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PubMed1985

Grading of prostatic cancer: II. The prognostic significance of the presence of multiple architectural patterns.

This second report in a series of three deals with the prognostic importance of the presence of multiple, histologically identifiable architectural patterns in prostatic carcinomas. In the previous paper three of 12 parameters studied were identified as being prognostically significant in patients with single architectural patterns (formations) present in their tumors. The three parameters are nuclear anaplasia, architecture ("glands"), and mitoses, if present. The questions of whether "the worst part of a tumor determines prognosis" or "the presence of differentiated formations improves prognosis" are investigated by applying these parameters to patients with multiple tumor formations. Overall and corrected survival served as parameters. It was shown that the parameters shown to be of importance for prognosis in tumors with single formations also have significant influence in patients with multiple formations. The worst formation determines prognosis, but patients with poorly differentiated tumors do significantly worse if their tumor is homogeneous. The presence of better-differentiated formations improves the prognosis of the worst formation. The observations made are discussed in view of the histopathogenesis of prostatic cancer.

Cell Nucleus↗
PubMed2000

A diamond-shaped zipper-like DNA architecture containing triads sandwiched between mismatches and tetrads.

The present study reports on the solution structure of the guanine plus adenine rich d(A(2)G(2)T(4)A(2)G(2)) 12-mer sequence which forms a unique fold in moderate NaCl solution. Proton resonance assignments for this sequence, which contains a pair of AAGG repeats separated by a T(4) linker segment, were aided by site-specific (15)N-labeling of guanine and adenine bases, as well as site-specific incorporation of 2,6-diaminopurine and 8-bromoadenine for adenine, 8-bromoguanine, 7-deazaguanine and inosine for guanine, and uracil and 5-bromouracil for thymine. The solution structure, which was solved by a combined NMR and intensity-refined computational approach, consists of a diamond-shaped architecture formed through dimerization of a pair of d(A(2)G(2)T(4)A(2)G(2)) hairpins. This 2-fold symmetric structure contains a quadruplex core consisting of a pair of symmetry-related G(syn).G(syn).G(anti). G(anti) tetrads, where adjacent strands have both parallel and anti-parallel neighbors and connecting T(4) segments which form diagonal loops. Each of the G(syn).G(syn).G(anti).G(anti) tetrads forms a platform on which stacks a T(anti).[A(syn)-A(anti)] triad containing a novel A(syn)-A(anti) platform step and a reversed Hoogsteen A(syn).T(anti) pair. We observe both base-base and base-sugar stacking interactions, with the latter occuring at a sheared A-G step where the sugar of the A stacks on the purine plane of the G. Unexpectedly, the topology of this sheared A(anti)-G(syn) step has many similarities with the C(anti)-G(syn) step in left-handed Z-DNA. The T.(A-A) triad is sandwiched between the G-tetrad on one side and a reversed Hoogsteen A(anti).T(anti) pair on the other. This intercalative topology is facilitated by a zipper-like motif where the A(anti) residue of the triad is interdigitated within a stretched A(anti)-G(syn) step. Our structural study reports on new aspects of A-A platforms, base triads, zipper-like interdigitation and sheared base steps, together with base-base and base-sugar stacking defining a diamond-like architecture for the d(A(2)G(2)T(4)A(2)G(2)) sequence. One can anticipate that mixed guanine-adenine sequences will exhibit a rich diversity of polymorphic architectures that will provide unique topologies for recognition by both nucleic acids and proteins.

DNA↗
PubMed2001

V-shaped scaffold: a new architectural motif identified in an A x (G x G x G x G) pentad-containing dimeric DNA quadruplex involving stacked G(anti) x G(anti) x G(anti) x G(syn) tetrads.

