Human-Computer Interaction with older people through ethnographical lenses: everyday interactions with ICT

Report for the scientific sojourn carried out at the School of Computing of the University of Dundee, United Kingdom, from 2010 to 2012. This document is a scientific report of the work done, main results, publications and accomplishment of the objectives of the 2-year post-doctoral research project with reference number BP-A 00239. The project has addressed the topic of older people (60+) and Information and Communication Technologies (ICT), which is a topic of growing social and research interest, from a Human-Computer Interaction perspective. Over a 2-year period (June 2010-June 2012), we have conducted classical ethnography of ICT use in a computer clubhouse in Scotland, addressing interaction barriers and strategies, social sharing practices in Social Network Sites, and ICT learning, and carried out rapid ethnographical studies related to geo-enabled ICT and e-government services towards supporting independent living and active ageing. The main results have provided a much deeper understanding of (i) the everyday use of Computer-Mediated Communication tools, such as video-chats and blogs, and its evolution as older people’s experience with ICT increases over time, (ii) cross-cultural aspects of ICT use in the north and south of Europe, (iii) the relevance of cognition over vision in interacting with geographical information and a wide range of ICT tools, despite common stereotypes (e.g. make things bigger), (iv) the important relationship offline-online to provide older people with socially inclusive and meaningful eservices for independent living and active ageing, (v) how older people carry out social sharing practices in the popular YouTube, (vi) their user experiences and (vii) the challenges they face in ICT learning and the strategies they use to become successful ICT learners over time. The research conducted in this project has been published in 17 papers, 4 in journals – two of which in JCR, 5 in conferences, 4 in workshops and 4 in magazines. Other public output consists of 10 invited talks and seminars.

Auditory-visual multisensory interactions in humans: timing, topography, directionality, and sources.

Current models of brain organization include multisensory interactions at early processing stages and within low-level, including primary, cortices. Embracing this model with regard to auditory-visual (AV) interactions in humans remains problematic. Controversy surrounds the application of an additive model to the analysis of event-related potentials (ERPs), and conventional ERP analysis methods have yielded discordant latencies of effects and permitted limited neurophysiologic interpretability. While hemodynamic imaging and transcranial magnetic stimulation studies provide general support for the above model, the precise timing, superadditive/subadditive directionality, topographic stability, and sources remain unresolved. We recorded ERPs in humans to attended, but task-irrelevant stimuli that did not require an overt motor response, thereby circumventing paradigmatic caveats. We applied novel ERP signal analysis methods to provide details concerning the likely bases of AV interactions. First, nonlinear interactions occur at 60-95 ms after stimulus and are the consequence of topographic, rather than pure strength, modulations in the ERP. AV stimuli engage distinct configurations of intracranial generators, rather than simply modulating the amplitude of unisensory responses. Second, source estimations (and statistical analyses thereof) identified primary visual, primary auditory, and posterior superior temporal regions as mediating these effects. Finally, scalar values of current densities in all of these regions exhibited functionally coupled, subadditive nonlinear effects, a pattern increasingly consistent with the mounting evidence in nonhuman primates. In these ways, we demonstrate how neurophysiologic bases of multisensory interactions can be noninvasively identified in humans, allowing for a synthesis across imaging methods on the one hand and species on the other.

T-Cell Receptors Binding Orientation over Peptide/MHC Class I Is Driven by Long-Range Interactions.

Crystallographic data about T-Cell Receptor - peptide - major histocompatibility complex class I (TCRpMHC) interaction have revealed extremely diverse TCR binding modes triggering antigen recognition. Understanding the molecular basis that governs TCR orientation over pMHC is still a considerable challenge. We present a simplified rigid approach applied on all non-redundant TCRpMHC crystal structures available. The CHARMM force field in combination with the FACTS implicit solvation model is used to study the role of long-distance interactions between the TCR and pMHC. We demonstrate that the sum of the coulomb interactions and the electrostatic solvation energies is sufficient to identify two orientations corresponding to energetic minima at 0° and 180° from the native orientation. Interestingly, these results are shown to be robust upon small structural variations of the TCR such as changes induced by Molecular Dynamics simulations, suggesting that shape complementarity is not required to obtain a reliable signal. Accurate energy minima are also identified by confronting unbound TCR crystal structures to pMHC. Furthermore, we decompose the electrostatic energy into residue contributions to estimate their role in the overall orientation. Results show that most of the driving force leading to the formation of the complex is defined by CDR1,2/MHC interactions. This long-distance contribution appears to be independent from the binding process itself, since it is reliably identified without considering neither short-range energy terms nor CDR induced fit upon binding. Ultimately, we present an attempt to predict the TCR/pMHC binding mode for a TCR structure obtained by homology modeling. The simplicity of the approach and the absence of any fitted parameters make it also easily applicable to other types of macromolecular protein complexes.

