literature would suggest
Biogenesis and transmembrane topology of the CHIP28 water channel at the endoplasmic reticulum.
CHIP28 is a 28-kD hydrophobic integral membrane protein that functions as a water channel in erythrocytes and renal tubule epithelial cell membranes. We examined the transmembrane topology of CHIP28 in the ER by engineering a reporter of translocation (derived from bovine prolactin) into nine sequential sites in the CHIP28 coding region. The resulting chimeras were expressed in Xenopus oocytes, and the topology of the reporter with respect to the ER membrane was determined by protease sensitivity. We found that although hydropathy analysis predicted up to seven potential transmembrane regions, CHIP28 spanned the membrane only four times. Two putative transmembrane helices, residues 52-68 and 143-157, reside on the lumenal and cytosolic surfaces of the ER membrane, respectively. Topology derived from these chimeric proteins was supported by cell-free translation of five truncated CHIP28 cDNAs, by N-linked glycosylation at an engineered consensus site in native CHIP28 (residue His69), and by epitope tagging of the CHIP28 amino terminus. Defined protein chimeras were used to identify internal sequences that direct events of CHIP28 topogenesis. A signal sequence located within the first 52 residues initiated nascent chain translocation into the ER lumen. A stop transfer sequence located in the hydrophobic region from residues 90-120 terminated ongoing translocation. A second internal signal sequence, residues 155-186, reinitiated translocation of a COOH-terminal domain (residues 186-210) into the ER lumen. Integration of the nascent chain into the ER membrane occurred after synthesis of 107 residues and required the presence of two membrane-spanning regions. From this data, we propose a structural model for CHIP28 at the ER membrane in which four membrane-spanning alpha-helices form a central aqueous channel through the lipid bilayer and create a pathway for water transport
From CFTR biology toward combinatorial pharmacotherapy:expanded classification of cystic fibrosis mutations
More than 2000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) have been described that confer a range of molecular cell biological and functional phenotypes. Most of these mutations lead to compromised anion conductance at the apical plasma membrane of secretory epithelia and cause cystic fibrosis (CF) with variable disease severity. Based on the molecular phenotypic complexity of CFTR mutants and their susceptibility to pharmacotherapy, it has been recognized that mutations may impose combinatorial defects in CFTR channel biology. This notion led to the conclusion that the combination of pharmacotherapies addressing single defects (e.g., transcription, translation, folding, and/or gating) may show improved clinical benefit over available low-efficacy monotherapies. Indeed, recent phase 3 clinical trials combining ivacaftor (a gating potentiator) and lumacaftor (a folding corrector) have proven efficacious in CF patients harboring the most common mutation (deletion of residue F508, ΔF508, or Phe508del). This drug combination was recently approved by the U.S. Food and Drug Administration for patients homozygous for ΔF508. Emerging studies of the structural, cell biological, and functional defects caused by rare mutations provide a new framework that reveals a mixture of deficiencies in different CFTR alleles. Establishment of a set of combinatorial categories of the previously defined basic defects in CF alleles will aid the design of even more efficacious therapeutic interventions for CF patients
GR-891: a novel 5-fluorouracil acyclonucleoside prodrug for differentiation therapy in rhabdomyosarcoma cells
Differentiation therapy provides an alternative treatment of cancer that overcomes the undesirable effects of classical chemotherapy, i.e. cytotoxicity and resistance to drugs. This new approach to cancer therapy focuses on the development of specific agents designed to selectively engage the process of terminal differentiation, leading to the elimination of tumorigenic cells and recovery of normal cell homeostasis. A series of new anti-cancer pyrimidine acyclonucleoside-like compounds were designed and synthesized by structural modifications of 5-fluorouracil, a drug which causes considerable cell toxicity and morbidity, and we evaluated their applicability for differentiation therapy in human rhabdomyosarcoma cells. We tested the pyrimidine derivative GR-891, (RS)-1-{[3-(2-hydroxyethoxy)-1-isopropoxy]propyl}-5-fluorouracil, an active drug which shows low toxicity in vivo and releases acrolein which is an aldehyde with anti-tumour activity. Both GR-891 and 5-fluorouracil caused time- and dose-dependent growth inhibition in vitro; however, GR-891 showed no cytotoxicity at low doses (22.5 μmol l−1 and 45 μmol l−1) and induced terminal myogenic differentiation in RD cells (a rhabdomyosarcoma cell line) treated for 6 days. Changes in morphological features and in protein organization indicated re-entry in the pathway of muscular maturation. Moreover, GR-891 increased adhesion capability mediated by the expression of fibronectin, and did not induce overexpression of P-glycoprotein, the mdr1 gene product, implicated in multidrug resistance. New acyclonucleoside-like compounds such as GR-891 have important potential advantages over 5-fluorouracil because of their lower toxicity and their ability to induce myogenic differentiation in rhabdomyosarcoma cells. Our results suggest that this drug may be useful for differentiation therapy in this type of tumour. 1999 Cancer Research Campaig
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