Accessibility Surfaces Research Articles

Critical Residues Involved in the Coassembly of L1 and L2 Capsid Proteins of Human Papillomavirus 16.

Human papillomaviruses (HPV) are small DNA viruses associated with cervical cancer, warts, and other epithelial tumors. Structural studies have shown that the HPV capsid consists of 360 copies of the major capsid protein, L1, arranged as 72 pentamers in a T=7 icosahedral lattice, coassembling with substoichiometric amounts of the minor capsid protein, L2. However, the residues involved in the coassembly of L1 and L2 remain undefined due to the lack of structure information. Here, we investigated the solvent accessibility surfaces (SASs) of the central cavity residues of the HPV16 L1 pentamer in the crystal structure because those internal exposed residues might mediate the association with L2. Twenty residues in L1 protein were selected to be analyzed, with four residues in the lumen of the L1 pentamer identified as important: F256, R315, Q317, and T340. Mutations to these four residues reduced the PsV (pseudovirus) infection capacity in 293FT cells, and mutations to R315, Q317, and T340 substantially perturb L2 from coassembling into L1 capsid. Compared with wild-type (WT) PsVs, these mutant PsVs also have a reduced ability to become internalized into host cells. Finally, we identified a stretch of negatively charged residues on L2 (amino acids [aa] 337 to 340 [EEIE]), mutations to which completely abrogate L2 assembly into L1 capsid and subsequently impair the endocytosis and infectivity of HPV16 PsVs. These findings shed light on the elusive coassembly between HPV L1 and L2. IMPORTANCE Over 200 types of HPV have been isolated, with several high-risk types correlated with the occurrence of cervical cancer. The HPV major capsid protein, L1, assembles into a T=7 icosahedral viral shell, and associates with the minor capsid protein, L2, which plays a critical role in the HPV life cycle. Despite the important role of the L2 protein, its structure and coassembly with L1 remain elusive. In this study, we analyzed the amino acid residues at the proposed interface between L1 and L2. Certain mutations at these sites decreased the amount of L2 protein assembled into the capsid, which, in turn, led to a decrease in viral infectivity. Knowledge about these residues and the coassembly of L1 and L2 could help to expand our understanding of HPV biology and aid in the development of countermeasures against a wide range of HPV types by targeting the L2 protein.

Synthesis, solvatochromism and dipole moment in the ground and excited states of substitute phenol derivative fluorescent Schiff base compounds

Three new fluorescent o-hydroxyaryl Schiff base derivatives are synthesized and their structures are characterized by NMR and FTIR spectroscopies. In this study, the solvent effect on the absorption and fluorescence spectral properties, Catalán and Taft-Kamlet solvatochromism models, and electric dipole moments in the ground and excited states, are investigated for synthesized compounds. Specific and non-specific solute–solvent interactions are investigated using Catalán and Taft-Kamlet solvatochromism models in various solvents with different polarities. Taft-Kamlet and Catalán solvatochromism models derived for absorption spectra indicate that solvent dipolarity/polarizability (π*) and solvent polarity (SP) are dominant in controlling absorption spectral shifts. As a result of solute–solvent interactions, absorption spectra exhibit positive solvatochromism, while fluorescence spectra show negative solvatochromism with the increase of solvent polarity. The ground state dipole moment is determined using the Bilot–Kawski method, and the excited state dipole moment is calculated using the Bilot–Kawski, Lippert–Mataga, Bakhshiev, modified Bilot-Kawski and Reichardt correlation methods. The dipole moments estimated in both ground and excited states confirm that Schiff base compounds are more polar in the excited state. The frontier molecular orbitals (HOMO and LUMO), molecular electrostatic potential (MEP), density of states (DOS) and solvent accessibility surfaces (SAS) of these compounds have been calculated using the DFT/B3LYP/6-311++G(d,p) level of theory.

Quantifying geographic accessibility to improve efficiency of entomological monitoring.