Repression and Protest Structural Models and Strategic Interactions

The recent wave of upheavals and revolts in Northern Africa and the Middle East goes back to an old question often raised by theories of collective action: does repression act as a negative or positive incentive for further mobilization? Through a review of the vast literature devoted to this question, this article aims to go beyond theoretical and methodological dead-ends. The article moves on to non-Western settings in order to better understand, via a macro-sociological and dynamic approach, the causal effects between mobilizations and repression. It pleads for a meso- and micro-level approach to this issue: an approach that puts analytical emphasis both on protest organizations and on individual activists' careers.

Size-dependent predation by Dugesia lugubris (Turbellaria) on Physa acuta (Gastropoda): experiments and model

1. We investigated experimentally predation by the flatworm Dugesia lugubris on the snail Physa acuta in relation to predator body length and to prey morphology [shell length (SL) and aperture width (AW)]. 2. SL and AW correlate strongly in the field, but display significant and independent variance among populations. In the laboratory, predation by Dugesia resulted in large and significant selection differentials on both SL and AW. Analysis of partial effects suggests that selection on AW was indirect, and mediated through its strong correlation with SL. 3. The probability P(ij) for a snail of size category i (SL) to be preyed upon by a flatworm of size category j was fitted with a Poisson-probability distribution, the mean of which increased linearly with predator size (i). Despite the low number of parameters, the fit was excellent (r2 = 0.96). We offer brief biological interpretations of this relationship with reference to optimal foraging theory. 4. The largest size class of Dugesia (>2 cm) did not prey on snails larger than 7 mm shell length. This size threshold might offer Physa a refuge against flatworm predation and thereby allow coexistence in the field. 5. Our results are further discussed with respect to previous field and laboratory observations on P acuta life-history patterns, in particular its phenotypic variance in adult body size.

Prediction of enzyme function by combining sequence similarity and protein interactions

Background: A number of studies have used protein interaction data alone for protein function prediction. Here, we introduce a computational approach for annotation of enzymes, based on the observation that similar protein sequences are more likely to perform the same function if they share similar interacting partners. Results: The method has been tested against the PSI-BLAST program using a set of 3,890 protein sequences from which interaction data was available. For protein sequences that align with at least 40% sequence identity to a known enzyme, the specificity of our method in predicting the first three EC digits increased from 80% to 90% at 80% coverage when compared to PSI-BLAST. Conclusion: Our method can also be used in proteins for which homologous sequences with known interacting partners can be detected. Thus, our method could increase 10% the specificity of genome-wide enzyme predictions based on sequence matching by PSI-BLAST alone.

The role of biotic interactions in shaping distributions and realised assemblages of species: implications for species distribution modelling.

Predicting which species will occur together in the future, and where, remains one of the greatest challenges in ecology, and requires a sound understanding of how the abiotic and biotic environments interact with dispersal processes and history across scales. Biotic interactions and their dynamics influence species' relationships to climate, and this also has important implications for predicting future distributions of species. It is already well accepted that biotic interactions shape species' spatial distributions at local spatial extents, but the role of these interactions beyond local extents (e.g. 10 km(2) to global extents) are usually dismissed as unimportant. In this review we consolidate evidence for how biotic interactions shape species distributions beyond local extents and review methods for integrating biotic interactions into species distribution modelling tools. Drawing upon evidence from contemporary and palaeoecological studies of individual species ranges, functional groups, and species richness patterns, we show that biotic interactions have clearly left their mark on species distributions and realised assemblages of species across all spatial extents. We demonstrate this with examples from within and across trophic groups. A range of species distribution modelling tools is available to quantify species environmental relationships and predict species occurrence, such as: (i) integrating pairwise dependencies, (ii) using integrative predictors, and (iii) hybridising species distribution models (SDMs) with dynamic models. These methods have typically only been applied to interacting pairs of species at a single time, require a priori ecological knowledge about which species interact, and due to data paucity must assume that biotic interactions are constant in space and time. To better inform the future development of these models across spatial scales, we call for accelerated collection of spatially and temporally explicit species data. Ideally, these data should be sampled to reflect variation in the underlying environment across large spatial extents, and at fine spatial resolution. Simplified ecosystems where there are relatively few interacting species and sometimes a wealth of existing ecosystem monitoring data (e.g. arctic, alpine or island habitats) offer settings where the development of modelling tools that account for biotic interactions may be less difficult than elsewhere.

