Conformational analysis of new 14-membered ring diketal dilactam macrocycles: molecular mechanics, liquid and solid state NMR studies

A conformational study of new diversely substituted 14-membered diketal dilactam macrocycles was conducted by NMR spectroscopy in liquid and solid states, molecular mechanics calculations and, for one compound, a previous X-ray analysis. The results obtained by the different techniques show that the conformations depend closely on whether the molecules are chiral or achiral and on the stereochemistry of the ketal OMe groups. In achiral compounds, the most stable conformation of each compound has, in both the liquid and solid states, the two NH–CO links positioned perpendicular to the macrocycle plane, lending to the trans-7,7′–OMe macrocycles 6b and 7b a rectangular [3434]-type structure. In contrast, in chiral compounds, the most stable conformations are not the same in the liquid and solid phases. In the liquid state the conformations are set by the presence of one or two N4–HO1′, N4′–HO1 intramolecular hydrogen bonds that position the amide group parallel to the macrocycle plane, whereas in the solid state the amide moieties again adopt a perpendicular position which can be stabilized, when the 3-R substituent is not too bulky, by intermolecular N–HOC bonds between parallel sheets, and exceptionally, in the cis-7,7′-OMe-3,3′-Ph compound 1c, by a π–π stacking effect between the phenyl group

Impact of the June 2018 Saddleworth Moor wildfires on air quality in northern England

The June 2018 Saddleworth Moor fires were some of the largest UK wildfires on record and lasted for approximately three weeks. They emitted large quantities of smoke, trace gases and aerosols which were transported downwind over the highly populated regions of Manchester and Liverpool. Surface observations of PM2.5 indicate that concentrations were 4–5.5 times higher than the recent seasonal average. State-of-the-art satellite measurements of total column carbon monoxide (TCCO) from the TROPOMI instrument on the Sentinel 5—Precursor (S5P) platform, coupled with measurements from a flight of the UK BAe-146–301 research aircraft, are used to quantify the substantial enhancement in emitted trace gases. The aircraft measured plume enhancements with near-fire CO and PM2.5 concentrations >1500 ppbv and >125 μg m−3 (compared to ~100 ppbv and ~5 μg m−3 background concentrations). Downwind fire-plume ozone (O3) values were larger than the near-fire location, indicating O3 production with distance from source. The near-fire O3:CO ratio was (ΔO3/ΔCO) 0.001 ppbv/ppbv, increasing downwind to 0.060–0.105 ppbv/ppbv, suggestive of O3 production enhancement downwind of the fires. Emission rates of CO and CO2 ranged between 1.07 (0.07–4.69) kg s−1 and 13.7 (1.73–50.1) kg s−1, respectively, similar to values expected from a medium sized power station

Atmospheric distribution of HCN from satellite observations and 3-D model simulations

Hydrogen cyanide (HCN) is an important tracer of biomass burning, but there are significant uncertainties in its atmospheric budget, especially its photochemical and ocean sinks. Here we use a tracer version of the TOMCAT global 3-D chemical transport model to investigate the physical and chemical processes driving the abundance of HCN in the troposphere and stratosphere over the period 2004–2016. The modelled HCN distribution is compared with version 4.1 of the Atmospheric Chemistry Experiment Fourier transform spectrometer (ACE-FTS) HCN satellite data, which provide profiles up to around 42 km, and with ground-based column measurements from the Network for the Detection of Atmospheric Composition Change (NDACC). The long-term ACE-FTS measurements reveal the strong enhancements in upper-tropospheric HCN due to large wildfire events in Indonesia in 2006 and 2015. Our 3-D model simulations confirm previous lower-altitude balloon comparisons that the currently recommended NASA Jet Propulsion Laboratory (JPL) reaction rate coefficient of HCN with OH greatly overestimates the HCN loss. The use of the rate coefficient proposed by Kleinböhl et al. (2006) in combination with the HCN oxidation by O(1D) gives good agreement between ACE-FTS observations and the model. Furthermore, the model photochemical loss terms show that the reduction in the HCN mixing ratio with height in the middle stratosphere is mainly driven by the O(1D) sink with only a small contribution from a reaction with OH. From comparisons of the model tracers with ground-based HCN observations we test the magnitude of the ocean sink in two different published schemes (Li et al., 2000, 2003). We find that in our 3-D model the two schemes produce HCN abundances which are very different to the NDACC observations but in different directions. A model HCN tracer using the Li et al. (2000) scheme overestimates the HCN concentration by almost a factor of 2, while a HCN tracer using the Li et al. (2003) scheme underestimates the observations by about one-third. To obtain good agreement between the model and observations, we need to scale the magnitudes of the global ocean sinks by factors of 0.25 and 2 for the schemes of Li et al. (2000) and Li et al. (2003), respectively. This work shows that the atmospheric photochemical sinks of HCN now appear well constrained but improvements are needed in parameterizing the major ocean uptake sink

Low-grade extraskeletal osteosarcoma of the chest wall: case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Low-grade extraskeletal osteosarcomas (ESOS) are extremely rare.</p> <p>Case presentation</p> <p>We present the first case of low-grade ESOS of the chest wall, which occurred in a 30-year-old man. Because of initial misdiagnosis and patient's refusal of surgery, the diagnosis was done after a 4-year history of a slowly growing mass in soft tissues, leading to a huge (30-cm diameter) calcified mass locally extended over the left chest wall. Final diagnosis was helped by molecular analysis of <it>MDM2 </it>and <it>CDK4 </it>oncogenes. Unfortunately, at this time, no surgical treatment was possible due to loco-regional extension, and despite chemotherapy, the patient died one year after diagnosis, five years after the first symptoms.</p> <p>Conclusion</p> <p>We describe the clinical, radiological and bio-pathological features of this unique case, and review the literature concerning low-grade ESOS. Our case highlights the diagnostic difficulties for such very rare tumours and the interest of molecular analysis in ambiguous cases.</p

PAMELA results on the cosmic-ray antiproton flux from 60 MeV to 180 GeV in kinetic energy

The satellite-borne experiment PAMELA has been used to make a new measurement of the cosmic-ray antiproton flux and the antiproton-to-proton flux ratio which extends previously published measurements down to 60 MeV and up to 180 GeV in kinetic energy. During 850 days of data acquisition approximately 1500 antiprotons were observed. The measurements are consistent with purely secondary production of antiprotons in the galaxy. More precise secondary production models are required for a complete interpretation of the results.Comment: 11 pages, 3 figures, 1 table. Accepted for publication in Physical Review Letter

Novel prokaryotic expression of thioredoxin-fused insulinoma associated protein tyrosine phosphatase 2 (IA-2), its characterization and immunodiagnostic application

Background The insulinoma associated protein tyrosine phosphatase 2 (IA-2) is one of the immunodominant autoantigens involved in the autoimmune attack to the beta-cell in Type 1 Diabetes Mellitus. In this work we have developed a complete and original process for the production and recovery of the properly folded intracellular domain of IA-2 fused to thioredoxin (TrxIA-2ic) in Escherichia coli GI698 and GI724 strains. We have also carried out the biochemical and immunochemical characterization of TrxIA-2icand design variants of non-radiometric immunoassays for the efficient detection of IA-2 autoantibodies (IA-2A). Results The main findings can be summarized in the following statements: i) TrxIA-2ic expression after 3 h of induction on GI724 strain yielded ≈ 10 mg of highly pure TrxIA-2ic/L of culture medium by a single step purification by affinity chromatography, ii) the molecular weight of TrxIA-2ic (55,358 Da) could be estimated by SDS-PAGE, size exclusion chromatography and mass spectrometry, iii) TrxIA-2ic was properly identified by western blot and mass spectrometric analysis of proteolytic digestions (63.25 % total coverage), iv) excellent immunochemical behavior of properly folded full TrxIA-2ic was legitimized by inhibition or displacement of [35S]IA-2 binding from IA-2A present in Argentinian Type 1 Diabetic patients, v) great stability over time was found under proper storage conditions and vi) low cost and environmentally harmless ELISA methods for IA-2A assessment were developed, with colorimetric or chemiluminescent detection. Conclusions E. coli GI724 strain emerged as a handy source of recombinant IA-2ic, achieving high levels of expression as a thioredoxin fusion protein, adequately validated and applicable to the development of innovative and cost-effective immunoassays for IA-2A detection in most laboratories.Fil: Guerra, Luciano Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Faccinetti, Natalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Trabucchi, Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Rovitto, Bruno David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Sabljic, Adriana Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Poskus, Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Iacono, Ruben Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Valdez, Silvina Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentin

Diversity of Meiofauna from the 9°50′N East Pacific Rise across a Gradient of Hydrothermal Fluid Emissions

Background: We studied the meiofauna community at deep-sea hydrothermal vents along a gradient of vent fluid emissions in the axial summit trought (AST) of the East Pacific Rise 9 degrees 50'N region. The gradient ranged from extreme high temperatures, high sulfide concentrations, and low pH at sulfide chimneys to ambient deep-sea water conditions on bare basalt. We explore meiofauna diversity and abundance, and discuss its possible underlying ecological and evolutionary processes. Methodology/Principal Findings: After sampling in five physico-chemically different habitats, the meiofauna was sorted, counted and classified. Abundances were low at all sites. A total of 52 species were identified at vent habitats. The vent community was dominated by hard substrate generalists that also lived on bare basalt at ambient deep-sea temperature in the axial summit trough (AST generalists). Some vent species were restricted to a specific vent habitat (vent specialists), but others occurred over a wide range of physico-chemical conditions (vent generalists). Additionally, 35 species were only found on cold bare basalt (basalt specialists). At vent sites, species richness and diversity clearly increased with decreasing influence of vent fluid emissions from extreme flow sulfide chimney (no fauna), high flow pompei worm (S: 4-7, H-loge': 0.11-0.45), vigorous flow tubeworm (S: 8-23; H-loge': 0.44-2.00) to low flow mussel habitats (S: 28-31; H-loge': 2.34-2.60). Conclusions/Significance: Our data suggest that with increasing temperature and toxic hydrogen sulfide concentrations and increasing amplitude of variation of these factors, fewer species are able to cope with these extreme conditions. This results in less diverse communities in more extreme habitats. The finding of many species being present at sites with and without vent fluid emissions points to a non endemic deep-sea hydrothermal vent meiofaunal community. This is in contrast to a mostly endemic macrofauna but similar to what is known for meiofauna from shallow-water vents