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PubMed2004

Structural plasticity associated with the beta-propeller architecture.

The beta-propeller architecture observed in protein tertiary structure and classified into the five different types according to number of 'blades' (or beta-sheets) and a sixth type classified according to the secondary structure composition of the blades (the beta beta alpha beta-molecular unit) is characterized by variations (or plasticity) in the structure. These correspond to the number of beta-strands associated with the blade, the number of amino acid residues associated with equivalent beta-strands in the different blades and the presence of alpha-helices and twisted beta-strands. We have generated a beta-sheet associated beta-strand pattern that may be important for protein structure prediction and modeling. Analysis of the beta-propellers extracted primarily from the SCOP database revealed there are 179 beta-propellers. The examination of the secondary structure corresponding to the beta-propeller using PDBsum that was useful to define the beta-sheet associated beta-strand pattern, combined with visualization on graphics display revealed structural plasticity associated with the beta-propeller architecture. Particularly, the type 6- and 7-bladed beta-propellers known to be associated with sequence and functional diversity are more common and associated with relatively more structural variations compared to the other beta-propeller types.

Databases, Protein↗
PubMed2004

A security architecture for interconnecting health information systems.

Several hereditary and other chronic diseases necessitate continuous and complicated health care procedures, typically offered in different, often distant, health care units. Inevitably, the medical records of patients suffering from such diseases become complex, grow in size very fast and are scattered all over the units involved in the care process, hindering communication of information between health care professionals. Web-based electronic medical records have been recently proposed as the solution to the above problem, facilitating the interconnection of the health care units in the sense that health care professionals can now access the complete medical record of the patient, even if it is distributed in several remote units. However, by allowing users to access information from virtually anywhere, the universe of ineligible people who may attempt to harm the system is dramatically expanded, thus severely complicating the design and implementation of a secure environment. This paper presents a security architecture that has been mainly designed for providing authentication and authorization services in web-based distributed systems. The architecture has been based on a role-based access scheme and on the implementation of an intelligent security agent per site (i.e. health care unit). This intelligent security agent: (a). authenticates the users, local or remote, that can access the local resources; (b). assigns, through temporary certificates, access privileges to the authenticated users in accordance to their role; and (c). communicates to other sites (through the respective security agents) information about the local users that may need to access information stored in other sites, as well as about local resources that can be accessed remotely.

Access to Information↗
PubMed2005

Towards shared patient records: an architecture for using routine data for nationwide research.

Ubiquitous information is currently one of the most challenging slogans in medical informatics research. An adequate architecture for shared electronic patient records is needed which can use data for multiple purposes and which is extensible for new research questions. We introduce eardap as architecture for using routine data for nationwide clinical research in a multihospital environment. eardap can be characterized as terminology-based. Main advantage of our approach is the extensibility by new items and new research questions. Once the definition of items for a research question is finished, a consistent, corresponding database can be created without any informatics skills. Our experiences in pediatric oncology in Germany have shown the applicability of eardap. The functions of our core system were in routine clinical use in several hospitals. We validated the terminology management system (TMS) and the module generation tool with the basic data set of pediatric oncology. The multiple usability depends mainly on the quality of item planning in the TMS. High quality harmonization will lead to a higher amount of multiply used data. When using eardap, special emphasis is to be placed on interfaces to local hospital information systems and data security issues.

Biomedical Research↗
PubMed2006

A model driven approach for the German health telematics architectural framework and security infrastructure.

Shared care concepts such as managed care and continuity of care are based on extended communication and cooperation between different health professionals or between them and the patient respectively. Health information systems and their components, which are very different in their structure, behavior, data and their semantics as well as regarding implementation details used in different environments for different purposes, have to provide intelligent interoperability. Therefore, flexibility, portability, and future orientation must be guaranteed using the newest development of model driven architecture. The ongoing work for the German health telematics platform based on an architectural framework and a security infrastructure is described in some detail. This concept of future proof health information networks with virtual electronic health records as core application starts with multifunctional electronic health cards. It fits into developments currently performed by many other developed countries.

