A First Principles Theory of Nuclear Magnetic Resonance J-Coupling in solid-state systems

A method to calculate NMR J-coupling constants from first principles in extended systems is presented. It is based on density functional theory and is formulated within a planewave-pseudopotential framework. The all-electron properties are recovered using the projector augmented wave approach. The method is validated by comparison with existing quantum chemical calculations of solution-state systems and with experimental data. The approach has been applied to verify measured J-coupling in a silicophosphate structure, Si5O(PO4)6Comment: 9 page

Robust Uptake of Magnetic Nanoparticles (MNPs) by Central Nervous System (CNS) Microglia: Implications for Particle Uptake in Mixed Neural Cell Populations

Magnetic nanoparticles (MNPs) are important contrast agents used to monitor a range of neuropathological processes; microglial cells significantly contribute to MNP uptake in sites of pathology. Microglial activation occurs following most CNS pathologies but it is not known if such activation alters MNP uptake, intracellular processing and toxicity. We assessed these parameters in microglial cultures with and without experimental ‘activation’. Microglia showed rapid and extensive MNP uptake under basal conditions with no changes found following activation; significant microglial toxicity was observed at higher particle concentrations. Based on our findings, we suggest that avid MNP uptake by endogenous CNS microglia could significantly limit uptake by other cellular subtypes in mixed neural cell populations

Quantum Monte Carlo study of a positron in an electron gas

Quantum Monte Carlo calculations of the relaxation energy, pair-correlation function, and annihilating-pair momentum density are presented for a positron immersed in a homogeneous electron gas. We find smaller relaxation energies and contact pair-correlation functions in the important low-density regime than predicted by earlier studies. Our annihilating-pair momentum densities have almost zero weight above the Fermi momentum due to the cancellation of electron-electron and electron-positron correlation effects

Differences in resistance to 5-fluorouracil as a function of cell cycle delay and not apoptosis.

A series of human embryo fibroblasts has previously been shown to display increasing resistance to the antimetabolites methotrexate (MTX) and N-phosphonacetyl-L-aspartate (PALA) with increasing tumorigenicity. This increased resistance was found to be further increased as a result of salvage pathway activity for purine and pyrimidine biosynthesis. A similar pattern of increasing resistance paralleling increasing tumorigenicity has now been shown to occur with 5-fluorouracil (5-FU), which is independent of salvage pathway activity. The KMS normal cell line was found to be more sensitive to 5-FU than either the immortalised KMST or tumorigenic KN-NM cell lines. Immunohistochemical analysis of the three cell lines demonstrated high levels of p53 protein in the KMST and KN-NM cell lines, but undetectable p53 levels in the KMS cell line. From these data it was hypothesised that a difference in p53 function may be causing the difference in the patterns of sensitivity observed in the three cell lines. P53 is now believed to function as a regulator of a G1 to S cell cycle checkpoint and as an inducer of apoptosis following DNA damage to the cell. The differences in sensitivity of the cell lines could not be explained by differences in the levels of apoptosis but could be attributed to differences in cell cycle response. Our evidence suggests that loss of cell cycle control, possibly through loss of p53 function, is an important factor in increasing the drug resistance of fibroblast cell lines

The growth kinetics of xenografts of human colorectal tumours in immune deprived mice.

The technique of labelled mitoses was used to examine cell proliferation within grafts of human colonic and rectal tumours in immune deprived mice. Most of the data were obtained on the first passage but in some cases up to the third passage was used. It was found to be difficult to obtain precise kinetic data on this type of tumour material, but the results did allow some estimates to be made, particularly of the duration of the G2 and S phases of the mitotic cycle. The average G2 duration was 6 h and the average S phase was 14 h. It is concluded that whilst xenografts may differ in a number of respects from the tumour in the patient, they nevertheless constitute a type of experimental tumour that is worthy of further study

The role of care home fees in the public costs and distributional effects of potential reforms to care home funding for older people in England

In England, Local Authorities (LAs) contribute to the care home fees of two-thirds of care home residents aged 65+ who pass a means test. LAs typically pay fees below those faced by residents excluded from state support. Most proposals for reform of the means test would increase the proportion of residents entitled to state support. If care homes receive the LA fee for more residents, they might increase fees for any remaining self-funders. Alternatively, the LA fee might have to rise. We use two linked simulation models to examine how alternative assumptions on post-reform fees affect projected public costs and financial gains to residents of three potential reforms to the means test. Raising the LA fee rate to maintain income per resident would increase the projected public cost of the reforms by between 22% and 72% in the base year. It would reduce the average gain to care home residents by between 8% and 12%. Raising post-reform fees for remaining self-funders or requiring pre-reform self-funders to meet the difference between the LA and self-funder fees, reduces the gains to residents by 28-37%. For one reform, residents in the highest income quintile would face losses if the self-funder fee rises. © 2012 Cambridge University Press

Alignment of multiple glial cell populations in 3D nanofiber scaffolds: toward the development of multicellular implantable scaffolds for repair of neural injury

Non-neuronal cells of the central nervous system (CNS), termed "neuroglia," play critical roles in neural regeneration; therefore, replacement of glial populations via implantable nanofabricated devices (providing a growth-permissive niche) is a promising strategy to enhance repair. Most constructs developed to date have lacked three-dimensionality, multiple glial populations and control over spatial orientations, limiting their ability to mimic in vivo neurocytoarchitecture. We describe a facile technique to incorporate multiple glial cell populations [astrocytes, oligodendrocyte precursor cells (OPCs) and oligodendrocytes] within a three-dimensional (3D) nanofabricated construct. Highly aligned nanofibers could induce elongation of astrocytes, while OPC survival, elongation and maturation required pre-aligned astrocytes. The potential to scale-up the numbers of constituent nanofiber layers is demonstrated with astrocytes. Such complex implantable constructs with multiple glial sub-populations in defined 3D orientations could represent an effective approach to reconstruct glial circuitry in neural injury sites