Detection of DHCMT long-term metabolite glucuronides with LC-MSMS as an alternative approach to conventional GC-MSMS analysis

Dehydrochloromethyltestosterone (DHCMT) is one of the most detected illicit used anabolic–androgenic steroids in professional sports. Therefore, a fast and accurate analysis of this substance is of great importance for a constructive fight against doping abuse. The conventional method for the analysis of this drug, GC-MSMS, is very sensitive and selective but also very time- and resource-consuming. With the presented work, a new approach for simple detection with LC-HRMSMS without any sample preparation is introduced. The method is based on the direct analysis of two newly described phase-II metabolites of the DHCMT long-term metabolite 4-chloro-18-nor-17β-hydroxymethyl-17α-methyl-5β-androst-13-en-3α-ol (M3). LC-HRMSMS, GC-MSMS, fractionation and derivatization experiments are combined to identify and characterize for the first time two different glucuronide-acid conjugates of this metabolite in positive human urine samples. In addition, a third glucuronide metabolite was identified, however without isomeric structure determination. The detection of these metabolites is particularly interesting for confirmation analyses, as the method is rapid and requires little sample material

Detection of DHCMT long-term metabolite glucuronides with LC-MSMS as an alternative approach to conventional GC-MSMS analysis

Dehydrochloromethyltestosterone (DHCMT) is one of the most detected illicit used anabolic–androgenic steroids in professional sports. Therefore, a fast and accurate analysis of this substance is of great importance for a constructive fight against doping abuse. The conventional method for the analysis of this drug, GC-MSMS, is very sensitive and selective but also very time- and resource-consuming. With the presented work, a new approach for simple detection with LC-HRMSMS without any sample preparation is introduced. The method is based on the direct analysis of two newly described phase-II metabolites of the DHCMT long-term metabolite 4-chloro-18-nor-17β-hydroxymethyl-17α-methyl-5β-androst-13-en-3α-ol (M3). LC-HRMSMS, GC-MSMS, fractionation and derivatization experiments are combined to identify and characterize for the first time two different glucuronide-acid conjugates of this metabolite in positive human urine samples. In addition, a third glucuronide metabolite was identified, however without isomeric structure determination. The detection of these metabolites is particularly interesting for confirmation analyses, as the method is rapid and requires little sample material

Reimann Brake Ramp for planar flow casting processes and analysis of ribbon gluing

Planar flow casting is a rapid solidification process used to manufacture thin, metallic ribbons, and foil. Liquid metal is forced through a nozzle against a heat-sink wheel, and it rapidly solidifies into thin ribbons. A puddle of molten metal, held by surface tension, forms between the nozzle and wheel. This study examines a well-defined periodic surface defect called herringbone (HB), which is commonly produced when casting zirconium based alloys. The presence of this defect is related to processing conditions and puddle dynamics. Its formation has been correlated with the pinning of the liquid puddle at the nozzle edge. Here, the uniformity of thickness along a ribbon was successfully controlled (over a length of 50 m) using the Reimann Brake Ramp, which reduces the wheel speed at the start of the cast. For the alloy used in this study, the variation in the dimensionless thickness parameter, , with the Euler number () at assigned values of followed an allometric scaling, with an exponent value close to the theoretical value of 1/3. Furthermore, the nozzle inclination was related to the ribbon thickness, , and the ribbon quality. Moreover, a newly developed automatized melt spinner permitted monitoring and controlling of the process parameters, elucidating the gluing phenomenon of the ribbon observed during the starting phase. The ribbon gluing was influenced by the puddle geometry, the recirculation in the puddle, and later, to the ribbon cooling rate. Within these results, high-quality ribbons with control thickness over a considerable length are achieved

Imaging signatures of the local density of states in an electronic cavity

We use Scanning Gate Microscopy to study electron transport through an open, gate-defined resonator in a Ga(Al)As heterostructure. Raster-scanning the voltage-biased metallic tip above the resonator, we observe distinct conductance modulations as a function of the tip-position and voltage. Quantum mechanical simulations reproduce these conductance modulations and reveal their relation to the partial local density of states in the resonator. Our measurements illustrate the current frontier between possibilities and limitations in imaging the local density of states in buried electron systems using scanning gate microscopy

Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability

Peer reviewedPublisher PD

Preventing violence against children in schools (PVACS): protocol for a cluster randomised controlled trial of the EmpaTeach behavioural intervention in Nyarugusu refugee camp.