Computer Security↗
PubMed2005

Inclusion of biological factors in parallel-architecture normal-tissue complication probability model for radiation-induced liver disease.

PURPOSE: To include biologic factors in parallel-architecture normal-tissue complication probability (NTCP) model for radiation-induced liver disease (RILD) after three-dimensional conformal radiotherapy (3D-CRT) for gastric or hepatic cancer. METHODS AND MATERIALS: A total of 151 patients (89 with hepatocellular carcinoma and 62 with gastric cancer) who received 3D-CRT to the liver were included (isocenter dose range 33.0 to 66.0 Gy; mean 48.0 Gy). RILD was defined as grade 3 or higher liver toxicity according to Common Toxicity Criteria Version 2.0 of the National Cancer Institute within 4 months after 3D-CRT. Possible correlations of patient-related or dosimetric factors with RILD were tested. Maximum-likelihood analysis estimated NTCP model parameters for group and subgroups. Goodness-of-fit analysis estimated deviance of NTCP model parameters between subgroups. RESULTS: RILD developed in 25 patients. Hepatitis B virus carrier status (p < 0.001) was the only significant independent factor. The 4 parallel NTCP model parameters, mean functional reserve (V(50)), width of functional reserve distribution (sigma), dose damage to 50% of liver subunits (D(50)), and slope parameter for subunit dose-response (k), were respectively, 0.54, 0.14, 50 Gy, 0.18 (group); 0.53, 0.07, 50 Gy, 4.6 x 10(-7) (carriers); 0.59, 0.12, 25 Gy, 59.8 (noncarriers). In carrier-state subgroups, goodness-of-fit deviance with 1 subgroup's parameter set would have been worse in the other group. Across subgroups, patients with RILD all had liver fraction damage (f) greater than 0.4 compared with wider distribution for the whole group. CONCLUSIONS: RILD is described with a parallel-architecture NTCP model for HBV carriers and noncarriers with a threshold effect greater than 0.4. The main difference is in slope parameter for subunit dose-response.

Adult↗
PubMed2004

A novel method for biomaterial scaffold internal architecture design to match bone elastic properties with desired porosity.

An often-proposed tissue engineering design hypothesis is that the scaffold should provide a biomimetic mechanical environment for initial function and appropriate remodeling of regenerating tissue while concurrently providing sufficient porosity for cell migration and cell/gene delivery. To provide a systematic study of this hypothesis, the ability to precisely design and manufacture biomaterial scaffolds is needed. Traditional methods for scaffold design and fabrication cannot provide the control over scaffold architecture design to achieve specified properties within fixed limits on porosity. The purpose of this paper was to develop a general design optimization scheme for 3D internal scaffold architecture to match desired elastic properties and porosity simultaneously, by introducing the homogenization-based topology optimization algorithm (also known as general layout optimization). With an initial target for bone tissue engineering, we demonstrate that the method can produce highly porous structures that match human trabecular bone anisotropic stiffness using accepted biomaterials. In addition, we show that anisotropic bone stiffness may be matched with scaffolds of widely different porosity. Finally, we also demonstrate that prototypes of the designed structures can be fabricated using solid free-form fabrication (SFF) techniques.

Animals↗
PubMed2006

In vivo architectural analysis of 3.2 mm clear corneal incisions for phacoemulsification using optical coherence tomography.

