Inactivation of dispatched 1 by the chameleon mutation disrupts Hedgehog signalling in the zebrafish embryo

AbstractSearches of zebrafish EST and whole genome shotgun sequence databases for sequences encoding the sterol-sensing domain (SSD) protein motif identified two sets of DNA sequences with significant homology to the Drosophila dispatched gene required for release of secreted Hedgehog protein. Using morpholino antisense oligonucleotides, we found that inhibition of one of these genes, designated Disp1, results in a phenotype similar to that of the “you-type” mutants, previously implicated in signalling by Hedgehog proteins in the zebrafish embryo. Injection of disp1 mRNA into embryos homozygous for one such mutation, chameleon (con) results in rescue of the mutant phenotype. Radiation hybrid mapping localised disp1 to the same region of LG20 to which the con mutation was mapped by meiotic recombination analysis. Sequence analysis of disp1 cDNA derived from homozygous con mutant embryos revealed that both mutant alleles are associated with premature termination codons in the disp1 coding sequence. By analysing the expression of markers of specific cell types in the neural tube, pancreas and myotome of con mutant and Disp1 morphant embryos, we conclude that Disp1 activity is essential for the secretion of lipid-modified Hh proteins from midline structures

Effect of reaction conditions on the distribution of hydroxyl functional groups in HEA- BMA copolymer

Non-functional monomer feedstocks containing alkyl meth(acrylate) components such as butyl acrylate (BA) and butyl methacrylate (BMA) have been replaced or augmented with functional monomers such as 2-hydroxyethyl methacrylate (HEMA) and 2-hydroxyethyl acrylate (HEA) to produce reactive polymer chains of lowered molecular weight (MW) for application in solvent-borne automotive coatings. The polar and functional reactants affects the radical copolymerization kinetics and introduces solvent dependencies.[1] A series of BMA/HEA experiments have been performed at 138 °C to determine the influence of these changing kinetic parameters under starved-feed semi-batch operating conditions. A comparison with BMA/BA copolymerization shows that the influence of hydrogen bonding is small, with the semi-batch system well controlled to HEA contents of up to 50 wt%. Thus, the experiments are well represented by a comprehensive generalized copolymerization model formulated in PREDICI® that considers relevant methacrylate and acrylate side-reactions and uses the chain growth parameters measured in previous kinetic investigations.[2] As well as controlling overall copolymer composition, understanding the distribution of the hydroxyl functional groups among the polymer chains is of importance, as non-functionalized lower-MW chains will not crosslink into the polymer network formed upon application of the coating. A series of BMA/HEA copolymers containing 6.25, 12.5 and 25 wt% HEA were synthesized with weight-average polymer MWs varied between 3000-10000 Da through manipulation of reaction temperature (138 and 160 °C) and initiator loading (2 to 4 mol% relative to monomer) during starved-feed semi-batch operation; at the higher temperature the influence of BMA depropagation becomes more apparent. The amount of non-functional material in the samples is experimentally determined by solvent extraction after forming a crosslinked film, and MWs and HEA contents of the extractable fractions are measured. These experimental results will be compared with predictions from the PREDICI® model as well as a kinetic Monte Carlo representation that calculates how the reactive groups are distributed as a function of polymer chain-length. [1] J. E. S. Schier, R. A. Hutchinson, “The influence of hydrogen bonding on radical chain-growth parameters for butyl methacrylate/2-hydroxyethyl acrylate solution copolymerization”, Polym. Chem. 2016, 7, 4567-4574. [2] J. E. S. Schier, M. Zhang, M. C. Grady, R. A. Hutchinson, “Modeling of Semi-batch Solution Radical Copolymerization of Butyl Methacrylate and 2-Hydroxyethyl Acrylate”, Macromol. React. Eng.. 2018, submitted

Experiencing space–time: the stretched lifeworlds of migrant workers in India

In the relatively rare instances when the spatialities of temporary migrant work, workers’ journeys, and labour-market negotiations have been the subject of scholarly attention, there has been little work that integrates time into the analysis. Building on a case study of low-paid and insecure migrant manual workers in the context of rapid economic growth in India, we examine both material and subjective dimensions of these workers’ spatiotemporal experiences. What does it mean to live life stretched out, multiplyattached to places across national space? What kinds of place attachments emerge for people temporarily sojourning in, rather than moving to, new places to reside and work? Our analysis of the spatiotemporalities of migrant workers’ experiences in India suggests that, over time, this group of workers use their own agency to seek to avoid the experience of humiliation and indignity in employment relations. Like David Harvey, we argue that money needs to be integrated into such analysis, along with space and time. The paper sheds light on processes of exclusion, inequality and diff erentiation, unequal power geometries, and social topographies that contrast with neoliberalist narratives of ‘Indian shining

Development of Readout Interconnections for the Si-W Calorimeter of SiD

The SiD collaboration is developing a Si-W sampling electromagnetic calorimeter, with anticipated application for the International Linear Collider. Assembling the modules for such a detector will involve special bonding technologies for the interconnections, especially for attaching a silicon detector wafer to a flex cable readout bus. We review the interconnect technologies involved, including oxidation removal processes, pad surface preparation, solder ball selection and placement, and bond quality assurance. Our results show that solder ball bonding is a promising technique for the Si-W ECAL, and unresolved issues are being addressed.Comment: 8 pages + title, 6 figure

Is Neolithic land use correlated with demography? An evaluation of pollen-derived land cover and radiocarbon-inferred demographic change from Central Europe

