Quantum dot labelling of adenovirus allows for highly sensitive single cell flow and imaging cytometry

A quantum dot method for highly efficient labelling of single adenoviral particles is developed. The technique has no impact on viral fitness and allows the imaging and tracking of virus binding and internalisation events using a variety of techniques including imaging cytometry and confocal microscopy. The method is applied to characterise the tropism of different adenoviral vectors

Population connectivity in marine systems : an overview

Author Posting. © Oceanography Society, 2007. This article is posted here by permission of Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 20, 3 (2007): 14-21.There is growing consensus that life within the world’s ocean is under considerable and increasing stress from human activities (Hutchings, 2000; Jackson et al., 2001). This unprecedented strain on both the structure and function of marine ecosystems has led to calls for new management approaches to counter anthropogenic impacts in the coastal ocean (Botsford et al., 1997; Browman and Stergiou, 2004: Pikitch et al., 2004). Spatial management, including Marine Protected Areas (MPAs), has been touted as a method for both conserving biodiversity and managing fisheries (Agardy, 1997). Continuing debates on the efficacy of MPAs have identified the need for models that capture the spatial dynamics of marine populations, especially with respect to larval dispersal (Willis et al., 2003; Sale et al., 2005). Theoretical studies suggest that population connectivity plays a fundamental role in local and metapopulation dynamics, community dynamics and structure, genetic diversity, and the resiliency of populations to human exploitation (Hastings and Harrison, 1994; Botsford et al., 2001). Modeling efforts have been hindered, however, by the paucity of empirical estimates of, and knowledge of the processes controlling, population connectivity in ocean ecosystems. While progress has been made with older life stages, the larval-dispersal component of connectivity remains unresolved for most marine populations. This lack of knowledge represents a fundamental obstacle to obtaining a comprehensive understanding of the population dynamics of marine organisms. Furthermore, a lack of spatial context that such information would provide has limited the ability of ecologists to evaluate the design and potential benefits of novel conservation and resource-management strategies.Over the years, we have each received support from a variety of agencies in support of research relevant to Population Connectivity; in addition to NSF, we acknowledge funding from the World Bank/GEF Coral Reef Targeted Research Program, University of Miami’s Maytag Chair in Ichthyology, the Oak Foundation, and the Woods Hole Oceanographic Institutio

Multicomponent analysis of the tumour microenvironment reveals low CD8 T cell number, low stromal caveolin-1 and high tenascin-C and their combination as significant prognostic markers in non-small cell lung cancer

The complex interplay of the tumour microenvironment (TME) and its role in disease progression and response to therapy is poorly understood. The majority of studies to date focus on individual components or molecules within the TME and so lack the power correlative analysis. Here we have performed a multi-parameter analysis of the TME in 62 resectable non-small cell lung cancer (NSCLC) specimens detailing number and location of immune infiltrate, assessing markers of cancer-associated fibroblasts, caveolin-1 and tenascin-C, and correlating with clinicopathological details, as well as markers of disease progression such as epithelial-to-mesenchymal transition (EMT). The influence of individual parameters on overall survival was determined in univariate and multivariate analysis and the combination of risk factors and interplay between components analysed. Low numbers of CD8 T cells, low stromal levels of caveolin-1 or high levels of tenascin-C were significant prognostic markers of decreased overall survival in both univariate and multivariate analysis. Patients with two or more risk factors had dramatically reduced overall survival and those with all three a median survival of just 7.5 months. In addition, low levels of tumour E-cadherin correlated with reduced immune infiltrate into the tumour nests, possibly linking EMT to the avoidance of CD8 T cell control. The multicomponent approach has allowed identification of the dominant influences on overall survival, and exploration of the interplay between different components of the TME in NSCLC

Dialogic science-policy networks for water security governance in the arid Americas

