The double Smiles rearrangement in neutral conditions leading to one of 10-(nitropyridinyl)dipyridothiazine isomers

© 2016 Elsevier B.V.Phenothiazines are reported to exhibit very promising anticancer, antibacterial, antifungal, anti-inflammatory activities, reversal of multidrug resistance and many other actions. Synthesis of phenotiazines is mostly carried cyclization of o-aminodiphenyl sulfides proceeded through the Smiles rearrangement. The modifications of the phenothiazine structure via the substitution of the benzene ring with the pyridine ring gave various pyridobenzothiazines and dipyridothiazines. The reaction of 3-amino-3’-nitro-2,2’-dipyridinyl sulfide with 4-chloro-3-nitropyridine in sole DMF led to one of four possible isomeric nitropyridinyldipyridothiazines. Two-dimensional 1H and 13C NMR experiments (COSY, ROESY, HSQC and HMBC) were used to reveal the right product structure as 10-(3'-nitro-4'-pyridinyl)dipyrido[2,3-b; 2',3’-e] [1,4]thiazine (10-(3'-nitro-4'-pyridinyl)-1,6-diazaphenothiazine). The final structure confirmation came from a single crystal X-ray analysis. This structure is the result of very rare reaction mechanism involving the double Smiles rearrangement of the S[sbnd]N type. The tricyclic dipyridothiazine system is unexpectedly almost planar, with the butterfly angle of 176.39(4)° between two pyridine rings and 174.17(6)° between the halves of the thiazine ring (the NCCS) planes. The pyridinyl substituent is rotated about N10[sbnd]C11 bond and oriented almost perpendicularly to the tricyclic ring system with the dihedral angle between the two planar systems of 94.93(3)°. The nitropyridinyl substituent is located quasi-equatorially with the S⋯N10‒C11 angle of 176.92(8)°. The nitro group is tilted from the pyridine ring by 128.44(8)°

Monte Carlo vs. Pencil Beam based optimization of stereotactic lung IMRT

<p>Abstract</p> <p>Background</p> <p>The purpose of the present study is to compare finite size pencil beam (fsPB) and Monte Carlo (MC) based optimization of lung intensity-modulated stereotactic radiotherapy (lung IMSRT).</p> <p>Materials and methods</p> <p>A fsPB and a MC algorithm as implemented in a biological IMRT planning system were validated by film measurements in a static lung phantom. Then, they were applied for static lung IMSRT planning based on three different geometrical patient models (one phase static CT, density overwrite one phase static CT, average CT) of the same patient. Both 6 and 15 MV beam energies were used. The resulting treatment plans were compared by how well they fulfilled the prescribed optimization constraints both for the dose distributions calculated on the static patient models and for the accumulated dose, recalculated with MC on each of 8 CTs of a 4DCT set.</p> <p>Results</p> <p>In the phantom measurements, the MC dose engine showed discrepancies < 2%, while the fsPB dose engine showed discrepancies of up to 8% in the presence of lateral electron disequilibrium in the target. In the patient plan optimization, this translates into violations of organ at risk constraints and unpredictable target doses for the fsPB optimized plans. For the 4D MC recalculated dose distribution, MC optimized plans always underestimate the target doses, but the organ at risk doses were comparable. The results depend on the static patient model, and the smallest discrepancy was found for the MC optimized plan on the density overwrite one phase static CT model.</p> <p>Conclusions</p> <p>It is feasible to employ the MC dose engine for optimization of lung IMSRT and the plans are superior to fsPB. Use of static patient models introduces a bias in the MC dose distribution compared to the 4D MC recalculated dose, but this bias is predictable and therefore MC based optimization on static patient models is considered safe.</p

Test–retest reliability of handgrip strength measurement in children and preadolescents

This is the final version. Available on open access from MDPI via the DOI in this record. The reliability of handgrip strength (HGS) measurement has been confirmed in adults but has been sparsely addressed in pediatric populations. The aims of this study are twofold: to determine whether sex, age and/or hand-dominance influence the test–retest differences and to establish the reliability level of the HGS measurement in typical developing pediatric participants. A total of 338 participants aged 7–13 years were tested using a digital handgrip strength (HGS) dynamometer (Jamar Plus+ Dynamometer) by the same rater on two testing trials separated by a one-day interval between sessions. The HGS testing was conducted according to the American Society of Hand Therapists recommendations. Relative and absolute reliability statistics were calculated. Age influenced the test–retest difference of the HGS measurement as children compared to preadolescents had lower intraclass correlation coefficients (0.95 vs. 0.98), standard error of measurement (SEM) (0.74 vs. 0.78 kg), smallest detectable difference (SDD) (2.05 vs. 2.16 kg) and higher values of the percentage value of SEM (5.48 vs. 3.44%), normalized SDD (15.52 vs. 9.61%) and a mean difference between the test and retest values (0.50 vs. 0.02 kg) for the dominant hand. The results indicate that the protocol using the Jamar digital handgrip dynamometer is a reliable instrument to measure HGS in participants aged 7–13 years with typical development. Clinicians and researchers therefore can have confidence in determining the minimally clinical effect for HGS

Measurement of the diffractive structure function in deep inelastic scattering at HERA

This paper presents an analysis of the inclusive properties of diffractive deep inelastic scattering events produced in $ep$ interactions at HERA. The events are characterised by a rapidity gap between the outgoing proton system and the remaining hadronic system. Inclusive distributions are presented and compared with Monte Carlo models for diffractive processes. The data are consistent with models where the pomeron structure function has a hard and a soft contribution. The diffractive structure function is measured as a function of \xpom, the momentum fraction lost by the proton, of $\beta$, the momentum fraction of the struck quark with respect to \xpom, and of $Q^2$. The \xpom dependence is consistent with the form \xpoma where $a~=~1.30~\pm~0.08~(stat)~^{+~0.08}_{-~0.14}~(sys)$ in all bins of $\beta$ and $Q^2$. In the measured $Q^2$ range, the diffractive structure function approximately scales with $Q^2$ at fixed $\beta$. In an Ingelman-Schlein type model, where commonly used pomeron flux factor normalisations are assumed, it is found that the quarks within the pomeron do not saturate the momentum sum rule.Comment: 36 pages, latex, 11 figures appended as uuencoded fil