Interactions of Adeno-associated virus Rep78 protein with the host cell

Abstract : Adeno-associated virus (AAV) is a small DNA virus belonging to the familiy of Parvoviridae. Its genome contains two genes : the rep gene encoding four non structural proteins (Rep78, 68, 52 and 40) implicated in transcription, replication and site-specific integration of the viral DNA and the cap gene encoding three capsid proteins. AAV does not cause any disease, but is studied in view of its potential use to treat several diseases. An interesting property of AAV is its antiproliferative effect. Two elements of AAV can inhibit cell growth. Firstly, the single stranded viral DNA is recognized in cells as damaged DNA leading to either a G2 block or cell death depending on p53 status. Secondly, the two larger Rep proteins (Rep78 and 68) also arrest the cell cycle when they are expressed at high levels. Rep78 in particular induces a complete cell cycle arrest in all the phases, including S phase. Such a strong S phase arrest is rarely seen in other conditions. It was thus interesting to determine how Rep78 could induce it. We found that this strong block is the consequence of Rep78's effects on at least two pathways. Rep78 induces a DNA damage response by producing nicks in the cellular chromatin. Furthermore, Rep78 can bind to the cellular phosphatase Cdc25A and prevent its binding to its substrates CDK2 and CDK1, thus inhibiting its activity. A mutational analysis of Rep78 protein determined that its endonuclease activity is responsible for the DNA damage response and its zinc finger domain for Cdc25A inhibition. The combined expression of two mutants each defective for one of these activities, or these two activities obtained independently of Rep78, could restore the complete cell cycle block, indicating that these two effects of Rep78 are likely to explain completely the cell cycle block it induces. Secondly, the lack of pathogenicity of AAV, its broad range of infection and its ability to integrate site-specifically in human chromosome 19 make it an interesting potential vector for gene therapy. However site-specific integration is only possible in the presence of Rep78/68 whose gene is removed in recombinant AAV vectors. In this part of the study, we tried to introduce Rep protein separately from recombinant AAV vectors to promote their site-specific integration. For that purpose, a fusion protein, TAT-Rep, comprising Rep78/68 joined to the human immunodeficiency virus Tat protein was produced. It had the ability to enter cells and remain active there for a short period. Its activity was sufficient to mediate transcription from the p5 promoter, second-strand synthesis of a recombinant AAV and probably site-specific integration. Résumé : Le virus associé à l'adénovirus (AAV) est un petit virus à ADN qui fait partie de la famille des Parvoviridae. Son génome contient deux gènes : le gène rep code pour quatre protéines (Rep78, 68, 52 et 40) qui participent à la transcription, la réplication et l'intégration du virus et le gène cap code pour les trois protéines de capside. AAV ne produit pas de maladie, mais pourrait au contraire être utilisé pour en soigner. Sa bénignité, sa capacité à infecter différents types de cellules et son intégration spécifique en font un vecteur potentiel pour la thérapie génique. Pour qu'il puisse s'intégrer spécifiquement, il a besoin de la protéine Rep78 ou 68, mais ce gène doit être enlevé des vecteurs pour la thérapie génique. Le but de la première partie de cette étude était d'introduire Rep78 ou 68 dans des cellules en même temps qu'un AAV recombinant, mais indépendamment afin de permettre une intégration spécifique. La stratégie utilisée était de produire une protéine de fusion (TAT-Rep) qui peut entrer dans des cellules si elle est présente dans leur milieu. Cette protéine entrait bien dans les cellules et y était active favorisant ainsi l'intégration spécifique. Une deuxième propriété d'AAV, son effet anti-prolifératif, est intéressante dans le cadre de certaines maladies comme le cancer. Deux éléments d'AAV en sont responsables. D'abord, son ADN simple brin active une réponse cellulaire à l'ADN endommagé et arrête les cellules en G2 ou provoque leur mort. De plus, la protéine Rep78 d'AAV peut fortement bloquer le cycle cellulaire à toutes les phases, même en phase S, ce qui est rare. C'est pourquoi nous avons essayé de comprendre cet effet. Nous avons remarqué que Rep78 doit agir sur deux fronts pour obtenir ce fort bloc. D'un côté, Rep78 introduit des coupures simple brin sur l'ADN de la cellule ce qui active une réponse cellulaire à l'ADN endommagé qui passe par ATM. D'un autre côté, Rep78 lie une phosphatase cellulaire, Cdc25A, et l'empêche ainsi de lier ses substrats CDK2 et CDK1 et donc d'être active. Finalement, à l'aide de mutants de Rep78, nous avons déterminé que l'activité endonuclease de Rep78 était nécessaire pour induire une réponse cellulaire via ATM et que le domaine C-terminal appelé «zinc finger » était responsable de la liaison avec Cdc25A. En co-exprimant deux mutants, qui n'ont chacun qu'un des effets de Rep78, ou en obtenant les deux effets de Rep78 indépendamment d'elle, nous avons obtenu un bloc complet du cycle cellulaire similaire à celui obtenu avec Rep78. Il est donc probable que ces deux effets de Rep78 sont suffisants pour expliquer comment elle arrive à arrêter le cycle cellulaire si efficacement.