Addressing wicked problems challenging water security requires participation from multiple stakeholders, often with conflicting visions, complicating the attainment of water-security goals and heightening the need for integrative and effective science-policy interfaces. Sustained multi-stakeholder dialogues within science-policy networks can improve adaptive governance and water system resilience. This paper describes what we define as “dialogic science-policy networks,” or interactions -- both in structural and procedural terms -- between scientists and policy-makers that are: 1) interdisciplinary, 2) international (here, inter-American), 3) cross-sectoral, 4) open, 5) continual and iterative in the long-term, and 6) flexible. By fostering these types of interactions, dialogic networks achieve what we call the 4-I criteria for effective science-policy dialogues: inclusivity, involvement, interaction, and influence. Here we present several water-security research and action projects where some of these attributes may be present. Among these, a more comprehensive form of a dialogic network was intentionally created via AQUASEC, a virtual center and network initially fostered by a series of grants from the Inter-American Institute for Global Change Research. Subsequently, AQUASEC has significantly expanded to other regions through direct linkages and additional program support for the International Water Security Network, supported by Lloyd's Register Foundation and other sources. This paper highlights major scientific and policy achievements of a notable suite of science-policy networks, shared practices, methods, and knowledge integrating science and policy, as well as the main barriers overcome in network development. An important gap that remains for future research is the assessment and evaluation of dialogic science-policy networks' long-term outcomes.Fil: Lutz Ley, America N.. El Colegio de Sonora; MéxicoFil: Scott, Christopher A.. University of Arizona; Estados UnidosFil: Wilder, Margaret. University of Arizona; Estados UnidosFil: Varady, Robert G.. University of Arizona; Estados UnidosFil: Ocampo Melgar, Anahi. Universidad de Chile.; ChileFil: Lara Valencia, Francisco. Arizona State University; Estados UnidosFil: Zuniga Teran, Adriana. University of Arizona; Estados UnidosFil: Buechler, Stephanie. University of Arizona; Estados UnidosFil: Díaz Caravantes, Rolando. El Colegio de Sonora; MéxicoFil: Ribeiro Neto, Alfredo. El Colegio de Sonora; MéxicoFil: Pineda Pablos, Nicólas. El Colegio de Sonora; MéxicoFil: Martin, Facundo Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; Argentin

An ammonia spectral map of the L1495-B218 filaments in the Taurus molecular cloud. I. Physical properties of filaments and dense cores

We present deep NH3 observations of the L1495-B218 filaments in the Taurus molecular cloud covering over a 3° angular range using the K-band focal plane array on the 100 m Green Bank Telescope. The L1495-B218 filaments form an interconnected, nearby, large complex extending over 8 pc. We observed NH3 (1, 1) and (2, 2) with a spectral resolution of 0.038 km s−1 and a spatial resolution of 31''. Most of the ammonia peaks coincide with intensity peaks in dust continuum maps at 350 and 500 μm. We deduced physical properties by fitting a model to the observed spectra. We find gas kinetic temperatures of 8–15 K, velocity dispersions of 0.05–0.25 km s−1, and NH3 column densities of 5 × 1012 to 1 × 1014 cm−2. The CSAR algorithm, which is a hybrid of seeded-watershed and binary dendrogram algorithms, identifies a total of 55 NH3 structures, including 39 leaves and 16 branches. The masses of the NH3 sources range from 0.05 to 9.5 ${{M}_{\odot }}$. The masses of NH3 leaves are mostly smaller than their corresponding virial mass estimated from their internal and gravitational energies, which suggests that these leaves are gravitationally unbound structures. Nine out of 39 NH3 leaves are gravitationally bound, and seven out of nine gravitationally bound NH3 leaves are associated with star formation. We also found that 12 out of 30 gravitationally unbound leaves are pressure confined. Our data suggest that a dense core may form as a pressure-confined structure, evolve to a gravitationally bound core, and undergo collapse to form a protostar

A Triple Protostar System Formed via Fragmentation of a Gravitationally Unstable Disk

Binary and multiple star systems are a frequent outcome of the star formation process, and as a result, almost half of all sun-like stars have at least one companion star. Theoretical studies indicate that there are two main pathways that can operate concurrently to form binary/multiple star systems: large scale fragmentation of turbulent gas cores and filaments or smaller scale fragmentation of a massive protostellar disk due to gravitational instability. Observational evidence for turbulent fragmentation on scales of $>$1000~AU has recently emerged. Previous evidence for disk fragmentation was limited to inferences based on the separations of more-evolved pre-main sequence and protostellar multiple systems. The triple protostar system L1448 IRS3B is an ideal candidate to search for evidence of disk fragmentation. L1448 IRS3B is in an early phase of the star formation process, likely less than 150,000 years in age, and all protostars in the system are separated by $<$200~AU. Here we report observations of dust and molecular gas emission that reveal a disk with spiral structure surrounding the three protostars. Two protostars near the center of the disk are separated by 61 AU, and a tertiary protostar is coincident with a spiral arm in the outer disk at a 183 AU separation. The inferred mass of the central pair of protostellar objects is $\sim$1 M$_{sun}$, while the disk surrounding the three protostars has a total mass of $\sim$0.30 M_{\sun}. The tertiary protostar itself has a minimum mass of $\sim$0.085 M$_{sun}$. We demonstrate that the disk around L1448 IRS3B appears susceptible to disk fragmentation at radii between 150~AU and 320~AU, overlapping with the location of the tertiary protostar. This is consistent with models for a protostellar disk that has recently undergone gravitational instability, spawning one or two companion stars.Comment: Published in Nature on Oct. 27th. 24 pages, 8 figure

3-dimensional patient-derived lung cancer assays reveal resistance to standards-of-care promoted by stromal cells but sensitivity to histone deacetylase inhibitors

There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low-passage patient tumor–derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by coculture with patient-derived cancer-associated fibroblasts (CAF). A range of solid tumors proved amenable to growth and pharmacologic testing in this 3D assay. A study of 30 early-stage non–small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standard-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to-patient tumors using significantly reduced animal numbers. Mol Cancer Ther; 15(4); 753–63. ©2016 AACR

Do ecosystem insecurity and social vulnerability lead to failure of water security?

Achieving water security for humans and ecosystems is a pervasive challenge globally. Extensive areas of the Americas are at significant risk of water insecurity, resulting from global-change processes coupled with regional and local impacts. Drought, flooding, and water quality challenges pose significant threats, while at the same time, rapid urban expansion, competing water demands, river modifications, and expanding global markets for water-intensive agricultural products drive water insecurity. This paper takes a social-ecological systems perspective, aiming to identify examples and pathways towards resilient ecosystems and social development. It draws on lessons from two science-policy network projects, one focusing on water scarcity in arid and semi-arid regions of Argentina, Chile, Brazil, Peru, Mexico and the United States; and the second addressing river and lake basins as sentinels of climate variability and human effects on water quantity and quality in Canada, the United States, Argentina, Colombia, Uruguay and Chile. Together, these ?complementary contrasts? provide an analytical basis to empirically examine stakeholder engagement, knowledge co-production and science-policy interaction supporting decision-making to achieve water security. The paper identifies four tenets for decision-making based on water-security-focused global-change science in the Americas: 1) Decision makers should focus on protecting ecosystems because water security (along with food and energy security) depend on them; 2) Water-use and allocation decisions ought to be made considering future environmental and societal vulnerabilities, especially climate projections; 3) Holistic approaches (at basin or other appropriate levels) are best suited to ensure social-ecological system resilience and reduce vulnerability; and 4) It is essential to support local/traditional livelihoods, and underserved populations to achieve equitable water security and ecosystem resilience.Fil: Scott, Christopher A.. University of Arizona; Estados UnidosFil: Zilio, Mariana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Harmon, Thomas Christopher. University of California; Estados UnidosFil: Zuniga Teran, Adriana. University of Arizona; Estados UnidosFil: Díaz Caravantes, Rolando. El Colegio de Sonora; MéxicoFil: Hoyos, Natalia. Universidad del Norte; ColombiaFil: Perillo, Gerardo Miguel E.. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Meza, Andrés Francisco. Pontificia Universidad Católica de Chile; ChileFil: Varady, Robert G.. University of Arizona; Estados UnidosFil: Neto, Alfredo Ribeiro. Universidade Federal da Bahia; BrasilFil: Velez, Maria Isabel. University Of Regina; CanadáFil: Martin, Facundo Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; ArgentinaFil: Escobar, Jaime. Universidad del Norte; ColombiaFil: Piccolo, Maria Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mussetta, Paula Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; ArgentinaFil: Montenegro, Suzana. Universidade Federal de Pernambuco; BrasilFil: Rusak, James A.. Ontario Ministry Of The Environment; CanadáFil: Pineda, Nicolas. El Colegio de Sonora; Méxic

