Fast single-cell biochemistry: theory, open source microscopy and applications

Fluorescence lifetime sensing enables researchers to probe the physicochemical environment of a fluorophore providing a window through which we can observe the complex molecular make-up of the cell. Fluorescence lifetime imaging microscopy (FLIM) quantifies and maps cell biochemistry, a complex ensemble of dynamic processes. Unfortunately, typical high-resolution FLIM systems exhibit rather limited acquisition speeds, often insufficient to capture the time evolution of biochemical processes in living cells. Here, we describe the theoretical background that justifies the developments of high-speed single photon counting systems. We show that systems with low dead-times not only result in faster acquisition throughputs but also improved dynamic range and spatial resolution. We also share the implementation of hardware and software as an open platform, show applications of fast FLIM biochemical imaging on living cells and discuss strategies to balance precision and accuracy in FLIM. The recent innovations and commercialisation of fast time-domain FLIM systems are likely to popularise FLIM within the biomedical community, to impact biomedical research positively and to foster the adoption of other FLIM techniques as well. While supporting and indeed pursuing these developments, with this work we also aim to warn the community about the possible shortcomings of fast single photon counting techniques and to highlight strategies to acquire data of high quality.We acknowledge funding from the Medical Research Council core grants (MC_UU_12022/1 and MC_UU_12022/8) to ARV

The Effect of Differential Limb Magnification on Abundance Analysis of Microlensed Dwarf Stars

Finite source effects can be important in observations of gravitational microlensing of stars. Near caustic crossings, for example, some parts of the source star will be more highly magnified than other parts. The spectrum of the star is then no longer the same as when it is unmagnified, and measurements of the atmospheric parameters and abundances will be affected. The accuracy of abundances measured from spectra taken during microlensing events has become important recently because of the use of highly magnified dwarf stars to probe abundance ratios and the abundance distribution in the Galactic bulge. In this paper, we investigate the effect of finite source effects on spectra by using magnification profiles motivated by two events to synthesize spectra for dwarfs between 5000K to 6200K at solar metallicity. We adopt the usual techniques for analyzing the microlensed dwarfs, namely, spectroscopic determination of temperature, gravity, and microturbulent velocity, relying on equivalent widths. We find that ignoring the finite source effects for the more extreme case results in errors in Teff < 45K, in log g of <0.1 dex and in microturbulent velocity of <0.1 km/s. In total, changes in equivalent widths lead to small changes in atmospheric parameters and changes in abundances of <0.06 dex, with changes in [FeI/H] of <0.03 dex. For the case with a larger source-lens separation, the error in [FeI/H] is <0.01 dex. This latter case represents the maximum effect seen in events whose lightcurves are consistent with a point-source lens, which includes the majority of microlensed bulge dwarfs published so far.Comment: 11 pages, 11 figures, submitted to Ap

Participatory development of decision support systems: which features of the process lead to improved uptake and better outcomes?

