Fatal poisoning in drug addicts in the Nordic countries in 2017

This study is the seventh report on fatal poisonings among drug addicts in the Nordic countries. In this report, we analyse data from the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. Data on gender, number of deaths, places of deaths, age, main intoxicants and substances detected in blood were recorded to obtain national and comparable Nordic data, and to allow comparison with earlier studies conducted in 1984, 1991, 1997, 2002, 2007 and 2012. The death rate (number of deaths per 100,000 inhabitants) was highest in Iceland (6.58) followed closely by Sweden (6.46) and then lowest in Denmark (4.29). The death rate increased in Finland (5.84), Iceland and Sweden and decreased in Denmark compared to earlier studies. The death rate in Norway, which has decreased since 2002, has stabilised around 5.7 as of 2017. Women accounted for 7-23% of the fatal poisonings. The percentage was lowest in Iceland and highest in Finland and Norway. The age range was 14-70 years. The median age (41 years) was highest in Denmark and Norway. The other countries had a median age between 33 and 35 years. Opioids were the main cause of death. Methadone remained the main intoxicant in Denmark, while heroin/morphine was still the main intoxicant in Norway, as was buprenorphine in Finland. However, the picture has changed in Sweden compared to 2012, where heroin/morphine caused most deaths in 2017. Sweden also experienced the highest number of deaths from fentanyl analogues (67 deaths) and buprenorphine (61 deaths). Deaths from fentanyl analogues also occurred in Denmark, Finland and Norway, but to a smaller extent. Over the years, the proportion of opioid deaths has decreased in all countries except Sweden, which has experienced an increase. This decline has been replaced by deaths from CNS stimulants like cocaine, amphetamine and methylenedioxymethamphetamine (MDMA). Cocaine deaths have occurred in all countries but most frequently in Denmark. MDMA deaths have increased in all countries but mostly in Finland. Poly-drug use was widespread, as seen in the earlier studies. The median number of detected drugs per case varied from 4-6. Heroin/morphine, methadone, buprenorphine, cocaine, amphetamine, methamphetamine, MDMA, tetrahydrocannabinol (THC) and benzodiazepines were frequently detected. Pregabalin and gabapentin were detected in all countries, especially pregabalin, which was detected in 42% of the Finnish cases. New psychoactive substances (NPS) occurred in all countries except Iceland. (C) 2020 Elsevier B.V. All rights reserved.Peer reviewe

GaAs:Mn nanowires grown by molecular beam epitaxy of (Ga,Mn)As at MnAs segregation conditions

GaAs:Mn nanowires were obtained on GaAs(001) and GaAs(111)B substrates by molecular beam epitaxial growth of (Ga,Mn)As at conditions leading to MnAs phase separation. Their density is proportional to the density of catalyzing MnAs nanoislands, which can be controlled by the Mn flux and/or the substrate temperature. Being rooted in the ferromagnetic semiconductor (Ga,Mn)As, the nanowires combine one-dimensional properties with the magnetic properties of (Ga,Mn)As and provide natural, self assembled structures for nanospintronics.Comment: 13 pages, 6 figure

Correlating the nanostructure and electronic properties of InAs nanowires

The electronic properties and nanostructure of InAs nanowires are correlated by creating multiple field effect transistors (FETs) on nanowires grown to have low and high defect density segments. 4.2 K carrier mobilities are ~4X larger in the nominally defect-free segments of the wire. We also find that dark field optical intensity is correlated with the mobility, suggesting a simple route for selecting wires with a low defect density. At low temperatures, FETs fabricated on high defect density segments of InAs nanowires showed transport properties consistent with single electron charging, even on devices with low resistance ohmic contacts. The charging energies obtained suggest quantum dot formation at defects in the wires. These results reinforce the importance of controlling the defect density in order to produce high quality electrical and optical devices using InAs nanowires.Comment: Related papers at http://pettagroup.princeton.ed

Unintentional high density p-type modulation doping of a GaAs/AlAs core-multi-shell nanowire

Achieving significant doping in GaAs/AlAs core/shell nanowires (NWs) is of considerable technological importance but remains a challenge due to the amphoteric behavior of the dopant atoms. Here we show that placing a narrow GaAs quantum well in the AlAs shell effectively getters residual carbon acceptors leading to an \emph{unintentional} p-type doping. Magneto-optical studies of such a GaAs/AlAs core multi-shell NW reveal quantum confined emission. Theoretical calculations of NW electronic structure confirm quantum confinement of carriers at the core/shell interface due to the presence of ionized carbon acceptors in the 1~nm GaAs layer in the shell. Micro-photoluminescence in high magnetic field shows a clear signature of avoided crossings of the $n=0$ Landau level emission line with the $n=2$ Landau level TO phonon replica. The coupling is caused by the resonant hole-phonon interaction, which points to a large 2D hole density in the structure.Comment: just published in Nano Letters (http://pubs.acs.org/doi/full/10.1021/nl500818k

