Community structure in co-inventor networks affects time to first citation for patents

We have investigated community structure in the co-inventor network of a given cohort of patents and related this structure to the dynamics of how these patents acquire their first citation. A statistically significant difference in the time lag until first citation is linked to whether or not this citation comes from a patent whose listed inventors share membership in the same communities as the inventors of the cited patent. Although the inventor-community structures identified by different community-detection algorithms differ in several aspects, including the community-size distribution, the magnitude of the difference in time to first citation is robustly exhibited. Our work is able to quantify the expected acceleration of knowledge flow within inventor communities and thereby further establishes the utility of network-analysis tools for studying innovation dynamics.Comment: 16 pages, 4 figures, BioMedCentral article style, to appear in Applied Network Science - special issue 'Community structure in networks

Edge pixel response studies of edgeless silicon sensor technology for pixellated imaging detectors

Silicon sensor technologies with reduced dead area at the sensor's perimeter are under development at a number of institutes. Several fabrication methods for sensors which are sensitive close to the physical edge of the device are under investigation utilising techniques such as active-edges, passivated edges and current-terminating rings. Such technologies offer the goal of a seamlessly tiled detection surface with minimum dead space between the individual modules. In order to quantify the performance of different geometries and different bulk and implant types, characterisation of several sensors fabricated using active-edge technology were performed at the B16 beam line of the Diamond Light Source. The sensors were fabricated by VTT and bump-bonded to Timepix ROICs. They were 100 and 200 μ m thick sensors, with the last pixel-to-edge distance of either 50 or 100 μ m. The sensors were fabricated as either n-on-n or n-on-p type devices. Using 15 keV monochromatic X-rays with a beam spot of 2.5 μ m, the performance at the outer edge and corners pixels of the sensors was evaluated at three bias voltages. The results indicate a significant change in the charge collection properties between the edge and 5th (up to 275 μ m) from edge pixel for the 200 μ m thick n-on-n sensor. The edge pixel performance of the 100 μ m thick n-on-p sensors is affected only for the last two pixels (up to 110 μ m) subject to biasing conditions. Imaging characteristics of all sensor types investigated are stable over time and the non-uniformities can be minimised by flat-field corrections. The results from the synchrotron tests combined with lab measurements are presented along with an explanation of the observed effects

Linking dynamic phenotyping with metabolite analysis to study natural variation in drought responses of Brachypodium distachyon

Drought is an important environmental stress limiting the productivity of major crops worldwide. Understanding drought tolerance and possible mechanisms for improving drought resistance is therefore a prerequisite to develop drought-tolerant crops that produce significant yields with reduced amounts of water. Brachypodium distachyon (Brachypodium) is a key model species for cereals, forage grasses and energy grasses. In this study, initial screening of a Brachypodium germplasm collection consisting of 138 different ecotypes exposed to progressive drought, highlighted the natural variation in morphology, biomass accumulation and responses to drought stress. A core set of ten ecotypes, classified as being either tolerant, susceptible or intermediate, in response to drought stress, were exposed to mild or severe (respectively 15% and 0% soil water content) drought stress and phenomic parameters linked to growth and colour changes were assessed. When exposed to severe drought stress, phenotypic data and metabolite profiling combined with multivariate analysis revealed a remarkable consistency in separating the selected ecotypes into their different pre-defined drought tolerance groups. Increases in several metabolites, including for the phytohormones jasmonic acid and salicylic acid, and TCA-cycle intermediates, were positively correlated with biomass yield and with reduced yellow pixel counts; suggestive of delayed senescence, both key target traits for crop improvement to drought stress. While metabolite analysis also separated ecotypes into the distinct tolerance groupings after exposure to mild drought stress, similar analysis of the phenotypic data failed to do so, confirming the value of metabolomics to investigate early responses to drought stress. The results highlight the potential of combining the analyses of phenotypic and metabolic responses to identify key mechanisms and markers associated with drought tolerance in both the Brachypodium model plant as well as agronomically important crops

Testing small molecule analogues of acanthocheilonema viteae immunomodulator ES-62 against clinically relevant allergens

ES-62 is a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae that protects against ovalbumin (OVA)-induced airway hyper-responsiveness in mice by virtue of covalently attached anti-inflammatory phosphorylcholine (PC) residues. We have recently generated a library of Small Molecule Analogues (SMAs) of ES-62 based around its active PC moiety as a starting point in novel drug development for asthma, and isolated two compounds - termed 11a and 12b – that mirror ES-62’s protective effects. In the present study we have moved away from OVA, a model allergen, to test the two SMAs against two clinically relevant allergens – house dust mite (HDM) and cockroach allergen (CR) extract. We show that whereas both SMAs offer some protection against development of lung allergic responses to CR, in particular reducing eosinophil infiltration, only SMA 12b is effective in protecting against eosinophil-dependent HDM-induced allergy. These data therefore suggest that helminth molecule-induced protection against model antigens may not necessarily translate to clinically relevant antigens. Nevertheless, in the present study we have managed to demonstrate that it is possible to produce synthetic drug-like molecules based on a parasitic worm product that show therapeutic potential with respect to asthma resulting from known triggers in humans

