127 research outputs found
A novel scene-recording spectroradiometer
In this paper we describe an innovative approach to providing both a
synthesised dual-beam capability and a permanent photographic record of the
precise area sensed by a spectroradiometer. These advances have been achieved
without modifying the spectroradiometer and may be used with a wide range of
commercially-available spectroradiometers
THE DYNAMIC NATURE OF CHROMATIN
Eukaryotic organisms contain their entire genome in the nucleus of their cells. In order to fit within the nucleus, genomic DNA wraps into nucleosomes, the basic, repeating unit of chromatin. Nucleosomes wrap around each other to form higher order chromatin structures. Here we study many factors that affect, or are effected by, chromatin structure including: (1) how low-dose inorganic arsenic (iAs) changes chromatin structures and their relation to global transcription and splicing patterns, and (2) how chromatin architectural proteins (CAPs) bind to and change nucleosome dynamics and DNA target site accessibility.
Despite iAsâs non-mutagenic nature, chronic exposure to low doses of iAs is associated with a higher risk of skin, lung, and bladder cancers. We sought to identify the genome-wide changes to chromatin structure and splicing profiles behind the cellâs adaptive response to iAs and its removal. Furthermore, we extended our investigation into cells that had the iAs insult removed. Our results show that the iAs-induced epithelial to mesenchymal transition and changes to the transcriptome are coupled with changes to the higher order chromatin structure and CAP binding patterns. We hypothesize that CAPs, which bind the entry/exit and linker DNA of nucleosomes, regulate DNA target site accessibility by altering of the rate of spontaneous dissociation of DNA from nucleosome.
Therefore, we investigated the effects of the repressive CAP histone H1, the activating CAP high mobility group D1 (HMGD1), and the neural CAP methyl CpG binding protein 2 (MeCP2) on the dynamics of short chromatin arrays and mononucleosomes and their effect on nucleosomal DNA accessibility. Using biochemical and biophysical analyses we show that all CAP-chromatin structures tested were susceptible to chromatin remodeling by ISWI and created more stable higher order structures than if CAPs were absent. Additionally, histone H1 and MeCP2 hinder model transcription factor Gal4 from binding its cognate DNA site within nucleosomal DNA.
Overall, we show that chromatin structure is dynamic and changes in response to environmental signals and that CAPs change nucleosome dynamics that help to regulate chromatin structures and impact transcriptional profiles
Absolute frequency measurement of the magnesium intercombination transition
We report on a frequency measurement of the clock
transition of Mg on a thermal atomic beam. The intercombination
transition has been referenced to a portable primary Cs frequency standard with
the help of a femtosecond fiber laser frequency comb. The achieved uncertainty
is which corresponds to an increase in accuracy of six
orders of magnitude compared to previous results. The measured frequency value
permits the calculation of several other optical transitions from to
the -level system for Mg, Mg and Mg. We describe in
detail the components of our optical frequency standard like the stabilized
spectroscopy laser, the atomic beam apparatus used for Ramsey-Bord\'e
interferometry and the frequency comb generator and discuss the uncertainty
contributions to our measurement including the first and second order Doppler
effect. An upper limit of in one second for the short term
instability of our optical frequency standard was determined by comparison with
a GPS disciplined quartz oscillator.Comment: 8 pages, 8 figure
Working time flexibility components and working time regimes in Europe: using company-level data across 21 countries
Working time ?exibility comprises a wide variety of arrangements, from part-time,
overtime, to long-term leaves. Theoretical approaches to grouping these arrangements
have been developed, but empirical underpinnings are rare. This article investigates
the bundles that can be found for various ?exible working time arrangements, using the
Establishment Survey on Working Time and WorkâLife Balance, 2004/2005, covering 21
EU member states and 13 industries. The results from the factor analyses con?rmed that
working time arrangements can be grouped into two bundles, one for the employee-centred
arrangements and second for the employer-centred arrangements, and that these two
bundles are separate dimensions.Wealso tested the stability of the factor analysisoutcome,
showing that although we ?nd some deviations from the pan-Europe and pan-industry
outcome, the naming of the components as ?exibility for employees and ?exibility for
employers can be considered rather stable. Lastly, we ?nd three country clusters for the 21
European countries using the bundle approach. The ?rst group includes the Northern
European countries along side Poland and Czech Republic, the second group the
continental European countries with UK and Ireland, and lastly, the southern European
countries with Hungary and Slovenia
Remote frequency measurement of the 1S0-3P1 transition in laser cooled Mg-24
We perform Ramsey-Bord\'e spectroscopy on laser-cooled magnesium atoms in
free fall to measure the 1S0 \rightarrow 3P1 intercombination transition
frequency. The measured value of 655 659 923 839 730 (48) Hz is consistent with
our former atomic beam measurement (Friebe et al 2008 Phys. Rev. A 78 033830).
We improve upon the fractional accuracy of the previous measurement by more
than an order of magnitude to 7e-14. The magnesium frequency standard was
referenced to a fountain clock of the Physikalisch-Technische Bundesanstalt
(PTB) via a phase-stabilized telecom fiber link and its stability was
characterized for interrogation times up to 8000 s. The high temperature of the
atomic ensemble leads to a systematic shift due to the motion of atoms across
the spectroscopy beams. In our regime, this leads to a counterintuitive
reduction of residual Doppler shift with increasing resolution. Our theoretical
model of the atom-light interaction is in agreement with the observed effect
and allows us to quantify its contribution in the uncertainty budget.Comment: 16 pages, 8 figures. Accepted in New Journal of Physic
Development of a context model to prioritize drug safety alerts in CPOE systems
Background: Computerized physician order entry systems (CPOE) can reduce the number of medication errors and adverse drug events (ADEs) in healthcare institutions. Unfortunately, they tend to produce a large number of partly irrelevant alerts, in turn leading to alert overload and causing alert fatigue. The objective of this work is to identify factors that can be used to prioritize and present alerts depending on the 'context' of a clinical situation. Methods: We used a combination of literature searches and expert interviews to identify and validate the possible context factors. The internal validation of the context factors was performed by calculating the inter-rater agreement of two researcher's classification of 33 relevant articles. Results: We developed a context model containing 20 factors. We grouped these context factors into three categories: characteristics of the patient or case (e. g. clinical status of the patient); characteristics of the organizational unit or user (e. g. professional experience of the user); and alert characteristics (e. g. severity of the effect). The internal validation resulted in nearly perfect agreement (Cohen's Kappa value of 0.97). Conclusion: To our knowledge, this is the first structured attempt to develop a comprehensive context model for prioritizing drug safety alerts in CPOE systems. The outcome of this work can be used to develop future tailored drug safety alerting in CPOE systems
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