PURPOSE: To analyze in vivo the architecture of clear corneal incisions (CCIs) for phacoemulsification using optical coherence tomography (OCT). SETTING: Anterior Segment Department, Asociacion Para Evitar la Ceguera en Mexico, Hospital Dr Luis Sanchez Bulnes, Mexico. METHODS: A prospective masked study analyzed 20 unsutured CCIs placed superiorly and created in a uniplanar fashion with a 3.2 mm slit-angled metal keratome. All wounds were evaluated with a retinal OCT model 1, 3, and 30 days postoperatively. Intraocular pressure (IOP) and incision leakage were checked. The architecture was described according to the angle of incidence, apposition of the epithelial and endothelial margins, and wound sealing. RESULTS: No leakage was detected. The angle varied from 33 to 85 degrees; angles greater than 75 degrees were done by a surgeon in training. Wound apposition at the epithelial margin was achieved in all cases. In contrast, imperfect apposition of the endothelial margin was seen in 45% of incisions on day 1 and in 15% on day 30. Incomplete sealing of the wound was seen by OCT in 25% of cases at 24 hours and persisted in 10% of all cases at 1 month. This gaping occurred on the endothelial side and never translated to the epithelial margin. No statistical correlation was found between gaping and the angle of the incision, IOP variations, or surgeon experience. CONCLUSIONS: Although in vivo CCIs caused minor anatomic imperfections, they were clinically stable independent of incision angle, IOP variation, and surgeon experience. Incision stability may be related to careful wound construction, epithelial viability, stromal edema, and efficient endothelial pumping.

Cornea↗
PubMed2006

The effect of ultrasound probe orientation on muscle architecture measurement.

The purpose of this paper was to examine how muscle architecture parameter (MAP) measurements made using brightness-mode ultrasonography (BMU) differ based on probe orientation. The human tibialis anterior muscle was imaged from nine different probe orientations during concentric contractions at four joint angles to determine the effect of probe orientation on the measurement of muscle architecture parameters. Ankle dorsi-flexion torque, tibialis anterior electromyography (EMG), and measures of MAP including fascicle length (FL), pennation angle (PA) and muscle thickness (MT) were collected. Statistically significant differences were found between joint angles for measures of FL and PA and between probe orientations for measures of FL and MT. A comparison of actual MAP values to a geometric model used by researchers to determine an ideal probe orientation show that the actual values vary to a greater extent and do not follow the trend predicted by the model. The results suggest that ultrasound probe orientation affects measures of MAP but the effect either cannot be predicted from a geometric model and/or the error in the measurement technique does not allow a comparison.

Adult↗
PubMed2004

Trimeric architecture of homomeric P2X2 and heteromeric P2X1+2 receptor subtypes.

Of the three major classes of ligand-gated ion channels, nicotinic receptors and ionotropic glutamate receptors are known to be organized as pentamers and tetramers, respectively. The architecture of the third class, P2X receptors, is under debate, although evidence for a trimeric assembly is accumulating. Here we provide biochemical evidence that in addition to the rapidly desensitising P2X1 and P2X3 receptors, the slowly desensitising subtypes P2X2, P2X4, and P2X5 are trimers of identical subunits. Similar (heteromeric) P2X subunits also formed trimers, as shown for co-expressed P2X1 and P2X2 subunits, which assembled efficiently to a P2X1+2 receptor that was exported to the plasma membrane. In contrast, P2X6 subunits, which are incapable of forming functional homomeric channels in Xenopus oocytes, were retained in the ER as apparent tetramers and high molecular mass aggregates. Altogether, we conclude from these data that a trimeric architecture is the structural hallmark of functional homomeric and heteromeric P2X receptors.

Animals↗
PubMed2006

Low resolution crystal structure of Arenicola erythrocruorin: influence of coiled coils on the architecture of a megadalton respiratory protein.

