Coarse-grained simulation of amphiphilic self-assembly

We present a computer simulation study of amphiphilic self assembly performed using a computationally efficient single-site model based on Gay-Berne and Lennard-Jones particles. Molecular dynamics simulations of these systems show that free self-assembly of micellar, bilayer and inverse micelle arrangements can be readily achieved for a single model parameterisation. This self-assembly is predominantly driven by the anisotropy of the amphiphile-solvent interaction, amphiphile-amphiphile interactions being found to be of secondary importance. While amphiphile concentration is the main determinant of phase stability, molecular parameters such as headgroup size and interaction strength also have measurable affects on system properties. </p

A Borescope Design Tool for Laser Measurements in Fluids

This paper presents the method, implementation and validation of a borescope probe design tool devised for the challenges of optical fluid measurement techniques. The design tool is capable of predicting the path and power distribution of the laser beam through the probe and into the region interest, ensuring a cost and time-efficient design process that removes the need for experimental trials. The associated code is available as supplementary material. Optical measurement techniques have become established methods within fluid dynamics research. In contrast, their application to turbomachinery rigs is usually limited due to the restricted optical access. A small number of studies have circumvented this problem by employing borescopes to introduce the laser beam into the measurement region but wider application is inhibited because these probes are difficult to design, expensive and usually require several iterations until a suitable design is achieved. The first part of the paper presents the structure of the software program and the mathematical modelling of the optics for predicting the beam path into the measurement region. The second part presents different design options and the manufacture of a typical probe with validation in a wind tunnel facility using volumetric velocimetry. The borescope results agree very well with measurements acquired using direct illumination through a window demonstrating the efficacy of the method

Competition of lattice and basis for alignment of nematic liquid crystals

Due to elastic anisotropy, two-dimensional patterning of substrates can promote weak azimuthal alignment of adjacent nematic liquid crystals. Here we consider how such alignment can be achieved using a periodic square lattice of circular or elliptical motifs. In particular, we examine ways in which the lattice and motif can combine to favor differing orientations. Using Monte Carlo simulation and continuum elasticity we find, for circular motifs, that the coverage fraction controls both the polar anchoring angle and a transition in the azimuthal orientation. If the circles are generalized to ellipses, arbitrary control of the effective easy axis and effective anchoring potential becomes achievable by appropriate tuning of the ellipse motif relative to the periodic lattice patterning. This has possible applications in both monostable and bistable liquid crystal device contexts

Gene-based outcome prediction in multiple cohorts of pediatric T-cell acute lymphoblastic leukemia: a Children's Oncology Group study

<p>Abstract</p> <p>Background</p> <p>Continuous complete clinical remission in T-cell acute lymphoblastic leukemia (T-ALL) is now approaching 80% due to the implementation of aggressive chemotherapy protocols but patients that relapse continue to have a poor prognosis. Such patients could benefit from augmented therapy if their clinical outcome could be more accurately predicted at the time of diagnosis. Gene expression profiling offers the potential to identify additional prognostic markers but has had limited success in generating robust signatures that predict outcome across multiple patient cohorts. This study aimed to identify robust gene classifiers that could be used for the accurate prediction of relapse in independent cohorts and across different experimental platforms.</p> <p>Results</p> <p>Using HG-U133Plus2 microarrays we modeled a five-gene classifier (5-GC) that accurately predicted clinical outcome in a cohort of 50 T-ALL patients. The 5-GC was further tested against three independent cohorts of T-ALL patients, using either qRT-PCR or microarray gene expression, and could predict patients with significantly adverse clinical outcome in each. The 5-GC featured the interleukin-7 receptor (<it>IL-7R</it>), low-expression of which was independently predictive of relapse in T-ALL patients. In T-ALL cell lines, low <it>IL-7R </it>expression was correlated with diminished growth response to IL-7 and enhanced glucocorticoid resistance. Analysis of biological pathways identified the NF-κB and Wnt pathways, and the cell adhesion receptor family (particularly integrins) as being predictive of relapse. Outcome modeling using genes from these pathways identified patients with significantly worse relapse-free survival in each T-ALL cohort.</p> <p>Conclusions</p> <p>We have used two different approaches to identify, for the first time, robust gene signatures that can successfully discriminate relapse and CCR patients at the time of diagnosis across multiple patient cohorts and platforms. Such genes and pathways represent markers for improved patient risk stratification and potential targets for novel T-ALL therapies.</p

