UV Spectra and Excitation Delocalization in DNA: Influence of the Spectral Width

The singlet excited states of the model DNA duplex (dA)10.(dT)10 are studied. Calculations are performed in the exciton theory framework. Molecular dynamics calculations provide the duplex geometry. The dipolar coupling is determined using atomic transition charges. The monomer transition energies are simulated by Gaussian functions resembling the absorption bands of nucleosides in aqueous solutions. Most of the excited states are found to be delocalized over at least two bases and result from the mixing of different monomer states. Their properties are only weakly affected by conformational changes of the double helix. On average, the highest oscillator strength is carried by the upper eigenstates. The duplex absorption spectra are shifted a few nanometers to higher energies with respect to the spectra of noninteracting monomers. The states with larger spatial extent are located close to the maximum of the absorption spectrum

Chiral ionic liquids based on L-cysteine derivatives for asymmetric aldol reaction

POCI-01-0145-FEDER–007265 PTDC/QUI-QOR/32406/2017 022161Structure, and consequently properties, of ionic liquids can be easily tailored by changing cation/anion combinations and/or attaching functional groups. By grafting enantiopure moieties to the framework of ionic liquid it is possible to prepare bioinspired chiral molecules that can serve as a reaction medium, additive or even asymmetric catalyst. In this context, new chiral ionic liquids (CILs), based on biomolecules, such as aminoacids (L-cysteine derivatives), have been synthesised and tested in asymmetric aldol condensation of aldehydes and ketones. The best results were obtained for CILs composed of S-methyl-L-cysteine cation and bis(trifluoromethane)sulfonimide anion, in the reaction of 2-or 4-nitrobenzaldehyde with acetone or cyclohexanone, giving the aldol product in moderate yields 70–76% and high ee values (up to 96%).publishersversionpublishe

Images as catalysts for meaning-making in medical pain encounters: a multidisciplinary analysis

The challenge for those treating or witnessing pain is to find a way of crossing the chasm of meaning between them and the person living with pain. This paper proposes that images can strengthen agency in the person with pain, particularly but not only in the clinical setting, and can create a shared space within which to negotiate meaning. It draws on multidisciplinary analyses of unique material resulting from two fine art/medical collaborations in London, UK, in which the invisible experience of pain was made visible in the form of co-created photographic images, which were then made available to other patients as a resource to use in specialist consultations. In parallel with the pain encounters it describes, the paper weaves together the insights of specialists from a range of disciplines whose methodologies and priorities sometimes conflict and sometimes intersect to make sense of each other’s findings. A short section of video footage where images were used in a pain consultation is examined in fine detail from the perspective of each discipline. The analysis shows how the images function as ‘transactional objects’ and how their use coincides with an increase in the amount of talk and emotional disclosure on the part of the patient and greater non-verbal affiliative behaviour on the part of the doctor. These findings are interpreted from the different disciplinary perspectives, to build a complex picture of the multifaceted, contradictory and paradoxical nature of pain experience, the drive to communicate it and the potential role of visual images in clinical settings

Exciton States of Dynamic DNA Double Helices: Alternating dCdG Sequences

The present communication deals with the excited states of the alternating DNA oligomer (dCdG)5·(dCdG)5 which correspond to the UV absorption band around 260 nm. Their properties are studied in the frame of the exciton theory, combining molecular dynamics simulations and quantum chemistry data. It is shown that the dipolar coupling undergoes important variations with the site and the helix geometry. In contrast, the energy of the monomer transitions within the double helix is not sensitive to the local environment. It is thus considered to be distributed over Gaussian curves whose maximum and width are derived from the experimental absorption spectra of nucleosides in aqueous solution. The influence of the spectral width on the excited state delocalization and the absorption spectra is much stronger than that of the oligomer plasticity. About half of the excited states are delocalized over at least two bases. Many of them result from the mixing of different monomer states and extend on both strands. The trends found in the simulated spectra, when going from non-interacting monomers to the duplex, are in agreement with experimental observations. Conformational changes enhance the diversity of the states which can be populated upon excitation at a given energy. The states with larger spatial extent are located close to the maximum of the absorption spectrum

A Fast and Efficient Incremental Approach toward Dynamic Community Detection

Community detection is a discovery tool used by network scientists to analyze the structure of real-world networks. It seeks to identify natural divisions that may exist in the input networks that partition the vertices into coherent modules (or communities). While this problem space is rich with efficient algorithms and software, most of this literature caters to the static use-case where the underlying network does not change. However, many emerging real-world use-cases give rise to a need to incorporate dynamic graphs as inputs. In this paper, we present a fast and efficient incremental approach toward dynamic community detection. The key contribution is a generic technique called $\Delta-screening$, which examines the most recent batch of changes made to an input graph and selects a subset of vertices to reevaluate for potential community (re)assignment. This technique can be incorporated into any of the community detection methods that use modularity as its objective function for clustering. For demonstration purposes, we incorporated the technique into two well-known community detection tools. Our experiments demonstrate that our new incremental approach is able to generate performance speedups without compromising on the output quality (despite its heuristic nature). For instance, on a real-world network with 63M temporal edges (over 12 time steps), our approach was able to complete in 1056 seconds, yielding a 3x speedup over a baseline implementation. In addition to demonstrating the performance benefits, we also show how to use our approach to delineate appropriate intervals of temporal resolutions at which to analyze an input network