Annelid erythrocruorins are extracellular respiratory complexes assembled from 180 subunits into hexagonal bilayers. Cryo-electron microscopic experiments have identified two different architectural classes. In one, designated type I, the vertices of the two hexagonal layers are partially staggered, with one hexagonal layer rotated by about 16 degrees relative to the other layer, whereas in the other class, termed type II, the vertices are essentially eclipsed. We report here the first crystal structure of a type II erythrocruorin, that from Arenicola marina, at 6.2 A resolution. The structure reveals the presence of long continuous triple-stranded coiled-coil "spokes" projecting towards the molecular center from each one-twelfth unit; interdigitation of these spokes provides the only contacts between the two hexagonal layers of the complex. This arrangement contrasts with that of a type I erythrocruorin from Lumbricus terrestris in which the spokes are broken into two triple-stranded coiled coils with a disjointed connection. The disjointed connection allows formation of a more compact structure in the type I architecture, with the two hexagonal layers closer together and additional extensive contacts between the layers. Comparison of sequences of the coiled-coil regions of various linker subunits shows that the linker subunits from type II erythrocruorins possess continuous heptad repeats, whereas a sequence gap places these repeats out of register in the type I linker subunits, consistent with a disjointed coiled-coil arrangement.

Amino Acid Sequence↗
PubMed2006

Subchondral bone micro-architectural alterations in osteoarthritis: a synchrotron micro-computed tomography study.

OBJECTIVES: We evaluated the three-dimensional (3D) micro-architecture of subchondral trabecular (Tb) bone in osteoarthritis (OA). Due to high signal-to-noise ratio and high resolution, micro-computed tomography (micro-CT) by synchrotron radiation is considered as the gold standard for bone micro-architecture imaging. DESIGN: Subchondral bone were extracted from femoral heads in OA cases in areas without cartilage (OAc-; n=6) and in adjacent areas with cartilage (OAc+; n=6) and compared to eight subchondral bone cores from osteoporosis cases (OP). The voxel size of images was 10.13 microm. We measured the bone volume fraction (BV/TV) and morphological parameters: Tb thickness (TbTh), Tb spacing (TbSp), Tb number (TbN), and bone surface/bone volume (BS/BV). The degree of anisotropy (DA), the connectivity by the Euler number and the degree of mineralization (DM) were equally assessed. RESULTS: BV/TV and morphological parameters showed significant differences between OAc- and OP samples (P<0.01 except TbTh: P<0.05) and between OAc- and OAc+ (0.05<P<0.01) but no difference between OAc+ and OP except TbN (P<0.01). The connectivity was higher in OAc- comparatively to OAc+ and OP. The DA were significantly different between OA and OP cases (P<0.01) but not between OAc- and OAc+ specimens. The DMs (mean+/-SD) were 0.817+/-0.142 g/cm(3), 0.873+/-0.161 g/cm(3), 0.906+/-0.156 g/cm(3) for OAc-, OAc+, OP (P<0.01), respectively. CONCLUSION: Subchondral bone changes were mainly observed in advanced OA, when cartilage has been deleted and preserved in adjacent area. These data suggest that subchondral bone changes would be rather secondary to the cartilage deterioration than a primitive mechanism of OA. Nevertheless, longitudinal data could bring more accurate conclusions.

Aged↗
PubMed2006

T(2) relaxation time mapping reveals age- and species-related diversity of collagen network architecture in articular cartilage.

OBJECTIVE: The magnetic resonance imaging (MRI) parameter T(2) relaxation time has been shown to be sensitive to the collagen network architecture of articular cartilage. The aim of the study was to investigate the agreement of T(2) relaxation time mapping and polarized light microscopy (PLM) for the determination of histological properties (i.e., zone and fibril organization) of articular cartilage. METHODS: T(2) relaxation time was determined at 9.4 T field strength in healthy adult human, juvenile bovine and juvenile porcine patellar cartilage, and related to collagen anisotropy and fibril angle as measured by quantitative PLM. RESULTS: Both T(2) and PLM revealed a mutually consistent but varying number of collagen-associated laminae (3, 3-5 or 3-7 laminae in human, porcine and bovine cartilage, respectively). Up to 44% of the depth-wise variation in T(2) was accounted for by the changing anisotropy of collagen fibrils, confirming that T(2) contrast of articular cartilage is strongly affected by the collagen fibril anisotropy. A good correspondence was observed between the thickness of T(2)-laminae and collagenous zones as determined from PLM anisotropy measurements (r=0.91, r=0.95 and r=0.91 for human, bovine and porcine specimens, respectively). CONCLUSIONS: According to the present results, T(2) mapping is capable of detecting histological differences in cartilage collagen architecture among species, likely to be strongly related to the differences in maturation of the tissue. This diversity in the MRI appearance of healthy articular cartilage should also be recognized when using juvenile animal tissue as a model for mature human cartilage in experimental studies.