Wnt4 is essential to normal mammalian lung development

AbstractWnt signaling is essential to many events during organogenesis, including the development of the mammalian lung. The Wnt family member Wnt4 has been shown to be required for the development of kidney, gonads, thymus, mammary and pituitary glands. Here, we show that Wnt4 is critical for proper morphogenesis and growth of the respiratory system. Using in situ hybridization in mouse embryos, we identify a previously uncharacterized site of Wnt4 expression in the anterior trunk mesoderm. This expression domain initiates as early as E8.25 in the mesoderm abutting the tracheoesophageal endoderm, between the fusing dorsal aortae and the heart. Analysis of Wnt4−/− embryos reveals severe lung hypoplasia and tracheal abnormalities; however, aortic fusion and esophageal development are unaffected. We find decreased cell proliferation in Wnt4−/− lung buds, particularly in tip domains. In addition, we observe reduction of the important lung growth factors Fgf9, Fgf10, Sox9 and Wnt2 in the lung bud during early stages of organogenesis, as well as decreased tracheal expression of the progenitor factor Sox9. Together, these data reveal a previously unknown role for the secreted protein Wnt4 in respiratory system development

Demonstration of a remotely piloted atmospheric measurement and charge release platform for geoengineering

Electric charge is always present in the lower atmosphere. If droplets or aerosols become charged, their behaviour changes, influencing collision, evaporation and deposition. Artificial charge release is an unexplored potential geoengineering technique for modifying fogs, clouds and rainfall. Central to evaluating these processes experimentally in the atmosphere is establishing an effective method for charge delivery. A small charge-delivering Remotely Piloted Aircraft has been specially developed for this, which is electrically propelled. It carries controllable bipolar charge emitters (nominal emission current ±5 µA) beneath each wing, with optical cloud and meteorological sensors integrated into the airframe. Meteorological and droplet measurements are demonstrated to 2 km altitude by comparison with a radiosonde, including within cloud, and successful charge emission aloft verified by using programmed flight paths above an upwards-facing surface electric field mill. This technological approach is readily scalable to provide non-polluting fleets of charge-releasing aircraft, identifying and targeting droplet regions with their own sensors. Beyond geoengineering, agricultural and biological aerosol applications, safe ionic propulsion of future electric aircraft also requires detailed investigation of charge effects on natural atmospheric droplet systems

‘It Takes Two Hands to Clap’: How Gaddi Shepherds in the Indian Himalayas Negotiate Access to Grazing

This article examines the effects of state intervention on the workings of informal institutions that coordinate the communal use and management of natural resources. Specifically it focuses on the case of the nomadic Gaddi shepherds and official attempts to regulate their access to grazing pastures in the Indian Himalayas. It is often predicted that the increased presence of the modern state critically undermines locally appropriate and community-based resource management arrangements. Drawing on the work of Pauline Peters and Francis Cleaver, I identify key instances of socially embedded ‘common’ management institutions and explain the evolution of these arrangements through dynamic interactions between individuals, communities and the agents of the state. Through describing the ‘living space’ of Gaddi shepherds across the annual cycle of nomadic migration with their flocks I explore the ways in which they have been able to creatively reinterpret external interventions, and suggest how contemporary arrangements for accessing pasture at different moments of the annual cycle involve complex combinations of the formal and the informal, the ‘traditional’ and the ‘modern’

Dynamic Analysis of Vascular Morphogenesis Using Transgenic Quail Embryos

Background: One of the least understood and most central questions confronting biologists is how initially simple clusters or sheet-like cell collectives can assemble into highly complex three-dimensional functional tissues and organs. Due to the limits of oxygen diffusion, blood vessels are an essential and ubiquitous presence in all amniote tissues and organs. Vasculogenesis, the de novo self-assembly of endothelial cell (EC) precursors into endothelial tubes, is the first step in blood vessel formation [1]. Static imaging and in vitro models are wholly inadequate to capture many aspects of vascular pattern formation in vivo, because vasculogenesis involves dynamic changes of the endothelial cells and of the forming blood vessels, in an embryo that is changing size and shape. Methodology/Principal Findings: We have generated Tie1 transgenic quail lines Tg(tie1:H2B-eYFP) that express H2B-eYFP in all of their endothelial cells which permit investigations into early embryonic vascular morphogenesis with unprecedented clarity and insight. By combining the power of molecular genetics with the elegance of dynamic imaging, we follow the precise patterning of endothelial cells in space and time. We show that during vasculogenesis within the vascular plexus, ECs move independently to form the rudiments of blood vessels, all while collectively moving with gastrulating tissues that flow toward the embryo midline. The aortae are a composite of somatic derived ECs forming its dorsal regions and the splanchnic derived ECs forming its ventral region. The ECs in the dorsal regions of the forming aortae exhibit variable mediolateral motions as they move rostrally; those in more ventral regions show significant lateral-to-medial movement as they course rostrally. Conclusions/Significance: The present results offer a powerful approach to the major challenge of studying the relative role(s) of the mechanical, molecular, and cellular mechanisms of vascular development. In past studies, the advantages of the molecular genetic tools available in mouse were counterbalanced by the limited experimental accessibility needed for imaging and perturbation studies. Avian embryos provide the needed accessibility, but few genetic resources. The creation of transgenic quail with labeled endothelia builds upon the important roles that avian embryos have played in previous studies of vascular development