Phase behaviour of DNA in presence of DNA-binding proteins

To characterize the thermodynamical equilibrium of DNA chains interacting with a solution of non-specific binding proteins, a Flory-Huggins free energy model was implemented. We explored the dependence on DNA and protein concentrations of the DNA collapse. For physiologically relevant values of the DNA-protein affinity, this collapse gives rise to a biphasic regime with a dense and a dilute phase; the corresponding phase diagram was computed. Using an approach based on Hamiltonian paths, we show that the dense phase has either a molten globule or a crystalline structure, depending on the DNA bending rigidity, which is influenced by the ionic strength. These results are valid at the thermodynamical equilibrium and should therefore be consistent with many biological processes, whose characteristic timescales range typically from 1 ms to 10 s. Our model may thus be applied to biological phenomena that involve DNA-binding proteins, such as DNA condensation with crystalline order, which occurs in some bacteria to protect their chromosome from detrimental factors; or transcription initiation, which occurs in clusters called transcription factories that are reminiscent of the dense phase characterized in this study.Comment: 20 pages, 9 figures, accepted for publication at The Biophysical Journa

Voting 'against all' in postcommunist Russia

Since the early 1990s voters in Russia (and most of the other post-Soviet republics) have been offered the opportunity to vote ‘against all’ parties and candidates. Increasing numbers have done so. The evidence of two post-election surveys indicates that ‘against all’ voters are younger than other voters, more urban and more highly educated. They do not reject liberal democracy, but are critical of the contemporary practice of Russian politics and find no parties that adequately reflect their views. With the ending of the ‘against all’ facility in 2006 and other changes in the Russian electoral system under the Putin presidency, levels of turnout are likely to fall further and the protest vote will seek other outlets within or outside the parliamentary system

The synthesis of 15 mu infrared horizon radiance profiles from meteorological data inputs

Computational computer program for modeling infrared horizon radiance profile using pressure and temperature profile input

Technology for large-scale translation of clinical practice guidelines : a pilot study of the performance of a hybrid human and computer-assisted approach

Background: The construction of EBMPracticeNet, a national electronic point-of-care information platform in Belgium, was initiated in 2011 to optimize quality of care by promoting evidence-based decision-making. The project involved, among other tasks, the translation of 940 EBM Guidelines of Duodecim Medical Publications from English into Dutch and French. Considering the scale of the translation process, it was decided to make use of computer-aided translation performed by certificated translators with limited expertise in medical translation. Our consortium used a hybrid approach, involving a human translator supported by a translation memory (using SDL Trados Studio), terminology recognition (using SDL Multiterm termbases) from medical termbases and support from online machine translation. This has resulted in a validated translation memory which is now in use for the translation of new and updated guidelines. Objective: The objective of this study was to evaluate the performance of the hybrid human and computer-assisted approach in comparison with translation unsupported by translation memory and terminology recognition. A comparison was also made with the translation efficiency of an expert medical translator. Methods: We conducted a pilot trial in which two sets of 30 new and 30 updated guidelines were randomized to one of three groups. Comparable guidelines were translated (a) by certificated junior translators without medical specialization using the hybrid method (b) by an experienced medical translator without this support and (c) by the same junior translators without the support of the validated translation memory. A medical proofreader who was blinded for the translation procedure, evaluated the translated guidelines for acceptability and adequacy. Translation speed was measured by recording translation and post-editing time. The Human Translation Edit Rate was calculated as a metric to evaluate the quality of the translation. A further evaluation was made of translation acceptability and adequacy. Results: The average number of words per guideline was 1,195 and the mean total translation time was 100.2 min/1,000 words. No meaningful differences were found in the translation speed for new guidelines. The translation of updated guidelines was 59 min/1,000 words faster (95% CI 2-115; P=.044) in the computer-aided group. Revisions due to terminology accounted for one third of the overall revisions by the medical proofreader. Conclusions: Use of the hybrid human and computer-aided translation by a non-expert translator makes the translation of updates of clinical practice guidelines faster and cheaper because of the benefits of translation memory. For the translation of new guidelines there was no apparent benefit in comparison with the efficiency of translation unsupported by translation memory (whether by an expert or non-expert translator

Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny.

The mammary gland undergoes cycles of growth and regeneration throughout reproductive life, a process that requires mammary stem cells (MaSCs). Whilst recent genetic fate-mapping studies using lineage-specific promoters have provided valuable insights into the mammary epithelial hierarchy, the true differentiation potential of adult MaSCs remains unclear. To address this, herein we utilize a stochastic genetic-labelling strategy to indelibly mark a single cell and its progeny in situ, combined with tissue clearing and 3D imaging. Using this approach, clones arising from a single parent cell could be visualized in their entirety. We reveal that clonal progeny contribute exclusively to either luminal or basal lineages and are distributed sporadically to branching ducts or alveoli. Quantitative analyses suggest that pools of unipotent stem/progenitor cells contribute to adult mammary gland development. Our results highlight the utility of tracing a single cell and reveal that progeny of a single proliferative MaSC/progenitor are dispersed throughout the epithelium.This work was supported by a grant from the Medical Research Council programme grant no. MR/J001023/1 (B.L-L. and C.J.W). F.M.D. was funded by a National Health and Medical Research Council CJ Martin Biomedical Fellowship (GNT1071074). O.B.H. was funded by a Wellcome Trust PhD studentship (105377/Z/14/Z)

The Catalytic Site Atlas 2.0: cataloging catalytic sites and residues identified in enzymes.

