2,722 research outputs found
Evaluation of Families Working Together: Final Report on behalf of Lincolnshire County Council
The University of Lincoln was commissioned by Lincolnshire County Council to provide an external evaluation of Families Working Together (FWT), a community budget pilot for supporting families with complex needs. This report outlines the data collected within the course of the research and the findings of the researchers
The 'I' of the Beholder
Between the 'viewing' and the 'Knowing' there is a world of dialogue that exists, and it is within that gaze of the audience perpetually subject the nature of time that the aesthetics of art comes aliv
Editorial: Combining Simulations, Theory, and Experiments into Multiscale Models of Biological Events
10.3389/fmolb.2021.797754Frontiers in Molecular Biosciences879775
Molecular dynamics simulations and docking of non-nucleoside reverse transcriptase inhibitors (NNRTIs): a possible approach to personalized HIV treatment : from 7th German Conference on Chemoinformatics: 25 CIC-Workshop Goslar, Germany, 6 - 8 November 2011
The human immunodeficiency virus (HIV) is currently ranked sixth in the worldwide causes of death [1]. One treatment approach is to inhibit reverse transcriptase (RT), an enzyme essential for reverse transcription of viral RNA into DNA before integration into the host genome [2]. By using non-nucleoside RT inhibitors (NNRTIs) [3], which target an allosteric binding site, major side effects can be evaded. Unfortunately, high genetic variability of HIV in combination with selection pressure introduced by drug treatment enables the virus to develop resistance against this drug class by developing point mutations. This situation necessitates treatment with alternative NNRTIs that target the particular RT mutants encountered in a patient.
Previously, proteochemometric approaches have demonstrated some success in predicting binding of particular NNRTIs to individual mutants; however a structurebased approach may help to further improve the predictive success of such models. Hence, our aim is to rationalize the experimental activity of known NNRTIs against a variety of RT mutants by combining molecular modeling, long-timescale atomistic molecular dynamics (MD) simulation sampling and ensemble docking. Initial control experiments on known inhibitor-RT mutant complexes using this protocol were successful, and the predictivity for further complexes is currently being evaluated. In addition to predictive power, MD simulations of multiple RT mutants are providing fundamental insight into the dynamics of the allosteric NNRTI binding site which is useful for the design of future inhibitors. Overall, work of this type is hoped to contribute to the development of predictive efficacy models for individual patients, and hence towards personalized HIV treatment options
Testing Gaussian random hypothesis with the cosmic microwave background temperature anisotropies in the three-year WMAP data
We test the hypothesis that the temperature of the cosmic microwave
background is consistent with a Gaussian random field defined on the celestial
sphere, using de-biased internal linear combination (DILC) map produced from
the 3-year WMAP data. We test the phases for spherical harmonic modes with l <=
10 (which should be the cleanest) for their uniformity, randomness, and
correlation with those of the foreground templates. The phases themselves are
consistent with a uniform distribution, but not for l <= 5, and the differences
between phases are not consistent with uniformity. For l=3 and l=6, the phases
of the CMB maps cross-correlate with the foregrounds, suggestion the presence
of residual contamination in the DLC map even on these large scales. We also
use a one-dimensional Fourier representation to assemble a_lm into the \Delta
T_l(\phi) for each l mode, and test the positions of the resulting maxima and
minima for consistency with uniformity randomness on the unit circle. The
results show significant departures at the 0.5% level, with the one-dimensional
peaks being concentrated around \phi=180 degs. This strongly significant
alignment with the Galactic meridian, together with the cross-correlation of
DILC phases with the foreground maps, strongly suggests that even the lowest
spherical harmonic modes in the map are significantly contaminated with
foreground radiation.Comment: submitted to ApJL, one paragraph is added in Section 3 and some more
in the Referenc
Linked health data for pharmacovigilance in children : Perceived legal and ethical issues for stakeholders and data guardians
Peer reviewedPublisher PD
Patient and primary care delays in the diagnostic pathway of gynaecological cancers : a systematic review of influencing factors
Funding This work was funded by an NHS Education for Scotland Clinical Academic Fellowship.Peer reviewedPublisher PD
Do pharmacists contribute to patients’ management of symptoms suggestive of cancer : a qualitative study
Funding This work was supported by the Sir Hugh Linstead Fellowship Award from Pharmacy Research UK. Acknowledgements The authors would like to acknowledge the support of the consultant physicians Marianne Nicolson, Russell Petty and Les Samuel Aberdeen Royal Infirmary with patient recruitment.Peer reviewedPostprin
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