Development of planar pixel modules for the ATLAS high luminosity LHC tracker upgrade

The high-luminosity LHC will present significant challenges for tracking systems. ATLAS is preparing to upgrade the entire tracking system, which will include a significantly larger pixel detector. This paper reports on the development of large area planar detectors for the outer pixel layers and the pixel endcaps. Large area sensors have been fabricated and mounted onto 4 FE-I4 readout ASICs, the so-called quad-modules, and their performance evaluated in the laboratory and testbeam. Results from characterisation of sensors prior to assembly, experience with module assembly, including bump-bonding and results from laboratory and testbeam studies are presented

Protein surface functionalisation as a general strategy for facilitating biomimetic mineralisation of ZIF-8

The durability of enzymes in harsh conditions can be enhanced by encapsulation within metal-organic frameworks (MOFs) via a process called biomimetic mineralisation. Herein we show that the surface charge and chemistry of a protein determines its ability to seed MOF growth. We demonstrate that chemical modification of amino acids on the protein surface is an effective method for systematically controlling biomimetic mineralisation by zeolitic imidazolate framework-8 (ZIF-8). Reaction of surface lysine residues with succinic (or acetic) anhydride facilitates biomimetic mineralisation by increasing the surface negative charge, whereas reaction of surface carboxylate moieties with ethylenediamine affords a more positively charged protein and hinders the process. Moreover, computational studies confirm that the surface electrostatic potential of a protein is a good indicator of its ability to induce biomimetic mineralisation. This study highlights the important role played by protein surface chemistry in encapsulation and outlines a general method for facilitating the biomimetic mineralisation of proteins

eIF4A RNA Helicase Associates with Cyclin-Dependent Protein Kinase A in Proliferating Cells and is Modulated by Phosphorylation

Eukaryotic initiation factor 4A (eIF4A) is a highly conserved RNA-stimulated ATPase and helicase involved in the initiation of messenger RNA translation. Previously, we found that eIF4A interacts with cyclin-dependent kinase A (CDKA), the plant ortholog of mammalian CDK1. Here, we show that this interaction occurs only in proliferating cells where the two proteins coassociate with 5′-cap-binding protein complexes, eIF4F or the plant-specific eIFiso4F. CDKA phosphorylates eIF4A on a conserved threonine residue (threonine-164) within the RNA-binding motif 1b TPGR. In vivo, a phospho-null (APGR) variant of the Arabidopsis (Arabidopsis thaliana) eIF4A1 protein retains the ability to functionally complement a mutant (eif4a1) plant line lacking eIF4A1, whereas a phosphomimetic (EPGR) variant fails to complement. The phospho-null variant (APGR) rescues the slow growth rate of roots and rosettes, together with the ovule-abortion and late-flowering phenotypes. In vitro, wild-type recombinant eIF4A1 and its phospho-null variant both support translation in cell-free wheat germ extracts dependent upon eIF4A, but the phosphomimetic variant does not support translation and also was deficient in ATP hydrolysis and helicase activity. These observations suggest a mechanism whereby CDK phosphorylation has the potential to down-regulate eIF4A activity and thereby affect translation

New interpretation of arterial stiffening due to cigarette smoking using a structurally motivated constitutive model

Cigarette smoking is the leading self-inflicted risk factor for cardiovascular diseases; it causes arterial stiffening with serious sequelea including atherosclerosis and abdominal aortic aneurysms. This work presents a new interpretation of arterial stiffening caused by smoking based on data published for rat pulmonary arteries. A structurally motivated “four fiber family” constitutive relation was used to fit the available biaxial data and associated best-fit values of material parameters were estimated using multivariate nonlinear regression. Results suggested that arterial stiffening caused by smoking was reflected by consistent increase in an elastin-associated parameter and moreover by marked increase in the collagen-associated parameters. That is, we suggest that arterial stiffening due to cigarette smoking appears to be isotropic, which may allow simpler phenomenological models to capture these effects using a single stiffening parameter similar to the approach in isotropic continuum damage mechanics. There is a pressing need, however, for more detailed histological information coupled with more complete biaxial mechanical data for a broader range of systemic arteries

Genetic architecture of variation in Arabidopsis thaliana rosettes

Rosette morphology across Arabidopsis accessions exhibits considerable variation. Here we report a high-throughput phenotyping approach based on automatic image analysis to quantify rosette shape and dissect the underlying genetic architecture. Shape measurements of the rosettes in a core set of Recombinant Inbred Lines from an advanced mapping population (Multiparent Advanced Generation Inter-Cross or MAGIC) derived from inter-crossing 19 natural accessions. Image acquisition and analysis was scaled to extract geometric descriptors from time stamped images of growing rosettes. Shape analyses revealed heritable morphological variation at early juvenile stages and QTL mapping resulted in over 116 chromosomal regions associated with trait variation within the population. Many QTL linked to variation in shape were located near genes related to hormonal signalling and signal transduction pathways while others are involved in shade avoidance and transition to flowering. Our results suggest rosette shape arises from modular integration of sub-organ morphologies and can be considered a functional trait subjected to selective pressures of subsequent morphological traits. On an applied aspect, QTLs found will be candidates for further research on plant architecture