Density functional theory studies of MTSL nitroxide side chain conformations attached to an activation loop

A quantum-mechanical (QM) method rooted on density functional theory (DFT) linked to the Stochastic Liouville equation (SLE) in the Fokker Planck (FP) form has been employed for the first time to sample the methane-thiosulfonate spin label (MTSL) conformational space attached to the Aurora-A kinase activation loop and to calculate the EPR spectrum. The features of the calculated energy surface allowed us to describe the system in a limited number of rotamers stabilized by interactions of the MTSL side chain and neighbouring residues. The relevant magnetic parameters and the electron paramagnetic resonance (EPR) spectrum were subsequently calculated from the trajectories of the spin probe in the protein environment. The comparison between theoretical and experimental continuous wave (CW) EPR spectra revealed some small differences in the EPR line shape which arises from the combinations of g- and A-values obtained from the conformations selected. The theoretical approach adopted in this work can be used to recognise the contribution of MTSL rotamers to the EPR spectrum in order to help extract structural/dynamics properties of protein from the experimental data

J -Driven dynamic nuclear polarization for sensitizing high field solution state NMR

Dynamic nuclear polarization (DNP) is widely used to enhance solid state nuclear magnetic resonance (NMR) sensitivity. Its efficiency as a generic signal-enhancing approach for liquid state NMR, however, decays rapidly with magnetic field B 0, unless mediated by scalar interactions arising only in exceptional cases. This has prevented a more widespread use of DNP in structural and dynamical solution NMR analyses. This study introduces a potential solution to this problem, relying on biradicals with exchange couplings J ex of the order of the electron Larmor frequency ω E. Numerical and analytical calculations show that in such J ex ≈ ± ω E cases a phenomenon akin to that occurring in chemically induced DNP (CIDNP) happens, leading to different relaxation rates for the biradical singlet and triplet states which are hyperfine-coupled to the nuclear α or β states. Microwave irradiation can then generate a transient nuclear polarization build-up with high efficiency, at all magnetic fields that are relevant in contemporary NMR, and for all rotational diffusion correlation times that occur in small- and medium-sized molecules in conventional solvents. </p

Diffusional Attenuation During Soft Pulses: a Zangger-Sterk Pure Shift iDOSY Experiment

Diffusion-ordered spectroscopy experiments in which existing delays in a parent pulse sequence are used for diffusion encoding – iDOSY experiments – are potentially attractive because of their simplicity and sensitivity. However the calculation of diffusional attenuation in Zangger-Sterk pure shift iDOSY experiments is a very difficult problem to attack analytically, and is more easily approached numerically. Numerical simulations show that for typical experimental conditions, the dependence of diffusional attenuation on diffusion-encoding gradient amplitude is well represented by a shifted Gaussian function. The shift in gradient can be calculated analytically for the limiting case where the selective pulse is replaced by a hard 180° pulse at its midpoint; numerical simulations show that the effect of using different shapes of selective pulse is to scale down this limiting gradient shift by a constant factor that depends on the pulse shape used. The practical consequence is that under the experimental conditions appropriate for small molecules, the pure shift iDOSY method should allow good diffusion coefficient measurements to be made if appropriate allowance is made for the change in effective diffusion-encoding gradient. Parallel sets of numerical simulations and experiments are presented, and a practical application of a Zangger-Sterk pure shift iDOSY experiment to a simple test mixture is illustrated.</p

Easing Migrants’ Access to Public Services:The Palermo’s Hackathon in the easyRights Project

Migrants face many barriers when accessing public services due to their lack of legal, procedural and language-related knowledge. This significantly limits their integration into the local community and civic status. Several studies and practices in the field have proved that co-creation is crucial for innovating and adopting solutions for migrants, increasing their visibility to cope with the needs of local service providers and fostering citizen engagement. The easyRights project aims at combining co-creation and intelligent language-oriented technologies to make it easier for migrants to understand and access the public services they need to use. This chapter presents the experience of one pilot of the easyRights project, aimed at empowering and supporting migrants in enrolling in the registry office of the Palermo municipality. To integrate ICT solutions, a hackathon initiative was organised to transform solution ideas into prototypes. During the 72-hour event, migrants, coders, programmers, social workers and lawyers joined forces to address the challenges migrants faced at each phase of the enrolment into the registry office. The chapter concludes with a focus on the unique outcome of Palermo’s hackathon. It encourages the municipality to reformulate the concept of migrants not as special citizens but rather as potential drivers of innovation processes acknowledging all citizens as a very diverse, fragmented whole, thus enriching the concept of citizenship. The chapter also describes the important role that the use of technology can play in achieving these objectives

Quantum mechanical MRI simulations: Solving the matrix dimension problem

We propose a solution to the matrix dimension problem in quantum mechanical simulations of MRI (magnetic resonance imaging) experiments on complex molecules. This problem is very old; it arises when Kronecker products of spin operators and spatial dynamics generators are taken—the resulting matrices are far too large for any current or future computer. However, spin and spatial operators individually have manageable dimensions, and we note here that the action by their Kronecker products on any vector may be computed without opening those products. This eliminates large matrices from the simulation process. MRI simulations for coupled spin systems of complex metabolites in three dimensions with diffusion, flow, chemical kinetics, and quantum mechanical treatment of spin relaxation are now possible. The methods described in this paper are implemented in versions 2.4 and later of the Spinach library.</p

Ultrafast Maximum-Quantum NMR Spectroscopy for the Analysis of Aromatic Mixtures

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