Chasing the dragon – an overview of heroin trafficking

There are many problems encountered during the attempt to tackle the heroin trade on a global level. Afghanistan is largely responsible for the production of heroin, providing a global distribution amount of 75%. The trafficking of heroin has continued using the traditional Balkan and Northern routes, however due to the increase in intelligence and border force controls, alternative routes are being established. This demonstrates a key issue being faced by law enforcement agencies. The development in strategies and techniques being used for undetected smuggling are growing, causing a lapse in the effectiveness of detection techniques currently being used. The failure in the success of tackling heroin production and trade towards Europe is being increasingly recognised, which has resulted in a shift in focus onto the organised crime groups involved in the heroin trade within mainland Europe and the United Kingdom. An estimated 5,300 organised crime groups are believed to be active within the United Kingdom with an annual cost of in the region of between £20-40 billion. The complexity and level of intelligence within organised crime has evolved rapidly, and this, along with the increasing levels of corruption within heroin trading countries, give reason for the continual loss of the war against heroin. Concluding that until corruption and the highest hierarchical levels within organised crime groups are overthrown, positive results against the heroin trade will remain unseen, demonstrating that these key areas require further attention by governmental agencies and policies if the war is to be won

Predicting protein function with hierarchical phylogenetic profiles: The Gene3D phylo-tuner method applied to eukaryotic Genomes

"Phylogenetic profiling'' is based on the hypothesis that during evolution functionally or physically interacting genes are likely to be inherited or eliminated in a codependent manner. Creating presence-absence profiles of orthologous genes is now a common and powerful way of identifying functionally associated genes. In this approach, correctly determining orthology, as a means of identifying functional equivalence between two genes, is a critical and nontrivial step and largely explains why previous work in this area has mainly focused on using presence-absence profiles in prokaryotic species. Here, we demonstrate that eukaryotic genomes have a high proportion of multigene families whose phylogenetic profile distributions are poor in presence-absence information content. This feature makes them prone to orthology mis-assignment and unsuited to standard profile-based prediction methods. Using CATH structural domain assignments from the Gene3D database for 13 complete eukaryotic genomes, we have developed a novel modification of the phylogenetic profiling method that uses genome copy number of each domain superfamily to predict functional relationships. In our approach, superfamilies are subclustered at ten levels of sequence identity from 30% to 100% - and phylogenetic profiles built at each level. All the profiles are compared using normalised Euclidean distances to identify those with correlated changes in their domain copy number. We demonstrate that two protein families will "auto-tune'' with strong co-evolutionary signals when their profiles are compared at the similarity levels that capture their functional relationship. Our method finds functional relationships that are not detectable by the conventional presence - absence profile comparisons, and it does not require a priori any fixed criteria to define orthologous genes

Incorporation of membrane proteins into large single bilayer vesicles. Application to rhodopsin.

A general procedure to incorporate membrane proteins in a native state into large single bilayer vesicles is described. The results obtained with rhodopsin from vertebrate and invertebrate retinas are presented. The technique involves: (a) the direct transfer of rhodopsin-lipid complexes from native membranes into ether or pentane, and (b) the sonication of the complex in apolar solvent with aqueous buffer followed by solvent evaporation under reduced pressure. The spectral properties of rhodopsin in the large vesicles are similar to those of rhodopsin in photoreceptors; furthermore, bleached bovine rhodopsin is chemically regenerable with 9-cis retinal. These results establish the presence of photochemically functional rhodopsin in the large vesicles. Freeze-fracture replicas of the vesicles reveal that both internal and external leaflets contain numerous particles approximately 80 A in diameter, indicating that rhodopsin is symmetrically distributed within the bilayer. More than 75% of the membrane area is incorporated into vesicles larger than 0.5 micron and approximately 40% into vesicles larger than 1 micron

Avoiding chromosome pathology when replication forks collide

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2013 Macmillan Publishers Limited.Chromosome duplication normally initiates through the assembly of replication fork complexes at defined origins1, 2. DNA synthesis by any one fork is thought to cease when it meets another travelling in the opposite direction, at which stage the replication machinery may simply dissociate before the nascent strands are finally ligated. But what actually happens is not clear. Here we present evidence consistent with the idea that every fork collision has the potential to threaten genomic integrity. In Escherichia coli this threat is kept at bay by RecG DNA translocase3 and by single-strand DNA exonucleases. Without RecG, replication initiates where forks meet through a replisome assembly mechanism normally associated with fork repair, replication restart and recombination4, 5, establishing new forks with the potential to sustain cell growth and division without an active origin. This potential is realized when roadblocks to fork progression are reduced or eliminated. It relies on the chromosome being circular, reinforcing the idea that replication initiation is triggered repeatedly by fork collision. The results reported raise the question of whether replication fork collisions have pathogenic potential for organisms that exploit several origins to replicate each chromosome.THe MRC, the Leverhulme Trust, and the BBSRC

Dynamo driven accretion discs and dwarf nova eruptions

We explore the consequences of a magnetic dynamo origin for the viscosity in accretion discs, for the structure and evolution of discs in dwarf nova systems. We propose that the rapid cooling that sets in at the end of a dwarf nova eruption acts to inhibit the Balbus-Hawley instability, and thereby to quench dynamo action and so reduce disc viscosity. We demonstrate that a modified disc instability model can reproduce the basic properties of dwarf nova eruptions, as well as some properties of quiescent discs. We also discuss some observational consequences of our model.Comment: uu-encoded gz-compressed Postscript file, 18 pages including 6 figures. ApJ in pres

Characterization of pathogenic germline mutations in human Protein Kinases

Background: Protein Kinases are a superfamily of proteins involved in crucial cellular processes such as cell cycle regulation and signal transduction. Accordingly, they play an important role in cancer biology. To contribute to the study of the relation between kinases and disease we compared pathogenic mutations to neutral mutations as an extension to our previous analysis of cancer somatic mutations. First, we analyzed native and mutant proteins in terms of amino acid composition. Secondly, mutations were characterized according to their potential structural effects and finally, we assessed the location of the different classes of polymorphisms with respect to kinase-relevant positions in terms of subfamily specificity, conservation, accessibility and functional sites.Results: Pathogenic Protein Kinase mutations perturb essential aspects of protein function, including disruption of substrate binding and/or effector recognition at family-specific positions. Interestingly these mutations in Protein Kinases display a tendency to avoid structurally relevant positions, what represents a significant difference with respect to the average distribution of pathogenic mutations in other protein families.Conclusions: Disease-associated mutations display sound differences with respect to neutral mutations: several amino acids are specific of each mutation type, different structural properties characterize each class and the distribution of pathogenic mutations within the consensus structure of the Protein Kinase domain is substantially different to that for non-pathogenic mutations. This preferential distribution confirms previous observations about the functional and structural distribution of the controversial cancer driver and passenger somatic mutations and their use as a proxy for the study of the involvement of somatic mutations in cancer development. © 2011 Izarzugaza et al; licensee BioMed Central Ltd

The admission of accession countries to an enlarged monetary union: a tentative assessment

The enlargement of the European monetary union to include the accession countries (ACs) will not lead to higher average inflation in the enlarged euro area, but only to inflation redistribution across countries if continuity of the monetary policy framework is preserved. In the short term, unanticipated shocks to the real exchange rate may instead affect aggregate inflation if member countries' economic structure differs. When comparing welfare, inflation and output stabilisation, we find that the size, differences in economic structure and the variance-covariance matrix of supply and real exchange rate shocks play a key role. The numerical results indicate that the implications for the euro area are significant only if we assume a strong real exchange rate appreciation and if ACs are weighted in terms of purchasing power parity standards. In the event of real exchange rate or country-specific supply shocks in ACs, the consequences would be limited for both the current and the enlarged euro area, but sizeable for ACs themselves. JEL Classification: E52, E58, F33, F40Accession Countries, Balassa-Samuelson Effect, European Monetary Union, Exchange Rate Regimes, monetary policy

The importance of electron temperature in silicon-based terahertz quantum cascade lasers

Quantum cascade lasers (QCLs) are compact sources of coherent terahertz radiation. Although all existing QCLs use III-V compound semiconductors, silicon-based devices are highly desirable due to the high thermal conductivity and mature processing technology. We use a semiclassical rate-equation model to show that Ge/SiGe THz QCL active region gain is strongly enhanced by reducing the electron temperature. We present a bound-to-continuum QCL design employing L-valley intersubband transitions, using high Ge fraction barriers to reduce interface roughness scattering, and a low electric field to reduce the electron temperature. We predict a gain of similar to 50 cm(-1), which exceeds the calculated waveguide losses. (C) 2009 American Institute of Physics. [doi: 10.1063/1.3237177

The Eastward Enlargement of the European Monetary Union

The enlargement of the European monetary union to include new EU Member States (NMs) will not lead to higher expected inflation in the enlarged euro area, but only to some redistribution of inflation at the country level, if the policy framework of the monetary authority remains invariant. Shocks to the real exchange rate may affect instead aggregate inflation, if member countries' economic structure differs. The numerical results indicate that the impact on steady state inflation of the current euro area is limited if participating countries are weighted on the basis of nominal GDP and if the upward pressure on the real exchange rate is postulated to be in line with most estimates of the Balassa-Samuelson effect. In the event of real exchange rate or country-specific supply shocks in NMs, the consequences are found to be limited for the current and the enlarged euro area, but sizeable for the NMs themselves.EMU; enlargement; East-Central Europe

Persistence of two genotypes of Neisseria gonorrhoeae during transmission.

Isolates of Neisseria gonorrhoeae were tested using a highly discriminatory typing method, opa typing, to examine the genetic diversity over a 2-year study period of isolates from all consecutive patients with gonorrhea attending the Genitourinary Medicine clinic in Sheffield, United Kingdom. Two opa genotypes were detected throughout the 2-year time period and comprised 41% of all strains tested. The persistence of two opa types was investigated further to determine the apparent genetic stability, by examining the ability of isolates to undergo intragenic and intergenic recombination and mutation in vitro. Intragenic recombination or mutation involving the opa genes of N. gonorrhoeae in the selected isolates was not detected, but intergenic recombination did occur. opa genes of N. gonorrhoeae in vivo appear to diversify primarily through intergenic recombination. Intergenic recombination in vivo would require the presence of a mixed gonococcal infection, in which an individual is concurrently colonized with more than one strain of N. gonorrhoeae. We propose that the level of diversity of opa genotypes in a population is linked to the degree of sexual mixing of individuals and the incidence of mixed infections of N. gonorrhoeae