BACKGROUND: We aim to test the effectiveness of the EmpaTeach intervention to prevent physical violence from teachers to students in Nyarugusu Refugee Camp, Tanzania. EmpaTeach is a 10-week, 14-session, classroom management and cognitive-behavioural therapy-based intervention for groups of teachers for delivery by lay personnel in resource-constrained settings. METHODS: We will conduct a two-arm cluster randomized controlled trial (RCT) with parallel assignment and an approximately 1:1 allocation ratio. All primary and secondary schools in Nyarugusu will be invited to participate. Whole schools will be stratified according to whether they are Congolese or Burundian, and primary or secondary schools, then randomised to active intervention or wait-list control conditions via a public meeting with headteachers. We will collect survey data from n = 500 teachers and at least n = 1500 students before the intervention, soon after, and at least 6 months after the end of the intervention. The primary outcome measure will be students' self-reports of experience of physical violence from school staff in the past week, measured using a modified version of the International Society for the Prevention of Child Abuse and Neglect Screening Tool-Child Institutional at the first follow-up after the intervention. Secondary outcomes include emotional violence, depressive symptoms and educational test scores. Analysis will be intention to treat, using repeat cross-sectional data from individuals. DISCUSSION: If successful, the EmpaTeach intervention would represent one of a handful of proven interventions to reduce violence from teachers to students in any setting. IRC provides an immediate platform for scale up of the intervention via its current work in more than 40 conflict-affected countries. TRIAL REGISTRATION: NCT03745573 , registered November 19, 2018 at clinicaltrials.gov, https://clinicaltrials.gov/ct2/show/NCT03745573

Long-term climate change commitment and reversibility: an EMIC intercomparison

This paper summarizes the results of an intercomparison project with Earth System Models of Intermediate Complexity (EMICs) undertaken in support of the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5). The focus is on long-term climate projections designed to: (i) quantify the climate change commitment of different radiative forcing trajectories, and (ii) explore the extent to which climate change is reversible on human timescales. All commitment simulations follow the four Representative Concentration Pathways (RCPs) and their extensions to 2300. Most EMICs simulate substantial surface air temperature and thermosteric sea level rise commitment following stabilization of the atmospheric composition at year-2300 levels. The meridional overturning circulation (MOC) is weakened temporarily and recovers to near pre-industrial values in most models for RCPs 2.6–6.0. The MOC weakening is more persistent for RCP 8.5. Elimination of anthropogenic CO2 emissions after 2300 results in slowly decreasing atmospheric CO2 concentrations. At year 3000 atmospheric CO2 is still at more than half its year-2300 level in all EMICs for RCPs 4.5–8.5. Surface air temperature remains constant or decreases slightly and thermosteric sea level rise continues for centuries after elimination of CO2 emissions in all EMICs. Restoration of atmospheric CO2 from RCP to pre-industrial levels over 100–1000 years requires large artificial removal of CO2 from the atmosphere and does not result in the simultaneous return to pre-industrial climate conditions, as surface air temperature and sea level response exhibit a substantial time lag relative to atmospheric CO2

Global-scale variations of the ratios of carbon to phosphorus in exported marine organic matter

The ratio of carbon (C) to phosphorus (P) in marine phytoplankton is thought to be constant throughout the worlds'oceans. Known as the Redfield ratio, this relationship describes the links between carbon and phosphorus cycling and marine ecosystems. However, variations in the stoichiometry of phytoplankton have recently been identified, in particular strong latitudinal variability. Here we assess the impact of this variability in the C:P ratio of biomass on the C:P ratio of organic matter that is exported to the deep ocean using a biogeochemical inverse-model based on a data-constrained ocean circulation model and a global database of dissolved inorganic carbon and phosphate measurements. We identify global patterns of variability in the C:P ratios of exported organic matter, with higher values in the nutrient-depleted subtropical gyres, where organic matter export is relatively low, and lower ratios in nutrient-rich upwelling zones and high-latitude regions, where organic matter export is high. This suggests that total carbon export is relatively constant throughout the oceans, in agreement with recent estimates of carbon fluxes. We conclude that the latitudinal patterns of C:P in exported organic matter are consistent with the large-scale stoichiometric variations in phytoplankton C:P. We suggest that a future expansion of nutrient-depleted waters could result in a shift to more efficient C export that compensates for the expected decline in productivity

Towards the total synthesis of providencin

Providencin is a highly oxygenated diterpenoid found in the sea plume Antillogorgia Kallos. It features a previously undescribed bicyclo[12.2.0]undecane carbon skeleton containing a tetrasubstituted cyclobutane ring, two trans-fused epoxides and a butenolide moiety. The absolute configuration of providencin remains to be proven. Biological testing revealed modest cytotoxic activity against several human cancer cell lines. This work presents the synthesis of an important building block en route to providencin based on a new retrosynthetic approach. Key steps are an enantioselective Lewis acid-catalyzed cycloaddition reaction to form the cyclobutane ring, a copper-assisted Stille-coupling under very mild conditions and the regioselective deprotection of just one of two trityl protecting groups.7