Crystal chemistry and hydrogen bonding of rustumite Ca10(Si2O7)2(SiO4)(OH)2Cl2 with variable OH, Cl, F

Three samples of the skarn mineral rustumite Ca10(Si2O7)2(SiO4)(OH)2Cl2, space group C2/c, a ≈7.6, b ≈ 18.5, c ≈ 15.5 Å, β ≈ 104°, with variable OH, Cl, F content were investigated by electron microprobe, single-crystal X-ray structure refinements, and Raman spectroscopy. “Rust1LCl” is a low chlorine rustumite Ca10(Si2O7)2(SiO4)(OH1.88F0.12)(Cl1.28,OH0.72) from skarns associated with the Rize batholith near Ikizedere, Turkey. “Rust2F” is a F-bearing rustumite Ca10(Si2O7)2(SiO4)(OH1.13F0.87) (Cl1 96OH0.04) from xenoliths in ignimbrites of the Upper Chegem Caldera, Northern Caucasus, Russia. “Rust3LClF” represents a low-Cl, F-bearing rustumite Ca10(Si2O7)2(SiO4)0.87(H4O4)0.13(OH1.01F0.99) (Cl1.00 OH1.00) from altered merwinite skarns of the Birkhin massif, Baikal Lake area, Eastern Siberia, Russia. Rustumite from Birkhin massif is characterized by a significant hydrogarnet-like or fluorine substitution at the apices of the orthosilicate group, leading to specific atomic displacements. The crystal structures including hydrogen positions have been refined from single-crystal X-ray data to R1 = 0.0205 (Rust1_LCl), R1 = 0.0295 (Rust2_F), and R1 = 0.0243 (Rust3_LCl_F), respectively. Depletion in Cl and replacement by OH is associated with smaller unit-cell dimensions. The substitution of OH by F leads to shorter hydrogen bonds O-H⋯F instead of O-H⋯OH. Raman spectra for all samples have been measured and confirm slight strengthening of the hydrogen bonds with uptake of F.This study discusses the complex crystal chemistry of the skarn mineral rustumite and may provide a wider understanding of the chemical reactions related to contact metamorphism of limestones.

Cryo-electron tomography of Kaposi's sarcoma-associated herpesvirus capsids reveals dynamic scaffolding structures essential to capsid assembly and maturation.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a recently discovered DNA tumor virus that belongs to the gamma-herpesvirus subfamily. Though numerous studies on KSHV and other herpesviruses, in general, have revealed much about their multilayered organization and capsid structure, the herpesvirus capsid assembly and maturation pathway remains poorly understood. Structural variability or irregularity of the capsid internal scaffolding core and the lack of adequate tools to study such structures have presented major hurdles to earlier investigations employing more traditional cryo-electron microscopy (cryoEM) single particle reconstruction. In this study, we used cryo-electron tomography (cryoET) to obtain 3D reconstructions of individual KSHV capsids, allowing direct visualization of the capsid internal structures and systematic comparison of the scaffolding cores for the first time. We show that B-capsids are not a structurally homogenous group; rather, they represent an ensemble of "B-capsid-like" particles whose inner scaffolding is highly variable, possibly representing different intermediates existing during the KSHV capsid assembly and maturation. This information, taken together with previous observations, has allowed us to propose a detailed pathway of herpesvirus capsid assembly and maturation.