Reputation based on punishment rather than generosity allows for evolution of cooperation in sizable groups

Cooperation among unrelated individuals can arise if decisions to help others can be based on reputation. While working for dyadic interactions, reputation-use in social dilemmas involving many individuals (e.g. public goods games) becomes increasingly difficult as groups become larger and errors more frequent. Reputation is therefore believed to have played a minor role for the evolution of cooperation in collective action dilemmas such as those faced by early humans. Here, we show in computer simulations that a reputation system based on punitive actions can overcome these problems and, compared to reputation system based on generous actions, (i) is more likely to lead to the evolution of cooperation in sizable groups, (ii) more effectively sustains cooperation within larger groups, and (iii) is more robust to errors in reputation assessment. Punishment and punishment reputation could therefore have played crucial roles in the evolution of cooperation within larger groups of humans.

Genetic interactions in the control of septation in Schizosaccharomyces pombe.

We have used genetic and molecular techniques to investigate the interactions among genes required for the initiation and regulation of septum formation in Schizosaccharomyces pombe. Our data suggest that the products of the cdc7, cdc11, cdc14 and cdc16 genes interact. These activities may regulate the function of the cdc15 gene product. A model for the control of septation in fission yeast is presented.

Tools and techniques to study ligand-receptor interactions and receptor activation by TNF superfamily members.

Ligands and receptors of the TNF superfamily are therapeutically relevant targets in a wide range of human diseases. This chapter describes assays based on ELISA, immunoprecipitation, FACS, and reporter cell lines to monitor interactions of tagged receptors and ligands in both soluble and membrane-bound forms using unified detection techniques. A reporter cell assay that is sensitive to ligand oligomerization can identify ligands with high probability of being active on endogenous receptors. Several assays are also suitable to measure the activity of agonist or antagonist antibodies, or to detect interactions with proteoglycans. Finally, self-interaction of membrane-bound receptors can be evidenced using a FRET-based assay. This panel of methods provides a large degree of flexibility to address questions related to the specificity, activation, or inhibition of TNF-TNF receptor interactions in independent assay systems, but does not substitute for further tests in physiologically relevant conditions.

Prevalence of comedications and effect of potential drug-drug interactions in the Swiss HIV Cohort Study.

BACKGROUND: Potential drug-drug interactions (PDDIs) might expand with new combination antiretroviral therapies (ART) and polypharmacy related to increasing age and comorbidities. We investigated the prevalence of comedications and PDDIs within a large HIV cohort, and their effect on ART efficacy and tolerability. METHODS: All medications were prospectively recorded in 1,497 ART-treated patients and screened for PDDIs using a customized version of the Liverpool drug interactions database. RESULTS: Overall, 68% (1,013/1,497) of patients had a comedication and 40% (599/1,497) had > or = 1 PDDI. Among patients with comedication, 2% (21/1,013) had red-flag interactions (contraindicated) and 59% (597/1,013) had orange-flag interactions (potential dose adjustment and/or close monitoring required). The latter involved mainly central nervous system drugs (49%), cardiovascular drugs (34%) and methadone (19%). In the multivariate analysis, factors associated with having a comedication were advanced age, female gender, obesity and HCV infection. Independent risk factors for PDDIs were regimens combining protease inhibitors and non-nucleoside reverse transcriptase inhibitors (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.44-6.48), > or = 2 comedications (OR 1.89, 95% CI 1.32-2.70), current illicit drug use (OR 2.00, 95% CI 1.29-3.10) and patients with HCV infection (OR 1.74, 95% CI 1.19-2.56). Viral response was similar in patients with and without PDDIs (84.5% versus 86.4%; P=0.386). During follow-up, ART was modified in 134 patients with comedication regardless of the presence of PDDIs (P=0.524). CONCLUSIONS: PDDIs increase with complex ART and comorbidities. No adverse effect was noted on ART efficacy or tolerability; however, most PDDIs affected comedication but were manageable through dose adjustment or monitoring.