DNA building blocks: keeping control of manufacture

Ribonucleotide reductase (RNR) is the only source for de novo production of the four deoxyribonucleoside triphosphate (dNTP) building blocks needed for DNA synthesis and repair. It is crucial that these dNTP pools are carefully balanced, since mutation rates increase when dNTP levels are either unbalanced or elevated. RNR is the major player in this homeostasis, and with its four different substrates, four different allosteric effectors and two different effector binding sites, it has one of the most sophisticated allosteric regulations known today. In the past few years, the structures of RNRs from several bacteria, yeast and man have been determined in the presence of allosteric effectors and substrates, revealing new information about the mechanisms behind the allosteric regulation. A common theme for all studied RNRs is a flexible loop that mediates modulatory effects from the allosteric specificity site (s-site) to the catalytic site for discrimination between the four substrates. Much less is known about the allosteric activity site (a-site), which functions as an on-off switch for the enzyme's overall activity by binding ATP (activator) or dATP (inhibitor). The two nucleotides induce formation of different enzyme oligomers, and a recent structure of a dATP-inhibited α6β2 complex from yeast suggested how its subunits interacted non-productively. Interestingly, the oligomers formed and the details of their allosteric regulation differ between eukaryotes and Escherichia coli Nevertheless, these differences serve a common purpose in an essential enzyme whose allosteric regulation might date back to the era when the molecular mechanisms behind the central dogma evolved

Structure of the Nucleotide Radical Formed during Reaction of CDP/TTP with the E441Q-α2β2 of E. coli Ribonucleotide Reductase

The Escherichia coli ribonucleotide reductase (RNR) catalyzes the conversion of nucleoside diphosphates to deoxynucleotides and requires a diferric-tyrosyl radical cofactor for catalysis. RNR is composed of a 1:1 complex of two homodimeric subunits: α and β. Incubation of the E441Q-α mutant RNR with substrate CDP and allosteric effector TTP results in loss of the tyrosyl radical and formation of two new radicals on the 200 ms to min time scale. The first radical was previously established by stopped flow UV/vis spectroscopy and pulsed high field EPR spectroscopy to be a disulfide radical anion. The second radical was proposed to be a 4′-radical of a 3′-keto-2′-deoxycytidine 5′-diphosphate. To identify the structure of the nucleotide radical [1′-[superscript 2]H], [2′-[superscript 2]H], [4′-[superscript 2]H], [5′-[superscript 2]H], [U−[superscript 13]C, [superscript 15]N], [U−[superscript 15]N], and [5,6 -[superscript 2]H] CDP and [β-[superscript 2]H] cysteine-α were synthesized and incubated with E441Q-α2β2 and TTP. The nucleotide radical was examined by 9 GHz and 140 GHz pulsed EPR spectroscopy and 35 GHz ENDOR spectroscopy. Substitution of [superscript 2]H at C4′ and C1′ altered the observed hyperfine interactions of the nucleotide radical and established that the observed structure was not that predicted. DFT calculations (B3LYP/IGLO-III/B3LYP/TZVP) were carried out in an effort to recapitulate the spectroscopic observations and lead to a new structure consistent with all of the experimental data. The results indicate, unexpectedly, that the radical is a semidione nucleotide radical of cytidine 5′-diphosphate. The relationship of this radical to the disulfide radical anion is discussed.National Institutes of Health (U.S.) (GM29595)(EB002804)(EB002026

Function of the Diiron Cluster of Escherichia coli Class Ia Ribonucleotide Reductase in Proton-Coupled Electron Transfer

The class Ia ribonucleotide reductase (RNR) from Escherichia coli employs a free-radical mechanism, which involves bidirectional translocation of a radical equivalent or “hole” over a distance of ~35 Å from the stable diferric/tyrosyl-radical (Y[subscript 122]•) cofactor in the β subunit to cysteine 439 (C[subscript 439]) in the active site of the α subunit. This long-range, intersubunit electron transfer occurs by a multistep “hopping” mechanism via formation of transient amino acid radicals along a specific pathway and is thought to be conformationally gated and coupled to local proton transfers. Whereas constituent amino acids of the hopping pathway have been identified, details of the proton-transfer steps and conformational gating within the β sununit have remained obscure; specific proton couples have been proposed, but no direct evidence has been provided. In the key first step, the reduction of Y[subscript 122]• by the first residue in the hopping pathway, a water ligand to Fe[subscript 1] of the diferric cluster was suggested to donate a proton to yield the neutral Y[subscript 122]. Here we show that forward radical translocation is associated with perturbation of the Mössbauer spectrum of the diferric cluster, especially the quadrupole doublet associated with Fe[subscript 1]. Density functional theory (DFT) calculations verify the consistency of the experimentally observed perturbation with that expected for deprotonation of the Fe[subscript 1]-coordinated water ligand. The results thus provide the first evidence that the diiron cluster of this prototypical class Ia RNR functions not only in its well-known role as generator of the enzyme’s essential Y[subscript 122]•, but also directly in catalysis.National Institutes of Health (U.S.) (GM-29595