Decision support systems (DSSs) are important in decision-making environments with conflicting interests. Many DSSs developed have not been used in practice. Experts argue that these tools do not respond to real user needs and that the inclusion of stakeholders in the development process is the solution. However, it is not clear which features of participatory development of DSSs result in improved uptake and better outcomes. A review of papers, reporting on case studies where DSSs and other decision tools (information systems, software and scenario tools) were developed with elements of participation, was carried out. The cases were analysed according to a framework created as part of this research; it includes criteria to evaluate the development process and the outcomes. Relevant aspects to consider in the participatory development processes include establishing clear objectives, timing and location of the process; keeping discussions on track; favouring participation and interaction of individuals and groups; and challenging creative thinking of the tool and future scenarios. The case studies that address these issues show better outcomes; however, there is a large degree of uncertainty concerning them because developers have typically neither asked participants about their perceptions of the processes and resultant tools nor have they monitored the use and legacy of the tools over the long term.The authors would like to thank COST Action FP0804-Forest Management Decision Support Systems (FORSYS) for financing a three month Short-Term Scientific Mission (STSM) in Forest Research (Roslin, UK) in 2012, making possible this research; Spanish Ministry of Economy and Competitiveness for supporting the project Multicriteria Techniques and Participatory Decision-Making for Sustainable Management (Ref. ECO2011-27369) where the leading author is involved; and the Regional Ministry of Education, Culture and Sports (Valencia, Spain) for financing a research fellowship (Ref. ACIF/2010/248).Valls Donderis, P.; Ray, D.; Peace, A.; Stewart, A.; Lawrence, A.; Galiana, F. (2013). Participatory development of decision support systems: which features of the process lead to improved uptake and better outcomes?. Scandinavian Journal of Forest Research. 29(1):71-83. https://doi.org/10.1080/02827581.2013.837950S7183291Arnstein, S. R. (1969). A Ladder Of Citizen Participation. Journal of the American Institute of Planners, 35(4), 216-224. doi:10.1080/01944366908977225Atwell, R. C., Schulte, L. A., & Westphal, L. M. (2011). Tweak, Adapt, or Transform: Policy Scenarios in Response to Emerging Bioenergy Markets in the U.S. Corn Belt. Ecology and Society, 16(1). doi:10.5751/es-03854-160110Barac, A., Kellner, K., & De Klerk, N. (2004). Land User Participation in Developing a Computerised Decision Support System for Combating Desertification. Environmental Monitoring and Assessment, 99(1-3), 223-231. doi:10.1007/s10661-004-4022-6Bennet, A., & Bennet, D. (2008). The Decision-Making Process in a Complex Situation. Handbook on Decision Support Systems 1, 3-20. doi:10.1007/978-3-540-48713-5_1Blackstock, K. L., Kelly, G. J., & Horsey, B. L. (2007). Developing and applying a framework to evaluate participatory research for sustainability. Ecological Economics, 60(4), 726-742. doi:10.1016/j.ecolecon.2006.05.014Breuer, N. E., Cabrera, V. E., Ingram, K. T., Broad, K., & Hildebrand, P. E. (2007). AgClimate: a case study in participatory decision support system development. Climatic Change, 87(3-4), 385-403. doi:10.1007/s10584-007-9323-7Bunch, M. J., & Dudycha, D. J. (2004). Linking conceptual and simulation models of the Cooum River: collaborative development of a GIS-based DSS for environmental management. Computers, Environment and Urban Systems, 28(3), 247-264. doi:10.1016/s0198-9715(03)00021-8Byrne, E., & Sahay, S. (2007). Participatory design for social development: A South African case study on community-based health information systems. Information Technology for Development, 13(1), 71-94. doi:10.1002/itdj.20052Cain, J. ., Jinapala, K., Makin, I. ., Somaratna, P. ., Ariyaratna, B. ., & Perera, L. . (2003). Participatory decision support for agricultural management. A case study from Sri Lanka. Agricultural Systems, 76(2), 457-482. doi:10.1016/s0308-521x(02)00006-9Chakraborty, A. (2011). Enhancing the role of participatory scenario planning processes: Lessons from Reality Check exercises. Futures, 43(4), 387-399. doi:10.1016/j.futures.2011.01.004Cinderby, S., Bruin, A. de, Mbilinyi, B., Kongo, V., & Barron, J. (2011). Participatory geographic information systems for agricultural water management scenario development: A Tanzanian case study. Physics and Chemistry of the Earth, Parts A/B/C, 36(14-15), 1093-1102. doi:10.1016/j.pce.2011.07.039Drew, C. H., Nyerges, T. L., & Leschine, T. M. (2004). Promoting Transparency of Long‐Term Environmental Decisions: The Hanford Decision Mapping System Pilot Project. Risk Analysis, 24(6), 1641-1664. doi:10.1111/j.0272-4332.2004.00556.xDriedger, S. M., Kothari, A., Morrison, J., Sawada, M., Crighton, E. J., & Graham, I. D. (2007). Using