Complexity and chirality indices for molecular informatics::differential geometry approach

Novel molecular complexity measures are designed based on the quantum molecular kinematics. The Hamiltonian matrix constructed in a quasi-topological approximation describes the temporal evolution of the modelled electronic system and determined the time derivatives for the dynamic quantities. This allows to define the average quantum kinematic characteristics closely related to the curvatures of the electron paths, particularly, the torsion reflecting the chirality of the dynamic system. A special attention has been given to the computational scheme for this chirality measure. The calculations on realistic molecular systems demonstrate reasonable behaviour of the proposed molecular complexity indices.

The role of lipid geometry in designing liposomes for the solubilisation of poorly water soluble drugs

Liposomes are well recognised for their ability to improve the delivery of a range of drugs. More commonly they are applied for the delivery of water-soluble drugs, but given their structural attributes, they can also be employed as solubilising agents for low solubility drugs as well as drug targeting agents. To further explore the potential of liposomes as solubilising agents, we have investigated the role of bilayer packaging in promoting drug solubilisation in liposome bilayers. The effect of alkyl chain length and symmetry was investigated to consider if using 'mis-matched' phospholipids could create 'voids' within the bilayers, and enhance bilayer loading capacity. Lipid packing was investigated using Langmuir studies, which demonstrated that increasing the alkyl chain length enhanced lipid packing, with condensed monolayers forming, whilst asymmetric lipids formed less condensed monolayers. However, this more open packing did not translate into improved drug loading, with the longer chain, condensed bilayers formed from long-chain, saturated lipids offering higher drug loading capacity. These studies demonstrate that liposomes formulated from longer chain, saturated lipids offer enhanced solubilisation capacity. However the molecular size, rather than lipophilicity, of the drug to be incorporated was also a key factor dominating bilayer incorporation efficiency. © 2012 Elsevier B.V. All rights reserved.

Cardiac dysfunction and cell damage across clinical stages of severity in growth-restricted fetuses

Objective - The purpose of this study was to assess cardiac function and cell damage in intrauterine growth-restricted (IUGR) fetuses across clinical Doppler stages of deterioration. Study Design - One hundred twenty appropriate-for-gestational-age and 81 IUGR fetuses were classified in stages 1/2/3 according umbilical artery present/absent/reversed end-diastolic blood flow, respectively. Cardiac function was assessed by modified-myocardial performance index, early-to-late diastolic filling ratios, cardiac output, and cord blood B-type natriuretic peptide; myocardial cell damage was assessed by heart fatty acid–binding protein, troponin-I, and high-sensitivity C-reactive protein. Results - Modified-myocardial performance index, blood B-type natriuretic peptide, and early-to-late diastolic filling ratios were increased in a stage-dependent manner in IUGR fetuses, compared with appropriate-for-gestational-age fetuses. Heart fatty acid–binding protein levels were higher in IUGR fetuses at stage 3, compared with control fetuses. Cardiac output, troponin-I, and high-sensitivity C-reactive protein did not increase in IUGR fetuses at any stage. Conclusion - IUGR fetuses showed signs of cardiac dysfunction from early stages. Cardiac dysfunction deteriorates further with the progression of fetal compromise, together with the appearance of biochemical signs of cell damage.

Effects of lipoic acid and dihydrolipoic acid on total erythrocytic thiols under conditions of restricted glucose in vitro

The effects of lipoic acid and dihydrolipoic acid were explored on total thiol maintenance in diabetic and non-diabetic human erythrocytes in vitro over 22 hr in a 37°C incubation system with no added glucose. Over 18-22.5 hr after treatment in both non-diabetic and diabetic cells, lipoic acid (1 mM) was associated with greater loss of cellular thiols than dihydrolipoic acid (1 mM), compared to respective control values. At 0.1 mM, in non-diabetic cells, although lipoic acid-treated cells' thiol levels were significantly lower than control, there was no significant difference between dihydrolipoic acid-treated cells and control cells regarding thiol levels. In addition, at 0.1 mM, dihydrolipoic acid-treated diabetic cells showed a reduction in thiol levels compared to control. At 0.01 mM, lipoic acid-treated cells had significantly lower measured thiol levels compared with diabetic cells exposed to dihydrolipoic acid, whereas in non-diabetic cells, dihydrolipoic acid-treated erythrocytic thiol levels were significantly greater than those treated with lipoic acid, although there were no other significant differences between the groups. At 22.5 hr, control values of methaemoglobin rose to 6.4 ± 1.1% in diabetic cells and 3.6 ± 2.1% in non-diabetic cells. Lipoic acid (1 mM) showed greater methaemoglobin formation in diabetic rather than non-diabetic cells (13.6 ± 1.5% versus 11.6 ± 1.5%), whereas dihydrolipoic acid-treated diabetic and non-diabetic cells were less potent in methaemoglobin generation (8.5 ± 2.4% and 8.4 ± 1.4%, respectively). These studies suggest that in certain circumstances such as hypoglycaemia, lipoic acid administration may actually be detrimental to cellular oxidant protection status. © 2006 The Authors.