BackgroundVector-borne diseases are important causes of mortality and morbidity in humans and livestock, particularly for poorer communities and countries in the tropics. Large-scale programs against these diseases, for example malaria, dengue and African trypanosomiasis, include vector control, and assessing the impact of this intervention requires frequent and extensive monitoring of disease vector abundance. Such monitoring can be expensive, especially in the later stages of a successful program where numbers of vectors and cases are low.Methodology/Principal findingsWe developed a system that allows the identification of monitoring sites where pre-intervention densities of vectors are predicted to be high, and travel cost to sites is low, highlighting the most efficient locations for longitudinal monitoring. Using remotely sensed imagery and an image classification algorithm, we mapped landscape resistance associated with on- and off-road travel for every gridded location (3m and 0.5m grid cells) within Koboko district, Uganda. We combine the accessibility surface with pre-existing estimates of tsetse abundance and propose a stratified sampling approach to determine the most efficient locations for longitudinal data collection. Our modelled predictions were validated against empirical measurements of travel-time and existing maps of road networks. We applied this approach in northern Uganda where a large-scale vector control program is being implemented to control human African trypanosomiasis, a neglected tropical disease (NTD) caused by trypanosomes transmitted by tsetse flies. Our accessibility surfaces indicate a high performance when compared to empirical data, with remote sensing identifying a further ~70% of roads than existing networks.Conclusions/SignificanceBy integrating such estimates with predictions of tsetse abundance, we propose a methodology to determine the optimal placement of sentinel monitoring sites for evaluating control programme efficacy, moving from a nuanced, ad-hoc approach incorporating intuition, knowledge of vector ecology and local knowledge of geographic accessibility, to a reproducible, quantifiable one.

Modelling walking accessibility: A case study of Ljubljana, Slovenia

Abstract Walkable access is recognised as one of the most important factors for deciding to walk instead of using other modes of transport. Distance has been less accurately taken into consideration in previous walking accessibility measures, however, as they are often based on an isotropic approach or on a fixed distance threshold. The objective of this paper is to present a method of modelling continuous walking accessibility to different amenities in a city, with an integrated network-based and distance-decay approach, applied to a case study of the city of Ljubljana, Slovenia. The approach is based on a web survey to obtain data on acceptable walking distances to different types of amenities. Several distance decay functions were analysed for each type of amenity from the cumulative frequency of responses. The best fitting functions were used to model the walking accessibility surfaces for individual amenities in the network, representing five domains (retail, services, recreation, education and transportation) and an overall walking accessibility index. Despite certain limitations and a further need to assess the validity of the methods, our distance-decay network-based approach is more accurate than the isotropic or even network-based modelling of walking distances in continuous or threshold approaches, as it enables the researcher to take into account the differences in propensities to walk to different amenities. The results can be used by city authorities and planners for implementing actions to improve walking accessibility in the most problematic areas.

Accesibilidad y conectividad geográfica en áreas rurales. Caso de la comuna de María Pinto, Chile

En América Latina y especialmente en Chile, las áreas rurales son espacios que todavía presentan brechas de desarrollo en torno a la accesibilidad y la conectividad geográfica del territorio. La geografía puede aportar enfoques conceptuales y metodológicos para superar las brechas espaciales. Este artículo apunta a determinar y categorizar la accesibilidad y conectividad geográfica que tiene la población rural respecto de su centro urbano. Consideramos el estudio de caso como enfoque para analizar este tema, abordando de este modo la situación de la comuna de María Pinto, localizada en la Región Metropolitana de Santiago, Chile. Los objetivos que guían esta investigación son: caracterizar la red vial existente, determinar la conectividad y la accesibilidad geográfica intracomunal y determinar áreas homogéneas de accesibilidad en relación con el centro urbano de la comuna de María Pinto. En la discusión y conclusiones planteamos la relevancia que estos conceptos tienen con la movilidad de la población rural como parte de las políticas de desarrollo.

Guided-Wave Tomographic Imaging of Plate Defects by Laser-Based Ultrasonic Techniques

Contact-guided-wave tests are impractical for investigating specimens with limited accessibility and rough surfaces or complex geometric features. A non-contact setup with a laser-ultrasonic transmitter and receiver is quite attractive for guided-wave inspection. In the present work, we developed a non-contact guided-wave tomography technique using the laser-ultrasonic technique in a plate. A method for Lamb-wave generation and detection in an aluminum plate with a pulsed laser-ultrasonic transmitter and Michelson-interferometer receiver was developed. The defect shape and area in the images obtained using laser scanning, showed good agreement with the actual defect. The proposed approach can be used as a non-contact online inspection and monitoring technique.

A regional model of road accessibility in Mexico: Accessibility surfaces and robustness analysis

This paper introduces an empirical accessibility model for Mexico based on land transport infrastructure. The model assesses an attraction-accessibility measure derived from a gravity framework. The measure is estimated on a regional basis and can be interpreted as the market potential of a region. We introduce three versions of the model: the first measures the potential restricted to the domestic market, the second considers the external sector, and the third is essentially a regional accessibility index, which captures the domestic market potential at regional level. We carry out an exhaustive analysis to test the robustness of the accessibility model and find that its behaviour is robust with respect to several criteria.

