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Architectural self-construction in nature and chemical synthesis.

The chemistry of squalene oxide (1) exemplifies that architectural complexity can be encoded in the structures of relatively simple, polyunsaturated molecules. When the concept of architectural self-construction is an integral part of the design of a chemical synthesis, powerful strategies can be uncovered. this article addresses studies which showed that polyunsaturated, 19-membered ring carbocycle contains all of the molecular information that is required to give the stereochemically complex polycyclic architecture of the cytotoxic natural product FR182877.

Chemistry, Pharmaceutical↗

Human skeletal muscle architecture studied in vivo by non-invasive imaging techniques: functional significance and applications.

The internal architecture plays an essential role in determining the functional features of skeletal muscle. Both length-force and force-velocity relationships depend on the spatial arrangement of muscle fibres in skeletal muscle. The degree of muscle pennation determines both the amount of contractile tissue packed along the tendons and fibre length, and is reflected by the force-generating capacity and shortening velocity of the muscle and by the elastic properties of the muscle-tendon complex. Until recently, knowledge on human muscle architecture was based on measurements performed on cadavers, whose muscle fibres were often shrunk by the preserving medium and by age. With the introduction of non-invasive imaging techniques, it has become possible to study muscle architecture in vivo at rest and the changes thereof upon contraction. This paper discusses the applications of these techniques, namely ultrasonography and nuclear magnetic resonance imaging, and their relevance in physiology and biomechanics.

Animals↗

Moral architecture: the influence of the York Retreat on asylum design.

Institutional and architectural history places the asylum alongside the prison and other institutional types whose architectural characteristics emphasized confinement and control. This history obfuscates important differences in how ideas about treatment were represented in the particular design of these institutions; in other words, how the structure of a place became part of its discourse. What becomes obvious in nineteenth-century, asylum architecture is the influence of a small Yorkshire private asylum built by a Quaker, William Tuke, in 1796. The York Retreat, in form, solidified the ideas of 'moral treatment' in design and in turn assumed an exalted character in the design of late nineteenth-century asylums. Every researcher working in the field of the history of insanity acknowledges the importance of this event and its impact on the discourse of insanity for the century to follow. Few however talk about how its unique design was incorporated as part of this discourse.

England↗

Effects of antiepileptic drugs on sleep architecture: a pilot study.

OBJECTIVES: The effects of antiepileptic drugs (AEDs) on sleep architecture are not well understood, especially in patients with localization-related epilepsy, in whom seizures themselves can disrupt sleep. To clarify the effects of AEDs on sleep architecture, we performed a prospective study, looking at sleep architecture in patients with epilepsy admitted for video-EEG monitoring. METHODS: Adult patients with localization-related epilepsy treated with a single AED and admitted between 10/1997 and 04/2001 were included. Control patients on no AEDs were also included. Both groups were withdrawn from other AEDs. Overnight polysomnography was recorded and was scored according to the standard method. Adult patients with localization-related epilepsy on no medication were also recorded and served as controls. Patients with no seizure during the recording and no seizure in the 24 h preceding the recording were analyzed in this paper. Patients with a seizure in the 24 h preceding the recording and patients with a seizure during the recording were analyzed separately. RESULTS: A total of 72 nights were recorded in 39 patients, and patients taking each AED were compared to controls. We did not find any statistically significant effect of carbamazepine (CBZ). Phenytoin (PHT) disrupted sleep by increasing stage 1 sleep (PHT: 13.2+/-7.3%; control: 7.7+/-4.8%; P=0.008), and decreasing slow wave sleep (SWS) (PHT: 7.9+/-4.2%; control: 11.3+/-4.4%; P=0.03) and REM sleep (PHT: 13.9+/-6.2; control: 18.8+/-5.1; P=0.01). Valproic acid (VPA) disrupted sleep by increasing stage 1 sleep (VPA: 16.8+/-9.8%; control: 7.7+/-4.8%; P=0.007). Gabapentin (GBP) improved sleep by increasing SWS (GBP: 19.4+/-4.2%; control: 11.3+/-4.4%; P=0.0009). PHT and VPA disrupt sleep in the absence of seizures, while CBZ and lamotrigine have no significant effects. GBP improves sleep by increasing SWS. CONCLUSIONS: AEDs have differing effects on sleep structure, which can be beneficial or detrimental. Consideration of these potential effects is important in maintaining optimal sleep in patients with epilepsy.