We report the results of an NMR study of unlabeled and uniformly (13)C,(15)N-labeled d(G(3)AG(2)T(3)G(3)AT) in 100 mM NaCl, conditions under which it forms a dimeric quadruplex containing several new topological features. The DNA oligomer chain in each symmetry-related monomer subunit undergoes three sharp turns to form a compact domain, with all the purine bases involved in pairing alignments. The first turn is of the double chain reversal type, the second is of the edgewise type, and the third represents a new alignment, the V-shaped type. Each monomer of the dimeric quadruplex contains two stacked G(anti) x G(anti) x G(anti) x G(syn) tetrads, one of which forms a newly identified A x (G x G x G x G) pentad, through sheared G.A mismatch formation. There is a break in one of the four G-G columns that link adjacent G x G x G x G tetrads within each monomer. This architectural interruption is compensated by a new topological feature of quadruplex architecture, the V-shaped scaffold. The missing G-G column results in an opening that could facilitate insertion of planar ligands into the quadruplex. The dimeric interface contains stacked A.(G.G.G.G) pentads, with each pentad containing four bases from one monomer and a syn G1 from the partner monomer. Several potential ligand-binding pockets, positioned towards either end of the folded architecture, were identifiable in a surface view of the solution structure of the dimeric d(G(3)AG(2)T(3)G(3)AT) quadruplex.

Base Sequence↗
PubMed1996

Empirical Recovery of Response Time Decomposition Rules II. Discriminability of Serial and Parallel Architectures

Among the possible response time (RT) decomposition rules, three are of a traditional interest: addition (serial RT architecture), minimum (parallel-OR architecture), and maximum (parallel-AND architecture). Given RT samples, one can decide which of these three operation is the true decomposition rule by choosing the operation producing the smallest Smirnov distance between the RT samples combined in a certain way, as described by E. N. Dzhafarov and J. M. Cortese (1996, Journal of Mathematical Psychology 40, 185-202). By means of Monte-Carlo simulations, we determine at what sample sizes this decision identifies the true decomposition rule reliably. The results indicate that for a broad class of RT distribution functions the sample sizes required are by an order of magnitude larger when the component times are stochastically independent than when they are perfectly positively stochastically interdependent. In both cases, however, the required sample sizes are realistically achievable in an experiment, provided the experimental factors selectively influencing component times are sufficiently effective. Addition and maximum are generally more difficult to discriminate than addition and minimum, which in turn are more difficult to discriminate than maximum and minimum.

Journal Article↗
PubMed2003

Development of a mathematical method for classifying and comparing tree architecture using parameters from a topological model of a trifurcating botanical tree.

This paper describes a model for the topological mapping of trifurcating botanical trees. The model was based on a system of modular units that represented the interconnectivity of shoot meristems (terminal segments) and internodes (internal segments) within whole plant canopies, organized with increasing centrifugal ordering. The model was capable of describing the dynamics of plant growth as expressed by changes in topological parameters over time. Preliminary calculations for experimental trees indicated that the model represents growth in a biologically sound manner. Methods are described for the calculation of the architecture parameters size, size-complexity, structural complexity, and tree asymmetry index (TAI). Parameter calculations were based on the mathematical principles developed for the classification of bifurcating dendrite trees, and were designed to both extract structural information, and to enable statistical comparison between trees of different size. Parameters were mathematically adjusted for trifurcation, and appeared to be able to represent quantitatively the architectural properties of tree structures. In addition to the calculation of the TAI for trifurcating trees, new methods were developed to enable comparisons to be made of the architectural complexity of trifurcating trees of differing size. These were based on the principle of the pair-wise comparison of the mean centrifugal order number (MCON) with respect to segments against highest order number. We argue and illustrate that this principle can be more informative than that of pair-wise comparison of the MCON against tree degree (topological size). Further improvements to this method were made by examining branching points (vertices) rather than segments (links) to calculate the MCON.

Models, Biological↗
PubMed1996

Role of tumor vascular architecture in nutrient and drug delivery: an invasion percolation-based network model.

Delivery of diffusible nutrients and drugs in tissues is limited in part by the distance over which substances must diffuse between the vascular space and the surrounding tissues and by upstream losses prior to local delivery by the blood. By examining the fractal behavior of two-dimensional vascular networks in the murine dorsal skinfold chamber preparation, we have identified distinct architectural features of normal and tumor vascular networks that lead to fundamentally different transport behavior. Normal capillaries which are relatively straight and regularly spaced are well modeled by the widely used Krogh cylinder model. In contrast, the fractal dimensions of tumor vascular networks suggest that the tortuous vessels and wide range of avascular spaces found in tumors are better represented by invasion percolation, a well-known statistical growth process governed by local substrate properties. Based on these observations, we have constructed a percolation-based model of tumor vascular growth that enables us to predict the effects of network architecture on transport. We find that the number of avascular spaces in tumors scales with the size of the spaces so that there will exist a few large avascular spaces and many smaller avascular spaces between vessels. We also find that the tortuosity of the vessels, as reflected by the elevated minimum path dimension, produces regions of locally flow-limited transport and reduces flow through the tumor as a whole. Our model helps to explain the long-standing paradox that tumor vasculature has a higher geometrical resistance than normal vasculature despite increases in vessel diameter. A comparison to oxygenation measurements in normal and tumor tissues shows that our model predicts the architectural obstacles to transport in tumors more accurately than the Krogh cylinder model. Our results suggest that clinical interventions that yield more regular vascular geometry may be useful as a supplement to those that improve arterial availability or decrease rates of consumption by the tissue.

Antineoplastic Agents↗
PubMed1984

Connective tissue influences on patterns of epithelial architecture and keratinization in skin and oral mucosa of the adult mouse.

Epithelial-mesenchymal interactions play an important role during embryogenesis but it is uncertain whether such interactions influence the maintenance of epithelial structure in the adult. To examine this problem, separated epithelial and connective tissue components of skin and mucosae from various regions of adult mice were homo-or heterotypically recombined and transplanted to histo-compatible hosts. The patterns of tissue architecture and keratinization of the resultant epithelia were examined for changes indicative of mesenchymal influences on the epithelial phenotype. Each type of epithelium, in some recombinations, fully conserved its normal pattern of phenotypic expression indicating that subepithelial connective tissue from all regions is permissive and that regionally-specific connective tissue influences are not necessary for conservation of epithelial specificity. In other recombinations, however, the epithelium acquired features of tissue architecture or keratinization typical of the epithelium normally associated with the connective tissue component, indicating directive influences from the connective tissue. The patterns of epithelial response observed suggest that there may be separate connective tissue influences on epithelial architecture and cyto-differentiation and that there is a regionally-related variation in the competence of epithelia to respond to these influences.

Animals↗
PubMed1991

Functionally complex muscles of the cat hindlimb. II. Mechanical and architectural heterogenity within the biceps femoris.

The goal of this study was to analyze the architecture of the cat biceps femoris (BF), a multifunctional hamstring muscle, and to evaluate the relationships between muscle architecture, limb position, and muscle function during natural movement. The BF muscle consists of three neuromuscular compartments: anterior (BFa), middle (BFm) and posterior (BFp). Each compartment is innervated by a separate nerve branch. Nerve branch stimulation and 2-dimensional surface EMG recordings showed that individual compartment territories were discrete and non-overlapping with well-defined borders. Comparisons of the three compartments revealed consistent differences in architecture, relationship to the skeleton, and function. The BFa crossed only the hip joint and appears to function as a pure hip extensor. The BFm had equal lever arm lengths to the hip and knee joints, appears to function as a hip extensor, and may contribute to knee flexion or femoral rotation. The BFp had a greater lever arm to the knee, functions as a knee flexor, and may contribute to hip extension, femoral rotation or ankle extension. Measurements of individual fascicles from the three compartments revealed a surprising range of lengths, 3.3-12.0 cm. Microdissection of gold-stained tissue showed that fascicles from all compartments were comprised of interdigitated, short fibers (range: 0.6-5.0 cm; average 2.14 cm) arranged in-series in fascicles, running parallel to the origin-insertion axis of each muscle compartment. In regions of fiber interdigitation, the fiber endings were round and tapered (taper lengths: 1-11 mm) although flat, tapering endings like ribbons were occasionally found. As hip and knee joint angles were varied over physiological ranges corresponding to minimal to maximal muscle length, fascicles of the three compartments changed length disproportionately. Long BFa fascicles maximally lengthened 10-18%, consistent with in vivo length measures during treadmill locomotion. However, the long BFp fascicles lengthened 25-45%, and the relatively short fascicles near the BFm/BFp border maximally lengthened 45-53%. How do these unexpectedly large length changes affect sarcomere lengths? Using laser diffraction to measure sarcomeres, static fascicle and sarcomere lengths were compared in muscles that went into rigor mortis after fixing the hip and knee joint angles. Sarcomeres within the short BFm/BFp and long BFp fascicles consistently lengthened proportionately less than the whole fascicle. It remains to be determined how and where the fascicle length changes are dissipated in the connective tissue between the interdigitated muscle fibers and whether such a series-compliance operates during the large excursions over which this muscle normally works.

Animals↗
PubMed1990

Three-dimensional architecture of the microvasculature in the rat foot-pad, with special reference to vasculature around the eccrine sweat glands. A scanning electron-microscopic study of corrosion casts.

The entire microvascular architecture in rat foot-pads including that of eccrine sweat glands was studied by scanning electron microscopy using a vascular corrosion-cast replication technique. In the central roofs of the pads, particularly elaborate capillary networks were arranged in rows perpendicular to the long axis of the foot. In the marginal regions of the pads, simple networks of capillaries were arranged in lamellar sheets parallel to the surface of the sole of the foot. Complex spongy networks of vascular trees were observed in the subcutaneous layer of the pads. These vessels were supplied by the pad artery, and then, after forming capillary networks in the roofs of the pads, they drained into the metatarsal vein. Rod-shaped cages of capillaries were observed around the eccrine sweat glands. One descending arteriole, arising from a connecting arteriole, and a few venules were connected with these capillary cages at their upper and lateral sides. Occasional arterio-venous and veno-venous anastomoses were also observed around the eccrine sweat glands. This microvascular architecture may adjust well to the mechanical and physiological conditions encountered in the foot-pads. The relation of the microvascular architecture around the eccrine sweat glands with their development is also discussed.

Animals↗
PubMed1985

Developmental microvascular architecture of the rat cerebellar cortex.

External and internal microvascular architectures of the developing rat cerebellar cortex, from embryonic day 18 to postnatal day 14 and in adults, were studied using a cerebrovascular casting method for scanning electron-microscopic observation. The external vascularization of the developing cerebellum showed the most significant alteration in vascular morphology at the stage of intensive proliferation of matrix cells in the external granular layer (EGL) from birth to postnatal day 4. It consisted of multiple luminal protrusion of the vessels, septum formation in the lumina, and small, ring-like anastomoses. Moreover, at the end of this stage, these structures of the vessels disappeared and the subarachnoid space was filled with newly-formed microvascular networks. Thereafter, architectural change of the developing pial vessels was mainly accomplished by elongation of each contorted vessel of the network. Concerning internal vascularization, a few vessels connected with the pial vessels were observed in the cerebellar plate forming a loose, simple network in the deeper neural parenchyma before the stage of foliation began. During the period of thickening of the EGL, however, there was no alteration in vascularity of the parenchyma other than the architectural changes proportionate to the newly-formed folia. It was during the synaptogenetic stage in the internal granular layer that the earliest intraneural vascular plexuses were formed. The vascular network in the molecular layer was formed after disappearance of the EGL. These findings suggest that vascular proliferation correlated with EGL-formation pertains to the pial vessels, and not the intraneural ones, which develop after neuronal cell migration in the developing cerebellum has taken place.

Animals↗
PubMed1991

Muscular architecture in the omasal laminae of cattle and sheep.

The muscular architecture of the bovine omasal laminae was examined. The omasal laminae had three thin smooth muscle layers which consisted of an intermediate layer and two lateral layers. The muscle bundles of the intermediate layers ran radially in the laminae and those of the two lateral layers ran parallel to the free border of the laminae. At the free border, three types of the muscular architecture were observed. In a histological study, the muscle bundles of the intermediate layer penetrated into the connective tissue around and smooth muscle fasciculi of the inner layer of the tunica muscularis of the omasal wall and attached to the bundles of both the inner layer and of the outer layer of the tunica muscularis. These results indicate that a re-evaluation of the muscular architecture in the omasal laminae is required to facilitate better understanding of the omasal morphology and physiology.

Animals↗
PubMed1995

Computer simulation modelling and visualization of 3D architecture of biological tissues. Simulation of the evolution of normal, metaplastic and dysplastic states of the nasal epithelium.

Recent technical improvements, such as 3D microscopy imaging, have shown the necessity of studying 3D biological tissue architecture during carcinogenesis. In the present paper a computer simulation model is developed allowing the visualization of the microscopic biological tissue architecture during the development of metaplastic and dysplastic lesions. The static part of the model allows the simulation of the normal, metaplastic and dysplastic architecture of an external epithelium. This model is associated to a knowledge base which contains only data on the nasal epithelium. The latter has been well studied by numerous authors and its lesional states are well known. An inference engine allows the initialization of the static model parameters. A statistical comparison between simulated epithelia and real epithelia is achieved by adjusting the parameter values during the simulation. The dynamic part of the model allows the simulation of a growth process on a 3D representation based on the static model. The main hypothesis is that nasal epithelium is submitted to a continuous transformation from normal to cancer through metaplasia and dysplasia. The evolution of each cell (represented by its nucleus) depends on its local environment and also on its heritage from its mother-cell. Simulation of tissue renewal of the nasal pseudostratified epithelium has been achieved. The evolution from normal to hyperplasia has been simulated. After modification of the cell cycle modelling, the simulation of the development of metaplastic foci has been obtained.

Cell Cycle↗
PubMed1993

Male mating speed in Drosophila melanogaster: differences in genetic architecture and in relative performance according to female genotype.

From a critical review of the literature on mating speed in Drosophila, the importance of fast mating in male fitness is questioned. The genetic architecture of male mating speed (MMS) has been evaluated in D. melanogaster through a populational analysis and a full 5 x 5 diallel cross between inbred lines. The results emphasize the fundamental role of the female genotype in both the absolute and the relative MMS performances. Somewhat different genetic architectures for MMS are revealed according to the female used in the tests. It is suggested that different parts of the complex genetic system involved in the male's "behavioral sexual phenotype" are relevant depending on the female's characteristics, thus causing the heterogeneity in the MMS genetic architecture. An overall picture reveals a genetic system characterized by additivity, dominance for fast mating, and no influence of the X chromosome. There results do not support strong natural selection favoring fast mating in Drosophila males.

Animals↗
PubMed1993

Architecture in cortical bone and ultrasound transmission velocity.

The square of ultrasound transmission velocity in a material is correlated to the modulus of elasticity, which is an indicator of its mechanical properties. This might make the measurement of ultrasound transmission velocity useful in the noninvasive diagnosis of bone diseases. Bone, however, is not an isotropic material but is architecturally structured. The aim of our study was to investigate and especially to quantify the influence of architecture in cortical bone on ultrasound transmission velocity. Twenty-two rectangular, flat specimens of cortical bone were prepared from diaphysis of fresh pig radius. Ultrasound transmission velocity was measured parallel and perpendicular to direction of Haversian channels. It was found to be 3647 +/- 41 m/s parallel to and 2821 +/- 29 m/s perpendicular to Haversian channels respectively (p < 0.001). Our results clearly indicate that there is an important influence of architecture in cortical bone on ultrasound transmission velocity which has to be taken into account in its clinical use.

Animals↗
PubMed1997

Benefits of distributed HIS/RIS-PACS integration and a proposed architecture.

The tight integration of the Hospital Information System/Radiology Information System (HIS/RIS) and the Picture Archive Communication System (PACS) has become a priority in modern healthcare delivery systems. Traditional paper-based systems are being replaced by gateway style interface engines. Gateways provide a tightly integrated link between the HIS/RIS and the PACS, increasing productivity by automating many mundane clerical tasks associated with paper-based systems. A centralized gateway, however, represents a processing bottleneck and single point of failure. A self-monitoring distributed gateway architecture that replicates essential services increases the fault tolerance and the overall availability of the gateway, while providing reduced, consistent transaction times. A possible distributed architecture is proposed as a means to realize the advantages of a distributed architecture.

Computer Systems↗
PubMed2001

Study status consistency and duplicate-read protection in a distributed architecture.

UNLABELLED: This presentation will discuss the benefits and pitfalls of implementing a study status and duplicate-read protection mechanism within a distributed picture archiving and communication system (PACS) architecture. There are many advantages to a distributed PACS network in which image studies are proactively pushed to reading stations before they are required by a radiologist. The absence of a central server, which serves on demand, makes managing study status and protecting against duplicate reads challenging. The system to manage study status and read access must be efficient, robust, and easy to administer. A system is presented that accomplishes these goals while maintaining the advantages of a distributed architecture. METHODS: The basic workflow of the system is that image studies acquired at a modality device are automatically sent to an archive server. Using a set of advanced routing rules, the archive automatically routes studies to diagnostic workstations where studies are candidates for diagnostic read. The workstations display a list of all local studies available for reading. A monitor application running on the workstations coordinates access to studies for diagnostic read. Once the status of a study has been changed, the workstations on the networks and the archive are notified, which causes the study to be automatically removed from any list on a workstation where it might be a read candidate. RESULTS: Implementation of this system provides a balanced workflow throughout the system while minimizing the need for costly high-speed network hardware. Additionally studies are read as soon as they are available by the next available radiologist. This workflow is enabled without the need for specific interaction by any of the radiologists on the network. By having the images available at the workstation in an organized worklist, this methodology increases the efficiency of the radiologist. CONCLUSION: The implementation of this system enables a radiology department, or even a specialty group within a department, to gain the benefit of a distributed system as well as the benefits provided by a central-server architecture. This can be done very cost effectively with minimal configuration overhead and hardware requirements.

Computer Systems↗
PubMed2003

Molecular marker dissection of rice (Oryza sativa L.) plant architecture under temperate and tropical climates.

Rice ( Oryza sativa L.) plants develop vertically with shoot elongation and horizontally with tillering. The purpose of this study was to identify and characterize genomic regions influencing the rice plant architecture by quantitative trait locus (QTL) analysis for the component traits: culm length (CL), panicle length (PnL), panicle number (PnN) and tiller number (TN). For this QTL analysis, 191 recombinant inbred lines (F(7)) derived from a cross of Milyang 23 (M23) and Akihikari (AK) were grown in 1995, 1996 and 1997 (May-Oct) in Joetsu, Japan (temperate climate), and in the 2000 dry season (Jan-Apr), the 2000 wet season (Jun-Oct) and the 2001 dry season in Los Baños, The Philippines (tropical climate). Results showed that rice plant architecture was influenced by 19 genomic regions categorized into five groups. In Group I, two regions (on chrs. 6 and 11) affected shoot elongation (CL and PnL) and tillering (PnN and TN) in opposite directions more significantly in Los Baños than in Joetsu. In Group II, two regions (chrs. 3 and 12) affected shoot elongation, whereas in Group III, five regions [chrs. 1 (two), 2, 3 and 9] affected only culm length (CL). Expressions of four regions of Group III were influenced by either tropical or temperate environments. In Group IV, seven regions (chrs. 1, 2, 4, 5, 6, 8 and 9) controlled panicle development (PnN or PnL), and in Group V, three regions (chrs. 1, 2 and 3) regulated tillering (PnN or TN). Characterizing these 19 genomic regions provided a detailed analysis of rice plant architecture with emphasis on the multiple effect and environmental responsive regions.

Genetic Markers↗
PubMed2006

Inheritance of inflorescence architecture in sorghum.

The grass inflorescence is the primary food source for humanity, and has been repeatedly shaped by human selection during the domestication of different cereal crops. Of all major cultivated cereals, sorghum [Sorghum bicolor (L.) Moench] shows the most striking variation in inflorescence architecture traits such as branch number and branch length, but the genetic basis of this variation is little understood. To study the inheritance of inflorescence architecture in sorghum, 119 recombinant inbred lines from an elite by exotic cross were grown in three environments and measured for 15 traits, including primary, secondary, and tertiary inflorescence branching. Eight characterized genes that are known to control inflorescence architecture in maize (Zea mays L.) and other grasses were mapped in sorghum. Two of these candidate genes, Dw3 and the sorghum ortholog of ramosa2, co-localized precisely with QTL of large effect for relevant traits. These results demonstrate the feasibility of using genomic and mutant resources from maize and rice (Oryza sativa L.) to investigate the inheritance of complex traits in related cereals.

Chromosome Mapping↗