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PubMed1987

Small artery occlusion: a theoretical approach to the definition of coronary architecture and resistance by a branching tree model.

The aim of this study was to evaluate the theoretical possibility of assessing the architecture of the coronary small artery circulation in vivo by the analysis of the increments in the total resistance of the vascular system caused by the progressive occlusion of the terminal vessels as would be possible in animal experiments by microsphere embolization. Different distributions of the resistance values of all the vessels have been obtained in branching tree models by means of only two parameters: (a) the resistance ratio between daughter and parent vessels at each branching site (KO); and (b) the resistance ratio between the two daughter vessels at each branching site (KV). Simulation of branching tree occlusion has been performed under two main conditions of resistance distribution: (1) symmetric resistance distribution, characterized by equal KO values at each branching site of the same level and by KV = 1, that is, equal resistance values for the vessel of the same level; and (2) asymmetric resistance distribution in dichotomous branching trees, wherein all the vessels may have different values of resistance; the variability in these values has however been restricted on the basis of physiological considerations. The analysis of the function of the total resistance vs the number of occluded vessels, obtained by a simulated progressive occlusion of the terminal vessels in these two systems, gives the following results: (1) in a symmetric branching tree, discontinuities are present in the occlusion function which permit identification of both the architecture and the resistance value of each single vessel of any unknown vascular tree; and (2) in the asymmetric model, the function does not allow a direct definition of the branching architecture and the values of resistance of each vessel; however, also in this case, any branching tree can be analyzed by means of a nonlinear optimization procedure which produces an equivalent symmetric branching tree. We conclude that, theoretically, the analysis of the occlusion function represents a valuable indirect approach to the quantitative study of the coronary microcirculation as well as of other vascular districts under steady flow conditions.

Animals↗
PubMed1993

Architectural patterns of high-grade prostatic intraepithelial neoplasia.

High-grade prostatic intraepithelial neoplasia (PIN) is characterized by cellular proliferations within pre-existing ducts and glands with cytologic changes mimicking adenocarcinoma, including prominent nucleoli, but lacking stromal invasion. To determine the architectural spectrum of high-grade PIN, 60 serially sectioned radical prostatectomy specimens with PIN and cancer were reviewed. Four common patterns of high-grade PIN were identified, usually with multiple patterns in each case: tufting (in 87% of cases), micropapillary (in 85% of cases), cribriform (in 32% of cases), and flat (in 28% of cases). Tumor grade was not significantly associated with any pattern of PIN. Luminal cytoplasmic apical blebs were found in all cases regardless of the pattern of PIN. A variety of associated architectural and cytologic features were observed with high-grade PIN: epithelial arches (in 60% of cases), cellular trabecular epithelial bars (in 22% of cases), "Roman" bridges (in 30% of cases), partial gland involvement (in 82% of cases), basal cell layer disruption with glandular budding (in 23% of cases), large cystic gland involvement (in 10% of cases), involvement by nodular hyperplasia (in 5% of cases), microcalcifications (in 8% of cases), proteinaceous luminal secretions (in 62% of cases), corpora amylacea (in 55% of cases), exfoliated cells of PIN (in 42% of cases), luminal crystalloids (in 3% of cases), and mucinous metaplasia (in 2% of cases). High-grade PIN exhibits a variety of architectural patterns while retaining the distinctive cytoplasmic apical blebs and diagnostic nuclear and nucleolar features. Identification of high-grade PIN warrants a further search for invasive carcinoma, but should not influence or dictate decisions regarding definitive therapy.

Adenocarcinoma↗
PubMed1994

Neural architectures for adaptive behavior.

How do animals use the same peripheral structures to generate different behavioral responses? Three different neuronal architectures have been proposed to mediate this task: dedicated circuitry; distributed circuitry; and reorganizing circuitry. This review will critically examine the evidence for these different architectures in invertebrate circuits, and then examine the evidence for them in more complex vertebrate circuits. The evidence suggests that these different architectures are unlikely to be found in pure form in most neural circuits, but are useful for guiding the experimental analysis of circuitry.

Adaptation, Psychological↗
PubMedDate not supplied

An object-based architecture for biomedical expert database systems.

Objects play a major role in both database and artificial intelligence research. In this paper, we present a novel architecture for expert database systems that introduces an object-based interface between relational databases and expert systems. We exploit a semantic model of the database structure to map relations automatically into object templates, where each template can be a complex combination of join and projection operations. Moreover, we arrange the templates into object networks that represent different views of the same database. Separate processes instantiate those templates using data from the base relations, cache the resulting instances in main memory, navigate through a given network's objects, and update the database according to changes made at the object layer. In the context of an immunologic-research application, we demonstrate the capabilities of a prototype implementation of the architecture. The resulting model provides enhanced tools for database structuring and manipulation. In addition, this architecture supports efficient bidirectional communication between database and expert systems through the shared object layer.

Database Management Systems↗
PubMed1990

The architecture of cancellous and cortical bone in femoral neck fracture.

The architecture of cancellous bone as well as quantity and quality is considered important in maintaining mechanical integrity. To determine whether abnormalities of architecture occur in femoral neck fracture we measured trabecular width and number in iliac crest bone biopsies of 68 women with femoral fracture and compared them with data from a postmortem series of age-matched women without known bone disease. Cortical thickness was measured in 27 of the fracture patients and 17 controls. After exclusion of ten biopsies with increased osteoid surface no significant difference was seen in mean trabecular width or number between fracture patients and subjects without fracture. Both thinning of trabeculae and loss of trabeculae contributed to low bone volume in femoral fracture patients. Direct measurements of trabecular number correlated with calculated mean trabecular plate density (P less than 0.001), and the percentage of trabeculae at any one of a range of trabecular widths in the fracture biopsies was similar to that in non-fracture subjects. No difference was seen in the architecture of cancellous bone with age, fracture trauma or between subcapital and intertrochanteric fracture in fracture subjects. Cortical thickness, however, was related to age in both fracture and control subjects (P less than 0.05). There was no difference in cortical thickness between age-matched fracture and control subjects. Patients with intertrochanteric fracture had lower cortical thickness (P less than 0.02) and were older (P less than 0.01) than patients with subcapital fracture.

Aged↗
PubMed1995

Analysis of clinical complication data for radiation hepatitis using a parallel architecture model.

PURPOSE: The detailed knowledge of dose volume distributions available from the three-dimensional (3D) conformal radiation treatment of tumors in the liver (reported elsewhere) offers new opportunities to quantify the effect of volume on the probability of producing radiation hepatitis. We aim to test a new parallel architecture model of normal tissue complication probability (NTCP) with these data. METHODS AND MATERIALS: Complication data and dose volume histograms from a total of 93 patients with normal liver function, treated on a prospective protocol with 3D conformal radiation therapy and intraarterial hepatic fluorodeoxyuridine, were analyzed with a new parallel architecture model. Patient treatment fell into six categories differing in doses delivered and volumes irradiated. By modeling the radiosensitivity of liver subunits, we are able to use dose volume histograms to calculate the fraction of the liver damaged in each patient. A complication results if this fraction exceeds the patient's functional reserve. To determine the patient distribution of functional reserves and the subunit radiosensitivity, the maximum likelihood method was used to fit the observed complication data. RESULTS: The parallel model fit the complication data well, although uncertainties on the functional reserve distribution and subunit radiosensitivity are highly correlated. CONCLUSION: The observed radiation hepatitis complications show a threshold effect that can be described well with a parallel architecture model. However, additional independent studies are required to better determine the parameters defining the functional reserve distribution and subunit radiosensitivity.

Hepatitis↗
PubMed1992

How musculotendon architecture and joint geometry affect the capacity of muscles to move and exert force on objects: a review with application to arm and forearm tendon transfer design.

This commentary reviews musculotendon architecture and the relation between architectural parameters and the force, speed, and excursion capacity of musculotendon units. It is hoped that this review will help provide the framework within which to appreciate the importance of the data presented by Lieber et al. Muscle fiber pennation hardly affects musculotendon output of forearm and hand muscles. Instead, physiologic cross-sectional area and muscle fiber length affect force capacity and speed and excursion capacity, respectively. How muscles with equal mass can have different force, speed, and excursion capacities is explained. Since the moment arm of a muscle (the shortest distance from the musculotendon unit to the joint center of rotation) transforms muscle output into musculotendon output, it is shown why the capacity for a muscle to exert force on an object, as during grasping, is directly proportional to its moment arm and why the range of joint movement and speed over which muscles exert force is inversely proportional to the moment arm. Finally, tendon, being not stiff in forearm and hand musculotendon units, also affects their output. Criteria are given for designing tendon transfer reconstructions from architectural data and moment arm data to best replicate the biomechanical function of the replaced muscle. To have the same capacity for imparting movement to objects and exerting force on them, the donor muscle should have the same moment arm/physiologic cross-sectional area product, the same fiber length/moment arm ratio, and the same tendon length/muscle fiber length ratio as the replaced muscle.

