A concise and stereoselective synthesis of (+/−)-erythro-methylphenidate

A concise and stereoselective synthesis of racemic erythro-methylphenidate (1) is described. The coupling reaction between piperidine-2-thione (3) and 2-bromo-2-phenylmethylacetate (4) afforded the β-enaminocarbonyl compound 2 in 60% yield by a modified Eschenmoser sulfide contraction reaction. In most cases the bicyclic thiazolidinone 5 was produced. Diastereoselective reduction of 2 in the presence of borohydrydes furnished the (+/−)-erythro-methylphenidate in good yields with dr >95%.     

A blind algorithm for reverberation-time estimation using subband decomposition of speech signals

An algorithm for blind estimation of reverberation time (RT) in speech signals is proposed. Analysis is restricted to the free-decaying regions of the signal, where the reverberation effect dominates, yielding a more accurate RT estimate at a reduced computational cost. A spectral decomposition is performed on the reverberant signal and partial RT estimates are determined in all signal subbands, providing more data to the statistical-analysis stage of the algorithm, which yields the final RT estimate. Algorithm performance is assessed using two distinct speech databases, achieving 91% and 97% correlation with the RTs measured by a standard nonblind method, indicating that the proposed method blindly estimates the RT in a reliable and consistent manner.     

Expanding the class of general exact solutions for interacting two field kinks

In this work we extend the range of applicability of a method recently introduced where coupled first-order nonlinear equations can be put into a linear form, and consequently be solved completely. Some general consequences of the present extension are then commented.     

Pionic deuterium

Data taking of the PIONIC HYDROGEN project has been completed with a high statistics study of the strong-interaction effects in πD by measuring the Kβ X-radiation for three different target densities with a high resolution Bragg crystal spectrometer. The πD hadronic shift will provide a constraint for the πN isospin scattering lengths extracted from the πH measurement. The hadronic width is directly related to pion production at threshold.     

Markov state models and NMR uncover an overlooked allosteric loop in p53

The tumor suppressor p53 is the most frequently mutated gene in human cancer, and thus reactivation of mutated p53 is a promising avenue for cancer therapy. Analysis of wildtype p53 and the Y220C cancer mutant long-timescale molecular dynamics simulations with Markov state models and validation by NMR relaxation studies has uncovered the involvement of loop L6 in the slowest motions of the protein. Due to its distant location from the DNA-binding surface, the conformational dynamics of this loop has so far remained largely unexplored. We observe mutation-induced stabilization of alternate L6 conformations, distinct from all experimentally-determined structures, in which the loop is both extended and located further away from the DNA-interacting surface. Additionally, the effect of the L6-adjacent Y220C mutation on the conformational landscape of the functionally-important loop L1 suggests an allosteric role to this dynamic loop and the inactivation mechanism of the mutation. Finally, the simulations reveal a novel Y220C cryptic pocket that can be targeted for p53 rescue efforts. Our approach exemplifies the power of the MSM methodology for uncovering intrinsic dynamic and kinetic differences among distinct protein ensembles, such as for the investigation of mutation effects on protein function.

Wildtype and Y220C L1 and L6 loops conformational landscape, with MSM-identified L6 states highlighted on the right.     

Partial Wave Analysis of Chiral NN Interactions

We analyze chiral interactions to N2LO in the light of proton–proton and neutron–proton scattering data published from 1950 to 2013 and discuss under which conditions the chiral constants can be extracted.     

Effective Interactions in the Delta-Shells Potential

We determine two-body Skyrme force parameters from a nucleon–nucleon interaction as a function of the maximal momentum fitting NN scattering data. We find general agreement with V _{low k} interactions based on high quality potentials.