Merging Continuous Flow Technology, Photochemistry and Biocatalysis to Streamline Steroid Synthesis

Since their structural elucidation in 1935, the introduction and substitution of functional groups and the modification of the steroidal scaffolds have been a fertile ground of research for synthetic and medicinal chemists. The discovery of steroids with hormonal and pharmacological activity has stimulated tremendous efforts to the development of highly selective and efficient synthetic procedures. Despite the progress made, steroid chemistry remains challenging and the preparation of steroidal compounds of pharmaceutical interests and in clinical practice, often requires long and elaborated synthesis. In recent years, a new impetus in the field came with the advent of enabling chemical technologies, such as continuous flow chemistry, which are exploited to overcome problems that arise from batch synthesis. Although it is still a niche sector, the use of flow technology in steroid synthesis and functionalization holds the premise to empower methodology development and to provide innovative tactics also for many hitherto uncharted chemistries. In this review, scientific contributions are reported and discussed in terms of flow set-up and advantages offered concerning process efficiency, optimization, waste minimization, safety improvement, easy scale-up and costs. We also highlight the main challenges, key improvements and the future trajectory in the application of continuous flow chemistry and its implementation to different disciplines such as photochemistry and biocatalysis with the ultimate goal of streamlining steroid synthesis

Precision Measurement of the 29Si, 33S, and 36Cl Binding Energies

The binding energies of 29Si, 33S, and 36Cl have been measured with a relative uncertainty $< 0.59 \times 10^{-6}$ using a flat-crystal spectrometer. The unique features of these measurements are 1) nearly perfect crystals whose lattice spacing is known in meters, 2) a highly precise angle scale that is derived from first principles, and 3) a gamma-ray measurement facility that is coupled to a high flux reactor with near-core source capability. The binding energy is obtained by measuring all gamma-rays in a cascade scheme connecting the capture and ground states. The measurements require the extension of precision flat-crystal diffraction techniques to the 5 to 6 MeV energy region, a significant precision measurement challenge. The binding energies determined from these gamma-ray measurements are consistent with recent highly accurate atomic mass measurements within a relative uncertainty of $4.3 \times 10^{-7}$. The gamma-ray measurement uncertainties are the dominant contributors to the uncertainty of this consistency test. The measured gamma-ray energies are in agreement with earlier precision gamma-ray measurements.Comment: 13 pages, 4 figure

Occupational asphyxiation by unknown compound(s): Environmental and toxicological approach

During a routine truck-tank washing operation, five healthy workers were found motionless inside an empty tanker. Four of them died inside the tanker while the fifth died the following day in hospital. Since the true nature of the fatal compound(s) were not known, a rigorous environmental and toxicological approach supported by autopsy findings was essential to clarify the cause of death.Environmental results indicated that H2S fumes arising from the liquid sulfur previously shipped were responsible for the serial deaths, also confirmed by a simulation performed on two similar truck-tanks.These environmental findings were supported by toxicological analyses through the measurement of thiosulfate, one of the main H2S metabolites. Abnormal thiosulfate concentrations from 1.1 to 186.2mg/kg were revealed in all post-mortem biological samples (blood, lung, liver, kidney, brain and fat). Finally, the cluster analysis performed on thiosulfate body distribution contributed to establishing the time of death according to the accident scene reconstruction.This report presents valuable findings in correctly identifying the cause of death in gas asphyxiation cases by unknown compound(s). © 2009 Elsevier Ireland Ltd

Bronchoalveolar lavage, sputum and exhaled clinically relevant inflammatory markers: values in healthy adults.

11noBronchoalveolar lavage (BAL), induced sputum and exhaled breath markers (exhaled nitric oxide and exhaled breath condensate) can each provide biological insights into the pathogenesis of respiratory disorders. Some of their biomarkers are also employed in the clinical management of patients with various respiratory diseases. In the clinical context, however, defining normal values and cut-off points is crucial. The aim of the present review is to investigate to what extent the issue of defining normal values in healthy adults has been pursued for the biomarkers with clinical value. The current authors reviewed data from literature that specifically addressed the issue of normal values from healthy adults for the four methodologies. Most studies have been performed for BAL (n = 9), sputum (n = 3) and nitric oxide (n = 3). There are no published studies for breath condensate, none of whose markers yet has clinical value. In healthy adult nonsmokers the cut-off points (mean+2sd) for biomarkers with clinical value were as follows. BAL: 16.7% lymphocytes, 2.3% neutrophils and 1.9% eosinophils; sputum: 7.7 x 10(6).mL(-1) total cell count and 2.2% eosinophils; nitric oxide: 20.2 ppb. The methodologies differ concerning the quantity and characteristics of available reference data. Studies focusing on obtaining reference values from healthy individuals are still required, more evidently for the new, noninvasive methodologies.nonemixedBALBI B; PIGNATTI P; CORRADI M; BAIARDI P; BIANCHI L; BRUNETTI G; RADAELI A; MOSCATO G; MUTTI A; SPANEVELLO A; MALERBA MBalbi, B; Pignatti, P; Corradi, M; Baiardi, P; Bianchi, L; Brunetti, G; Radaeli, A; Moscato, G; Mutti, A; Spanevello, Antonio; Malerba, M