Arm↗
PubMed1996

Mechanisms of Neural Architecture for Visual Contrast and Brightness Perception.

A neural architecture is proposed that serves as a framework for further empirical as well as theoretical investigations for a unified theory for contrast and brightness perception. The work further extends the brightness perception model developed by Grossberg and Todorovic. The proposed new computational architecture utilizes a (retinal) preprocessing stage with center-surround antagonisms of both polarities. The preprocessed data are shown to multiplex contrast as well as luminance information that can be de-multiplexed subsequently using a scheme of cross-channel interaction. Based on a hypothesized luminance-related channel, a three-stage process is suggested for brightness reconstruction. The separate channel for the representation of luminance-related information provides a key mechanism to assign the reconstructed brightness to an absolute reference level. The architecture provides a framework for the analysis of processes in brightness perception. Copyright 1996 Elsevier Science Ltd.

Journal Article↗
PubMed1989

The extracellular matrix architecture relating to myotendinous pattern formation in the distal part of the developing chick limb: an ultrastructural, histochemical and immunocytochemical analysis.

In the later developmental stages (Hamburger and Hamilton, 25-34) the distal part of the chick leg possesses a distinctive extracellular matrix (ECM) architecture which relates to myotendinous patterning. There are two components: firstly, a system of dorsoventrally oriented fibrils which link the two ectodermal surfaces through the undifferentiated distal mesenchyme and secondly, a 'mesenchyme lamina' originates at the basement membrane distally, but proximally runs through the mesoderm, subjacent and parallel to the basement membrane. The 'mesenchyme lamina' appears to be a precursor of developing tendons and is spatially related to the distal tips of the myogenic blocks. As developing tendons form on the inner surface of the lamina at its proximal end, it becomes less distinct and disappears. Further dorsoventral fibrils run from the 'mesenchyme lamina' into the developing condensations and chondrogenic elements of the phalanges. The architecture of the ECM was revealed by silver and lectin staining (peanut and Ricinus communis agglutinins, PNA and RCA I), by immunocytochemistry (for fibronectin, tenascin, collagen type I) and by ultrastructural analysis. Both components stain with silver, PNA following neuraminidase digestion, RCA I, tenascin and collagen type I. However, the dorsoventral fibrils are positive for fibronectin and negative for PNA, while conversely the mesenchyme lamina is positive for PNA but much less so for fibronectin. Tenascin has been shown to be a specialized mesenchyme component of tendons and myotendinous junctions (Chiquet and Fambrough, 1984). Such a basement membrane forming a 'mesenchyme lamina' appears to be unique in epithelial-mesenchymal developing systems and points to an ectodermal role in tendon pattern formation within the mesenchyme. We discuss the possible role of mechanical force in converting the dorsoventral tenascin-positive fibrils into the localized pattern of tendon insertions into the proximal parts of the phalanges. Distally the dorsoventral fibrils may shape the digital plate by pulling together the two ectodermal surfaces. A similar ECM architecture is found in corresponding stages in the developing wing.

Animals↗
PubMed1995

Modifying the helical structure of DNA by design: recruitment of an architecture-specific protein to an enforced DNA bend.