participatory design to develop (public) health decision support systems through GIS. International Journal of Health Geographics, 6(1), 53. doi:10.1186/1476-072x-6-53Evers, M. (2008). An analysis of the requirements for DSS on integrated river basin management. Management of Environmental Quality: An International Journal, 19(1), 37-53. doi:10.1108/14777830810840354Iivari, N. (2011). Participatory design in OSS development: interpretive case studies in company and community OSS development contexts. Behaviour & Information Technology, 30(3), 309-323. doi:10.1080/0144929x.2010.503351Innes, J. E., & Booher, D. E. (1999). Consensus Building and Complex Adaptive Systems. Journal of the American Planning Association, 65(4), 412-423. doi:10.1080/01944369908976071Jakku, E., & Thorburn, P. J. (2010). A conceptual framework for guiding the participatory development of agricultural decision support systems. Agricultural Systems, 103(9), 675-682. doi:10.1016/j.agsy.2010.08.007Jessel, B., & Jacobs, J. (2005). Land use scenario development and stakeholder involvement as tools for watershed management within the Havel River Basin. Limnologica, 35(3), 220-233. doi:10.1016/j.limno.2005.06.006Kautz, K. (2011). Investigating the design process: participatory design in agile software development. Information Technology & People, 24(3), 217-235. doi:10.1108/09593841111158356Kowalski, K., Stagl, S., Madlener, R., & Omann, I. (2009). Sustainable energy futures: Methodological challenges in combining scenarios and participatory multi-criteria analysis. European Journal of Operational Research, 197(3), 1063-1074. doi:10.1016/j.ejor.2007.12.049Lawrence, A. (2006). ‘No Personal Motive?’ Volunteers, Biodiversity, and the False Dichotomies of Participation. Ethics, Place & Environment, 9(3), 279-298. doi:10.1080/13668790600893319Mao, J., & Song, W. (2008). Empirical study of distinct features and challenges of joint development of information systems: The case of ABC bank. Tsinghua Science and Technology, 13(3), 414-419. doi:10.1016/s1007-0214(08)70066-xMenzel, S., Nordström, E.-M., Buchecker, M., Marques, A., Saarikoski, H., & Kangas, A. (2012). Decision support systems in forest management: requirements from a participatory planning perspective. European Journal of Forest Research, 131(5), 1367-1379. doi:10.1007/s10342-012-0604-yMoote, M. A., Mcclaran, M. P., & Chickering, D. K. (1997). RESEARCH: Theory in Practice: Applying Participatory Democracy Theory to Public Land Planning. Environmental Management, 21(6), 877-889. doi:10.1007/s002679900074Peleg, M., Shachak, A., Wang, D., & Karnieli, E. (2009). Using multi-perspective methodologies to study users’ interactions with the prototype front end of a guideline-based decision support system for diabetic foot care. International Journal of Medical Informatics, 78(7), 482-493. doi:10.1016/j.ijmedinf.2009.02.008Pretty, J. N. (1995). Participatory learning for sustainable agriculture. World Development, 23(8), 1247-1263. doi:10.1016/0305-750x(95)00046-fReed MS. 2008. Stakeholder participation for environmental management: a literature review. Sustainability Research Institute, School of Earth and Environment, University of Leeds.Reed, M. S., & Dougill, A. J. (2010). Linking degradation assessment to sustainable land management: A decision support system for Kalahari pastoralists. Journal of Arid Environments, 74(1), 149-155. doi:10.1016/j.jaridenv.2009.06.016Rowe, G., & Frewer, L. J. (2000). Public Participation Methods: A Framework for Evaluation. Science, Technology, & Human Values, 25(1), 3-29. doi:10.1177/016224390002500101Schielen, R. M. J., & Gijsbers, P. J. A. (2003). DSS-large rivers: developing a DSS under changing societal requirements. Physics and Chemistry of the Earth, Parts A/B/C, 28(14-15), 635-645. doi:10.1016/s1474-7065(03)00109-8Sheppard, S. R. J., & Meitner, M. (2005). Using multi-criteria analysis and visualisation for sustainable forest management planning with stakeholder groups. Forest Ecology and Management, 207(1-2), 171-187. doi:10.1016/j.foreco.2004.10.032Thursky, K. A., & Mahemoff, M. (2007). User-centered design techniques for a computerised antibiotic decision support system in an intensive care unit. International Journal of Medical Informatics, 76(10), 760-768. doi:10.1016/j.ijmedinf.2006.07.011Webler, S. T., Thomas. (1999). Voices from the Forest: What Participants Expect of a Public Participation Process. Society & Natural Resources, 12(5), 437-453. doi:10.1080/089419299279524Van Meensel, J., Lauwers, L., Kempen, I., Dessein, J., & Van Huylenbroeck, G. (2012). Effect of a participatory approach on the successful development of agricultural decision support systems: The case of Pigs2win. Decision Support Systems, 54(1), 164-172. doi:10.1016/j.dss.2012.05.002Von Geibler, J., Kristof, K., & Bienge, K. (2010). Sustainability assessment of entire forest value chains: Integrating stakeholder perspectives and indicators in decision support tools. Ecological Modelling, 221(18), 2206-2214. doi:10.1016/j.ecolmodel.2010.03.02