The transformation of natural landscapes in Middle Europe began in the Neolithic as a result of the introduction of food-producing economies. This paper examines the relation between land-cover and demographic change in a regionally restricted case study. The study area is the Western Lake Constance area which has very detailed palynological as well as archaeological records. We compare land-cover change derived from nine pollen records using a pseudo-biomisation approach with 14C date probability density functions from archaeological sites which serve as a demographic proxy. We chose the Lake Constance area as a regional example where the pollen signal integrates a larger spatial pattern. The land-cover reconstructions for this region show first notable impacts at the Middle to Young Neolithic transition. The beginning of the Bronze Age is characterised by increases of arable land and pasture/meadow, whereas the deciduous woodland decreases dramatically. Changes in the land-cover classes show a correlation with the 14C density curve: the correlation is best with secondary woodland in the Young Neolithic which reflects the lake shore settlement dynamics. In the Early Bronze Age, the radiocarbon density correlates with open land-cover classes, such as pasture, meadow and arable land, reflecting a change in the land-use strategy. The close overall correspondence between the two archives implies that population dynamics and land-cover change were intrinsically linked. We therefore see human impact as a key driver for vegetation change in the Neolithic. Climate might have an influence on vegetation development, but the changes caused by human land use are clearly detectable from Neolithic times, at least in these densely settled, mid-altitude landscapes

The ROTSE-III Robotic Telescope System

The observation of a prompt optical flash from GRB990123 convincingly demonstrated the value of autonomous robotic telescope systems. Pursuing a program of rapid follow-up observations of gamma-ray bursts, the Robotic Optical Transient Search Experiment (ROTSE) has developed a next-generation instrument, ROTSE-III, that will continue the search for fast optical transients. The entire system was designed as an economical robotic facility to be installed at remote sites throughout the world. There are seven major system components: optics, optical tube assembly, CCD camera, telescope mount, enclosure, environmental sensing & protection and data acquisition. Each is described in turn in the hope that the techniques developed here will be useful in similar contexts elsewhere.Comment: 19 pages, including 4 figures. To be published in PASP in January, 2003. PASP Number IP02-11

Enabling Future Science and Human Exploration with NASA's Next Generation near Earth and Deep Space Communications and Navigation Architecture

The National Aeronautics and Space Administration (NASA) is studying alternatives for the United States space communications architecture through the 2040 timeframe. This architecture provides communication and navigation services to both human exploration and science missions throughout the solar system. Several of NASA's key space assets are approaching their end of design life and major systems are in need of replacement. The changes envisioned in the relay satellite architecture and capabilities around both Earth and Mars are significant undertakings and occur only once or twice each generation, and therefore is referred to as NASA's next generation space communications architecture. NASA's next generation architecture will benefit from technology and services developed over recent years. These innovations will provide missions with new operations concepts, increased performance, and new business and operating models. Advancements in optical communications will enable high-speed data channels and the use of new and more complex science instruments. Modern multiple beam/multiple access technologies such as those employed on commercial high throughput satellites will enable enhanced capabilities for on-demand service, and with new protocols will help provide Internet-like connectivity for cooperative spacecraft to improve data return and coordinate joint mission objectives. On-board processing with autonomous and cognitive networking will play larger roles to help manage system complexity. Spacecraft and ground systems will coordinate among themselves to establish communications, negotiate link connectivity, and learn to share spectrum to optimize resource allocation. Spacecraft will autonomously navigate, plan trajectories, and handle off-nominal events. NASA intends to leverage the ever-expanding capabilities of the satellite communications industry and foster its continued growth. NASA's technology development will complement and extend commercial capabilities to meet unique space environment requirements and to provide capabilities that are beyond the commercial marketplace. The progress of the communications industry, including the emerging global space internet segment and its planned constellations of 100's of satellites offer additional opportunities for new capability and mission concepts. The opportunities and challenges of a future space architecture require an optimal solution encompassing a global perspective. The concepts and technologies intentionally define an architecture that applies not only to NASA, but to other U.S. government agencies, international space and government agencies, and domestic and international industries to advance the openness, interoperability, and affordability of space communications. Cooperation among the worlds space agencies, their capabilities, standards, operations, and interoperability are key to advancing humankind's understand of the universe and extending human presence into the solar system

The influence of gene expression time delays on Gierer-Meinhardt pattern formation systems

There are numerous examples of morphogen gradients controlling long range signalling in developmental and cellular systems. The prospect of two such interacting morphogens instigating long range self-organisation in biological systems via a Turing bifurcation has been explored, postulated, or implicated in the context of numerous developmental processes. However, modelling investigations of cellular systems typically neglect the influence of gene expression on such dynamics, even though transcription and translation are observed to be important in morphogenetic systems. In particular, the influence of gene expression on a large class of Turing bifurcation models, namely those with pure kinetics such as the Gierer–Meinhardt system, is unexplored. Our investigations demonstrate that the behaviour of the Gierer–Meinhardt model profoundly changes on the inclusion of gene expression dynamics and is sensitive to the sub-cellular details of gene expression. Features such as concentration blow up, morphogen oscillations and radical sensitivities to the duration of gene expression are observed and, at best, severely restrict the possible parameter spaces for feasible biological behaviour. These results also indicate that the behaviour of Turing pattern formation systems on the inclusion of gene expression time delays may provide a means of distinguishing between possible forms of interaction kinetics. Finally, this study also emphasises that sub-cellular and gene expression dynamics should not be simply neglected in models of long range biological pattern formation via morphogens

European Research on Magnetic Nanoparticles for Biomedical Applications: Standardisation Aspects

Magnetic nanoparticles have many applications in biomedicine and other technical areas. Despite their huge economic impact, there are no standardised procedures available to measure their basic magnetic properties. The International Organization for Standardization is working on a series of documents on the definition of characteristics of magnetic nanomaterials. We review previous and ongoing European research projects on characteristics of magnetic nanoparticles and present results of an online survey among European researchers