A risk assessment methodology for the use of lasers in the entertainment industry

Lasers have been used in the entertainment industry since 1964, when they were used in the film Goldfinger. Laser display shows commenced in about 1973. It would be reasonable to expect laser safety to have been adequately addressed over the last twenty-five years. This research showed that the industry was not able to assess the risks from its work. A national survey of the competence of enforcing officers showed that they rarely had the necessary expertise to judge the safety of shows. Therefore, there was often a wide gulf between the laser companies and those responsible for enforcing entertainment and health and safety legislation. A hazard assessment methodology has been developed which considers any laser show as a series of modules which may have different hazards associated with them at different stages of the life cycle, and different people would potentially be exposed to these hazards. A number of laser radiation exposure situations have been assessed, including audience scanning. A theoretical understanding of the laser scanning issues and the application of measurement techniques to enable assessments to be carried out against internationally recognised maximum permissible exposure levels were developed. The conclusion was that the practice of audience scanning was not acceptable in its current form. A number of laser companies worldwide have accepted this view as a direct result of this research. A means of presenting the risk assessment for a laser display has been developed which provides benefits for the laser company, the venue manager, event promoter and the enforcing officer. It is recognised that a complete assessment may not be possible in the time available and a focused approach to the assessment is presented. In summary, if audience scanning is intended, the assessment is complex, but if this practice is not intended then the assessment can be straightforward. Suggestions are made for applying the risk assessment methodology to other laser applications

Double Strand Breaks Can Initiate Gene Silencing and SIRT1-Dependent Onset of DNA Methylation in an Exogenous Promoter CpG Island

Chronic exposure to inducers of DNA base oxidation and single and double strand breaks contribute to tumorigenesis. In addition to the genetic changes caused by this DNA damage, such tumors often contain epigenetically silenced genes with aberrant promoter region CpG island DNA hypermethylation. We herein explore the relationships between such DNA damage and epigenetic gene silencing using an experimental model in which we induce a defined double strand break in an exogenous promoter construct of the E-cadherin CpG island, which is frequently aberrantly DNA hypermethylated in epithelial cancers. Following the onset of repair of the break, we observe recruitment to the site of damage of key proteins involved in establishing and maintaining transcriptional repression, namely SIRT1, EZH2, DNMT1, and DNMT3B, and the appearance of the silencing histone modifications, hypoacetyl H4K16, H3K9me2 and me3, and H3K27me3. Although in most cells selected after the break, DNA repair occurs faithfully with preservation of activity of the promoter, a small percentage of the plated cells demonstrate induction of heritable silencing. The chromatin around the break site in such a silent clone is enriched for most of the above silent chromatin proteins and histone marks, and the region harbors the appearance of increasing DNA methylation in the CpG island of the promoter. During the acute break, SIRT1 appears to be required for the transient recruitment of DNMT3B and subsequent methylation of the promoter in the silent clones. Taken together, our data suggest that normal repair of a DNA break can occasionally cause heritable silencing of a CpG island–containing promoter by recruitment of proteins involved in silencing. Furthermore, with contribution of the stress-related protein SIRT1, the break can lead to the onset of aberrant CpG island DNA methylation, which is frequently associated with tight gene silencing in cancer

Eye hazards of laser 'pointers' in perspective

Eight years ago media coverage of incidents involving laser pointers in which individuals claimed to have suffered eye damage resulted in a perspective being published in this journal.1 The final sentence concluded ‘laser pointers, pens or key rings if used appropriately are not an eye hazard, and even if used inappropriately will not cause permanent eye damage’. This statement has been supported by the finding that until recently no irreversible eye injuries had been reported for a period of almost 15 years other than those caused by deliberate and prolonged viewing of laser beams.2 During this time period pointers have been freely available with an estimated 500 000 to c1.2 million laser pointers in circulation

Fluorine containing cyclopropanes : synthesis of aryl substituted all-cis 1,2,3-trifluorocylopropanes, a facially polar motif

We thank the EPSRC for financial support (GR: EP/R013799/1) and we are grateful to the Chinese Scholarship Council (CSC) for Ph.D Studentship support (ZF).The synthesis of substituted all-cis-1,2,3-trifluorocylopropanes are described for the first time. The three fluorines located on each of the cyclopropyl carbons with a stereochemistry where they are all on the same face of the cyclopropane, imparts a significant polarity to the molecule, and the inherent conformational rigidity and lowering of Log P makes this motif attractive for exploration as a substituent for pharmaceuticals and agrochemicals research.PostprintPeer reviewe

From genomes to systems

A report on the 2nd Conference of the Consortium for Post-Genome Science (CPGS) 'Genomes to Systems', Manchester, UK, 1-3 September 2004

Fluorinated liquid crystals: evaluation of selectively fluorinated facially polarised cyclohexyl motifs for liquid crystal applications

