Development and validation of a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method including 25 novel synthetic opioids in hair and subsequent analysis of a Swiss opioid consumer cohort

Major public health concern is raised by the evidence that common drugs like heroin are now frequently laced or replaced with highly potent novel synthetic opioids (NSOs). The objective of this study was to explore the prevalence and patterns of NSOs in a cohort of Swiss opioid users by hair analysis. Hair analysis is considered an ideal tool for retrospective consumption monitoring. Hair samples from 439 opioid users in Zurich were analyzed. Study inclusion required a previous positive hair test result for heroin metabolites, oxycodone, fentanyl, methadone, or tramadol. The samples were extracted with a two‐step extraction procedure, followed by a targeted LC–MS/MS (QTRAP® 6500+) analysis in multiple reaction monitoring mode for a total of 25 NSOs. The method underwent full validation and demonstrated good selectivity and sensitivity with limits of detection (LOD) as low as 0.1 pg/mg. The analyzed sample cohort demonstrated a positivity rate for NSOs of 2.5%, including the following NSOs: butyrylfentanyl, acrylfentanyl, furanylfentanyl, methoxyacetylfentanyl, ocfentanil, U‐47700, isobutyrylfentanyl and benzylfentanyl. Furthermore, we were able to identify specific consumption patterns among drug users. The results indicate that hair analysis is a valuable tool for investigating the prevalence of NSOs in drug‐using populations, which seems to be low in the case of Swiss opioid users. Nevertheless, the results highlight the need for sensitive analytical detection methods in forensic toxicology to identify and monitor substance distribution in different populations

The elevated Curie temperature and half-metallicity in the ferromagnetic semiconductor Lax_{x}Eu1−x_{1-x}O

Here we study the effect of La doping in EuO thin films using SQUID magnetometry, muon spin rotation ($\mu$SR), polarized neutron reflectivity (PNR), and density functional theory (DFT). The $\mu$SR data shows that the La$_{0.15}$Eu$_{0.85}$O is homogeneously magnetically ordered up to its elevated $T_{\rm C}$. It is concluded that bound magnetic polaron behavior does not explain the increase in $T_{\rm C}$ and an RKKY-like interaction is consistent with the $\mu$SR data. The estimation of the magnetic moment by DFT simulations concurs with the results obtained by PNR, showing a reduction of the magnetic moment per La$_{x}$Eu$_{1-x}$O for increasing lanthanum doping. This reduction of the magnetic moment is explained by the reduction of the number of Eu-4$f$ electrons present in all the magnetic interactions in EuO films. Finally, we show that an upwards shift of the Fermi energy with La or Gd doping gives rise to half-metallicity for doping levels as high as 3.2 %.Comment: 7 pages, 11 figure

Torpor in marsupials: Recent advances

We report new findings about torpor in marsupials with regard to three energy demanding processes: (i) development and growth, (ii) reproduction, and (iii) rewarming. Young marsupials use torpor extensively after they develop endothermy, and torpor is generally deeper and longer than in the same individuals when they reach adult size. Adult marsupials also employ torpor during pregnancy and/or lactation to reduce energy expenditure and perhaps to store fat for later use. Moreover, to enhance the energy-conserving potential of torpor, desert marsupials bask during arousal to minimize energy costs of rewarming. We show that the functions of torpor extend beyond merely reducing energy expenditure during food shortages and that torpor can save substantial amounts of energy even during the rewarming process

Breed and Swine Lymphocyte Antigen Haplotype Differences in Agglutination Titers Following Vaccination with B. Bronchiseptica

