Is There a Causal Association between Genotoxicity and the Imposex Effect?

There is a growing body of evidence that indicates common environmental pollutants are capable of disrupting reproductive and developmental processes by interfering with the actions of endogenous hormones. Many reports of endocrine disruption describe changes in the normal development of organs and tissues that are consistent with genetic damage, and recent studies confirm that many chemicals classified to have hormone-modulating effects also possess carcinogenic and mutagenic potential. To date, however, there have been no conclusive examples linking genetic damage with perturbation of endocrine function and adverse effects in vivo. Here, we provide the first evidence of DNA damage associated with the development of imposex (the masculinization of female gastropods considered to be the result of alterations to endocrine-mediated pathways) in the dog-whelk Nucella lapillus. Animals (n = 257) that displayed various stages of tributyltin (TBT)-induced imposex were collected from sites in southwest England, and their imposex status was determined by physical examination. Linear regression analysis revealed a very strong relationship (correlation coefficient of 0.935, p < 0.0001) between the degree of imposex and the extent of DNA damage (micronucleus formation) in hemocytes. Moreover, histological examination of a larger number of dog-whelks collected from sites throughout Europe confirmed the presence of hyperplastic growths, primarily on the vas deferens and penis in both TBT-exposed male snails and in females that exhibited imposex. A strong association was found between TBT body burden and the prevalence of abnormal growths, thereby providing compelling evidence to support the hypothesis that environmental chemicals that affect reproductive processes do so partly through DNA damage pathways

Focused Deterrence and the Prevention of Violent Gun Injuries: Practice, Theoretical Principles, and Scientific Evidence

Focused deterrence strategies are a relatively new addition to a growing portfolio of evidence-based violent gun injury prevention practices available to policy makers and practitioners. These strategies seek to change offender behavior by understanding the underlying violence-producing dynamics and conditions that sustain recurring violent gun injury problems and by implementing a blended strategy of law enforcement, community mobilization, and social service actions. Consistent with documented public health practice, the focused deterrence approach identifies underlying risk factors and causes of recurring violent gun injury problems, develops tailored responses to these underlying conditions, and measures the impact of implemented interventions. This article reviews the practice, theoretical principles, and evaluation evidence on focused deterrence strategies. Although more rigorous randomized studies are needed, the available empirical evidence suggests that these strategies generate noteworthy gun violence reduction impacts and should be part of a broader portfolio of violence prevention strategies available to policy makers and practitioners

Statistical Power of Model Selection Strategies for Genome-Wide Association Studies

Genome-wide association studies (GWAS) aim to identify genetic variants related to diseases by examining the associations between phenotypes and hundreds of thousands of genotyped markers. Because many genes are potentially involved in common diseases and a large number of markers are analyzed, it is crucial to devise an effective strategy to identify truly associated variants that have individual and/or interactive effects, while controlling false positives at the desired level. Although a number of model selection methods have been proposed in the literature, including marginal search, exhaustive search, and forward search, their relative performance has only been evaluated through limited simulations due to the lack of an analytical approach to calculating the power of these methods. This article develops a novel statistical approach for power calculation, derives accurate formulas for the power of different model selection strategies, and then uses the formulas to evaluate and compare these strategies in genetic model spaces. In contrast to previous studies, our theoretical framework allows for random genotypes, correlations among test statistics, and a false-positive control based on GWAS practice. After the accuracy of our analytical results is validated through simulations, they are utilized to systematically evaluate and compare the performance of these strategies in a wide class of genetic models. For a specific genetic model, our results clearly reveal how different factors, such as effect size, allele frequency, and interaction, jointly affect the statistical power of each strategy. An example is provided for the application of our approach to empirical research. The statistical approach used in our derivations is general and can be employed to address the model selection problems in other random predictor settings. We have developed an R package markerSearchPower to implement our formulas, which can be downloaded from the Comprehensive R Archive Network (CRAN) or http://bioinformatics.med.yale.edu/group/