Design and analysis for three level hierarchical structures with count response

In numerous intervention studies and education field trials, random assignment to treatment occurs in clusters rather than at the level of observation. This departure of random assignment of units may be due to logistics, political feasibility, or ecological validity. Data within the same cluster or grouping are often correlated. Application of traditional regression techniques, which assume independence between observations, to clustered data produce consistent parameter estimates. However such estimators are often inefficient as compared to methods which incorporate the clustered nature of the data into the estimation procedure (Neuhaus 1993).1 Multilevel models, also known as random effects or random components models, can be used to account for the clustering of data by estimating higher level, or group, as well as lower level, or individual variation. Designing a study, in which the unit of observation is nested within higher level groupings, requires the determination of sample sizes at each level. This study investigates the design and analysis of various sampling strategies for a 3-level repeated measures design on the parameter estimates when the outcome variable of interest follows a Poisson distribution. ^ Results study suggest that second order PQL estimation produces the least biased estimates in the 3-level multilevel Poisson model followed by first order PQL and then second and first order MQL. The MQL estimates of both fixed and random parameters are generally satisfactory when the level 2 and level 3 variation is less than 0.10. However, as the higher level error variance increases, the MQL estimates become increasingly biased. If convergence of the estimation algorithm is not obtained by PQL procedure and higher level error variance is large, the estimates may be significantly biased. In this case bias correction techniques such as bootstrapping should be considered as an alternative procedure. For larger sample sizes, those structures with 20 or more units sampled at levels with normally distributed random errors produced more stable estimates with less sampling variance than structures with an increased number of level 1 units. For small sample sizes, sampling fewer units at the level with Poisson variation produces less sampling variation, however this criterion is no longer important when sample sizes are large. ^ 1Neuhaus J (1993). “Estimation efficiency and Tests of Covariate Effects with Clustered Binary Data”. Biometrics , 49, 989–996^

COMPARISON OF THE ORGANIZATIONAL STRUCTURES AND EFFECTIVENESS OF THE INVESTOR-OWNED AND VOLUNTARY MULTIHOSPITAL SECTORS

Objectives. The central objective of this study was to systematically examine the internal structure of multihospital systems, determining the management principles used and the performance levels achieved in medical care and administrative areas.^ The Universe. The study universe consisted of short-term general American hospitals owned and operated by multihospital corporations. Corporations compared were the investor-owned (for-profit) and the voluntary multihospital systems. The individual hospital was the unit of analysis for the study.^ Theoretical Considerations. The contingency theory, using selected aspects of the classical and human relations schools of thought, seemed well suited to describe multihospital organization and was used in this research.^ The Study Hypotheses. The main null hypotheses generated were that there are no significant differences between the voluntary and the investor-owned multihospital sectors in their (1) hospital structures and (2) patient care and administrative performance levels.^ The Sample. A stratified random sample of 212 hospitals owned by multihospital systems was selected to equally represent the two study sectors. Of the sampled hospitals approached, 90.1% responded.^ The Analysis. Sixteen scales were constructed in conjunction with 16 structural variables developed from the major questions and sub-items of the questionnaire. This was followed by analysis of an additional 7 structural and 24 effectiveness (performance) measures, using frequency distributions. Finally, summary statistics and statistical testing for each variable and sub-items were completed and recorded in 38 tables.^ Study Findings. While it has been argued that there are great differences between the two sectors, this study found that with a few exceptions the null hypotheses of no difference in organizational and operational characteristics of non-profit and for-profit hospitals was accepted. However, there were several significant differences found in the structural variables: functional specialization, and autonomy were significantly higher in the voluntary sector. Only centralization was significantly different in the investor owned. Among the effectiveness measures, occupancy rate, cost of data processing, total manhours worked, F.T.E. ratios, and personnel per occupied bed were significantly higher in the voluntary sector. The findings indicated that both voluntary and for-profit systems were converging toward a common hierarchical corporate management approach. Factors of size and management style may be better descriptors to characterize a specific multihospital group than its profit or nonprofit status. (Abstract shortened with permission of author.) ^

A fatigue damage model for seismic response of RC structures

Numerous damage models have been developed in order to analyze seismic behavior. Among the different possibilities existing in the literature, it is very clear that models developed along the lines of continuum damage mechanics are more consistent with the definition of damage as a phenomenon with mechanical consequences because they include explicitly the coupling between damage and mechanical behavior. On the other hand, for seismic processes, phenomena such as low cycle fatigue may have a pronounced effect on the overall behavior of the frames and, therefore, its consideration turns out to be very important. However, most of existing models evaluate the damage only as a function of the maximum amplitude of cyclic deformation without considering the number of cycles. In this paper, a generalization of the simplified model proposed by Cipollina et al. [Cipollina A, López-Hinojosa A, Flórez-López J. Comput Struct 1995;54:1113–26] is made in order to include the low cycle fatigue. Such a model employs in its formulation irreversible thermodynamics and internal state variable theory.

A damage model for seismic retrofitting of structures

Numerous damage models have been developed in order to analyse the seismic behavior. Among the different possibilities existing in the literature, it is very clear that models developed along the lines of Continuum Damage Mechanics are more consistent with the definition of damage like a phenomenon with mechanical consequences as they include explicitly the coupling between damage and mechanical behavior. On the other hand, for seismic processes, phenomena such as low cycle fatigue may have a pronounced effect on the overall behavior of the frames and, therefore, its consideration turns out to be very important. However, many of existing models evaluate the damage only as a function of the maximum amplitude of cyclic deformation without considering the number of cycles. In this paper, a generalization of the simplified model proposed by Flórez is made in order to include the low cycle fatigue. Such model employs in its formulation irreversible thermodynamics and internal state variable theory.

Crack width control in RC elements with recycled steel fibres and applications to integral structures : theoretical and experimental study

El presente trabajo trata de elementos reforzados con barras de armadura y Fibras Metálicas Recicladas (FMR). El objetivo principal es mejorar el comportamiento a fisuración de elementos sometidos a flexión pura y a flexión compuesta, aumentando en consecuencia las prestaciones en servicio de aquellas estructuras con requerimientos estrictos con respecto al control de fisuración. Entre éstas últimas se encuentran las estructuras integrales, es decir aquellas estructuras sin juntas (puentes o edificios), sometidas a cargas gravitatorias y deformaciones impuestas en los elementos horizontales debidas a retracción, fluencia y temperatura. Las FMR son obtenidas a partir de los neumáticos fuera de uso, y puesto que el procedimiento de reciclado se centra en el caucho en vez que en el acero, su forma es aleatoria y con longitud variable. A pesar de que la eficacia del fibrorefuerzo mediante FMR ha sido demostrada en investigaciones anteriores, la innovación que representa este trabajo consiste en proponer la acción combinada de barras convencionales y FMR en la mejora del comportamiento a fisuración. El objetivo es por tanto mejorar la sostenibilidad del proyecto de la estructura en HA al utilizar materiales reciclados por un lado, y aumentando por el otro la durabilidad. En primer lugar, se presenta el estado del arte con respecto a la fisuración en elementos de HA, que sucesivamente se amplía a elementos reforzados con barras y fibras. Asimismo, se resume el método simplificado para el análisis de columnas de estructuras sin juntas ya propuesto por Pérez et al., con particular énfasis en aquellos aspectos que son incompatibles con la acción de las fibras a nivel seccional. A continuación, se presenta un modelo para describir la deformabilidad seccional y la fisuración en elementos en HA, que luego se amplía a aquellos elementos reforzados con barras y fibras, teniendo en cuenta también los efectos debidos a la retracción (tension stiffening negativo). El modelo es luego empleado para ampliar el método simplificado para el análisis de columnas. La aportación consiste por tanto en contar con una metodología amplia de análisis para este tipo de elementos. Seguidamente, se presenta la campaña experimental preliminar que ha involucrado vigas a escala reducida sometidas a flexión simple, con el objetivo de validar la eficiencia y la usabilidad en el hormigón de las FMR de dos diferentes tipos, y su comportamiento con respecto a fibras de acero comerciales. Se describe a continuación la campaña principal, consistente en ensayos sobre ocho vigas en flexión simple a escala 1:1 (variando contenido en FRM, Ø/s,eff y recubrimiento) y doce columnas a flexión compuesta (variando contenido en FMR, Ø/s,eff y nivel de fuerza axil). Los resultados obtenidos en la campaña principal son presentados y comentados, resaltando las mejoras obtenidas en el comportamiento a fisuración de las vigas y columnas, y la rigidez estructural de las columnas. Estos resultados se comparan con las predicciones del modelo propuesto. Los principales parámetros estudiados para describir la fisuración y el comportamiento seccional de las vigas son: la separación entre fisuras, el alargamiento medio de las armaduras y la abertura de fisura, mientras que en los ensayos de las columnas se ha contrastado las leyes momento/curvatura, la tensión en las barras de armadura y la abertura de fisura en el empotramiento en la base. La comparación muestra un buen acuerdo entre las predicciones y los resultados experimentales. Asimismo, se nota la mejora en el comportamiento a fisuración debido a la incorporación de FMR en aquellos elementos con cuantías de armadura bajas en flexión simple, en elementos con axiles bajos y para el control de la fisuración en elementos con grandes recubrimientos, siendo por tanto resultados de inmediato impacto en la práctica ingenieril (diseño de losas, tanques, estructuras integrales, etc.). VIIIComo punto final, se presentan aplicaciones de las FMR en estructuras reales. Se discuten dos casos de elementos sometidos a flexión pura, en particular una viga simplemente apoyada y un tanque para el tratamiento de agua. En ambos casos la adicción de FMR al hormigón lleva a mejoras en el comportamiento a fisuración. Luego, utilizando el método simplificado para el análisis en servicio de columnas de estructuras sin juntas, se calcula la máxima longitud admisible en casos típicos de puentes y edificación. En particular, se demuestra que las limitaciones de la práctica ingenieril actual (sobre todo en edificación) pueden ser aumentadas considerando el comportamiento real de las columnas en HA. Finalmente, los mismos casos son modificados para considerar el uso de MFR, y se presentan las mejoras tanto en la máxima longitud admisible como en la abertura de fisura para una longitud y deformación impuesta. This work deals with elements reinforced with both rebars and Recycled Steel Fibres (RSFs). Its main objective is to improve cracking behaviour of elements subjected to pure bending and bending and axial force, resulting in better serviceability conditions for these structures demanding keen crack width control. Among these structures a particularly interesting type are the so-called integral structures, i.e. long jointless structures (bridges and buildings) subjected to gravitational loads and imposed deformations due to shrinkage, creep and temperature. RSFs are obtained from End of Life Tyres, and due to the recycling process that is focused on the rubber rather than on the steel they come out crooked and with variable length. Although the effectiveness of RSFs had already been proven by previous research, the innovation of this work consists in the proposing the combined action of conventional rebars and RSFs to improve cracking behaviour. Therefore, the objective is to improve the sustainability of RC structures by, on the one hand, using recycled materials, and on the other improving their durability. A state of the art on cracking in RC elements is firstly drawn. It is then expanded to elements reinforced with both rebars and fibres (R/FRC elements). Finally, the simplified method for analysis of columns of long jointless structures already proposed by Pérez et al. is resumed, with a special focus on the points that conflict when taking into account the action of fibres. Afterwards, a model to describe sectional deformability and cracking of R/FRC elements is presented, taking also into account the effect of shrinkage (negative tension stiffening). The model is then used to implement the simplified method for columns. The novelty represented by this is that a comprehensive methodology to analyse this type of elements is presented. A preliminary experimental campaign consisting in small beams subjected to pure bending is described, with the objective of validating the effectiveness and usability in concrete of RSFs of two different types, and their behaviour when compared with commercial steel fibres. With the results and lessons learnt from this campaign in mind, the main experimental campaign is then described, consisting in cracking tests of eight unscaled beams in pure bending (varying RSF content, Ø/s,eff and concrete cover) and twelve columns subjected to imposed displacement and axial force (varying RSF content, Ø/s,eff and squashing load ratio). The results obtained from the main campaign are presented and discussed, with particular focus on the improvement in cracking behaviour for the beams and columns, and structural stiffness for the columns. They are then compared with the proposed model. The main parameters studied to describe cracking and sectional behaviours of the beam tests are crack spacing, mean steel strain and crack width, while for the column tests these were moment/curvature, stress in rebars and crack with at column embedment. The comparison showed satisfactory agreement between experimental results and model predictions. Moreover, it is pointed out the improvement in cracking behaviour due to the addition of RSF for elements with low reinforcement ratios, elements with low squashing load ratios and for crack width control of elements with large concrete covers, thus representing results with a immediate impact in engineering practice (slab design, tanks, integral structures, etc.). Applications of RSF to actual structures are finally presented. Two cases of elements in pure bending are presented, namely a simple supported beam and a water treatment tank. In both cases the addition of RSF to concrete leads to improvements in cracking behaviour. Then, using the simplified model for the serviceability analysis of columns of jointless structures, the maximum achievable jointless length of typical cases of a bridge and building is obtained. In XIIparticular, it is shown how the limitations of current engineering practice (this is especially the case of buildings) can be increased by considering the actual behaviour of RC supports. Then, the same cases are modified considering the use of RSF, and the improvements both in maximum achievable length and in crack width for a given length and imposed strain at the deck/first floor are shown.

Smart aeronautical structures: development and experimental validation of a structural health monitoring system for damage detection

En muchas áreas de la ingeniería, la integridad y confiabilidad de las estructuras son aspectos de extrema importancia. Estos son controlados mediante el adecuado conocimiento de danos existentes. Típicamente, alcanzar el nivel de conocimiento necesario que permita caracterizar la integridad estructural implica el uso de técnicas de ensayos no destructivos. Estas técnicas son a menudo costosas y consumen mucho tiempo. En la actualidad, muchas industrias buscan incrementar la confiabilidad de las estructuras que emplean. Mediante el uso de técnicas de última tecnología es posible monitorizar las estructuras y en algunos casos, es factible detectar daños incipientes que pueden desencadenar en fallos catastróficos. Desafortunadamente, a medida que la complejidad de las estructuras, los componentes y sistemas incrementa, el riesgo de la aparición de daños y fallas también incrementa. Al mismo tiempo, la detección de dichas fallas y defectos se torna más compleja. En años recientes, la industria aeroespacial ha realizado grandes esfuerzos para integrar los sensores dentro de las estructuras, además de desarrollar algoritmos que permitan determinar la integridad estructural en tiempo real. Esta filosofía ha sido llamada “Structural Health Monitoring” (o “Monitorización de Salud Estructural” en español) y este tipo de estructuras han recibido el nombre de “Smart Structures” (o “Estructuras Inteligentes” en español). Este nuevo tipo de estructuras integran materiales, sensores, actuadores y algoritmos para detectar, cuantificar y localizar daños dentro de ellas mismas. Una novedosa metodología para detección de daños en estructuras se propone en este trabajo. La metodología está basada en mediciones de deformación y consiste en desarrollar técnicas de reconocimiento de patrones en el campo de deformaciones. Estas últimas, basadas en PCA (Análisis de Componentes Principales) y otras técnicas de reducción dimensional. Se propone el uso de Redes de difracción de Bragg y medidas distribuidas como sensores de deformación. La metodología se validó mediante pruebas a escala de laboratorio y pruebas a escala real con estructuras complejas. Los efectos de las condiciones de carga variables fueron estudiados y diversos experimentos fueron realizados para condiciones de carga estáticas y dinámicas, demostrando que la metodología es robusta ante condiciones de carga desconocidas. ABSTRACT In many engineering fields, the integrity and reliability of the structures are extremely important aspects. They are controlled by the adequate knowledge of existing damages. Typically, achieving the level of knowledge necessary to characterize the structural integrity involves the usage of nondestructive testing techniques. These are often expensive and time consuming. Nowadays, many industries look to increase the reliability of the structures used. By using leading edge techniques it is possible to monitoring these structures and in some cases, detect incipient damage that could trigger catastrophic failures. Unfortunately, as the complexity of the structures, components and systems increases, the risk of damages and failures also increases. At the same time, the detection of such failures and defects becomes more difficult. In recent years, the aerospace industry has done great efforts to integrate the sensors within the structures and, to develop algorithms for determining the structural integrity in real time. The ‘philosophy’ has being called “Structural Health Monitoring” and these structures have been called “smart structures”. These new types of structures integrate materials, sensors, actuators and algorithms to detect, quantify and locate damage within itself. A novel methodology for damage detection in structures is proposed. The methodology is based on strain measurements and consists in the development of strain field pattern recognition techniques. The aforementioned are based on PCA (Principal Component Analysis) and other dimensional reduction techniques. The use of fiber Bragg gratings and distributed sensing as strain sensors is proposed. The methodology have been validated by using laboratory scale tests and real scale tests with complex structures. The effects of the variable load conditions were studied and several experiments were performed for static and dynamic load conditions, demonstrating that the methodology is robust under unknown load conditions.

Smart Structures. La arquitectura inteligente de José Miguel de Prada Poole

En 1968, el arquitecto español José Miguel de Prada Poole (Valladolid 1938) inicia sus investigaciones sobre Estructuras Pneumáticas de Respuesta Variable, influido por la cibernética y las incipientes técnologías de computación. La ciencia de la cibernética se basa en que tanto los humanos como las máquinas forman parte de un sistema de control y respuesta, es decir, un sistema de mensajes. Conocedor de las teorías de Norbert Wiener, padre de la cibernética, Prada Poole asumió el cambio de paradigma que convertía la comunicación en el instrumento esencial para entender la sociedad y la arquitectura.

Debonding identification in FRP-plated RC structures using PZT sensors

The application of the Electro-Mechanical Impedance (EMI) method for damage detection in Structural Health Monitoring has noticeable increased in recent years. EMI method utilizes piezoelectric transducers for directly measuring the mechanical properties of the host structure, obtaining the so called impedance measurement, highly influenced by the variations of dynamic parameters of the structure. These measurements usually contain a large number of frequency points, as well as a high number of dimensions, since each frequency range swept can be considered as an independent variable. That makes this kind of data hard to handle, increasing the computational costs and being substantially time-consuming. In that sense, the Principal Component Analysis (PCA)-based data compression has been employed in this work, in order to enhance the analysis capability of the raw data. Furthermore, a Support Vector Machine (SVM), which has been widespread used in machine learning and pattern recognition fields, has been applied in this study in order to model any possible existing pattern in the PCAcompress data, using for that just the first two Principal Components. Different known non-damaged and damaged measurements of an experimental tested beam were used as training input data for the SVM algorithm, using as test input data the same amount of cases measured in beams with unknown structural health conditions. Thus, the purpose of this work is to demonstrate how, with a few impedance measurements of a beam as raw data, its healthy status can be determined based on pattern recognition procedures.

A very limited number of keywords (main patterns) describes all sequences of the human variable heavy (VH) and κ (Vκ) domains

Sequences of the variable heavy (VH) and κ (Vκ) domains of Ig structures were divided into 21 fragments that correspond to strands, loops, or parts of these structural units of the variable domains. Amino acid sequences of fragments (termed “words”) were collected from the 1,172 human heavy and 668 human κ chains available in the Kabat database. Statistical analysis of words of 17 fragments was performed (fragments that comprise the complementary determining regions′ fragments will not be discussed in this paper). The number of different words (those with different residues in at least one position) ranged, for various fragments, from 11 to 75 in the κ chains, and from 23 to 189 in the heavy chains. The main result of this study is that very few keywords, or main patterns of words, were necessary to describe over 90% of the sequences (no more than two keywords per fragment in the κ and no more than five per fragment in the heavy chains). No identical keywords were found for different fragments of the variable domains. Keywords of aligned fragments of the VH and Vκ domains were different in all but two instances. Thus, knowing the keywords, one can determine whether any given small part of a sequence belongs to a heavy or κ chain and predict its precise localization in the sequence. In addition, by using all of the keywords obtained through analysis of the Kabat database, it was possible to describe completely the sequences of the human VH and Vκ germ-line segments.

Structures of two molluscan hemocyanin genes: Significance for gene evolution

We present here the description of genes coding for molluscan hemocyanins. Two distantly related mollusks, Haliotis tuberculata and Octopus dofleini, were studied. The typical architecture of a molluscan hemocyanin subunit, which is a string of seven or eight globular functional units (FUs, designated a to h, about 50 kDa each), is reflected by the gene organization: a series of eight structurally related coding regions in Haliotis, corresponding to FU-a to FU-h, with seven highly variable linker introns of 174 to 3,198 bp length (all in phase 1). In Octopus seven coding regions (FU-a to FU-g) are found, separated by phase 1 introns varying in length from 100 bp to 910 bp. Both genes exhibit typical signal (export) sequences, and in both cases these are interrupted by an additional intron. Each gene also contains an intron between signal peptide and FU-a and in the 3′ untranslated region. Of special relevance for evolutionary considerations are introns interrupting those regions that encode a discrete functional unit. We found that five of the eight FUs in Haliotis each are encoded by a single exon, whereas FU-f, FU-g, and FU-a are encoded by two, three and four exons, respectively. Similarly, in Octopus four of the FUs each correspond to an uninterrupted exon, whereas FU-b, FU-e, and FU-f each contain a single intron. Although the positioning of the introns between FUs is highly conserved in the two mollusks, the introns within FUs show no relationship either in location nor phase. It is proposed that the introns between FUs were generated as the eight-unit polypeptide evolved from a monomeric precursor, and that the internal introns have been added later. A hypothesis for evolution of the ring-like quaternary structure of molluscan hemocyanins is presented.

Three quaternary structures for a single protein.

The structure of a multisubunit protein (immunoglobulin light chain) was solved in three crystal forms, differing only in the solvent of crystallization. The three structures were obtained at high ionic strength and low pH, high ionic strength and high pH, and low ionic strength and neutral pH. The three resulting "snapshots" of possible structures show that their variable-domain interactions differ, reflecting their stabilities under specific solvent conditions. In the three crystal forms, the variable domains had different rotational and translational relationships, whereas no alteration of the constant domains was found. The critical residues involved in the observed effect of the solvent are tryptophans and histidines located between the two variable domains in the dimeric structure. Tryptophan residues are commonly found in interfaces between proteins and their subunits, and histidines have been implicated in pH-dependent conformation changes. The quaternary structure observed for a multisubunit protein or protein complex in a crystal may be influenced by the interactions of the constituents within the molecule or complex and/or by crystal packing interactions. The comparison of buried surface areas and hydrogen bonds between the domains forming the molecule and between the molecules forming the crystals suggest that, for this system, the interactions within the molecule are most likely the determining factors.

Analysis of the relation between the sequence and secondary and three-dimensional structures of immunoglobulin molecules.

Methods of structural and statistical analysis of the relation between the sequence and secondary and three-dimensional structures are developed. About 5000 secondary structures of immunoglobulin molecules from the Kabat data base were predicted. Two statistical analyses of amino acids reveal 47 universal positions in strands and loops. Eight universally conservative positions out of the 47 are singled out because they contain the same amino acid in > 90% of all chains. The remaining 39 positions, which we term universally alternative positions, were divided into five groups: hydrophobic, charged and polar, aromatic, hydrophilic, and Gly-Ala, corresponding to the residues that occupied them in almost all chains. The analysis of residue-residue contacts shows that the 47 universal positions can be distinguished by the number and types of contacts. The calculations of contact maps in the 29 antibody structures revealed that residues in 24 of these 47 positions have contacts only with residues of antiparallel beta-strands in the same beta-sheet and residues in the remaining 23 positions always have far-away contacts with residues from other beta-sheets as well. In addition, residues in 6 of the 47 universal positions are also involved in interactions with residues of the other variable or constant domains.

Multi-level visualisation using Gaussian process latent variable models

Projection of a high-dimensional dataset onto a two-dimensional space is a useful tool to visualise structures and relationships in the dataset. However, a single two-dimensional visualisation may not display all the intrinsic structure. Therefore, hierarchical/multi-level visualisation methods have been used to extract more detailed understanding of the data. Here we propose a multi-level Gaussian process latent variable model (MLGPLVM). MLGPLVM works by segmenting data (with e.g. K-means, Gaussian mixture model or interactive clustering) in the visualisation space and then fitting a visualisation model to each subset. To measure the quality of multi-level visualisation (with respect to parent and child models), metrics such as trustworthiness, continuity, mean relative rank errors, visualisation distance distortion and the negative log-likelihood per point are used. We evaluate the MLGPLVM approach on the ‘Oil Flow’ dataset and a dataset of protein electrostatic potentials for the ‘Major Histocompatibility Complex (MHC) class I’ of humans. In both cases, visual observation and the quantitative quality measures have shown better visualisation at lower levels.