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Nanometric summation architecture based on optical near-field interaction between quantum dots.

A nanoscale data summation architecture is proposed and experimentally demonstrated based on the optical near-field interaction between quantum dots. Based on local electromagnetic interactions between a few nanometric elements via optical near fields, we can combine multiple excitations at a certain quantum dot, which allows construction of a summation architecture. Summation plays a key role for content-addressable memory, which is one of the most important functions in optical networks.

Journal Article↗

Genetic architecture of smoking behavior: a study of Finnish adult twins.

Both genetic and environmental factors affect smoking initiation and maintenance, but less is known about the genetic architecture of various other smoking-related behaviors. The aim of this study is to examine the genetic architecture of smoking behavior in a large twin cohort. Questionnaires with an extensive smoking history section were mailed to same-sex adult twins of the Finnish twin cohort. The final study population included 2923 monozygotic and 6018 dizygotic twin pairs aged 24 to 88 years. Two-stage bivariate genetic modeling of age at initiation with amount smoked (less than 20 cigarettes per day vs. 20 or more) and age at initiation with smoking cessation was done by using the Mx statistical package. For men the heritability estimate for age at initiation was .59 (95% confidence interval [CI] .49-.69), for amount smoked .54 (95% CI .45-.62) and for smoking cessation .58 (95% CI .50-.65). For women the heritability estimates were .36 (95% CI .28-.43), .61 (95% CI .46-.70) and .50 (95% CI .39-.60), respectively. The genetic correlations between age at initiation and amount smoked or smoking cessation were at most .22 in magnitude, indicating that genetic influences in age at initiation accounted for at most about 4% of the genetic factors in amount smoked or in cessation. Genetic factors are important in amount smoked and smoking cessation and they are largely independent of genetic influences on age at initiation. This has implications for defining phenotypes in searches for genes underlying smoking behaviors.

Age Factors↗

An architecture for distributed visual memory.

The development of autonomous as well as situated robots is one of the great remaining challenges and involves a number of different scientific disciplines. In spite of recent dramatic progress, it remains worthwhile to examine natural systems, because their abilities are still out of reach. Motivated by research work done in the fields of cognitive systems, visual perception, and psychology of memory we designed and implemented a memory architecture for visual tasks. Structural and functional concepts of the memory architecture were modeled on the ones found in natural systems. We present an efficient implementation based on parallel programming techniques. The memory module is integrated into a distributed system for speech and image analysis, which is currently developed in the Sonderforschungsbereich (SFB) 360, Situated Artificial Communicators, where a hybrid vision system combining neural and semantic networks is used.

Animals↗

Constitutively active cytoplasmic c-Jun N-terminal kinase 1 is a dominant regulator of dendritic architecture: role of microtubule-associated protein 2 as an effector.

Normal functioning of the nervous system requires precise regulation of dendritic shape and synaptic connectivity. Here, we report a severe impairment of dendritic structures in the cerebellum and motor cortex of c-Jun N-terminal kinase 1 (JNK1)-deficient mice. Using an unbiased screen for candidate mediators, we identify the dendrite-specific high-molecular-weight microtubule-associated protein 2 (MAP2) as a JNK substrate in the brain. We subsequently show that MAP2 is phosphorylated by JNK in intact cells and that MAP2 proline-rich domain phosphorylation is decreased in JNK1-/- brain. We developed compartment-targeted JNK inhibitors to define whether a functional relationship exists between the physiologically active, cytosolic pool of JNK and dendritic architecture. Using these, we demonstrate that cytosolic, but not nuclear, JNK determines dendritic length and arbor complexity in cultured neurons. Moreover, we confirm that MAP2-dependent process elongation is enhanced after activation of JNK. Using JNK1-/- neurons, we reveal a dominant role for JNK1 over ERK in regulating dendritic arborization, whereas ERK only regulates dendrite shape under conditions in which JNK activity is low (JNK1-/- neurons). These results reveal a novel antagonism between JNK and ERK, potentially providing a mechanism for fine-tuning the dendritic arbor. Together, these data suggest that JNK phosphorylation of MAP2 plays an important role in defining dendritic architecture in the brain.