Genetic differences in immune response to B. bronchiseptica after vaccination with a commercial B. bronchiseptica bacterin were investigated in 1,069 8-wk-old pigs. These pigs were from 65 litters born in the spring and 66 litters born in the fall of 1982 and were purebreds from the Chester White (n = 128), Duroc (n = 281), Hampshire (n = 143), Landrace (n = 309) and Yorkshire (n = 208) breeds. Each litter was raised separately. Individual pigs were vaccinated im at 4 and 6 wk of age with 2 ml of B. bronchiseptica bacterin. At 8 wk of age, 8 ml of blood were collected from each animal and serum prepared to determine agglutinating antibody titers against B. bronchiseptica bacterin by a bacterial agglutination method. In addition, lymphocytes were separated from 1 ml of heparinized blood and used to determine Swine Lymphocyte Antigen (SLA) haplotypes by using cytotoxic antibodies against the SLA complex. Antisera for 3 SLA haplotypes were made available by the National Institutes of Health. Results indicated that breed of pig (P\u3c.01) and dam of pig (P\u3c.01) affected the immune response of the pig after B. bronchiseptica vaccination. Higher immune response was also associated (P\u3c.05) with one of the SLA haplotypes tested. Heritability estimates for immune response following vaccination were .10 ± .12 (half-sib) and .42 ± .19 (full-sib). Results suggest that the relationship of the SLA complex to immune response in the pig and nonadditive genetic and maternal effects on immune response should be further investigated

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

Understanding Strain‐Induced Phase Transformations in BiFeO3 Thin Films

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113160/1/advs201500041.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113160/2/advs201500041-sup-0001-S1.pd

Physics at a Fermilab Proton Driver

This report documents the physics case for building a 2 MW, 8 GeV superconducting linac proton driver at Fermilab.Comment: 52 pages, 15 figure

Old World megadroughts and pluvials during the Common Era

Climate model projections suggest widespread drying in the Mediterranean Basin and wetting in Fennoscandia in the coming decades largely as a consequence of greenhouse gas forcing of climate. To place these and other “Old World” climate projections into historical perspective based on more complete estimates of natural hydroclimatic variability, we have developed the “Old World Drought Atlas” (OWDA), a set of year-to-year maps of tree-ring reconstructed summer wetness and dryness over Europe and the Mediterranean Basin during the Common Era. The OWDA matches historical accounts of severe drought and wetness with a spatial completeness not previously available. In addition, megadroughts reconstructed over north-central Europe in the 11th and mid-15th centuries reinforce other evidence from North America and Asia that droughts were more severe, extensive, and prolonged over Northern Hemisphere land areas before the 20th century, with an inadequate understanding of their causes. The OWDA provides new data to determine the causes of Old World drought and wetness and attribute past climate variability to forced and/or internal variability

A major genetic locus in <i>Trypanosoma brucei</i> is a determinant of host pathology

The progression and variation of pathology during infections can be due to components from both host or pathogen, and/or the interaction between them. The influence of host genetic variation on disease pathology during infections with trypanosomes has been well studied in recent years, but the role of parasite genetic variation has not been extensively studied. We have shown that there is parasite strain-specific variation in the level of splenomegaly and hepatomegaly in infected mice and used a forward genetic approach to identify the parasite loci that determine this variation. This approach allowed us to dissect and identify the parasite loci that determine the complex phenotypes induced by infection. Using the available trypanosome genetic map, a major quantitative trait locus (QTL) was identified on T. brucei chromosome 3 (LOD = 7.2) that accounted for approximately two thirds of the variance observed in each of two correlated phenotypes, splenomegaly and hepatomegaly, in the infected mice (named &lt;i&gt;TbOrg1&lt;/i&gt;). In addition, a second locus was identified that contributed to splenomegaly, hepatomegaly and reticulocytosis (&lt;i&gt;TbOrg2&lt;/i&gt;). This is the first use of quantitative trait locus mapping in a diploid protozoan and shows that there are trypanosome genes that directly contribute to the progression of pathology during infections and, therefore, that parasite genetic variation can be a critical factor in disease outcome. The identification of parasite loci is a first step towards identifying the genes that are responsible for these important traits and shows the power of genetic analysis as a tool for dissecting complex quantitative phenotypic traits