UBR2 of the N-end rule pathway is required for chromosome stability via histone ubiquitylation in spermatocytes and somatic cells

The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB) repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known as the recognition component of a major cellular proteolytic system, is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells. © 2012 Kwon et al

The Ecological and Ethical Consumption Development Prospects in Poland Compared with the Western European Countries

An overview of the Western European literature shows that one of the most distinct trends in consumption that has been noted in the recent years is globally increasing environmental and social awareness. The issue of consumers' behaviours and attitudes towards "socially responsible products" has been gaining importance in Polish economy as well. This article evaluates the development prospects of ethical and ecological consumption in Poland vis-à-vis Western European countries. The comparative analysis being part of the article utilizes primary sources of information, i.e. interviews with a representative sample of Polish adults, as well as secondary sources of information. A factor analysis or, more precisely, a principal component analysis, allowed dividing Polish consumers into groups that were typologically homogeneous in respect of their sensitivity to various aspects of business ethics and ecology.Przegląd literatury zachodnio-europejskiej pozwala stwierdzić, że jednym z najbardziej zauważalnych trendów w sferze konsumpcji w ostatnich latach jest coraz większa świadomość ekologiczna i społeczna w wymiarze globalnym. Problematyka zachowań i postaw konsumentów wobec produktów "społecznie odpowiedzialnych" nabiera coraz większego znaczenia także w polskiej gospodarce. Celem artykułu jest ocena perspektyw rozwoju etyczneji ekologicznej konsumpcji w Polsce na tle krajów zachodnio-europejskich. Analizę porównawczą prowadzono bazując na źródłach wtórych jak i badaniach pierwotnych realizowanych na reprezentatywnej próbie losowej dorosłych mieszkańców Polski. W oparciu o analizę czynnikową, a dokładniej metodę analizy głównych składowych, dokonano także podziału polskich konsumentów na jednorodne grupy typologiczne pod względem ich wrażliwości na różne aspekty związane z ekologią i etyką

Technical performance and diagnostic utility of the new Elecsys (R) neuron-specific enolase enzyme immunoassay

This international multicenter study was designed to evaluate the technical performance of the new double-monoclonal, single-step Elecsys neuron-specific enolase (NSE) enzyme immunoassay (EIA) and to assess its utility as a sensitive and specific test for the diagnosis of small-cell lung cancer (SCLC). Intra and interassay coefficients of variation, determined in five control or serum specimens in six laboratories, ranged from 0.7 to 5.3 (interlaboratory median: 1.3%) and from 1.3 to 8.5 (interlaboratory median: 3.4%), respectively. Laboratory-to-laboratory comparability was excellent with respect to recovery and interassay coefficients of variation. The test was linear between 0.0 and 320 ng/ml (highest measured concentration). There was a significant correlation between NSE concentrations measured using the Elecsys NSE and the established Cobas Core NSE EIA II in all subjects (n=723) and in patients with lung cancer (n=333). However, NSE concentrations were systematically lower (approximately 9%) with the Elecsys NSE than with the comparison test. Based on a specificity of 95% in comparison with the group suffering from benign lung diseases (n=183), the cutoff value for the discrimination between malignant and benign conditions was set at 21.6 ng/ml. NSE was raised in 73.4% of SCLC patients (n=188) and was significantly higher (p<0.01) in extensive (87.8%) as opposed to limited disease (56.7%). NSE was also elevated in 16.0% of the cases with non-small cell lung cancer (NSCLC, n=374). It is concluded that the Elecsys NSE EIA is a reliable and accurate diagnostic procedure for the measurement of NSE in serum samples. The special merits of this new assay are the wide measuring range (according to manufacturers declaration up to 370 ng/ml) and a short incubation time of 18 min

Optical Properties of Guanine Nanowires: Experimental and Theoretical Study

International audienceLong nanowires formed by ca. 800 guanine tetrads (G4-wires) are studied in phosphate buffer containing sodium cations. Their room temperature optical properties are compared to those of the monomeric chromophore 2-deoxyguanine monophosphate (dGMP). When going from dGMP to G4-wires, both the absorption and the fluorescence spectra change. Moreover, the fluorescence quantum yield increases by a factor of 7.3 whereas the average fluorescence lifetime increases by more than 2 orders of magnitude, indicating emission associated with weakly allowed transitions. The behavior of G4-wires is interpreted in the light of a theoretical study performed in the frame of the exciton theory combining data from molecular dynamics and quantum chemistry. These calculations, carried out for a quadruplex composed of three tetrads, reveal the existence of various exciton states having different energies and oscillator strengths. The degree of delocalization of the quadruplex Franck−Condon excited states is larger than those found for longer duplexes following the same methodology. The slower excited-state relaxation in G4-wires compared to dGMP is explained by emission from exciton states, possibly limited on individual tetrads, whose coherence is reserved by the reduced mobility of guanines due to multiple Hoogsteen hydrogen bonds