Comparison of Selected Methods for Individual Decontamination of Chemical Warfare Agents

This study addresses the individual decontamination of chemical warfare agents (CWA) and other hazardous substances. The individual decontamination applies to contaminated body surfaces, protective clothing and objects immediately after contamination, performed individually or by mutual assistance using prescribed or improvised devices. The article evaluates the importance of individual decontamination, security level for Fire and Rescue Service Units of the Czech Republic (FRS CR) and demonstrates some of the devices. The decontamination efficiency of selected methods (sorbent, glove and sponge, two-chamber foam device and wiping with alcohol) was evaluated for protective clothing and painted steel plate contaminated with O-ethyl-S-(diisopropylaminoethyl)-methylthiophosphonate (VX), sulfur mustard, o-cresol and acrylonitrile. The methods were assessed from an economic point of view and with regard to specific user parameters, such as the decontamination of surfaces or materials with poor accessibility and vertical surfaces, the need for a water rinse as well as toxic waste and its disposal.

Shaping chromatin for repair

To counteract the adverse effects of various DNA lesions, cells have evolved an array of diverse repair pathways to restore DNA structure and to coordinate repair with cell cycle regulation. Chromatin changes are an integral part of the DNA damage response, particularly with regard to the types of repair that involve assembly of large multiprotein complexes such as those involved in double strand break (DSB) repair and nucleotide excision repair (NER). A number of phosphorylation, acetylation, methylation, ubiquitylation and chromatin remodeling events modulate chromatin structure at the lesion site. These changes demarcate chromatin neighboring the lesion, afford accessibility and binding surfaces to repair factors and provide on-the-spot means to coordinate repair and damage signaling. Thus, the hierarchical assembly of repair factors at a double strand break is mostly due to their regulated interactions with posttranslational modifications of histones. A large number of chromatin remodelers are required at different stages of DSB repair and NER. Remodelers physically interact with proteins involved in repair processes, suggesting that chromatin remodeling is a requisite for repair factors to access the damaged site. Together, recent findings define the roles of histone post-translational modifications and chromatin remodeling in the DNA damage response and underscore possible differences in the requirements for these events in relation to the chromatin context.

Identification of Membrane-Contacting Loops of the Catalytic Domain of Cytochrome P450 2C2 by Tryptophan Fluorescence Scanning

The catalytic domain of cytochrome P450 is thought to contact the lipid core of the endoplasmic reticulum membrane based on antibody epitope accessibility, protease susceptibility, and hydrophobic surfaces present on P450 structures of solubilized forms of the proteins. Quenching by nitroxide spin label-modified phospholipids of the fluorescence of tryptophan residues substituted into cytochrome P450 2C2, modified to contain tryptophan only at position 120, was used to identify regions of P450 inserted into the lipid core and to estimate the depth of penetration. Consistent with the proposed models of cytochrome P450-membrane interaction, the fluorescence of tryptophans inserted at residues 36 and 69 in the two segments of P450 2C2 flanking the A-helix and at residue 380 in the beta2-2 strand was quenched by nitroxide spin labels on carbon 5 of the fatty acid tails of the phospholipids within the lipid bilayer. The fluorescence of tryptophan at 380 was also strongly quenched by a spin label on carbon 12 of the fatty acids suggesting it was deepest in the membrane. However, fluorescence of tryptophan substituted at residue 225 in the F-G loop, which was predicted to be in the lipid bilayer, was not quenched by the spin labels at carbons 5 and 12 of the fatty acids. The pattern of quenching of fluorescence for tryptophans at the other positions tested, 80, 189, 239, and 347, was similar to the parent protein indicating they were not inserted into the lipid bilayer as expected. The results are consistent with an orientation of cytochrome P450 2C2 in the membrane in which positions 36, 69, and 380 are inserted into the lipid bilayer and residues 80 and 225 are near or within the phospholipid headgroup region. In this orientation, the F-G loop, which contains residue 225, could form a dimerization interface as was observed in the P450 2C8 crystal structure (Schoch, G. A., et al. (2004) J. Biol. Chem. 279, 9497).

Type II Cadherin Ectodomain Structures: Implications for Classical Cadherin Specificity

Type I and II classical cadherins help to determine the adhesive specificities of animal cells. Crystal-structure determination of ectodomain regions from three type II cadherins reveals adhesive dimers formed by exchange of N-terminal beta strands between partner extracellular cadherin-1 (EC1) domains. These interfaces have two conserved tryptophan side chains that anchor each swapped strand, compared with one in type I cadherins, and include large hydrophobic regions unique to type II interfaces. The EC1 domains of type I and type II cadherins appear to encode cell adhesive specificity in vitro. Moreover, perturbation of motor neuron segregation with chimeric cadherins depends on EC1 domain identity, suggesting that this region, which includes the structurally defined adhesive interface, encodes type II cadherin functional specificity in vivo.