Organic chemistry of low-mass star-forming cores I: 7 mm spectroscopy of Chamaeleon MMS1

Observations are presented of emission lines from organic molecules at frequencies 32 - 50 GHz in the vicinity of Chamaeleon MMS1. This chemically-rich dense cloud core habours an extremely young, very low-luminosity protostellar object and is a candidate first hydrostatic core. Column densities are derived and emission maps are presented for species including polyynes, cyanopolyynes, sulphuretted carbon-chains and methanol. The polyyne emission peak lies about 5000 AU from the protostar, whereas methanol peaks about 15,000 AU away. Averaged over the telescope beam, the molecular hydrogen number density is calculated to be 10^6 cm^-3 and the gas kinetic temperature is in the range 5 - 7 K. The abundances of long carbon chains are very large, and are indicative of a non-equilibrium carbon chemistry; C6H and HC7N column densities are 5.9 (+2.9 -1.3) \times 10^11 cm^-2 and 3.3 (+8.0 -1.5) \times 10^12 cm^-2, respectively, which are similar to the values found in the most carbon-chain-rich protostars and prestellar cores known, and are unusually large for star-forming gas. Column density upper limits were obtained for the carbon-chain anions C4H- and C6H-, with anion-to-neutral ratios [C4H-]/[C4H] < 0.02% and [C6H-]/[C6H] < 10%, consistent with previous observations in interstellar clouds and low-mass protostars. Deuterated HC3N and c-C3H2 were detected. The [DC3N]/[HC3N] ratio of approximately 4% is consistent with the value typically found in cold interstellar gas

Men and Women Exhibit a Differential Bias for Processing Movement versus Objects

Sex differences in many spatial and verbal tasks appear to reflect an inherent low-level processing bias for movement in males and objects in females. We explored this potential movement/object bias in men and women using a computer task that measured targeting performance and/or color recognition. The targeting task showed a ball moving vertically towards a horizontal line. Before reaching the line, the ball disappeared behind a masking screen, requiring the participant to imagine the movement vector and identify the intersection point. For the color recognition task, the ball briefly changed color before disappearing beneath the mask and participants were required only to identify the color shade. Results showed that targeting accuracy for slow and fast moving balls was significantly better in males compared to females. No sex difference was observed for color shade recognition. We also studied a third, dual attention task comprised of the first two, where the moving ball briefly changed color randomly just before passing beneath the masking screen. When the ball changed color, participants were required only to identify the color shade. If the ball didn't change color, participants estimated the intersection point. Participants in this dual attention condition were first tested with the targeting and color tasks alone and showed results that were similar to the previous groups tested on a single task. However, under the dual attention condition, male accuracy in targeting, as well as color shade recognition, declined significantly compared to their performance when the tasks were tested alone. No significant changes were found in female performance. Finally, reaction times for targeting and color choices in both sexes correlated highly with ball speed, but not accuracy. Overall, these results provide evidence of a sex-related bias in processing objects versus movement, which may reflect sex differences in bottom up versus top-down analytical strategies