Automating unobtrusive personalized services in ambient media environments

The final publication is available at Springer via http://dx.doi.org/10.1007/s11042-013-1634-2In the age of ambient media, people are surrounded by lots of physical objects (media objects) for rendering the digital world in the natural environment. These media objects should interact with users in a way that is not disturbing for them. To address this issue, this work presents a design and automation strategy for augmenting the world around us with personalized ambient media services that behave in a considerate manner. That is, ambient services are capable of adjusting its obtrusiveness level (i.e., the extent to which each service intrudes the user¿s mind) by using the appropriate media objects for each user¿s situation.This work has been developed with the support of MICINN, under the project EVERYWARE TIN2010-18011, and the support of the Christian Doppler Forschungsgesellschaft and the BMWFJ, Austria.Serral Asensio, E.; Gil Pascual, M.; Valderas Aranda, PJ.; Pelechano Ferragud, V. (2014). Automating unobtrusive personalized services in ambient media environments. Multimedia Tools and Applications. 71(1):159-178. https://doi.org/10.1007/s11042-013-1634-2S159178711Bencomo N, Grace P, Flores-Cortés CA, Hughes D, Blair GS (2008) Genie: supporting the model driven development of reflective, component-based adaptive systems. In: ICSE, pp 811–814Blumendorf M, Lehmann G, Albayrak S (2010) Bridging models and systems at runtime to build adaptive user interfaces. In: Proc. of EICS 2010. ACM, pp 9–18Brown DM (2010) Communicating design: developing web site documentation for design and planning, 2nd edn. New Riders PressCalinescu R (2011) When the requirements for adaptation and high integrity meet. In: Proceedings of the 8th workshop on assurances for self-adaptive systems, ASAS ’11. ACM, New York, pp 1–4Filieri A, Ghezzi C, Tamburrelli G (2011) Run-time efficient probabilistic model checking. In: Proceedings of the 33rd International Conference on Software Engineering, ICSE ’11. ACM, New York, pp 341–350Gershenfeld N, Krikorian R, Cohen D (2004) The internet of things. Sci Am 291(4):46–51Gibbs WW (2005) Considerate computing. Sci Am 292(1):54–61Gulliksen J, Goransson B, Boivie I, Blomkvist S, Persson J, Cajander A (2003) Key principles for user-centred systems design. Behav Inform Technol 22:397–409Hinckley K, Horvitz E (2001) Toward more sensitive mobile phones. In: Proc. of the UIST ’01, pp 191–192Ho J, Intille SS (2005) Using context-aware computing to reduce the perceived burden of interruptions from mobile devices. In: Proc. of CHI ’05. ACM, pp 909–918Horvitz E, Kadie C, Paek T, Hovel D (2003) Models of attention in computing and communication: from principles to applications. Commun ACM 46:52–59Ju W, Leifer L (2008) The design of implicit interactions: making interactive systems less obnoxious. Des Issues 24(3):72–84Kortuem G, Kawsar F, Fitton D, Sundramoorthy V (2010) Smart objects as building blocks for the internet of things. IEEE Internet Comput 14(1):44–51Lewis JR (1995) Ibm computer usability satisfaction questionnaires: psychometric evaluation and instructions for use. Int J Hum Comput Interact 7(1):57–78Lugmayr A, Risse T, Stockleben B, Laurila K, Kaario J (2009) Semantic ambient media—an introduction. Multimed Tools Appl 43(3):337–359Mattern F (2003) From smart devices to smart everyday objects. In: Proc. Smart Objects Conf. (SOC 03). Springer, pp 15–16Morin B, Barais O, Jezequel JM, Fleurey F, Solberg A (2009) Models run.time to support dynamic adaptation. Comput 42(10):44–51Nelson L, Churchill EF (2005) User experience of physical-digital object systems: implications for representation and infrastructure. Paper presented at smart object systems workshop, in cojunction with ubicomp 2005Paternò F (2002) Concurtasktrees: an engineered approach to model-based design of interactive systems. In: L.E. Associates (ed) The handbook of analysis for human-computer interaction, pp 483–500Paternò F (2003) From model-based to natural development. HCI International, pp 592–596Ramchurn SD, Deitch B, Thompson MK, Roure DCD, Jennings NR, Luck M (2004) Minimising intrusiveness in pervasive computing environments using multi-agent negotiation. MobiQuitous ’04, pp 364–372Runeson P, Höst M (2009) Guidelines for conducting and reporting case study research in software engineering. Empir Softw Eng 14(2):131–164Schmidt A (2000) Implicit human computer interaction through context. Pers Technol 4(2–3):191–199Serral E, Valderas P, Pelechano V (2010) Supporting runtime system evolution to adapt to user behaviour. In: Proc. of CAiSE’10, pp 378–392Serral E, Valderas P, Pelechano V (2010) Towards the model driven development of context-aware pervasive systems. PMC 6(2):254–280Siegemund F (2004) A context-aware communication platform for smart objects. In: Proc of the int conf on pervasive computing. Springer, pp 69–86Streitz NA, Rocker C, Prante T, Alphen Dv, Stenzel R, Magerkurth C (2005) Designing smart artifacts for smart environments. Comput 38(3):41–49. doi: 10.1109/MC.2005.92Thiesse F, Kohler M (2008) An analysis of usage-based pricing policies for smart products. Electron Mark 18(3):232–241. doi: 10.1080/10196780802265751Vastenburg MH, Keyson DV, de Ridder H (2008) Considerate home notification systems: a field study of acceptability of notifications in the home. Pers Ubiquit Comput 12(8):555–56

Variations on a theme: diversification of cuticular hydrocarbons in a clade of cactophilic Drosophila

<p>Abstract</p> <p>Background</p> <p>We characterized variation and chemical composition of epicuticular hydrocarbons (CHCs) in the seven species of the <it>Drosophila buzzatii </it>cluster with gas chromatography/mass spectrometry. Despite the critical role of CHCs in providing resistance to desiccation and involvement in communication, such as courtship behavior, mating, and aggregation, few studies have investigated how CHC profiles evolve within and between species in a phylogenetic context. We analyzed quantitative differences in CHC profiles in populations of the <it>D. buzzatii </it>species cluster in order to assess the concordance of CHC differentiation with species divergence.</p> <p>Results</p> <p>Thirty-six CHC components were scored in single fly extracts with carbon chain lengths ranging from C₂₉to C₃₉, including methyl-branched alkanes, <it>n</it>-alkenes, and alkadienes. Multivariate analysis of variance revealed that CHC amounts were significantly different among all species and canonical discriminant function (CDF) analysis resolved all species into distinct, non-overlapping groups. Significant intraspecific variation was found in different populations of <it>D. serido </it>suggesting that this taxon is comprised of at least two species. We summarized CHC variation using CDF analysis and mapped the first five CHC canonical variates (CVs) onto an independently derived <it>period </it>(<it>per</it>) gene + chromosome inversion + mtDNA COI gene for each sex. We found that the COI sequences were not phylogenetically informative due to introgression between some species, so only <it>per </it>+ inversion data were used. Positive phylogenetic signal was observed mainly for CV1 when parsimony methods and the test for serial independence (TFSI) were used. These results changed when no outgroup species were included in the analysis and phylogenetic signal was then observed for female CV3 and/or CV4 and male CV4 and CV5. Finally, removal of divergent populations of <it>D. serido </it>significantly increased the amount of phylogenetic signal as up to four out of five CVs then displayed positive phylogenetic signal.</p> <p>Conclusions</p> <p>CHCs were conserved among species while quantitative differences in CHC profiles between populations and species were statistically significant. Most CHCs were species-, population-, and sex-specific. Mapping CHCs onto an independently derived phylogeny revealed that a significant portion of CHC variation was explained by species' systematic affinities indicating phylogenetic conservatism in the evolution of these hydrocarbon arrays, presumptive waterproofing compounds and courtship signals as in many other drosophilid species.</p

Clinical Implication of Targeting of Cancer Stem Cells

The existence of cancer stem cells (CSCs) is receiving increasing interest particularly due to its potential ability to enter clinical routine. Rapid advances in the CSC field have provided evidence for the development of more reliable anticancer therapies in the future. CSCs typically only constitute a small fraction of the total tumor burden; however, they harbor self-renewal capacity and appear to be relatively resistant to conventional therapies. Recent therapeutic approaches aim to eliminate or differentiate CSCs or to disrupt the niches in which they reside. Better understanding of the biological characteristics of CSCs as well as improved preclinical and clinical trials targeting CSCs may revolutionize the treatment of many cancers. Copyright (c) 2012 S. Karger AG, Base