Animals↗

Functional magnetic resonance imaging examination of two modular architectures for switching multiple internal models.

An internal model is a neural mechanism that can mimic the input-output properties of a controlled object such as a tool. Recent research interests have moved on to how multiple internal models are learned and switched under a given context of behavior. Two representative computational models for task switching propose distinct neural mechanisms, thus predicting different brain activity patterns in the switching of internal models. In one model, called the mixture-of-experts architecture, switching is commanded by a single executive called a "gating network," which is different from the internal models. In the other model, called the MOSAIC (MOdular Selection And Identification for Control), the internal models themselves play crucial roles in switching. Consequently, the mixture-of-experts model predicts that neural activities related to switching and internal models can be temporally and spatially segregated, whereas the MOSAIC model predicts that they are closely intermingled. Here, we directly examined the two predictions by analyzing functional magnetic resonance imaging activities during the switching of one common tool (an ordinary computer mouse) and two novel tools: a rotated mouse, the cursor of which appears in a rotated position, and a velocity mouse, the cursor velocity of which is proportional to the mouse position. The switching and internal model activities temporally and spatially overlapped each other in the cerebellum and in the parietal cortex, whereas the overlap was very small in the frontal cortex. These results suggest that switching mechanisms in the frontal cortex can be explained by the mixture-of-experts architecture, whereas those in the cerebellum and the parietal cortex are explained by the MOSAIC model.

Adult↗

Biomechanics of Schlemm's canal endothelial cells: influence on F-actin architecture.

Aqueous humor drains from the eye through Schlemm's canal, a small endothelial-lined collecting duct. Schlemm's canal endothelial cells may be important in controlling the pressure within the eye (and hence are of interest in glaucoma), and are subject to an unusual combination of shear stress and a basal-to-apical pressure gradient. We sought to characterize this biomechanical environment and determine its effects on F-actin architecture in situ. A theoretical model of flow in Schlemm's canal was used to estimate shear stresses applied to endothelial cells by flowing aqueous humor. Alignment of Schlemm's canal endothelial cells in human eyes was quantified by scanning electron microscopy. F-actin architecture was visualized by fluorescent labeling and compared for closely adjacent cells exposed to different biomechanical environments. We found that, despite the relatively low flow rate of aqueous humor, shear stresses experienced by Schlemm's canal endothelial cells could reach those in the arterial system. Schlemm's canal endothelial cells showed a statistically significant preferential alignment, consistent with a shear-mediated effect. Schlemm's canal endothelial cells subjected to a basal-to-apical pressure gradient due to transendothelial flow showed a prominent marginal band of F-actin with relatively few cytoplasmic filaments. Adjacent cells not subject to this gradient showed little marginal F-actin, with a denser cytoplasmic random network. We conclude that Schlemm's canal endothelial cells experience physiologically significant levels of shear stress, promoting cell alignment. We speculate that this may help control the calibre of Schlemm's canal. F-actin distribution depends critically on the presence or absence of transendothelial flow and its associated pressure gradient. In the case of this pressure gradient, mechanical reinforcement around the cell periphery by F-actin seems to be critical.

Actins↗

A study of age-related architectural changes that are most damaging to bones.

Osteoporosis-related bone damage causes major socioeconomic problems. For efficient use of therapeutic agents, it is necessary to be able to reliably identify patients with high propensity for nontraumatic fracture. Age-related bone loss imposes several architectural changes in bone; one of the few ways to estimate damage due to individual changes, and hence determine the most serious types of damage, is via the analysis of suitable mathematical models. Anatomical sites such as the vertebral body, proximal femur, and distal radius are locations where most age-related fractures occur. The inner porous (or trabecular) bone from these sites, which resemble disordered cubic networks, play a significant role in load transmission at these sites. Analysis of a mathematical model of porous bone is used to show that perforation of elements of the network is the most damaging architectural change to a bone. We also show that an expression for bone strength, derived on this basis, can capture changes in strength caused by the inclusion of other features like thinning of trabecular bone and the anisotropy of the network. We finally argue that bone density, which is currently the most routinely used diagnostic, cannot be a reliable surrogate for bone strength.