The authors thank the European Research Council for and Advanced Grant and DO’H acknowledges the Royal Society for a Wolfson Merit Award.This paper explores the synthesis of a series of prototype negative dielectric liquid crystalline (LC) compounds which contain fluorinated cyclohexane motifs. The series are analogues and differ only in that they contain between one to four fluorine atoms. The stereochemistry is such that all of the fluorines/C-F bonds are on one face of the cyclohexane ring. This follows from the recent recognition that cyclohexanes with fluorines orientated in one direction, perpendicular to the ring have a strong molecular dipole, a characteristic that might be an advantage in the design of negative dielectric materials. However it is found that the increased polarity, particularly with two or more oriented C-F bonds, leads to higher melting points and poorer solubility in test matrix formulations, relative to hydrocarbon liquid crystals. This arises due to electrostatic intermolecular interactions between the polarised cyclohexyl and aryl rings. The study highlights that in order to take advantage of these polar cyclohexane motifs for liquid crystal design, appropriate scaffolds are required which are free of aromatic rings and contain peripheral solubilising motifs.PostprintPostprintPeer reviewe

Evaluation of elicitation methods to quantify Bayes linear models

The Bayes linear methodology allows decision makers to express their subjective beliefs and adjust these beliefs as observations are made. It is similar in spirit to probabilistic Bayesian approaches, but differs as it uses expectation as its primitive. While substantial work has been carried out in Bayes linear analysis, both in terms of theory development and application, there is little published material on the elicitation of structured expert judgement to quantify models. This paper investigates different methods that could be used by analysts when creating an elicitation process. The theoretical underpinnings of the elicitation methods developed are explored and an evaluation of their use is presented. This work was motivated by, and is a precursor to, an industrial application of Bayes linear modelling of the reliability of defence systems. An illustrative example demonstrates how the methods can be used in practice

Consistent Application of Maximum Entropy to Quantum-Monte-Carlo Data

Bayesian statistics in the frame of the maximum entropy concept has widely been used for inferential problems, particularly, to infer dynamic properties of strongly correlated fermion systems from Quantum-Monte-Carlo (QMC) imaginary time data. In current applications, however, a consistent treatment of the error-covariance of the QMC data is missing. Here we present a closed Bayesian approach to account consistently for the QMC-data.Comment: 13 pages, RevTeX, 2 uuencoded PostScript figure

Janus all-cis 2,3,4,5,6-pentafluorocyclohexyl building blocks applied to medicinal chemistry and bioactives discovery chemistry

We thank EPSRC for a grant (EP/R013799/1) and Studentships (JLC) through the EPSRC CRITICAT CDT programme and also the Chinese Scholarship Council (CY).Monoalkylated derivatives of the unusually polar all- cis 2,3,4,5,6- pentafluorocyclohexyl (Janus face) motif are prepared starting from an aryl hydrogenation of 2,3,4,5,6- pentafluorophenylacetate methyl ester 15 . The method used Zeng's Rh(CAAC) carbene catalyst 4 in the hydrogenation following the protocol developed by Glorius. The resultant Janus pentafluorocyclohexylacetate methyl ester 16 was converted to the corresponding alcohol 18 , aldehyde 13 , bromide 29 and azide 14 through functional group manipulations, and some of these building blocks were used in Ugi-multicomponent and Cu-catalysed click reactions. NBoc protected pentafluoroarylphenylalanine methyl ester 35 was also subject to an aryl hydrogenation, and then deprotection to generate the Janus face ß-pentafluorocyclohexyl-alanine amino acid 15 , which was incorporated into representative members of an emerging class of candidate antiviral compounds. Log P measurements demonstrate that the all- cis 2,3,4,5,6-pentafluorocyclohexyl ring system is more polar than a phenyl ring. In overview the paper introduces new building blocks containing this Janus ring and demonstrates their progression to molecules typically used in bioactives discovery programmes.Publisher PDFPeer reviewe

The Gene Cluster for Fluorometabolite Biosynthesis in Streptomyces cattleya: A Thioesterase Confers Resistance to Fluoroacetyl-Coenzyme A

SummaryA genomic library of Streptomyces cattleya was screened to isolate a gene cluster encoding enzymes responsible for the production of fluorine-containing metabolites. In addition to the previously described fluorinase FlA which catalyzes the formation of 5′-fluoro-5′-deoxyadenosine from S-adenosylmethionine and fluoride, 11 other putative open reading frames have been identified. Three of the proteins encoded by these genes have been characterized. FlB was determined to be the second enzyme in the pathway, catalyzing the phosphorolytic cleavage of 5′-fluoro-5′-deoxyadenosine to produce 5-fluoro-5-deoxy-D-ribose-1-phosphate. The enzyme FlI was found to be an S-adenosylhomocysteine hydrolase, which may act to relieve S-adenosylhomocysteine inhibition of the fluorinase. Finally, flK encodes a thioesterase which catalyzes the selective breakdown of fluoroacetyl-CoA but not acetyl-CoA, suggesting that it provides the producing strain with a mechanism for resistance to fluoroacetate