Carbonyl-ene reactions catalyzed by bis(oxazoline) copper (II) complexes proceed by a facile stepwise mechanism: DFT and ONIOM (DFT:PM3) studies

The mechanism of a carbonyl-ene addition reaction catalyzed by a bis(oxazoline) copper (II) complex has been studied using DFT methods. We find that the reaction proceeds by a stepwise mechanism with very low barriers and have identified the role of the metal catalyst. We find that the more computationally economic ONIOM method gives accurate geometries for the stationary structures on the potential energy surface but that accurate energetics must be calculated at the full DFT level.     

Quantitative magnetic resonance imaging of vertebral bodies: a T1 and T2 study

Multiple point T1 and T2 values of 424 vertebral bodies were measured and analysed. The influence of several factors including age, sex, location in the spine and status of neighbouring discs on the measured relaxation times were evaluated. The results indicate limitations in the region of interest approach. Vertebral bodies of different age, sex and location in the spine could not be distinguished. For heterogeneous tissues a more advanced form of image analysis appears to be essential. Diurnal factors resulting from the stress of normal ambulatory activity caused increased variation in vertebral body relaxation time values.     

On the optimal design of tandem queueing systems with finite buffers

We consider tandem queueing systems that can be formulated as a continuous-time Markov chain, and investigate how to maximize the throughput when the queue capacities are limited. We consider various constrained optimization problems where the decision variables are of one or more of the following types: (1) expected service times, (2) queue capacities, and (3) the number of servers at the respective stations. After surveying our previous studies of this kind, we open up consideration of three new problems by presenting some numerical results that should give some insight into the general form of the optimal design.     

YOYO as a Dye to Track Penetration of LK15 DNA Complexes in Spheroids: Use and Limits

To elucidate the reasons underlying the poor penetration of non-viral vectors in tissues, relating transport properties to physico-chemical parameters of vectors may be crucial. These properties can be influenced by the presence of multiples labels that are used. Therefore utilizing a vector with minimum of labels preferably not more than one is important to studying penetration in tissues. The cell impermeant bisintercalating dye YOYO-1 was found suitable to both monitor the formation of complexes between DNA and an amphipathic peptide LK15 and, to track their penetration in HCT116 spheroids by confocal microscopy. The results revealed a limited decrease of fluorescence ascribed to the high affinity of YOYO-1 to bind DNA. The residual fluorescence of complexes can be exploited to monitor penetration into spheroids, after correction for YOYO-1 attenuation, and to revealing hyaluronidase-induced reduced binding. Hence high affinity dyes such as YOYO-1 with inefficiently quenched fluorescence may be important to establish a relation between novel medicines characteristics and penetration in tissues.     

Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion

Background  

Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion.