The major transcriptional regulatory protein of herpes simplex virus type 1 includes a protease resistant DNA binding domain

Herpes simplex virus type 1 expresses five immediateearly (IE) polypeptides. In the absence of functional Vmw175 (the product of IE gene 3) activation of transcription of later classes of viral genes and repression of IE gene expression does not occur. The recognition of specific DNA sequences by Vmw175 requires, as determined by sensitivity to mutation, a part of the protein highly conserved in the corresponding proteins of related herpes viruses. However, mutations in other parts of the protein can also disrupt specific DNA binding. This paper shows that the DNA binding domain of Vmw175 can be liberated as a functional unit by digestion with proteinase K. Analysis of mutant Vmw175 proteinsshowed that the proteinase K resistant domain has an amino terminus between amino acid residues 229 and 292, while its carboxy terminus is between residues 495 and 518. Mutations outside this region which affect DNA binding by the intact protein do not eliminate binding of the proteinase K resistant domain. This implies that direct DNA binding by Vmw175 involves a linear subsection of the polypeptide, and that mutations in other parts of the polypeptide which affect DNA binding of the whole protein do so by indirect means

Sensitivity of the mussel Mytilus edulis to substrate‑borne vibration in relation to anthropogenically generated noise

© 2015 Inter-Research. Many anthropogenic activities in the oceans involve direct contact with the seabed (for example pile driving), creating radiating particle motion waves. However, the consequences of these waveforms to marine organisms are largely unknown and there is little information on the ability of invertebrates to detect vibration, or indeed the acoustic component of the signal. We quantified sensitivity of the marine bivalve Mytilus edulis to substrate-borne vibration by exposure to vibration under controlled conditions. Sinusoidal excitation by tonal signals at frequencies within the range 5 to 410 Hz was applied during the tests, using the 'staircase' method of threshold determination. Thresholds were related to mussel size and to seabed vibration data produced by anthropogenic activities. Clear behavioural changes were observed in response to the vibration stimulus. Thresholds ranged from 0.06 to 0.55 m s -2 (acceleration, root mean squared), with valve closure used as the behavioural indicator of reception and response. Thresholds were shown to be within the range of vibrations measured in the vicinity of anthropogenic operations such as pile driving and blasting. The responses show that vibration is likely to impact the overall fitness of both individuals and mussel beds of M. edulis due to disruption of natural valve periodicity, which may have ecosystem and commercial implications. The observed data provide a valuable first step to understanding the impacts of such vibration upon a key coastal and estuarine invertebrate which lives near industrial and construction activity, and illustrate that the role of seabed vibration should not be underestimated when assessing the impacts of noise pollution

Use of mathematical derivatives (time-domain differentiation) on chromatographic data to enhance the detection and quantification of an unknown 'rider' peak

Two samples of an anticancer prodrug, AQ4N, were submitted for HPLC assay and showed an unidentified impurity that eluted as a 'rider' on the tail of the main peak. Mathematical derivatization of the chromatograms offered several advantages over conventional skimmed integration. A combination of the second derivative amplitude and simple linear regression gave a novel method for estimating the true peak area of the impurity peak. All the calculation steps were carried out using a widely available spreadsheet program. (C) 2003 Elsevier B.V. All rights reserved

Identifying and understanding inequalities in child welfare intervention rates: quantitative evidence from a comparison of the four UK countries

This is the working paper for the journal article that was later published under a different title. See: Bywaters P, Scourfield J, Jones C, Sparks T, Elliott M, Hooper J, McCartan C, Shapira M, Bunting L & Daniel B (2020) Child welfare inequalities in the four nations of the UK. Journal of Social Work, 20 (2), pp. 193-215. https://doi.org/10.1177/1468017318793479 With full-text available from: http://hdl.handle.net/1893/27484 First paragraph: In the public health field, much attention has been paid to measuring and analysing differences in mortality and morbidity between and within countries. While recognising problems in ensuring that data is genuinely comparable between and within different countries, sufficient convergence is managed through the WHO Global Health Observatory for data on over 1000 indicators of population health to be gathered from 194 countries (http://www.who.int/gho/en/). There is a substantial body of work that underpins judgements about relative rates of sickness and death and discussions of contributory causal factors. It supports a focus on understanding and combatting both underlying and more immediate causes of health inequalities (WHO, 2008). Reducing health inequalities is seen as an essential element for maximising the health of populations (Acheson 1998; Marmot 2010).This is the working paper for the journal article that was later published under a different title. See: Bywaters P, Scourfield J, Jones C, Sparks T, Elliott M, Hooper J, McCartan C, Shapira M, Bunting L & Daniel B (2020) Child welfare inequalities in the four nations of the UK. Journal of Social Work, 20 (2), pp. 193-215. https://doi.org/10.1177/1468017318793479 With full-text available from: http://hdl.handle.net/1893/2748

Analysis of imatinib in bone marrow and plasma samples of chronic myeloid leukaemia patients using solid phase extraction LC-ESI-MS

The LC-ESI-MS was developed and validated for the analysis of imatinib in plasma and bone marrow samples using deuterated imatinib (D(8)-IM) as an internal standard. The biological samples were extracted using Strata-X-C SPE cartridges and separated on C<sub>8</sub> column (50 x 3 mm, 3 µm), and methanol: 0.1% formic acid (70:30) was delivered at the rate of 0.7 ml/min as a mobile phase. Imatinib was quantified in samples by monitoring the ions m/z 494.3 for imatinib and 502.3 for D<sub>8</sub>-imatinib on mass spectrometer. The method was linear in the concentration range of 1-1500 ng/250 µl in spiked human plasma samples and limit of quantification was 5 ng/mL. Inter-day and intra-day variations in spiked human plasma spiked with 50, 250 and 500 ng /mL were less than 3.16%. The repeatability and reproducibility and other parameters of the methods were also validated. The method was employed for the analysis of the imatinib in human plasma and bone marrow samples. The drug levels in bone marrow and plasma samples were correlated to the degree of cytogenetic response. No significant difference of imatinib level between blood and bone marrow in IM-treated patients dosed to steady state was observed

Reducing inappropriate antibiotics prescribing: The role of online commentary on physical examination findings

Objective: This study investigates the relationship of ‘online commentary’(contemporaneous physician comments about physical examination [PE] findings) with (i) parent questioning of the treatment recommendation and (ii) inappropriate antibiotic prescribing. Methods: A nested cross-sectional study of 522 encounters motivated by upper respiratory symptoms in 27 California pediatric practices (38 pediatricians). Physicians completed a post-visit survey regarding physical examination findings, diagnosis, treatment, and whether they perceived the parent as expecting an antibiotic. Taped encounters were coded for ‘problem’ online commentary (PE findings discussed as significant or clearly abnormal) and ‘no problem’ online commentary (PE findings discussed reassuringly as normal or insignificant). Results: Online commentary during the PE occurred in 73% of visits with viral diagnoses (n = 261). Compared to similar cases with ‘no problem’ online commentary, ‘problem’ comments were associated with a 13% greater probability of parents uestioning a non-antibiotic treatment plan (95% CI 0-26%, p = .05,) and a 27% (95% CI: 2-52%, p < .05) greater probability of an inappropriate antibiotic prescription. Conclusion: With viral illnesses, problematic online comments are associated with more pediatrician-parent conflict over non-antibiotic treatment recommendations. This may increase inappropriate antibiotic prescribing. Practice implications: In viral cases, physicians should consider avoiding the use of problematic online commentary

Properties and applications of pyrethroids.

Improved understanding of the factors determining the insecticidal activity, the mammalian toxicity, and the stability in air and light of natural and synthetic pyrethroids has led to a series of new compounds with a very favorable combination of properties. Their characteristics include outstanding potency to insects, low toxicity to mammals associated with rapid metabolic breakdown and, in appropriate cases, adequate stability on plant surfaces even in bright sunlight. Initial tests indicate that even the more stable compounds are degraded rapidly in soil, so if the trials at present in progress reveal no toxicological or environmental hazards, within a few years synthetic pyrethroids should be available to control a wide range of domestic, veterinary, horticultural, agricultural, and forest pests at low rates of application