BACKGROUND: Proteins can force DNA to adopt distorted helical structures that are rarely if ever observed in naked DNA. The ability to synthesize DNA that contains defined helical aberrations would offer a new avenue for exploring the structural and energetic plasticity of DNA. Here we report a strategy for the enforcement of non-canonical helical structures through disulfide cross-linking; this approach is exemplified by the design and synthesis of an oligonucleotide containing a pronounced bend. RESULTS: A localized bend was site-specifically introduced into DNA by the formation of a disulfide cross-link between the 5' adenines of a 5'-AATT-3' region in complementary strands of DNA. The DNA bend was characterized by high-resolution NMR structure determination of a cross-linked dodecamer and electrophoretic mobility assays on phased multimers, which together indicate that the cross-linked tetranucleotide induces a helical bend of approximately 30 degrees and a modest degree of unwinding. The enforced bend was found to stimulate dramatically the binding of an architecture-specific protein, HMG-D, to the DNA. DNase I foot-printing analysis revealed that the protein is recruited to the section of DNA that is bent. CONCLUSIONS: The present study reports a novel approach for the investigation of non-canonical DNA structures and their recognition by architecture-specific proteins. The mode of DNA bending induced by disulfide cross-linking resembles that observed in structures of protein-DNA complexes. The results reveal common elements in the DNA-binding mode employed by sequence-specific and architecture-specific HMG proteins.

Cross-Linking Reagents↗
PubMed1992

Implications of architecture for the pathogenesis and prevention of vertebral fracture.

Rapid loss of cancellous bone after menopause occurs by a mechanism that removes some structural elements completely, leaving those that remain more widely separated and less well connected. Slow loss of cancellous bone continues by a mechanism that reduces the thickness of the structural elements that survive the initial phase of rapid loss. Both processes have advanced further in patients with vertebral compression fracture due to osteoporosis, than in healthy subjects of similar age; whether this is because they began sooner, proceeded more rapidly or continued for longer is unknown. This overall concept, first developed about ten years ago, has now been confirmed by a variety of different methods including node-strut analysis, star volume and the change in curvature with profile dilation. Because part of the architectural contribution to compressive strength is captured by non-invasive densitometric methods, and the contribution of cortical bone to compressive strength is significant, it has been difficult to demonstrate an independent architectural component of bone fragility by in vitro comparison of structural measurements with biomechanical testing. Nevertheless, three independent clinical studies, comparing subjects with and without vertebral fracture, have each strongly suggested an independent architectural contribution to fracture risk. Complete removal of structural elements is initiated by focal perforation of trabecular plates, but the mechanism of perforation remains controversial.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1996

Using functional loading to influence bone mass and architecture: objectives, mechanisms, and relationship with estrogen of the mechanically adaptive process in bone.

There is increasing evidence that load-bearing is an important, if not the most important, functional influence on bone mass and architecture. Load-bearing most probably exerts its influence through the dynamic strains engendered in the bone tissue. Mechanically adaptive bone modeling and remodeling can be regarded as a homeostatic mechanism regulating functional bone strains at each location throughout the skeleton. Because most long bones are loaded in a certain amount of bending normal function, strains vary across the bones' cross-section. Both the longitudinal curvature and cross-sectional shape of a number of bones engender strains during functional loading rather than reduce them. Bone's adaptive response to load-bearing therefore results in functional strains which are neither uniform in distribution nor minimal in magnitude. Not all aspects of bone's strain environment are equally effective as influences on bone architecture. Unusual strain distributions, high strains, and high strain rates seem to be particularly osteogenic. The osteogenic response which follows exposure to such strains appears to saturate after only a few loading cycles. This is consistent with adaptive bone (re)modeling being sensitive to strain "errors," which are not repeated frequently, rather than the repetitious strain cycles engendered during normal predominant activities. Exercise regimens designed to control bone architecture can usefully capitalize on this feature of the adaptive (re)modeling response. Each exercise session need not be prolonged but should include as many novel strain distributions as possible, preferably involving high peak strains and strain rates. To maintain any level of bone mass requires a continued, loading-related osteoregulatory stimulus. Exposure to appropriate load-bearing exercise needs therefore to be repeated, probably at daily or alternate-daily intervals. In short-term experiments in rat bones, estrogen amplifies the osteogenic response to a single period of loading. The features of postmenopausal bone loss are consistent with the etiology of the condition being primarily withdrawal of estrogen's contribution to bone's mechanically adaptive response.

Adaptation, Physiological↗
PubMed2006

Plaque biofilms: the effect of chemical environment on natural human plaque biofilm architecture.

The architecture of microbial biofilms especially the outer regions have an important influence on the interaction between biofilm and local environment particularly on the flux of materials into and out of biofilm compartments and as a consequence, biofilm metabolic behaviour. In the case of dental plaque biofilms, architecture will determine access of nutrients including acidogenic substrates and therapeutic materials to the microbial biomass and to the underlying tooth surface. Manipulation of this architecture may offer a means of altering mass transfer into the whole biofilm and biomass and raises the possibility of improving access of therapeutics. Plaque biofilms formed in vivo on human enamel were subjected to a number of different chemical conditions while under observation by confocal laser scanning microscopy in reflection mode. In this way the outer 50-100 microm or so of the biofilms was examined. Density and distribution of biomass were recorded as degree of reflectance. The amount and density of biofilm biomass increased from the plaque saliva interface towards the interior. Plaque biofilms were robust and little affected by mechanical manipulation, high ionic strength or low pH (2.5). Detergent (SLS), however, often appeared to either remove biomass and/or dramatically reduce its density.

Biofilms↗
PubMed2026

Shared genetic architecture and therapeutic targets across paediatric immune-mediated diseases.

OBJECTIVES: Paediatric-onset immune-mediated inflammatory diseases (IMIDs), including juvenile idiopathic arthritis and related rheumatic diseases, remain genetically undercharacterised. We aimed to define shared and category-specific genetic architecture across paediatric IMIDs, compare signals with adult IMIDs, and identify therapeutic opportunities. METHODS: We analysed 24 paediatric IMIDs classified as autoimmune, polygenic-autoinflammatory, mixed-pattern, or allergic. Genome-wide association analyses included 18,086 cases and 131,019 controls of European ancestry. We estimated single nucleotide polymorphism (SNP)-based heritability, genetic correlations, and polygenic overlap; performed subset-based meta-analysis; and conducted functional annotation, gene prioritisation, pathway and protein network analyses, adult-IMID comparison, and drug-target prioritisation. RESULTS: SNP-based heritability ranged from 28.9% for allergic IMIDs to 61.9% for autoimmune IMIDs. Genetic correlation and polygenic modelling supported partial sharing across categories with category-specific components. Meta-analysis identified 39 genome-wide significant loci outside the Major Histocompatibility Complex (MHC) region, including 15 previously unreported loci; 19 loci were shared between categories. Gene-prioritisation and protein interaction analyses identified a core MHC-centred antigen-presentation network, with category-enriched modules involving complement, innate/barrier pathways, epithelial biology, and type 2 immunity. Enriched pathways included nuclear factor κB signalling, T helper 17 related pathways, Janus kinase-signal transducer and activator of transcription signalling, programmed cell death protein 1/programmed death‑ligand 1, cytotoxic T‑lymphocyte associated protein 4 regulation, and osteoclast differentiation, several of which are relevant to rheumatic diseases. Paediatric IMIDs shared broad polygenic architecture with adult IMIDs, whereas top-ranked genes converged strongly with adult rheumatic diseases. Priority Index analysis identified 178 high-scoring genes, including 43 approved or investigational IMID drug targets. CONCLUSIONS: Paediatric-onset IMIDs share core pathways with adult forms but exhibit distinct genetic architecture shaped by age-specific immune and neurodevelopmental biology. These findings provide a genomic framework for paediatric precision medicine, guiding classification, risk prediction, and therapeutic development.

Humans↗
PubMed2005

Cyclic loading response of bioprosthetic heart valves: effects of fixation stress state on the collagen fiber architecture.

Biologically derived, chemically modified collagenous tissues are being increasingly used to fabricate cardiac valve prostheses and as biomaterials in cardiovascular repair. A stress-free state during chemical modification has been shown to preserve the collagen fiber architecture of the native tissue, potentially preserving native mechanical properties and improving prostheses durability. However, it is not known if the native collagen fiber architecture is stable during long-term in vivo operation. To address this question, we obtained porcine aortic valves chemically treated at (i) 0 mmHg transvalvular pressure (with 40 mmHg aortic pressure) and (ii) 4 mmHg transvalvular pressure, then subjected the valves to 0, 1 x 10(6), 50 x 10(6), and 200 x 10(6) in vitro accelerated wear testing (AWT) cycles. The resulting changes in collagen fiber architecture were quantified using small angle light scattering analysis (SALS). SALS measurements indicated that collagen fibers in the 0 mmHg pressure-fixed leaflets became more aligned between 1 x 10(6) and 50 x 10(6) AWT cycles. In contrast, only minor changes (not statistically significant) in collagen fiber orientation occurred in the 4 mmHg pressure-fixed valvular tissue with cycling. It was also noted that although the 0 mmHg group was fixed without transvalvular pressure, distention of the root induced significant changes in collagen structure of the leaflets. Overall, our observations suggest that the native collagen fiber crimp of the 0 mmHg pressure-fixed leaflets were rapidly lost after only 50 x 10(6) AWT cycles (equivalent to approximately 1.6 patient years) and thus may not be maintained over a sufficient period of time to be clinically beneficial. Further, the collagen structure of the native aortic valve is exquisitely sensitive to dimensional change in the aortic root-independent of the presence of transvalvular pressure. Our findings also suggest that without in vivo remodeling, any collagenous tissue used to fabricate BHV may undergo similar degenerative, irreversible changes in vivo.

Aortic Valve↗
PubMed2005

Biologically active lipid A antagonist embedded in a multilayered polyelectrolyte architecture.

Recently [Jessel N, Schwinte P, Donohue R, Lavalle P, Boulmedais F, Darcy R, et al. Pyridylamino-beta-cyclodextrin as a molecular chaperone for lipopolysaccharide embedded in a multilayered polyelectrolyte architecture. Adv Funct Mater 2004;14:963-9], we demonstrated the biological activity of a lipopolysaccharide from Escherichia coli incorporated into layer-by-layer films made of poly (l-lysine) and poly (l-glutamic acid) and containing a polycationic beta-cyclodextrin (CD) with chaperone properties. Here we develop innovative architectures containing a complex made of a charged beta-cyclodextrin and a lipid A antagonist (LAA) as potential systems for local endotoxin antagonistic activity. We examine the biological activity of these architectures. The CD-LAA complex adsorbed on top, or embedded into the polyelectrolyte films keeps its LPS antagonistic activity on both murine and human macrophages for at least 24h.

Animals↗
PubMed2004

Sub-chronic administration of zolpidem affects modifications to rat sleep architecture.

Gamma-aminobutyric acidA receptor (GABAAR) modulators constitute the majority of clinically relevant sedative-hypnotics. Animal studies have clearly demonstrated sedative efficacy for these compounds in acute studies. However, relatively less is known regarding their efficacy under brief periods of repeat administration or following intermittent dosing. Therefore zolpidem, a short-acting GABAAR modulator with selectivity for the type-I (omega1) benzodiazepine receptor, was studied for efficacy in altering rat sleep architecture as determined by electrocorticogram (ECoG) and electromyogram (EMG) activity over a 7-day sub-chronic administration period. Zolpidem caused significant reductions in wakefulness entries and rapid eye movement (REM) sleep entries and duration, with increases in Delta sleep duration throughout the administration period. Examination of sleep architecture 24 h after cessation of sub-chronic zolpidem administration revealed a decrease in Delta sleep, suggesting that repeated zolpidem administration might elicit enduring modifications to sleep organization. This was not seen following similar dosing of diazepam. The efficacy of sub-chronic administration of zolpidem to alter sleep architecture was enhanced when the administration regimen was repeated following a 7-day hiatus. Significant increases in Delta sleep duration, with significant decreases in light sleep and wakefulness were observed during the repeated exposure to zolpidem. Therefore, sub-chronic administration of zolpidem affected lasting modifications in sleep organization that appeared both 1 day following administration and during reiterated administration without eliciting tolerance.

Animals↗
PubMed2006

A Parallel Architecture perspective on language processing.

This article sketches the Parallel Architecture, an approach to the structure of grammar that contrasts with mainstream generative grammar (MGG) in that (a) it treats phonology, syntax, and semantics as independent generative components whose structures are linked by interface rules; (b) it uses a parallel constraint-based formalism that is nondirectional; (c) it treats words and rules alike as pieces of linguistic structure stored in long-term memory. In addition to the theoretical advantages offered by the Parallel Architecture, it lends itself to a direct interpretation in processing terms, in which pieces of structure stored in long-term memory are assembled in working memory, and alternative structures are in competition. The resulting model of processing is compared both with processing models derived from MGG and with lexically driven connectionist architectures.

Communication↗