Aging↗

Effect of acute exposure to loud occupational noise during daytime on the nocturnal sleep architecture, heart rate, and cortisol secretion in healthy volunteers.

OBJECTIVES: Noise is one of the commonest physical stressors to which industrial workers are exposed. Many workers complain of symptoms associated with a non-specific generalized stress response, including disturbed sleep. However, industrial workers may be exposed to more than one source of stress and it is not possible to completely attribute the disturbed nocturnal sleep and changes in heart rate to the effects of loud noise alone. This study was done to find out whether acute exposure of healthy individuals to loud occupational noise during the daytime would cause changes in their nocturnal sleep architecture, heart rate during sleep and serum cortisol levels. METHODS: Baseline polysomnography was done on ten subjects who were exposed for eight hours either to continuous occupational background noise levels of >75dB(A), or a quiet environment. Sleep polysomnography was done on the night prior to and after exposure. Blood was collected for serum cortisol estimation at night prior to sleep and in the morning after waking up. Statistical analysis was done by repeated measures ANOVA with Tukey's post test. RESULTS: The sleep efficiency was less than 80% and the total time spent in Rapid Eye Movement (REM) sleep, Slow Wave Sleep (SWS) and the REM onset latency were significantly decreased on the night after exposure to noise. There was a significant increase in stage shifts. The percentage fall in heart rate during sleep was decreased compared to the baseline values. The serum cortisol levels in the morning after exposure to noise was significantly increased. CONCLUSION: Workers exposed to loud background occupational noise react to the stress and show changes in nocturnal sleep architecture and heart rate which may be contributed to the exposure to noise.

Adolescent↗

Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones.

The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function.

Animals↗

The three-dimensional architecture of the myosalpinx in the sheep as revealed by scanning electron microscopy.

The three-dimensional (3-D) architecture of the myosalpinx in the sheep was studied by scanning electron microscopy after the removal of interstitial connective tissue with NaOH digestion. In the extramural portion of the tubo-uterine junction, the myosalpinx is made up of densely packed, circularly arranged superficial fibers and of innermost loose fiber bundles following an almost longitudinal course. In the isthmus and ampulla, the myosalpinx is constituted by oblique bundles of variable length, which run around the tube and merge into the surrounding musculature, giving rise to a plexiform arrangement. The present 3-D observations demonstrate that the sheep myosalpinx consists mainly of single muscular fibers and more complex bundles which show a multiple spatial arrangement and a plexiform distribution. Such a muscular architecture is more likely suited for stirring rather than pushing the embryos and gametes through the tube.

Animals↗

Formation and phosphorylation of the PINCH-1-integrin linked kinase-alpha-parvin complex are important for regulation of renal glomerular podocyte adhesion, architecture, and survival.

Alterations in the cellular architecture, adhesion, and/or loss of glomerular podocytes are causal factors in the development of proteinuria and the progression to end-stage renal failure. With the use of an inducible podocyte differentiation system, it was found that the cellular levels of PINCH-1, integrin linked kinase (ILK), and alpha-parvin, cytoplasmic components of cell-extracellular matrix adhesions, were significantly increased during podocyte differentiation. Concomitantly, an increased amount of the PINCH-1-ILK-alpha-parvin complex was detected in the differentiated, foot process-containing podocytes. Overexpression of the PINCH-1-binding ankyrin repeat domain of ILK but not that of a PINCH-1-binding defective mutant form of the ankyrin domain effectively inhibited the formation of the PINCH-1-ILK-alpha-parvin complex. Disruption of the PINCH-1-ILK-alpha-parvin complex significantly reduced the podocyte-matrix adhesion and foot process formation. Furthermore, a marked increase of apoptosis in the podocytes in which the assembly of the PINCH-1-ILK-alpha-parvin complex was compromised was detected. Inhibition of ILK with a small compound inhibitor also altered podocyte cytoskeleton and increased apoptosis. Finally, it is shown that alpha-parvin is phosphorylated in podocytes. Mutations at the alpha-parvin N-terminal proline-directed serine phosphorylation sites reduced its complex formation with ILK and resulted in defects in podocyte adhesion, architecture, and survival. These results provide important evidence for a crucial role of the PINCH-1-ILK-alpha-parvin complex in the control of podocyte adhesion, morphology, and survival.

Actinin↗

Endothelin-a receptor blockade improves renal microvascular architecture and function in experimental hypercholesterolemia.

Hypercholesterolemia (HC) may trigger early renal injury, partly by impairing the function or the structure of renal microvessels (MV). The endothelin (ET) system is upregulated in HC and can have an impact on the renal microcirculation by regulating MV tone, growth factors, and remodeling. It was hypothesized that ET-A blockade would protect the HC kidney by improving the function and attenuating the damage of intrarenal MV. Single-kidney function and hemodynamic responses to endothelium-dependent challenge were assessed in pigs after 12 wk of experimental HC, HC and chronic supplementation with the ET receptor A blocker ABT-627 (HC+ET-A, 0.75 mg/kg per d), and normal controls. Renal MV architecture then was studied ex vivo using three-dimensional microcomputed tomography imaging, and growth factors and remodeling pathways were explored in renal tissue. The HC kidney showed increased MV density compared with normal (77.68 +/- 5.1 versus 62.9 +/- 4.8 vessels/cm(2); P = 0.04) but blunted endothelial function. Chronic ET-A blockade in HC upregulated renal vascular growth factors, further increased renal MV density (139.9 +/- 8.4 vessels/cm(2); P = 0.001 versus normal and HC), and decreased renal tissue and MV remodeling. Furthermore, ET-A blockade in HC decreased MV tortuosity and improved MV endothelial function, suggesting accelerated stabilization and maturation of neo-vessels. Modulation of renal MV architecture and function in HC is mediated partly by the endogenous ET system. Notably, ET-A blockade enhanced the proliferation and facilitated the maturation of renal MV in the HC kidney and improved renal MV remodeling and function. This study suggests novel renoprotective effects of ET-A blockers and supports further exploration of strategies that target the ET pathway in HC and atherosclerosis.

Animals↗

The molecular basis of lymphoid architecture and B cell responses: implications for immunodeficiency and immunopathology.

Immune responses usually take place in secondary lymphoid organs such as spleen and lymph nodes. Most lymphocytes within these organs are in transit, yet lymphoid organ structure is highly organized; T and B cells segregate into separate regions. B cell compartments include naïve cells within follicles, marginal zones and B-1 cells. Interactions between TNF family molecules on hematopoietic cells and their receptors on mesenchymal cells guide the initial phase of lymphoid organogenesis, and regulate chemokine secretion that mediates subsequent T-B cell segregation. Recruitment of B cells into different compartments depends on both the milieu established during organogenesis, and the threshold for B cell receptor signaling, which is modulated by numerous coreceptors. Novel intrafollicular (germinal center) and extrafollicular (plasma cell) compartments are established when B cells respond to antigen. These divergent B cell responses are mediated by different patterns of gene expression, and influenced again by BCR signaling threshold and cellular interactions that depend on normal lymphoid architecture. Aberrant B cell responses are reviewed in the light of these principles taking into account the molecular and architectural aspects of immunopathology. Histological features of immunodeficiency reflect defects of B cell recruitment or differentiation. B cell hyper-reactivity may arise from altered BCR signaling thresholds (autoimmunity), defects in stimuli that guide differentiation in response to antigen (follicular hyperplasia vs plasmacytosis), or defective B cell gene expression. Interestingly, in diseases such as rheumatoid arthritis, Sjogren's syndrome and Hashimoto's thyroiditis lymphoid organogenesis may be recapitulated in non-lymphoid parenchyma, under the influence of molecular interactions similar to those that operate during embryogenesis.

Animals↗

Architecture for knowledge-based and federated search of online clinical evidence.

BACKGROUND: It is increasingly difficult for clinicians to keep up-to-date with the rapidly growing biomedical literature. Online evidence retrieval methods are now seen as a core tool to support evidence-based health practice. However, standard search engine technology is not designed to manage the many different types of evidence sources that are available or to handle the very different information needs of various clinical groups, who often work in widely different settings. OBJECTIVES: The objectives of this paper are (1) to describe the design considerations and system architecture of a wrapper-mediator approach to federate search system design, including the use of knowledge-based, meta-search filters, and (2) to analyze the implications of system design choices on performance measurements. METHODS: A trial was performed to evaluate the technical performance of a federated evidence retrieval system, which provided access to eight distinct online resources, including e-journals, PubMed, and electronic guidelines. The Quick Clinical system architecture utilized a universal query language to reformulate queries internally and utilized meta-search filters to optimize search strategies across resources. We recruited 227 family physicians from across Australia who used the system to retrieve evidence in a routine clinical setting over a 4-week period. The total search time for a query was recorded, along with the duration of individual queries sent to different online resources. RESULTS: Clinicians performed 1662 searches over the trial. The average search duration was 4.9 +/- 3.2 s (N = 1662 searches). Mean search duration to the individual sources was between 0.05 s and 4.55 s. Average system time (ie, system overhead) was 0.12 s. CONCLUSIONS: The relatively small system overhead compared to the average time it takes to perform a search for an individual source shows that the system achieves a good trade-off between performance and reliability. Furthermore, despite the additional effort required to incorporate the capabilities of each individual source (to improve the quality of search results), system maintenance requires only a small additional overhead.

Decision Making, Computer-Assisted↗

Macroscopic structure of articular cartilage of the tibial plateau: influence of a characteristic matrix architecture on MRI appearance.

OBJECTIVE: The purpose of our study was to describe the structural organization of the extracellular matrix of articular cartilage of the tibial plateau and its influence on MRI appearance. MATERIALS AND METHODS: Spin-echo images of 11 resected tibial plateaus acquired at 7 T were compared with the structure of the extracellular matrix as shown by fracture sectioning the samples in the plane of imaging. Four samples were scanned at two different orientations relative to the main magnetic field (B(0)). T2 maps were acquired in two orientations on three of these four samples. RESULTS: On the basis of the presence of reproducible regional variations in the shape of the matrix, a characteristic matrix architecture was described. The location of peak signal intensity and T2 on MRI correlated with the level at which the matrix was estimated to be aligned at approximately 55 degrees to B(0) (r = 0.91). This correlation of matrix orientation relative to B(0) with T2 and signal intensity on MRI was not altered by regional variations in the shape of the matrix or by imaging samples at two different orientations. CONCLUSION: The structure of the extracellular matrix, through its orientation-dependent influence on T2 decay, exerts a strong influence on the MRI appearance of cartilage. At the tibial plateau, a characteristic matrix architecture is associated with an equally characteristic MRI appearance.

Adult↗

Glucoamylase from Thermoanaerobacterium thermosaccharolyticum: Sequence studies and analysis of the macromolecular architecture of the enzyme.

A chromosomal DNA fragment with a length of 2,025 bp, carrying the structural gene coding for glucoamylase in Thermoanaerobacterium thermosaccharolyticum, was cloned and sequenced. It coded for 695 amino acids, representing a polypeptide with a predicted molecular mass of 77.5 kDa. The deduced amino acid sequence exhibited high homologies with the glucoamylase sequence of another bacterial glucoamylase (Clostridium sp. G0005) and with fungal glucoamylases. The catalytic domain (amino acids 271 to 695) of the T. thermosaccharolyticum enzyme shared a high degree of similarity (five conserved regions) with the catalytic domain of Aspergillus awamori glucoamylase. By comparing the secondary structure of the sequence of the catalytic domain of the T. thermosaccharolyticum enzyme with that of glucoamylase from A. awamori, and on the basis of X-ray crystallographic data available for the A. awamori enzyme, it turned out that, most probably, both enzymes have a catalytic domain organized into an "(alpha/alpha)(6)-barrel" and an overall size and shape that is very similar. These findings confirm and extend our working model for the macromolecular architecture of the T. thermosaccharolyticum glucoamylase obtained, in earlier experiments, by electron microscopy of negatively stained isolated enzyme molecules. Antibodies for an enzyme-specific peptide located near the active site were successfully applied for inhibition studies of enzyme activity and for electron microscopic epitope mapping. A study comparing the site of attachment of this kind of antibody to the T. thermosaccharolyticum glucoamylase molecule with the expected attachment site as deduced from the A. awamori enzyme structure confirmed the close similarity of both glucoamylases regarding the macromolecular architecture of that part of the enzyme carrying the catalytic center, though helices H9, H10, and H11 in peripheral parts of the A. awamori enzyme are missing in the T. thermosaccharolyticum enzyme.

Journal Article↗

[Morphology and microvascular architecture of the filiform papillae in the rat].

This study was an attempt in order to investigate microvascular architecture in various kinds of the filiform papillae of the rat utilizing the plastic injection method. Filiform papillae of the rat were grouped into three types; the simple and the giant conical and the true filiform. Additionally, the simple conical papillae could be subgrouped into type I, II and digitiform papillae, and the forked filiform as an intermediate form between the giant conical and the true filiform, based on their function and microvasculature. The capillary loop of the true filiform papillae was the simplest, hair-pin loop. The basic form of the loop was similar to the loop of the simple conical type I, II, and digitiform papillae respectively, although that of type II, having two or three ascending crura, was the most complicated of the three. Capillary loops of the giant conical papillae consisted of three or five ascending crura which passed upward in the pharyngeal side, the descending crura consisted or similar capillaries and passed downward at the lingual apex side. Each of the crura possessed its own loop. It can be said conclusively that this detailed investigation of the intrapapillary microvascular architecture in the rat has enabled a morphological classification of the papillae to be made.

Animals↗

Spontaneous reassociation of dispersed adult rat pancreatic islet cells into aggregates with three-dimensional architecture typical of native islets.

Islets of Langerhans consist of four major endocrine cell types assembled in a highly organized manner critical for their function. The molecular forces governing islet cellular architecture are not understood. We determined whether adult rat islet cells carry information necessary for orderly assembly. Dispersed cells from adult rat islets were maintained in static suspension culture for 6 days. During this time the cells reassociated to form numerous aggregates. These aggregates were approximately half the size of native islets with a commensurate reduction in DNA and insulin content. However, both cellular composition and organization were remarkably similar to that of adult rat islets, in which the beta-cells form a central core surrounded by a discontinuous mantle of non-beta-cells. Thus, immunoperoxidase staining showed that in the aggregates, just as in intact islets cultured in parallel, 26% of the cells were non-beta-cells and of these, 94% were clearly peripheral. Non-beta-cells were similarly found to be peripheral, with beta-cells located centrally, even when the ratio of non-beta-cells to beta-cells had been altered. This was achieved by sorting the two cell populations by fluorescence-activated flow cytometry, resulting in aggregates with 79% non-beta-cells and 21% beta-cells. Insulin release from the aggregates was stimulated approximately ninefold by raising glucose from 50 to 300 mg/dl, which was comparable to that found for intact islets. The spontaneous formation of isletlike aggregates displaying appropriate cellular architecture indicates that the signals (molecules) needed for such organization are intrinsic to islet cells and are still expressed by them in adult life.

Animals↗