Characterization of clastic sedimentary enviroments by clustering algorithm and several statistical approaches — case study, Sava Depression in Northern Croatia

Abstract This study demonstrates a method to identify and characterize some facies of turbiditic depositional environments. The study area is a hydrocarbon field in the Sava Depression (Northern Croatia). Its Upper Miocene reservoirs have been proved to represent a lacustrine turbidite system. In the workflow, first an unsupervised neural network was applied as clustering method for two sandstone reservoirs. The elements of the input vectors were the basic petrophysical parameters. In the second step autocorrelation surfaces were used to reveal the hidden anisotropy of the grid. This anisotropy is supposed to identify the main continuity directions in the geometrical analyses of sandstone bodies. Finally, in the description of clusters several parametric and nonparametric statistics were used to characterize the identified facies. Obtained results correspond to the previously published interpretation of those reservoir facies

Biomarkers of nucleic acid oxidation, polymorphism in, and expression of, hOGG1 gene in styrene-exposed workers.

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Reduction in the uncertainty of the neutron-capture cross section of 210Bi: Impact of a precise multipolarity measurement of the 2− → 1− main ground-state transition

International audience; The mixing ratio of the main 320-keV, M1 + E2 ground-state γ transition in 210Bi has been more precisely quantified, allowing a significant reduction in the uncertainty of measurements of the neutron-capture cross section to the ground state of 210Bi from 25% to 0.9%. Accurate values for neutron-capture cross sections to both the ground and long-lived 9− isomeric state at 271 keV in 210Bi are of particular importance as Pb-Bi finds increased usage in Accelerator Driven Systems

Spectroscopic investigation of quantum confinement effects in ion implanted silicon-on-sapphire films

Crystalline Silicon-on-Sapphire (SOS) films were implanted with boron (B$^+$) and phosphorous (P$^+$) ions. Different samples, prepared by varying the ion dose in the range $10^{14}$ to 5 x $10^{15}$ and ion energy in the range 150-350 keV, were investigated by the Raman spectroscopy, photoluminescence (PL) spectroscopy and glancing angle x-ray diffraction (GAXRD). The Raman results from dose dependent B$^+$ implanted samples show red-shifted and asymmetrically broadened Raman line-shape for B$^+$ dose greater than $10^{14}$ ions cm$^{-2}$. The asymmetry and red shift in the Raman line-shape is explained in terms of quantum confinement of phonons in silicon nanostructures formed as a result of ion implantation. PL spectra shows size dependent visible luminescence at $\sim$ 1.9 eV at room temperature, which confirms the presence of silicon nanostructures. Raman studies on P$^+$ implanted samples were also done as a function of ion energy. The Raman results show an amorphous top SOS surface for sample implanted with 150 keV P$^+$ ions of dose 5 x $10^{15}$ ions cm$^{-2}$. The nanostructures are formed when the P$^+$ energy is increased to 350 keV by keeping the ion dose fixed. The GAXRD results show consistency with the Raman results.Comment: 9 Pages, 6 Figures and 1 Table, \LaTex format To appear in SILICON(SPRINGER

(n,&#947;) reactions on rare Ca isotopes: Valence-hole - Coreexcitation couplings in47Ca

Recent results on the structure of 47Ca will be presented. The nucleus of interest was populated via the cold-neutron capture 46Ca(n,\u3b3) reaction, on a rare 46Ca target, during the EXILL experimental campaign at the nuclear reactor of Institut Laue- Langevin in Grenoble. High-resolution \u3b3-ray spectroscopy, performed with a composite array of HPGe detectors, enabled the identification of new transitions deexciting states between the neutron-capture level and the ground state. Experimental data will be compared with a novel microscopic theoretical model, currently under development, specifically designed to describe the low-lying structure of odd-mass nuclei with one valence particle/hole outside a spherical doubly-magic core, using the Skyrme effective interaction self-consistently

Contrasting properties of particle-particle and hole-hole excitations in 206Tl and 210Bi nuclei

A complete-spectroscopy investigation of low-lying, low-spin states in the one-proton-hole and one-neutron-hole nucleus 206Tl has been performed by using thermal neutron capture and \u3b3-coincidence technique with the FIPPS Ge array at ILL Grenoble. The new experimental results, together with data for the one-proton-particle and one-neutron-particle nucleus 210Bi (taken from a previous study done at ILL in the EXILL campaign), allowed for an extensive comparison with predictions of shell-model calculations performed with realistic interactions. No phenomenological adjustments were introduced in the calculations. In 210Bi, state energies, transition multipolarities and decay branchings agree well with theory for the three well separated multiplets of states which dominate the low-lying excitations. On the contrary, in 206Tl significant discrepancies are observed: in the same energy region, six multiplets were identified, with a significant mixing among them being predicted, as a consequence of the smaller energy separation between the active orbitals. The discrepancies in 206Tl are attributed to the larger uncertainties in the determination of the off-diagonal matrix elements of the realistic shell-model interaction with respect to the calculated diagonal matrix elements, the only ones playing a major role in the case of 210Bi. The work points to the need of more advanced approaches in the construction of the realistic interactions