397 research outputs found
Conditions for Autonomy in the Information Society: Disentangling as a public service
An ambition for a democratic information society is providing services that maintain and even enhance citizensâ mastery and control of their life situation. Analyzing public services from a citizen autonomy perspective can indicate where the service and its IT-systems do not support user autonomy. We analyze a public service and discuss it as a sociomaterial entanglement. Based on our data on citizensâ use of a public service we identify a need to distinguish between entanglements and imbrications and suggest the notion of disentangling in order to characterize the way in which the public service advisors help the citizens. From at a design perspective we look for openings for change and improvement. Different types of entanglements need different types of competencies to address them. We make a distinction between entanglement and imbrication to open up a space for change. Finally, we discuss how the notion of disentangling tax issues can support citizen autonomy
How Can I Help You? A chatbotâs answers to citizensâ information needs
AI-based chatbots are becoming an increasingly common part of the front-line of public services. Through natural language, users can write simple queries to a chatbot which answers with appropriate information. We have investigated how a public chatbot operates in actual practice and how it answers the citizensâ questions about the rules and regulations for welfare benefits. We use the concept of citizensâ information needs to determine the quality of the chatbotâs answers. Information needs are often not formulated from the start as answerable questions. We analyse logs from chat sessions between the chatbot and the citizens, and focus on problems that arise, e.g., that the chatbot gives irrelevant answers or omits important information. The paper shows how the inner workings of the chatbot shapes the answerable questions. We conclude that responsible use of AI (such as chatbots) is a matter of design of the overall service and includes acknowledging that the AI itself can never be responsible
A staging scheme for the development of the moth midge Clogmia albipunctata.
Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from Public Library of Science via the DOI in this record.Model organisms, such as Drosophila melanogaster, allow us to address a wide range of biological questions with experimental rigour. However, studies in model species need to be complemented by comparative studies if we are to fully understand the functional properties and evolutionary history of developmental processes. The establishment of new model organisms is crucial for this purpose. One of the first essential steps to establish a species as an experimental model is to carefully describe its life cycle and development. The resulting staging scheme serves as a framework for molecular studies, and allows us to homologise developmental processes between species. In this paper, we have characterised the life cycle and development of an emerging non-drosophilid dipteran model system: the moth midge Clogmia albipunctata. In particular, we focus on early embryogenesis (cleavage and blastoderm cycles before gastrulation), on formation and retraction of extraembryonic tissues, and on formation of the germ line. Considering the large evolutionary distance between the two species (approximately 250 million years), we find that the development of C. albipunctata is remarkably conserved compared to D. melanogaster. On the other hand, we detect significant differences in morphology and timing affecting the development of extraembryonic tissues and the germ line. Moreover, C. albipunctata shows several heterochronic shifts, and lacks head involution and associated processes during late stages of development.The laboratory of Johannes Jaeger and this study in particular was funded by the MEC-EMBL agreement for the EMBL/CRG Research Unit in Systems Biology, by SGR grant 406 from the Catalan funding agency AGAUR, by grants BFU2009-10184 & BFU2012-33775 from the Spanish Ministry of Science (MICINN, now called MINECO), and by ERANet: ERASysBio+ grant EUI2009-04045 (MODHEART). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
A staging scheme for the development of the scuttle fly Megaselia abdita
This is the final version of the article. Available from the publisher via the DOI in this record.Model organisms, such as Drosophila melanogaster, provide powerful experimental tools for the study of development. However, approaches using model systems need to be complemented by comparative studies for us to gain a deeper understanding of the functional properties and evolution of developmental processes. New model organisms need to be established to enable such comparative work. The establishment of new model system requires a detailed description of its life cycle and development. The resulting staging scheme is essential for providing morphological context for molecular studies, and allows us to homologise developmental processes between species. In this paper, we provide a staging scheme and morphological characterisation of the life cycle for an emerging non-drosophilid dipteran model system: the scuttle fly Megaselia abdita. We pay particular attention to early embryogenesis (cleavage and blastoderm stages up to gastrulation), the formation and retraction of extraembryonic tissues, and the determination and formation of germ (pole) cells. Despite the large evolutionary distance between the two species (approximately 150 million years), we find that M. abdita development is remarkably similar to D. melanogaster in terms of developmental landmarks and their relative timing.Funding: The laboratory of Johannes Jaeger and this study in particular was funded by the MEC-EMBL agreement for the EMBL/CRG Research Unit in Systems
Biology, by SGR grant 406 from the Catalan funding agency AGAUR, by grants BFU2009-10184 & BFU2012-33775 from the Spanish Ministry of Science (MICINN,
now called MINECO), and by ERANet: ERASysBio+ grant EUI2009-04045 (MODHEART). The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript
Noise Minimization in Eukaryotic Gene Expression