Understanding which are the catalytic residues in an enzyme and what function they perform is crucial to many biology studies, particularly those leading to new therapeutics and enzyme design. The original version of the Catalytic Site Atlas (CSA) (http://www.ebi.ac.uk/thornton-srv/databases/CSA) published in 2004, which catalogs the residues involved in enzyme catalysis in experimentally determined protein structures, had only 177 curated entries and employed a simplistic approach to expanding these annotations to homologous enzyme structures. Here we present a new version of the CSA (CSA 2.0), which greatly expands the number of both curated (968) and automatically annotated catalytic sites in enzyme structures, utilizing a new method for annotation transfer. The curated entries are used, along with the variation in residue type from the sequence comparison, to generate 3D templates of the catalytic sites, which in turn can be used to find catalytic sites in new structures. To ease the transfer of CSA annotations to other resources a new ontology has been developed: the Enzyme Mechanism Ontology, which has permitted the transfer of annotations to Mechanism, Annotation and Classification in Enzymes (MACiE) and UniProt Knowledge Base (UniProtKB) resources. The CSA database schema has been re-designed and both the CSA data and search capabilities are presented in a new modern web interface

Femtosecond nonlinear ultrasonics in gold probed with ultrashort surface plasmons

Fundamental interactions induced by lattice vibrations on ultrafast time scales become increasingly important for modern nanoscience and technology. Experimental access to the physical properties of acoustic phonons in the THz frequency range and over the entire Brillouin zone is crucial for understanding electric and thermal transport in solids and their compounds. Here, we report on the generation and nonlinear propagation of giant (1 percent) acoustic strain pulses in hybrid gold/cobalt bilayer structures probed with ultrafast surface plasmon interferometry. This new technique allows for unambiguous characterization of arbitrary ultrafast acoustic transients. The giant acoustic pulses experience substantial nonlinear reshaping already after a propagation distance of 100 nm in a crystalline gold layer. Excellent agreement with the Korteveg-de Vries model points to future quantitative nonlinear femtosecond THz-ultrasonics at the nano-scale in metals at room temperature

Particle Collisions on Stringy Black Hole Background

The collision of two particles in the background of a Sen black hole is studied. With the equations of motion of the particles, the center-of-mass energy is investigated when the collision takes place at the horizon of a Sen black hole. For an extremal Sen black hole, we find that the center-of-mass energy will be arbitrarily high with two conditions: (1) spin $a\neq 0$ and (2) one of the colliding particles has the critical angular momentum $l_{\text{c}}=2$. For a nonextremal Sen black hole, we show that, in order to obtain an unlimited center-of-mass energy, one of the colliding particles should have the critical angular momentum $l'_{\text{c}}=2 r_{+}/a$ ($r_{+}$ is the radius of the outer horizon for a nonextremal black hole). However, a particle with the angular momentum $l=l'_{\text{c}}$ could not approach the black hole from outside of the horizon through free fall, which implies that the collision with arbitrarily high center-of-mass energy could not take place. Thus, there is an upper bound of the center-of-mass energy for the nonextremal black hole. We also obtain the maximal center-of-mass energy for a near-extremal black hole and the result implies that the Planck-scale energy is hard to be approached. Furthermore, we also consider the back-reaction effects. The result shows that, neglecting the gravitational radiation, it has a weak effect on the center-of-mass energy. However, we argue that the maximum allowed center-of-mass energy will be greatly reduced to below the Planck-scale when the gravitational radiation is included.Comment: 17 pages, 4 figures, published versio

An Analysis of Resting-State Functional Transcranial Doppler Recordings from Middle Cerebral Arteries

Functional transcrannial Doppler (fTCD) is used for monitoring the hemodynamics characteristics of major cerebral arteries. Its resting-state characteristics are known only when considering the maximal velocity corresponding to the highest Doppler shift (so called the envelope signals). Significantly more information about the resting-state fTCD can be gained when considering the raw cerebral blood flow velocity (CBFV) recordings. In this paper, we considered simultaneously acquired envelope and raw CBFV signals. Specifically, we collected bilateral CBFV recordings from left and right middle cerebral arteries using 20 healthy subjects (10 females). The data collection lasted for 15 minutes. The subjects were asked to remain awake, stay silent, and try to remain thought-free during the data collection. Time, frequency and time-frequency features were extracted from both the raw and the envelope CBFV signals. The effects of age, sex and body-mass index were examined on the extracted features. The results showed that the raw CBFV signals had a higher frequency content, and its temporal structures were almost uncorrelated. The information-theoretic features showed that the raw recordings from left and right middle cerebral arteries had higher content of mutual information than the envelope signals. Age and body-mass index did not have statistically significant effects on the extracted features. Sex-based differences were observed in all three domains and for both, the envelope signals and the raw CBFV signals. These findings indicate that the raw CBFV signals provide valuable information about the cerebral blood flow which can be utilized in further validation of fTCD as a clinical tool. © 2013 Sejdić et al