Site-restricted web searches for data collection in regional dialectology

This article presents a new method for data collection in regional dialectology based on site-restricted web searches. The method measures the usage and determines the distribution of lexical variants across a region of interest using common web search engines, such as Google or Bing. The method involves estimating the proportions of the variants of a lexical alternation variable over a series of cities by counting the number of webpages that contain the variants on newspaper websites originating from these cities through site-restricted web searches. The method is evaluated by mapping the 26 variants of 10 lexical variables with known distributions in American English. In almost all cases, the maps based on site-restricted web searches align closely with traditional dialect maps based on data gathered through questionnaires, demonstrating the accuracy of this method for the observation of regional linguistic variation. However, unlike collecting dialect data using traditional methods, which is a relatively slow process, the use of site-restricted web searches allows for dialect data to be collected from across a region as large as the United States in a matter of days.

Towards the in silico identification of class II restricted T-cell epitopes:a partial least squares iterative self-consistent algorithm for affinity prediction

Motivation: The immunogenicity of peptides depends on their ability to bind to MHC molecules. MHC binding affinity prediction methods can save significant amounts of experimental work. The class II MHC binding site is open at both ends, making epitope prediction difficult because of the multiple binding ability of long peptides. Results: An iterative self-consistent partial least squares (PLS)-based additive method was applied to a set of 66 pep- tides no longer than 16 amino acids, binding to DRB1*0401. A regression equation containing the quantitative contributions of the amino acids at each of the nine positions was generated. Its predictability was tested using two external test sets which gave r pred =0.593 and r pred=0.655, respectively. Furthermore, it was benchmarked using 25 known T-cell epitopes restricted by DRB1*0401 and we compared our results with four other online predictive methods. The additive method showed the best result finding 24 of the 25 T-cell epitopes. Availability: Peptides used in the study are available from http://www.jenner.ac.uk/JenPep. The PLS method is available commercially in the SYBYL molecular modelling software package. The final model for affinity prediction of peptides binding to DRB1*0401 molecule is available at http://www.jenner.ac.uk/MHCPred. Models developed for DRB1*0101 and DRB1*0701 also are available in MHC- Pred

Learning higher-level features with convolutional restricted Boltzmann machines for sentiment analysis

In recent years, learning word vector representations has attracted much interest in Natural Language Processing. Word representations or embeddings learned using unsupervised methods help addressing the problem of traditional bag-of-word approaches which fail to capture contextual semantics. In this paper we go beyond the vector representations at the word level and propose a novel framework that learns higher-level feature representations of n-grams, phrases and sentences using a deep neural network built from stacked Convolutional Restricted Boltzmann Machines (CRBMs). These representations have been shown to map syntactically and semantically related n-grams to closeby locations in the hidden feature space. We have experimented to additionally incorporate these higher-level features into supervised classifier training for two sentiment analysis tasks: subjectivity classification and sentiment classification. Our results have demonstrated the success of our proposed framework with 4% improvement in accuracy observed for subjectivity classification and improved the results achieved for sentiment classification over models trained without our higher level features.

Gratings in novel fibre geometry for applications in shape sensing

A long period grating (LPG) fabricated in progressive three-layered (PTL) fibre is described. The grating with a period of 391µm, had dual attenuation bands associated with a particular cladding mode. The dual attenuation bands have been experimentally characterised for their spectral sensitivity to bending, which resulted in the highest sensitivity to bending seen for this particular fibre and temperature. The spectral characteristics of the fibre have been modelled giving good agreement to the experimental data as well as showing that the attenuation bands are both associated with the second order HE/EH2,n cladding mode.

Formation and precise geometry control of SNAP microresonators by external electrostatic fields

In SNAP (Surface nanoscale axial photonics) resonators propagation of a slow whispering gallery mode along an optical fiber is controlled by nanoscale variation of the effective radius of the fiber [1]. Similar behavior can be realized in so - called nanobump microresonators in which the introduced variation of the effective radius is asymmetric, i.e. depends on the axial coordinate [2]. The possibilities of realization of such structures “on the fly” in an optical fiber by applying external electrostatic fields to it is discussed in this work. It is shown that local variations in effective radius of the fiber and in its refractive index caused by external electric fields can be large enough to observe SNAP structure - like behavior in an originally flat optical fiber. Theoretical estimations of the introduced refractive index and effective radius changes and results of finite element calculations are presented. Various effects are taken into account: electromechanical (piezoelectricity and electrostriction), electro-optical (Pockels and Kerr effects) and elasto-optical effect. Different initial fibre cross-sections are studied. The aspects of use of linear isotropic (such as silica) and non-linear anisotropic (such as lithium niobate) materials of the fiber are discussed. REFERENCES [1] M. Sumetsky, J. M. Fini, Opt. Exp. 19, 26470 (2011). [2] L. A. Kochkurov, M. Sumetsky, Opt. Lett. 40, 1430 (2015).