All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or ânoise.â Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection
Strengthening Human Autonomy. In the era of autonomous technology
âAutonomous technologiesâ refers to systems that make decisions without explicit human control or interaction. This conceptual paper explores the notion of autonomy by first exploring human autonomy, and then using this understanding to analyze how autonomous technology could or should be modelled. First, we discuss what human autonomy means. We conclude that it is the overall space for actionârather than the degree of controlâand the actual choices, or number of choices, that constitutes human autonomy. Based on this, our second discussion leads us to suggest the term datanomous to denote technology that builds on, and is restricted by, its own data when operating autonomously. Our conceptual exploration brings forth a more precise definition of human autonomy and datanomous systems. Finally, we conclude this exploration by suggesting that human autonomy can be strengthened by datanomous technologies, but only if they support the human space for action. It is the purpose of human activity that determines if technology strengthens or weakens human autonomy
Replacing red and processed meat with lean or fatty fish and all-cause and cause specific mortality in Norwegian women. the Norwegian Women and Cancer Study (NOWAC): A prospective cohort study
Nordic Nutrition Recommendations recommend reducing red and processed meat and increasing fish consumption, but the impact of this
replacement on mortality is understudied. This study investigated the replacement of red and processed meat with fish in relation to mortality. Of
83 304 women in the Norwegian Women and Cancer Study (NOWAC) study, 9420 died during a median of 21·0 years of follow-up. The hazard
ratios (HR) for mortality were estimated using Cox proportional hazards regression with analyses stratified on red and processed meat intake due
to non-linearity. Higher processed meat (> 30 g/d), red and processed meat (> 50 g/d), and fatty fish consumption were associated with higher
mortality, while red meat and lean fish consumption were neutral or beneficial. Among women with higher processed meat intake (> 30 g/d),
replacing 20 g/d with lean fish was associated with lower all-cause (HR 0·92, 95 % CI 0·89, 0·96), cancer (HR 0·92, 95 % CI 0·88, 0·97) and CVD
mortality (HR 0·82, 95 % CI 0·74, 0·90), while replacing with fatty fish was associated with lower CVD mortality (HR 0·87, 95 % CI 0·77, 0·97), but
not with all-cause or cancer mortality. Replacing processed meat with fish among women with lower processed meat intake (†30 g/d) or
replacing red meat with fish was not associated with mortality. Replacing processed meat with lean or fatty fish may lower the risk of premature
deaths in Norwegian women, but only in women with high intake of processed meat. These findings suggest that interventions to reduce
processed meat intake should target high consumers
Progression of Interstitial Fibrosis and Tubular Atrophy in Low Immunological Risk Renal Transplants Monitored by Sequential Surveillance Biopsies : The Influence of TAC Exposure and Metabolism
The combination of tacrolimus (TAC) and mycophenolate is the most widely employed maintenance immunosuppression in renal transplants. Different surrogates of tacrolimus exposure or metabolism such as tacrolimus trough levels (TAC-C), coefficient of variation of tacrolimus (CV-TAC-C), time in therapeutic range (TTR), and tacrolimus concentration dose ratio (C/D) have been associated with graft outcomes. We explore in a cohort of low immunological risk renal transplants (n = 85) treated with TAC, mycophenolate mofetil (MMF), and steroids and then monitored by paired surveillance biopsies the association between histological lesions and TAC-C at the time of biopsy as well as CV-TAC-C, TTR, and C/D during follow up. Interstitial inflammation (i-Banff score â„ 1) in the first surveillance biopsy was associated with TAC-C (odds ratio (OR): 0.69, 95% confidence interval (CI): 0.50-0.96; p = 0.027). In the second surveillance biopsy, inflammation was associated with time below the therapeutic range (OR: 1.05 and 95% CI: 1.01-1.10; p = 0.023). Interstitial inflammation in scarred areas (i-IFTA score â„ 1) was not associated with surrogates of TAC exposure/metabolism. Progression of interstitial fibrosis/tubular atrophy (IF/TA) was observed in 35 cases (41.2%). Multivariate regression logistic analysis showed that mean C/D (OR: 0.48; 95% CI: 0.25-0.92; p = 0.026) and IF/TA in the first biopsy (OR: 0.43, 95% CI: 0.24-0.77, p = 0.005) were associated with IF/TA progression between biopsies. A low C/D ratio is associated with IF/TA progression, suggesting that TAC nephrotoxicity may contribute to fibrosis progression in well immunosuppressed patients. Our data support that TAC exposure is associated with inflammation in healthy kidney areas but not in scarred tissu
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Systematic Exploration of Synergistic Drug Pairs
Drug synergy allows a therapeutic effect to be achieved with lower doses of component drugs. Drug synergy can result when drugs target the products of genes that act in parallel pathways (âspeciïŹc synergyâ). Such cases of drug synergy should tend to correspond to synergistic genetic interaction between the corresponding target genes. Alternatively, âpromiscuous synergyâ can arise when one drug non-speciïŹcally increases the effects of many other drugs, for example, by increased bioavailability. To assess the relative abundance of these drug synergy types, we examined 200 pairs of antifungal drugs in S. cerevisiae. We found 38 antifungal synergies, 37 of which were novel. While 14 cases of drug synergy corresponded to genetic interaction, 92% of the synergies we discovered involved only six frequently synergistic drugs. Although promiscuity of four drugs can be explained under the bioavailability model, the promiscuity of Tacrolimus and Pentamidine was completely unexpected. While many drug synergies correspond to genetic interactions, the majority of drug synergies appear to result from non-speciïŹc promiscuous synergy
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