Interrogating cellular perception and decision making with optogenetic tools.

Optogenetics promises to deepen our understanding of how cells perceive and respond to complex and dynamic signals and how this perception regulates normal and abnormal function. In this study, we present our vision for how these nascent tools may transform our view of fundamental cell biological processes

Structure and chemistry in the northwestern condensation of the Serpens molecular cloud core

We present single-dish and interferometric observations of gas and dust in the core of the Serpens molecular cloud, focusing on the northwestern condensation. Single-dish molecular line observations are used to probe the structure and chemistry of the condensation while high-resolution images of CS and CH_(3)0H are combined with continuum observations from λ = 1.3 mm to λ = 3.5 cm to study the subcondensations and overall distribution of dust. For the northwestern condensation, we derive a characteristic density of 3 x 10^5 cm^(-3) and an estimated total mass of approximately 70 M_⊙. We find compact molecular emission associated with the far-infrared source S68 FIRS 1, and with a newly detected subcondensation named S68 N. Comparison of the large-and small-scale emission reveals that most of the material in the northwest condensation is not directly associated with these compact sources, suggesting a youthful age for this region. CO J = 1 approaches 0 observations indicate widespread outflow activity. However, no unique association of embedded objects with outflows is possible with our observations. The SiO emission is found to be extended with the overall emission centered about S68 FIRS 1; the offset of the peak emission from all of the known continuum sources and the coincidence between the blueshifted SiO emission and blueshifted high-velocity gas traced by CO and CS is consistent with formation of SiO in shocks. Derived abundances of CO and HCO^(+) are consistent with quiescent and other star-forming regions while CS, HCN, and H2CO abundances indicate mild depletions within the condensation. Spectral energy distribution fits to S68 FIRS 1 indicate a modest luminosity (50-60 L_⊙), implying that it is a low-mass (0.5-3 M_⊙) young stellar object. Radio continuum observations of the triple source toward S68 FIRS 1 indicate that the lobe emission is varying on timescales ≤ 1 yr while the central component is relatively constant over ~14 yr. The nature of a newly detected compact emission region, S68 N, is less certain due to the absence of firm continuum detections; based on its low luminosity (<5 L_⊙) and strong molecular emission, S68 N may be prestellar subcondensation of gas and dust

Insight into High-quality Aerodynamic Design Spaces through Multi-objective Optimization

An approach to support the computational aerodynamic design process is presented and demonstrated through the application of a novel multi-objective variant of the Tabu Search optimization algorithm for continuous problems to the aerodynamic design optimization of turbomachinery blades. The aim is to improve the performance of a specific stage and ultimately of the whole engine. The integrated system developed for this purpose is described. This combines the optimizer with an existing geometry parameterization scheme and a well- established CFD package. The system’s performance is illustrated through case studies – one two-dimensional, one three-dimensional – in which flow characteristics important to the overall performance of turbomachinery blades are optimized. By showing the designer the trade-off surfaces between the competing objectives, this approach provides considerable insight into the design space under consideration and presents the designer with a range of different Pareto-optimal designs for further consideration. Special emphasis is given to the dimensionality in objective function space of the optimization problem, which seeks designs that perform well for a range of flow performance metrics. The resulting compressor blades achieve their high performance by exploiting complicated physical mechanisms successfully identified through the design process. The system can readily be run on parallel computers, substantially reducing wall-clock run times – a significant benefit when tackling computationally demanding design problems. Overall optimal performance is offered by compromise designs on the Pareto trade-off surface revealed through a true multi-objective design optimization test case. Bearing in mind the continuing rapid advances in computing power and the benefits discussed, this approach brings the adoption of such techniques in real-world engineering design practice a ste