Adult↗
PubMedDate not supplied

Large-scale modeling of the primary visual cortex: influence of cortical architecture upon neuronal response.

A large-scale computational model of a local patch of input layer 4 [Formula: see text] of the primary visual cortex (V1) of the macaque monkey, together with a coarse-grained reduction of the model, are used to understand potential effects of cortical architecture upon neuronal performance. Both the large-scale point neuron model and its asymptotic reduction are described. The work focuses upon orientation preference and selectivity, and upon the spatial distribution of neuronal responses across the cortical layer. Emphasis is given to the role of cortical architecture (the geometry of synaptic connectivity, of the ordered and disordered structure of input feature maps, and of their interplay) as mechanisms underlying cortical responses within the model. Specifically: (i) Distinct characteristics of model neuronal responses (firing rates and orientation selectivity) as they depend upon the neuron's location within the cortical layer relative to the pinwheel centers of the map of orientation preference; (ii) A time independent (DC) elevation in cortico-cortical conductances within the model, in contrast to a "push-pull" antagonism between excitation and inhibition; (iii) The use of asymptotic analysis to unveil mechanisms which underly these performances of the model; (iv) A discussion of emerging experimental data. The work illustrates that large-scale scientific computation--coupled together with analytical reduction, mathematical analysis, and experimental data, can provide significant understanding and intuition about the possible mechanisms of cortical response. It also illustrates that the idealization which is a necessary part of theoretical modeling can outline in sharp relief the consequences of differing alternative interpretations and mechanisms--with final arbiter being a body of experimental evidence whose measurements address the consequences of these analyses.

Action Potentials↗
PubMed2004

Nest architecture, activity pattern, worker density and the dynamics of disease transmission in social insects.

The role of disease in the organization of insect colonies has become an important focus of research in evolutionary pathobiology, in which the relationship of sociality and disease transmission can be comparatively and experimentally analysed. In this paper we use an individual-based model of disease transmission to assess how an epidemic is influenced by worker density and activity level, the probability of disease transmission, and the structural organization of the nest. First, we observed in our model a nonlinear interaction between worker density and the probability of disease transmission: high levels of both factors interact to enhance the likelihood of an epidemic. Additionally, when we incorporated in our model the empirical observation that only a fraction of the worker population in social insect colonies is active at any given point in time, results suggested that relatively low levels of worker movement can have a significant impact on the spread of disease, slowing its transmission through the colony. Finally, we found that nests having even a simple spatial separation of chambers could delay the spread of infection and diminish the severity of an outbreak. The effect of nest structure in delaying infection spread became more pronounced as nest architecture became increasingly unidimensional, as in the case of simple gallery nests. Therefore, nest architecture and worker activity patterns might indeed exert considerable influence on the dynamics of epidemics in social insects and should be incorporated into models of disease transmission.

Animals↗
PubMed2004

Optimization modeling of plant root architecture for water and phosphorus acquisition.