Personalization for unobtrusive service interaction

Increasingly, mobile devices play a key role in the communication between users and the services embedded in their environment. With ever greater number of services added to our surroundings, there is a need to personalize services according to the user needs and environmental context avoiding service behavior from becoming overwhelming. In order to prevent this information overload, we present a method for the development of mobile services that can be personalized in terms of obtrusiveness (the degree in which each service intrudes the user's mind) according to the user needs and preferences. That is, services can be developed to provide their functionality at different obtrusiveness levels depending on the user by minimizing the duplication of efforts. On the one hand, we provide mechanisms for describing the obtrusiveness degree required for a service. On the other hand, we make use of Feature Modeling techniques in order to define the obtrusiveness level adaptation in a declarative manner. An experiment was conducted in order to put in practice the proposal and evaluate the user acceptance for the personalization capabilities provided by our approach. © Springer-Verlag London Limited 2011.This work has been developed with the support of MICINN under the project EVERYWARE TIN2010-18011 and co-financed with ERDF, in the grants program FPU.Gil Pascual, M.; Giner Blasco, P.; Pelechano Ferragud, V. (2012). Personalization for unobtrusive service interaction. Personal and Ubiquitous Computing. 16(5):543-561. https://doi.org/10.1007/s00779-011-0414-0S543561165Abrams M, Phanouriou C, Batongbacal AL, Williams SM, Shuster JE (1999) Uiml: an appliance-independent xml user interface language. In: WWW ’99. Elsevier, North-Holland, pp 1695–1708Ballagas R, Borchers J, Rohs M, Sheridan JG (2006) The smart phone: a ubiquitous input device. IEEE Pervas Comput 5(1):70Balme L, Demeure A, Barralon N, Coutaz J, Calvary G (2004) Cameleon-rt: a software architecture reference model for distributed, migratable, and plastic user interfaces. In: EUSAI, pp 291–302Benavides D, Cortés RA, Trinidad P (2005) Automated reasoning on feature models. In: LNCS, advanced information systems engineering: 17th international conference, CAiSE 2005 3520, pp 491–503Blomquist A, Arvola M (2002) Personas in action: ethnography in an interaction design team. In: Proceedings of NordiCHI ’02. ACM, New York, NY, pp 197–200Bright A, Kay J, Ler D, Ngo K, Niu W, Nuguid A (2005) Adaptively recommending museum tours. In: Nick Ryan Tullio Salmon Cinotti GR (ed) Proceedings of workshop on smart environments and their applications to cultural heritage. Archaeolingua, pp 29–32Brown DM (2010) Communicating design: developing web site documentation for design and planning, 2nd edn. 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In: Proceedings of SPLCDuarte C, Carriço L (2006) A conceptual framework for developing adaptive multimodal applications. In: Proceedings of IUI ’06. ACM, New York, pp 132–139Evans (2003) Domain-driven design: tacking complexity In the heart of software. Addison-Wesley Longman Publishing Co., Inc., BostonsFavre JM (2004) Foundations of model (Driven) (Reverse) engineering: models—Episode I: stories of the fidus papyrus and of the solarus. In: Bezivin J, Heckel R (eds) Language engineering for model-driven software development, no. 04101, Dagstuhl seminar proceedings. Dagstuhl, GermanyFischer G (2001) User modeling in human–computer interaction. User Model User-Adap Inter 11(1–2):65–86Gibbs WW (2005) Considerate computing. Scientific American 292(1):54–61Giner P, Cetina C, Fons J, Pelechano V (2010) Developing mobile workflow support in the internet of things. IEEE Pervas Comput 9(2):18–26Giner P, Cetina C, Fons J, Pelechano V (2011) Implicit interaction design for pervasive workflows. Pers Ubiquit Comput 1–10Gulliksen J, Goransson B, Boivie I, Blomkvist S, Persson J, Cajander A (2003) Key principles for user-centred systems design. Behav Inform Technol 22:397–409Hinckley K, Horvitz E (2001) Toward more sensitive mobile phones. In: Proceedings of the UIST ’01. ACM, New York, pp 191–192Ho J, Intille SS (2005) Using context-aware computing to reduce the perceived burden of interruptions from mobile devices. In: Proceedings of CHI ’05. ACM, New York, pp 909–918Horvitz E, Kadie C, Paek T, Hovel D (2003) Models of attention in computing and communication: from principles to applications. Commun ACM 46(3):52–59Ju W, Leifer L (2008) The design of implicit interactions: making interactive systems less obnoxious. Des Issues 24(3):72–84Lewis JR (1995) Ibm computer usability satisfaction questionnaires: psychometric evaluation and instructions for use. Int J Hum-Comput Interact 7(1):57–78Limbourg Q, Vanderdonckt J, Michotte B, Bouillon L, López-Jaquero V (2004) Usixml: a language supporting multi-path development of user interfaces. In: EHCI/DS-VIS, pp 200–220Mao JY, Vredenburg K, Smith PW, Carey T (2001) User-centered design methods in practice: a survey of the state of the art. In: CASCON ’01. IBM Press, New York, p 12McCrickard DS, Chewar CM (2003) Attuning notification design to user goals and attention costs. Commun ACM 46:67–72Mori G, Paternò F, Santoro C (2002) Ctte: support for developing and analyzing task models for interactive system design. IEEE Trans Softw Eng 28(8):797–813Mori G, Paternò F, Santoro C (2004) Design and development of multidevice user interfaces through multiple logical descriptions. IEEE Trans Softw Eng 30(8):507–520Myers B, Hudson SE, Pausch R (2000) Past, present, and future of user interface software tools. ACM Trans Comput-Hum Interact 7(1):3–28OMG (2006) Business process modeling notation (BPMN) specification. OMG Final Adopted SpecificationPaternò F, Santoro C (2003) A unified method for designing interactive systems adaptable to mobile and stationary platforms. Interact Comput 15(3):349–366Puerta A, Eisenstein J (2002) Ximl: a common representation for interaction data. In: Proceedings of IUI ’02. ACM, New York, pp 214–215Ramchurn SD, Deitch B, Thompson MK, Roure DCD, Jennings NR, Luck M (2004) Minimising intrusiveness in pervasive computing environments using multi-agent negotiation. In: First international conference on mobile and ubiquitous systems, pp 364–372Rumbaugh J, Jacobson I, Booch G (1998) The unified modeling language reference manual. Addison-Wesley, LondonSchobbens PY, Heymans P, Trigaux JC, Bontemps Y (2007) Generic semantics of feature diagrams. 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Commun ACM 46(3):30–33Weiser M, Brown JS (1997) The coming age of calm technology, pp 75–85Weld DS, Anderson C, Domingos P, Etzioni O, Gajos K, Lau T, Wolf S (2003) Automatically personalizing user interfaces. In: IJCAI ’03, pp 1613–161

