Ab initio molecular dynamics calculations of ion hydration free energies

We apply ab initio molecular dynamics (AIMD) methods in conjunction with the thermodynamic integration or "lambda-path" technique to compute the intrinsic hydration free energies of Li+, Cl-, and Ag+ ions. Using the Perdew-Burke-Ernzerhof functional, adapting methods developed for classical force field applications, and with consistent assumptions about surface potential (phi) contributions, we obtain absolute AIMD hydration free energies (Delta G(hyd)) within a few kcal/mol, or better than 4%, of Tissandier 's [J. Phys. Chem. A 102, 7787 (1998)] experimental values augmented with the SPC/E water model phi predictions. The sums of Li+/Cl- and Ag+/Cl- AIMD Delta G(hyd), which are not affected by surface potentials, are within 2.6% and 1.2 % of experimental values, respectively. We also report the free energy changes associated with the transition metal ion redox reaction Ag++Ni+-> Ag+Ni2+ in water. The predictions for this reaction suggest that existing estimates of Delta G(hyd) for unstable radiolysis intermediates such as Ni+ may need to be extensively revised.Comment: 18 pages, 8 figures. This version is essentially the one published in J. Chem. Phy

Inspiring the next generation: the RCUK School-University Partnership Initiative (SUPI) summary report

Copy of the final report of the RCUK-SUPI Project (2014-2018). Provides an overview of key lessons relating to engagement activities designed to inspire the next generation of researchers

Optimizing memory function in temporal lobe epilepsy

PURPOSE: The study aimed to assess whether engagement in a memory training programme and performing internet brain training exercises improve memory function in people with temporal lobe epilepsy (TLE). METHODS: Seventy-seven people with TLE, complaining of memory difficulties, completed the study. Participants ranged in age from 19 to 67 years and 40 had left TLE. Participants were randomised to one of four conditions; Group 1: traditional memory training, Group 2: Lumosity, an on-line cognitive training programme, Group 3: traditional memory training and Lumosity, and Group 4: no training. Memory efficiency and mood were assessed at baseline and three months later. RESULTS: Group analyses indicated improved verbal recall after training (p<0.001) and improved subjective ratings (p<0.007). More participants reported a lessening of the memory burden (p<0.007) after training; differences were significant between Groups 1 and 3 compared to Group 4. Lumosity use was not associated with changes in the memory outcome measures but there was a relationship with depression ratings and the number of memory games played (p<0.01). Conventional memory training, IQ, and post-surgical status were associated with positive memory outcomes. CONCLUSIONS: The study indicates traditional memory rehabilitation techniques can help reduce the burden of memory impairment in TLE. There was no evidence that Lumosity the on-line cognitive training programme had specific advantages. Positive change was not universal and larger studies will be required to explore factors associated with successful outcomes

Electron-electron interaction in multiwall carbon nanotubes

Magnetic susceptibility $\chi$ of pristine and brominated arc-produced sample of multiwall carbon nanotubes was measured from 4.2 to 400 K. An additional contribution $\Delta \chi(T)$ to diamagnetic susceptibility $\chi(T)$ of carbon nanotubes was found at T $<$ 50 K for both samples. It is shown that $\Delta \chi(T)$ are dominated by quantum correction to $\chi$ for interaction electrons (interaction effects-IE). The IE shows a crossover from two-dimensional to three-dimensional at $B$ = 5.5 T. The effective interaction between electrons for interior layers of nanotubes are repulsion and the electron-electron interaction $\lambda$$_c$ was estimated to be $\lambda_c\sim$ 0.26.Comment: 10 pages, 7 figure

Field emission properties of nano-composite carbon nitride films

A modified cathodic arc technique has been used to deposit carbon nitride thin films directly on n+ Si substrates. Transmission Electron Microscopy showed that clusters of fullerene-like nanoparticles are embedded in the deposited material. Field emission in vacuum from as-grown films starts at an electric field strength of 3.8 V/micron. When the films were etched in an HF:NH4F solution for ten minutes, the threshold field decreased to 2.6 V/micron. The role of the carbon nanoparticles in the field emission process and the influence of the chemical etching treatment are discussed.Comment: 22 pages, 8 figures, submitted to J. Vac. Sc. Techn.

Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections

Temporal lobe epilepsy, the most prevalent form of chronic focal epilepsy, is associated with a high prevalence of cognitive impairment but the responsible underlying pathological mechanisms are unknown. Tau, the microtubule-associated protein, is a hallmark of several neurodegenerative diseases including Alzheimer’s disease and chronic traumatic encephalopathy. We hypothesized that hyperphosphorylated tau pathology is associated with cognitive decline in temporal lobe epilepsy and explored this through clinico-pathological study. We first performed pathological examination on tissue from 33 patients who had undergone temporal lobe resection between ages 50 and 65 years to treat drug-refractory temporal lobe epilepsy. We identified hyperphosphorylated tau protein using AT8 immunohistochemistry and compared this distribution to Braak patterns of Alzheimer’s disease and patterns of chronic traumatic encephalopathy. We quantified tau pathology using a modified tau score created specifically for analysis of temporal lobectomy tissue and the Braak staging, which was limited without extra-temporal brain areas available. Next, we correlated tau pathology with pre- and postoperative cognitive test scores and clinical risk factors including age at time of surgery, duration of epilepsy, history of secondary generalized seizures, history of head injury, handedness and side of surgery. Thirty-one of 33 cases (94%) showed hyperphosphorylated tau pathology in the form of neuropil threads and neurofibrillary tangles and pre-tangles. Braak stage analysis showed 12% of our epilepsy cohort had a Braak staging III-IV compared to an age-matched non-epilepsy control group from the literature (8%). We identified a mixture of tau pathology patterns characteristic of Alzheimer’s disease and chronic traumatic encephalopathy. We also found unusual patterns of subpial tau deposition, sparing of the hippocampus and co-localization with mossy fibre sprouting, a feature of temporal lobe epilepsy. We demonstrated that the more extensive the tau pathology, the greater the decline in verbal learning (Spearman correlation, r = −0.63), recall (r = −0.44) and graded naming test scores (r = −0.50) over 1-year post-temporal lobe resection (P < 0.05). This relationship with tau burden was also present when examining decline in verbal learning from 3 months to 1 year post-resection (r = −0.54). We found an association between modified tau score and history of secondary generalized seizures (likelihood-ratio χ2, P < 0.05) however there was no clear relationship between tau pathology and other clinical risk factors assessed. Our findings suggest an epilepsy-related tauopathy in temporal lobe epilepsy, which contributes to accelerated cognitive decline and has diagnostic and treatment implications

A functional assay for serum detection of antibodies against SARS-CoV-2 nucleoprotein.

The humoral immune response to SARS-CoV-2 results in antibodies against spike (S) and nucleoprotein (N). However, whilst there are widely available neutralization assays for S antibodies, there is no assay for N-antibody activity. Here, we present a simple in vitro method called EDNA (electroporated-antibody-dependent neutralization assay) that provides a quantitative measure of N-antibody activity in unpurified serum from SARS-CoV-2 convalescents. We show that N antibodies neutralize SARS-CoV-2 intracellularly and cell-autonomously but require the cytosolic Fc receptor TRIM21. Using EDNA, we show that low N-antibody titres can be neutralizing, whilst some convalescents possess serum with high titres but weak activity. N-antibody and N-specific T-cell activity correlates within individuals, suggesting N antibodies may protect against SARS-CoV-2 by promoting antigen presentation. This work highlights the potential benefits of N-based vaccines and provides an in vitro assay to allow the antibodies they induce to be tested