An optimization model is presented that examines the relationship between root architecture and multiple resource acquisition, specifically water and phosphorus in spatially heterogeneous environments. The basal root growth angle of an individual common bean plant, which determines the orientation and localization of the bulk of the root system, was modeled as the decision variable. The total payoff to the plant, the benefit obtained from water and phosphorus acquisition, minus the costs of spatial competition between roots, is given as a function of the (x,y) coordinates of the basal root in two-dimensional Cartesian space. We obtained a general solution and applied it to four unique environmental cases which are as follows: (1) the case of uniformly distributed water and phosphorus; (2) the case of localized shallow phosphorus; (3) the case of localized deep water; and (4) the case of shallow phosphorus and deep water. The general solution states that the optimal basal root growth angle will occur at the point where the total rate of change in the value of the resources acquired equals the total rate of change in cost that results from locating the root deeper in the soil. An optimizing plant locates its roots deeper in the soil profile until the marginal benefit exactly equals the marginal cost. The model predicts that the basal root angle of an optimizing plant will be shallower for Case 2 and deeper for Case 3, relative to the basal root angle obtained in the case of uniformly distributed water and phosphorus. The optimal basal root angle for Case 4 will depend on the marginal rate of substitution of water availability for phosphorus availability that occurs with depth. Empirical observations of bean root architecture in the greenhouse and in the field confirm model results and are discussed. In addition, the potential importance of phenotypic plasticity and phenotypic variation are discussed in relation to optimization of traits and adaptation to spatially heterogeneous environments.

Adaptation, Physiological↗
PubMed2004

An information-processing analysis of the functional architecture of the primate neocortex.

Working at the systems level of analysis, we will use the term functional architecture to concern what processing components exist, how they are interconnected, and what information-processing functions each is involved in. In this paper, experimental evidence for the primate neocortex is analysed for conclusions concerning the existence of neural areas, for corticocortical connectivity among neural areas, and for the involvement of each cortical neural area in the functioning of the brain. We characterize the information-processing function for each neural area in terms of the types of information it is associated with, and conceive of its activity as processing, storage and transmission of data of the corresponding types for that area. We also adapt concepts of goal, plan, sequence, event and context for the description of information processing in the neocortex. This analysis shows that the primate neocortex consists in the main of a perception hierarchy, an action hierarchy and connections between them. In other words, from an information-processing point of view, the primate neocortex has a hierarchical perception-action architecture.

Animals↗
PubMed2004

Architecture of CRM1/Exportin1 suggests how cooperativity is achieved during formation of a nuclear export complex.

CRM1/Exportin1 mediates the nuclear export of proteins bearing a leucine-rich nuclear export signal (NES) by forming a cooperative ternary complex with the NES-bearing substrate and the small GTPase Ran. We present a structural model of human CRM1 based on a combination of X-ray crystallography, homology modeling, and electron microscopy. The architecture of CRM1 resembles that of the import receptor transportin1, with 19 HEAT repeats and a large loop implicated in Ran binding. Residues critical for NES recognition are identified adjacent to the cysteine residue targeted by leptomycin B (LMB), a specific CRM1 inhibitor. We present evidence that a conformational change of the Ran binding loop accounts for the cooperativity of Ran- and substrate binding and for the selective enhancement of CRM1-mediated export by the cofactor RanBP3. Our findings indicate that a single architectural and mechanistic framework can explain the divergent effects of RanGTP on substrate binding by many import and export receptors.

Active Transport, Cell Nucleus↗
PubMedDate not supplied

Framewise phoneme classification with bidirectional LSTM and other neural network architectures.

In this paper, we present bidirectional Long Short Term Memory (LSTM) networks, and a modified, full gradient version of the LSTM learning algorithm. We evaluate Bidirectional LSTM (BLSTM) and several other network architectures on the benchmark task of framewise phoneme classification, using the TIMIT database. Our main findings are that bidirectional networks outperform unidirectional ones, and Long Short Term Memory (LSTM) is much faster and also more accurate than both standard Recurrent Neural Nets (RNNs) and time-windowed Multilayer Perceptrons (MLPs). Our results support the view that contextual information is crucial to speech processing, and suggest that BLSTM is an effective architecture with which to exploit it.

Algorithms↗