Sail or sink: novel behavioural adaptations on water in aerially dispersing species

Background Long-distance dispersal events have the potential to shape species distributions and ecosystem diversity over large spatial scales, and to influence processes such as population persistence and the pace and scale of invasion. How such dispersal strategies have evolved and are maintained within species is, however, often unclear. We have studied long-distance dispersal in a range of pest-controlling terrestrial spiders that are important predators within agricultural ecosystems. These species persist in heterogeneous environments through their ability to re-colonise vacant habitat by repeated long-distance aerial dispersal (“ballooning”) using spun silk lines. Individuals are strictly terrestrial, are not thought to tolerate landing on water, and have no control over where they land once airborne. Their tendency to spread via aerial dispersal has thus been thought to be limited by the costs of encountering water, which is a frequent hazard in the landscape. Results In our study we find that ballooning in a subset of individuals from two groups of widely-distributed and phylogenetically distinct terrestrial spiders (linyphiids and one tetragnathid) is associated with a hitherto undescribed ability of those same individuals to survive encounters with both fresh and marine water. Individuals that showed a high tendency to adopt ‘ballooning’ behaviour adopted elaborate postures to seemingly take advantage of the wind current whilst on the water surface. Conclusions The ability of individuals capable of long-distance aerial dispersal to survive encounters with water allows them to disperse repeatedly, thereby increasing the pace and spatial scale over which they can spread and subsequently exert an influence on the ecosystems into which they migrate. The potential for genetic connectivity between populations, which can influence the rate of localized adaptation, thus exists over much larger geographic scales than previously thought. Newly available habitat may be particularly influenced given the degree of ecosystem disturbance that is known to follow new predator introductions

Loss of ubiquitin E2 Ube2w rescues hypersensitivity of Rnf4 mutant cells to DNA damage

SUMO and ubiquitin play important roles in the response of cells to DNA damage. These pathways are linked by the SUMO Targeted ubiquitin Ligase Rnf4 that catalyses transfer of ubiquitin from a ubiquitin loaded E2 conjugating enzyme to a polySUMO modified substrate. Rnf4 can functionally interact with multiple E2s, including Ube2w, in vitro. Chicken cells lacking Rnf4 are hypersensitive to hyroxyurea, DNA alkylating drugs and DNA crosslinking agents, but this sensitivity is suppressed by simultaneous depletion of Ube2w. Cells depleted of Ube2w alone are not hypersensitive to the same DNA damaging agents. Similar results were also obtained in human cells. These data indicate that Ube2w does not have an essential role in the DNA damage response, but is deleterious in the absence of Rnf4. Thus, although Rnf4 and Ube2w functionally interact in vitro, our genetic experiments indicate that in response to DNA damage Ube2w and Rnf4 function in distinct pathways