ADOPT: a tool for predicting adoption of agricultural innovations

A wealth of evidence exists about the adoption of new practices and technologies in agriculture but there does not appear to have been any attempt to simplify this vast body of research knowledge into a model to make quantitative predictions across a broad range of contexts. This is despite increasing demand from research, development and extension agencies for estimates of likely extent of adoption and the likely timeframes for project impacts. This paper reports on the reasoning underpinning the development of ADOPT (Adoption and Diffusion Outcome Prediction Tool). The tool has been designed to: 1) predict an innovation‘s likely peak extent of adoption and likely time for reaching that peak; 2) encourage users to consider the influence of a structured set of factors affecting adoption; and 3) engage R, D & E managers and practitioners by making adoptability knowledge and considerations more transparent and understandable. The tool is structured around four aspects of adoption: 1) characteristics of the innovation, 2) characteristics of the population, 3) actual advantage of using the innovation, and 4) learning of the actual advantage of the innovation. The conceptual framework used for developing ADOPT is described.Adoption, Diffusion, Prediction, Research and Development/Tech Change/Emerging Technologies,

Crossing the Brown Dwarf Desert Using Adaptive Optics: A Very Close L-Dwarf Companion to the Nearby Solar Analog HR 7672

We have found a very faint companion to the active solar analog HR 7672 (HD 190406; GJ 779; 15 Sge). Three epochs of high resolution imaging using adaptive optics (AO) at the Gemini-North and Keck II Telescopes demonstrate that HR 7672B is a common proper motion companion, with a separation of 0.79" (14 AU) and a 2.16 um flux ratio of 8.6 mags. Using follow-up K-band spectroscopy from Keck AO+NIRSPEC, we measure a spectral type of L4.5+/-1.5. This is the closest ultracool companion around a main sequence star found to date by direct imaging. We estimate the primary has an age of 1-3 Gyr. Assuming coevality, the companion is most likely substellar, with a mass of 55-78 Mjup based on theoretical models. The primary star shows a long-term radial velocity trend, and we combine the radial velocity data and AO imaging to set a firm (model-independent) lower limit of 48 Mjup. In contrast to the paucity of brown dwarf companions at <~4 AU around FGK dwarfs, HR 7672B implies that brown dwarf companions do exist at separations comparable to those of the giant planets in our own solar system. Its presence is at variance with scenarios where brown dwarfs form as ejected stellar embryos. Moreover, since HR 7672B is likely too massive to have formed in a circumstellar disk as planets are believed to, its discovery suggests that a diversity of physical processes act to populate the outer regions of exoplanetary systems.Comment: Astrophysical Journal, in pres

Phase I/II Clinical Trials Using Gene-Modified Adult Hematopoietic Stem Cells for HIV: Lessons Learnt

Gene therapy for individuals infected with HIV has the potential to provide a once-only treatment that will act to reduce viral load, preserve the immune system, and mitigate cumulative toxicities associated with highly active antiretroviral therapy (HAART). The authors have been involved in two clinical trials (phase I and phase II) using gene-modified adult hematopoietic stem cells (HSCs), and these are discussed as prototypic trials within the general field of HSC gene therapy trials for HIV. Taken as a group these trials have shown (i) the safety of both the procedure and the anti-HIV agents themselves and (ii) the feasibility of the approach. They point to the requirement for (i) the ability to transduce and infuse as many as possible gene-containing HSC and/or (ii) high engraftment and in vivo expansion of these cells, (iii) potentially increased efficacy of the anti-HIV agent(s) and (iv) automation of the cell processing procedure

A meta-analytic review of the relationship between neurocognition, metacognition and functional outcome in schizophrenia

Previous research has identified that neurocognition predicts functional outcome in schizophrenia to a greater extent than psychopthology. More contemporary authors have begun to explore the role of metacognition as a mediating variable between neurocognition and functional outcome. The present review sought to extend the known work by synthesising the results reported in individual studies to see if these results are consistently found across samples. Relevant search strategies were entered into Medline (PubMed), PsychINFO and Embase. The present meta-analysis encompassed 17 studies (N=1060) investigating the relationship between neurocognition and metacognition and 7 studies investigating the relationship between metacognition and functional outcome (N=645). A small-to-moderate mean effect size was found between neurocognition and metacognition (effect size range .13 -.58,) and a small-to-moderate effect size was found between metacognition and functional outcome (range .17 - .57). Study findings suggest that relationships between variables are consistently found across samples and that future research should focus on investigating this relationship at earlier stages of illness, in female cohorts and across cognitive domains. Greater investigation is required in functional outcome, differentiating the impact of metacognition on functional capacity and other domains of functional outcome