Lattice-gas simulations of Domain Growth, Saturation and Self-Assembly in Immiscible Fluids and Microemulsions

We investigate the dynamical behavior of both binary fluid and ternary microemulsion systems in two dimensions using a recently introduced hydrodynamic lattice-gas model of microemulsions. We find that the presence of amphiphile in our simulations reduces the usual oil-water interfacial tension in accord with experiment and consequently affects the non-equilibrium growth of oil and water domains. As the density of surfactant is increased we observe a crossover from the usual two-dimensional binary fluid scaling laws to a growth that is {\it slow}, and we find that this slow growth can be characterized by a logarithmic time scale. With sufficient surfactant in the system we observe that the domains cease to grow beyond a certain point and we find that this final characteristic domain size is inversely proportional to the interfacial surfactant concentration in the system.Comment: 28 pages, latex, embedded .eps figures, one figure is in colour, all in one uuencoded gzip compressed tar file, submitted to Physical Review

GRB 090426: The Environment of a Rest-Frame 0.35-second Gamma-Ray Burst at Redshift z=2.609

We present the discovery of an absorption-line redshift of z = 2.609 for GRB 090426, establishing the first firm lower limit to a redshift for a gamma-ray burst with an observed duration of <2 s. With a rest-frame burst duration of T_90z = 0.35 s and a detailed examination of the peak energy of the event, we suggest that this is likely (at >90% confidence) a member of the short/hard phenomenological class of GRBs. From analysis of the optical-afterglow spectrum we find that the burst originated along a very low HI column density sightline, with N_HI < 3.2 x 10^19 cm^-2. Our GRB 090426 afterglow spectrum also appears to have weaker low-ionisation absorption (Si II, C II) than ~95% of previous afterglow spectra. Finally, we also report the discovery of a blue, very luminous, star-forming putative host galaxy (~2 L*) at a small angular offset from the location of the optical afterglow. We consider the implications of this unique GRB in the context of burst duration classification and our understanding of GRB progenitor scenarios.Comment: Submitted to MNRA

A global perspective on the trophic geography of sharks

Sharks are a diverse group of mobile predators that forage across varied spatial scales and have the potential to influence food web dynamics. The ecological consequences of recent declines in shark biomass may extend across broader geographic ranges if shark taxa display common behavioural traits. By tracking the original site of photosynthetic fixation of carbon atoms that were ultimately assimilated into muscle tissues of 5,394 sharks from 114 species, we identify globally consistent biogeographic traits in trophic interactions between sharks found in different habitats. We show that populations of shelf-dwelling sharks derive a substantial proportion of their carbon from regional pelagic sources, but contain individuals that forage within additional isotopically diverse local food webs, such as those supported by terrestrial plant sources, benthic production and macrophytes. In contrast, oceanic sharks seem to use carbon derived from between 30° and 50° of latitude. Global-scale compilations of stable isotope data combined with biogeochemical modelling generate hypotheses regarding animal behaviours that can be tested with other methodological approaches.This research was conducted as part of C.S.B.’s Ph.D dissertation, which was funded by the University of Southampton and NERC (NE/L50161X/1), and through a NERC Grant-in-Kind from the Life Sciences Mass Spectrometry Facility (LSMSF; EK267-03/16). We thank A. Bates, D. Sims, F. Neat, R. McGill and J. Newton for their analytical contributions and comments on the manuscripts.Peer reviewe

The measurement of bilingual abilities: central challenges

In this handbook chapter I analyse the concept of bilingual abilities. Bilinguals vary widely in what they can do with their languages or in the ways in which they use their languages on a daily basis. This means that there is a great deal of variability in what the term covers. While many researchers subscribe to the holistic view of bilingualism, in the academic literature bilinguals are still often described in negative terms as having a "deficit" in one or another subsystem of their languages. The key aim of this chapter is to identify what makes individuals with bilingual abilities unique speaker-hearers in their own right, avoiding the fractional view of bilingualism, and how these abilities can be measured

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio