Epithermal Neutron Beam Interference with Cardiac Pacemakers

Peer reviewe

Impacts of winter feeding of reindeer on vegetation and soil in the sub-Arctic: insights from a feeding experiment

The overall impacts of winter feeding, including the effects of both forage and reindeer (Rangifer tarandus), were studied in an experiment in the Hammastunturi herding cooperative (68°N), Finland, with 300 reindeer in a sub-xeric heath forest (35 ha) during March/April 2009 and 2010. The feeding practices on the 50 plots were: (1) feeding with grass silage+hay with leftovers cleared in the spring; (2) feeding with grass silage+hay with leftovers not cleared; and (3) feeding with pellets. In addition, (4) unfenced and (5) fenced control plots were included, on which the reindeer were not fed. No invasive plant species introduced through grass silage+hay were observed on the plots. The coverage of Deschampsia flexuosa increased on grass silage+hay plots after the first winter, and both coverage and height of the grass increased after the second winter. The coverage of Dicranum sp. and Pleurozium schreberi was lower on plots where reindeer were fed with grass silage (leftover silage not cleared) vs. controls. Some dwarf shrubs, e.g., Calluna vulgaris, showed a similar response after the second winter. The N content of Empetrum nigrum was higher on grass silage plots (leftover silage not cleared) after the first winter vs. controls. After two winters, the N content of both E. nigrum and Vaccinium myrtillus was increased. Of the soil variables studied, C/N decreased on grass silage+hay plots vs. fenced controls. We conclude that even a moderate level of feeding may cause changes that can lead to a gradual shift from nutrient-poor heath forest towards a more nutrient-rich type

Mechanisms of polyamine catabolism-induced acute pancreatitis

Abstract Acute pancreatitis is an autodigestive disease, in which the pancreatic tissue is damaged by the digestive enzymes produced by the acinar cells. Among the tissues in the mammalian body, pancreas has the highest concentration of the natural polyamine, spermidine. We have found that pancreas is very sensitive to acute decreases in the concentrations of the higher polyamines, spermidine and spermine. Activation of polyamine catabolism in transgenic rats overexpressing SSAT (spermidine/spermine-N 1 -acetyltransferase) in the pancreas leads to rapid depletion of these polyamines and to acute necrotizing pancreatitis. Replacement of the natural polyamines with methylated polyamine analogues before the induction of acute pancreatitis prevents the development of the disease. As premature trypsinogen activation is a common, early event leading to tissue injury in acute pancreatitis in human and in experimental animal models, we studied its role in polyamine catabolism-induced pancreatitis. Cathepsin B, a lysosomal hydrolase mediating trypsinogen activation, was activated just 2 h after induction of SSAT. Pre-treatment of the rats with bismethylspermine prevented pancreatic cathepsin B activation. Analysis of tissue ultrastructure by transmission electron microscopy revealed early dilatation of rough endoplasmic reticulum, probable disturbance of zymogen packaging, appearance of autophagosomes and later disruption of intracellular membranes and organelles. Based on these results, we suggest that rapid eradication of polyamines from cellular structures leads to premature zymogen activation and autodigestion of acinar cells

Maintaining a Linked Data Cloud and Data Service for Second World War History

One of the great promises of Linked Data is to provide a shared data infrastructure into which new data can be imported and aligned with, forming a sustainable, ever growing Linked Data Cloud (LDC). This paper studies and evaluates this idea in the context of the WarSampo LDC that provides a data infrastructure for Second World War related ontologies and data in Finland, including several mutually linked graphs, totaling ca 12 million triples. Two data integration case studies are presented, where the original WarSampo LDC and the related semantic portal were first extended by a dataset of hundreds of war cemeteries and thousands of photographs of them, and then by another dataset of over 4450 Finnish prisoners of war. As a conclusion, lessons learned are explicated, based on hands-on experience in maintaining the WarSampo LDC in a production environment.Peer reviewe

New approaches to model and study social networks

We describe and develop three recent novelties in network research which are particularly useful for studying social systems. The first one concerns the discovery of some basic dynamical laws that enable the emergence of the fundamental features observed in social networks, namely the nontrivial clustering properties, the existence of positive degree correlations and the subdivision into communities. To reproduce all these features we describe a simple model of mobile colliding agents, whose collisions define the connections between the agents which are the nodes in the underlying network, and develop some analytical considerations. The second point addresses the particular feature of clustering and its relationship with global network measures, namely with the distribution of the size of cycles in the network. Since in social bipartite networks it is not possible to measure the clustering from standard procedures, we propose an alternative clustering coefficient that can be used to extract an improved normalized cycle distribution in any network. Finally, the third point addresses dynamical processes occurring on networks, namely when studying the propagation of information in them. In particular, we focus on the particular features of gossip propagation which impose some restrictions in the propagation rules. To this end we introduce a quantity, the spread factor, which measures the average maximal fraction of nearest neighbors which get in contact with the gossip, and find the striking result that there is an optimal non-trivial number of friends for which the spread factor is minimized, decreasing the danger of being gossiped.Comment: 16 Pages, 9 figure

Structure and tie strengths in mobile communication networks

Electronic databases, from phone to emails logs, currently provide detailed records of human communication patterns, offering novel avenues to map and explore the structure of social and communication networks. Here we examine the communication patterns of millions of mobile phone users, allowing us to simultaneously study the local and the global structure of a society-wide communication network. We observe a coupling between interaction strengths and the network's local structure, with the counterintuitive consequence that social networks are robust to the removal of the strong ties, but fall apart following a phase transition if the weak ties are removed. We show that this coupling significantly slows the diffusion process, resulting in dynamic trapping of information in communities, and find that when it comes to information diffusion, weak and strong ties are both simultaneously ineffective.Comment: 30 pages (manuscript + supplementary material), 11 figure

Poxviruses and paramyxoviruses use a conserved mechanism of STAT1 antagonism to inhibit interferon signaling.

The induction of interferon (IFN)-stimulated genes by STATs is a critical host defense mechanism against virus infection. Here, we report that a highly expressed poxvirus protein, 018, inhibits IFN-induced signaling by binding to the SH2 domain of STAT1, thereby preventing the association of STAT1 with an activated IFN receptor. Despite encoding other inhibitors of IFN-induced signaling, a poxvirus mutant lacking 018 was attenuated in mice. The 2.0 Å crystal structure of the 018:STAT1 complex reveals a phosphotyrosine-independent mode of 018 binding to the SH2 domain of STAT1. Moreover, the STAT1-binding motif of 018 shows similarity to the STAT1-binding proteins from Nipah virus, which, similar to 018, block the association of STAT1 with an IFN receptor. Overall, these results uncover a conserved mechanism of STAT1 antagonism that is employed independently by distinct virus families

Hull Consistency Under Monotonicity

International audienceWe prove that hull consistency for a system of equations or inequalities can be achieved in polynomial time providing that the underlying functions are monotone with respect to each variable. This result holds including when variables have multiple occurrences in the expressions of the functions, which is usually a pitfall for interval-based contractors. For a given constraint, an optimal contractor can thus be enforced quickly under monotonicity and the practical significance of this theoretical result is illustrated on a simple example

A general approach for the site-selective modification of native proteins, enabling the generation of stable and functional antibody-drug conjugates.

Antibody-drug conjugates (ADCs) are a class of targeted therapeutics that utilize the specificity of antibodies to selectively deliver highly potent cytotoxins to target cells. Although recent years have witnessed significant interest in ADCs, problems remain with the standard linkage chemistries used for cytotoxin-antibody bioconjugation. These typically (1) generate unstable constructs, which may lead to premature cytotoxin release, (2) often give a wide variance in drug-antibody ratios (DAR) and (3) have poor control of attachment location on the antibody, resulting in a variable pharmacokinetic profile. Herein, we report a novel divinylpyrimidine (DVP) linker platform for selective bioconjugation via covalent re-bridging of reduced disulfide bonds on native antibodies. Model studies using the non-engineered trastuzumab antibody validate the utility of this linker platform for the generic generation of highly plasma-stable and functional antibody constructs that incorporate variable biologically relevant payloads (including cytotoxins) in an efficient and site-selective manner with precise control over DAR. DVP linkers were also used to efficiently re-bridge both monomeric and dimeric protein systems, demonstrating their potential utility for general protein modification, protein stabilisation or the development of other protein-conjugate therapeutics.AstraZeneca, Cambridge Trusts, EPSRC, BBSRC, Royal Society, MR