Semiempirical Predictions of Chemical Degradation Reaction Mechanisms of CL-20 as Related to Molecular Structure

Combining computer chemistry calculation with experimental verification is useful both in proving concepts and what is chemically possible. Computational predictions, using MOPAC quantum mechanical and classical force field mechanics, were used to investigate most likely first-tier intermediates of cyclic and cage cyclic nitramines—comparing bond lengths and angles, heats of formation, steric energy, dipole moments, solvent accessibility and electrostatic potential surfaces, partial charges, and Highest Occupied Molecular Orbitals/Lowest Unoccupied Molecular Orbitals (HOMO/LUMO) energies. Two competing modes of degradation are summarized: through addition of hydroxide ions and through addition of photo-induced free radicals. UV/VIS measured concentrations and followed the course of reactions. FTIR followed CL-20 degradation through alkali hydrolysis, where FTIR measurements verified theoretical predictions.

Urban Expansion Simulation of Southeast England Using Population Surface Modelling and Cellular Automata

The question of where to accommodate future urban expansion has become a politically sensitive issue in many regions. Against the backdrop of ‘urban compaction’ policy, this study uses population surface modelling and cellular automata (CA) to conduct an empirical urban growth simulation for Southeast England. This implementation leads to a consideration of the proper balance between the theoretical abstraction of self-organised growth and empirical constraints to land development. Specifically, we use 1991 and 1997 postcode directories to construct population surfaces. From these, the distributions of developed and vacant (rural) land are derived. Development potential is assessed through accessibility surfaces, which are constructed from the travel/commuting time to major London rail termini, to motorway junctions, and to principal settlements. Through investigating the frequencies of land development in relation to the accessibility surfaces, we can begin to understand the distribution of land development in this region. Based on this empirical relationship, the transition rules of a CA simulation of future urban expansion are constructed. In addition, government population projections at the county level are used to constrain simulation to the year 2020. The study demonstrates the utility of empirical CA in urban growth modelling; in particular the importance of empirically informed CA simulation rules in characterising the distribution of land development.

Accessibility and Economic Development in Europe

VICKERMAN R., SPIEKERMANN K. and WEGENER M. (1999) Accessibility and economic development in Europe, Reg. Studies 33 , 1-15. There is continuing debate on the role of transport infrastructure and changes in accessibility on regional economic development. The emphasis in recent European Union policy on the development of trans-European Networks (TENs) provides a focus for a re-evaluation. Much of the debate assumes that improvements in accessibility will lead to economic development and, by implication, to greater cohesion. This paper identifies some of the major difficulties in defining a simple measure of accessibility for use in such studies and proceeds to evaluate new measures of time-space and accessibility surfaces which allow for greater disaggregation at a spatial and sectoral level. An assessment of the implications for regional development in the EU is then made. The conclusions cast doubt on the ability of TENs to promote greater convergence in both accessibility and economic development. VICKERMAN R., SPIEKERMANN K. et WEGENER M. (1999) Accessibilite´ et de´veloppement e´conomique en Europe, Reg. Studies 33 , 1-15. Le role de l'infrastructure de transport et de l'accessibilite´ dans le de´veloppement e´conomique re´gional est toujours un sujet très controverse´. Dans le cadre de l'Union europe´enne, la politique re´cente a mis l'accent sur le de´veloppement des re´seaux transeurope´ens, ce qui permet une re´e´valuation. Dans une large mesure, le de´bat laisse supposer qu'une meilleure accessibilite´ incitera au de´veloppement e´conomique et, par la suite, à plus de cohe´sion. L'article distingue quelques-unes des plus grandes difficulte´s quant à la de´finition d'une mesure simple de l'accessibilite´ qui pourrait etre employe´e dans de telles e´tudes, et e´value de nouvelles mesures de l'espace-temps et de l'accessibilite´ qui permettraient une division plus importante sur le plan ge´ographique et du point de vue sectoriel. On fait le bilan des conse´quences pour l'ame´nagement du territoire au sein de l'Union europe´enne. La conclusion met en doute la capacite´ des re´seaux transeurope´ens à promouvoir une meilleure convergence quant à l'accessibilite´ et au de´veloppement e´conomique. VICKERMAN R., SPIEKERMANN K. und WEGENER M. (1999) Zugänglichkeit und wirtschaftliche Entwicklung in Europa, Reg. Studies 33 , 1-15. Die Debatte über die Rolle von Verkehrsinfrastruktur und Wandel der Zugänglichkeit auf regionalwirtschaftliche Entwicklung hält weiterhin an. Die Betonung der Entwicklung transeuropäischer Netzwerke (TEN) in den letzten politischen Diskussionen der EU liefert einen Brennpunkt für eine erneute Einschätzung. In der Debatte wird oft vorausgesetzt, daß verbesserte Zugänglichkeit zu wirtschaftlicher Entwicklung, und implizite zu stärkerem Zusammenhalt, führen wird. Dieser Aufsatz identifiziert einige der Hauptschwierigkeiten bei der Definition eines einfachen Maßstabs der Zugänglichkeit zur Anwendung bei derartigen Studien, und beurteilt dann neue Maßstäbe der Zeit-Raum und Zugänglichkeitsoberfläche, welche größere Disaggregation auf räumlicher wie auf Sektorenebene gestatten. Anschließend wird eine Einschätzung der Implikationen für die Regionalentwicklung in der EU vorgenommen. Sie Schlußfolgerungen lassen Zweifel an der Fähigkeit transeuropäischer Netzwerke aufkommen, größere Konvergenz von Zugänglichkeit und wirtschaftlicher Entwicklung herbeizuführen.

A New Algorithm for Graph‐theoretic Nodal Accessibility Measurement

Accessibility is a useful concept in the study of the spatial structure of a region, if it can be calibrated appropriately. While graph‐theoretic analysis has been used widely as a measurement scheme for the nodal accessibility in various transport networks, several limitations have been pointed out in the existing graph‐theoretic accessibility measurements. This study proposes a new algorithm for deriving the nodal accessibility measure, as an attempt to improve the conventional graph‐theoretic accessibility measurements. Corrections are made in such a way that irrelevant loops are excluded and relevant indirect connection paths are included selectively. In particular, the new algorithm is developed for intraurban subway networks, and includes the characteristics of intraurban subway traffic behavior. The concept of inconvenience of transfer is introduced, which is one of the most influential factors in the intraurban subway traffic. Nodal differentiation is allowed, if the nodes play different roles in the travel behavior and eventually in the accessibility. For this purpose, we employ a weighting procedure, according to which the influence of transfer on a sequence of linkages is taken into account. The new accessibility measurement scheme is then applied to the Seoul subway network. Here GIS techniques are utilized to generate accessibility surfaces from the discrete nodal accessibility values, and the changes in the spatial structure of the nodal accessibility are analyzed. Finally, based on the resulting changes in the spatial structure of accessibility in the subway network, the direction of changes in the land value and the land use pattern in Seoul is discussed.

Security patterns and surface model in landscape ecological planning

It is demonstrated that there are potential spatial patterns, called security patterns (SPs), composed of strategic portions and positions of the landscape that have critical significance in safeguarding and controlling certain ecological processes. Components of security patterns have the quality of initiative, coordination and efficiency, and are, therefore, strategically important in landscape change in biological conservation. SPs can be identified according to the properties on a general surface model of flows. Potential surfaces (accessibility surfaces) are developed using landscape resistance to represent the dynamics of horizontal ecological processes (species movement). Four strategic landscape portions and positions are identified on the potential surfaces: buffer zones, inter-source linkages, radiating routes and strategic points. These components, specified by certain quantitative and qualitative parameters, together with the identified sources (native habitats), compose the ecological SPs at various security levels. SPs may vary with the target species. Individual SPs for various target species or groups can be combined in cases when overall ecological SPs are needed. These SPs could be used by defenders of ecological processes as defensive frontiers and strategies of spatial bartering in landscape changes. A case study is presented following the discussion on the concept and method of ecological security patterns. The GIS (geographical information systems) is intensively applied in the case study.

Evolution of the motorway network and changing levels of accessibility in Great Britain

The long-term role of road transport infrastructure in promoting, maintaining and developing the economic system is an important one which has received relatively little research attention. The road network supports a variety of dependent economic activity and serves to integrate the economic system over space. More specifically the enhancement of the motorway network over the years in Britain will have affected the accessibility surface of the nation. This paper considers accessibility changes between the components of the urban system which are the result of postwar motorway construction. Three accessibility surfaces are considered based on various stages in the motorway building programme. A standard market potential accessibility measure is used to capture those accessibility changes which are due to the motorway effect over various periods of time and those which are due to the employment effect. The calculations are founded on the travel modes of cars and heavy goods vehicles (HGVs) based on a generalized measure of cost impedance. The results are presented for the familiar set of 19 local labour market area types based on some 280 functional urban regions and for the 11 Standard Regions based on some 852 amalgamated jobcentre office areas.