Adult↗

Novel zoom endoscopy technique for visualizing the microvascular architecture in gastric mucosa.

We have developed and established a zoom endoscopy technique based on visualization of the mucosal microvascular architecture in units as small as the capillary in the normal stomach and early gastric cancer. With regard to the microvascular architecture of the normal stomach, the findings differed according to the section of the stomach. The gastric body showed a honeycomb-like subepithelial capillary network pattern with collecting venule, whereas the gastric antrum showed a coil-shaped subepithelial capillary network pattern. Regarding early gastric cancer, the following findings seemed to be specific for differentiated carcinoma: (1) a demarcation line between the cancerous and the noncancerous mucosa, (2) the disappearance of the regular subepithelial capillary network pattern, and (3) the presence of an irregular microvascular pattern. These findings, which were visualized by magnified observation, could be useful in clinical practice when we attempt to make a correct endoscopic diagnosis of flat reddened lesions (gastritis vs cancer) and when we attempt to determine the precise horizontal margin of early gastric cancer. This could help us to perform successful endoscopic resection based on endoscopic findings alone. In conclusion, our zoom endoscopy for visualizing the microvascular architecture in gastric mucosa could be a new system for diagnosing early gastric cancer.

Diagnosis, Differential↗

Treatment with human parathyroid hormone (1-34) for 18 months increases cancellous bone volume and improves trabecular architecture in ovariectomized cynomolgus monkeys (Macaca fascicularis).

A key feature of postmenopausal osteoporosis is the loss of trabecular bone mass and connectivity. The current study focuses on these parameters in the assessment of long-term (12 and 18 months) parathyroid hormone (PTH) therapy and its withdrawal (6 months) in the ovariectomized cynomolgus monkey (Macaca fascicularis), a well-characterized model for bone changes associated with postmenopausal osteoporosis. We used static and dynamic histomorphometric parameters to assess the amount and architecture of cancellous bone in four clinically important sites for osteoporotic fractures, including the lumbar vertebra, femoral neck, distal radius, and iliac crest. Recombinant human PTH(1-34) was administered daily to two groups for 18 months at 1.0 microg/kg per day (n = 19) and 5.0 microg/kg per day (n = 21). To study the effects of PTH withdrawal, two groups were administered PTH(1-34) daily for 12 months at 1.0 microg/kg per day (n = 20) and 5.0 microg/kg per day (n = 20), followed by daily administration of vehicle for 6 months. Sham-ovariectomized and ovariectomized (ovx) groups each received daily injections of vehicle for 18 months. Treatment with PTH had minimal effects on bone formation rates at the timepoints studied, but markedly increased cancellous bone volume relative to ovx monkeys in iliac crest biopsies at 6 and 15 months, as well as in terminal specimens of lumbar vertebrae, femoral neck, and distal radius after 18 months. At all sites, PTH significantly improved trabecular architecture, as evidenced by increased trabecular number (Tb.N) and decreased trabecular separation (Tb.Sp), with no significant change in trabecular thickness (Tb.Th). The mechanism of these structural changes is suggested by qualitative observations of trabecular tunneling observed in the iliac crest and vertebra. Longitudinal tunneling of thickened individual trabeculae is hypothesized to convert them into multiple trabeculae, resulting in a normalization of Tb.Th, but an increase in Tb.N. A significant positive effect on cancellous bone volume was still apparent after a 3-6 month withdrawal period following 12 months of PTH treatment in the iliac crest, vertebra, and femoral neck. Corresponding increases in Tb.N and decreases in Tb.Sp also remained significant after PTH withdrawal at these three sites. The distal radius was relatively insensitive to PTH treatment or its withdrawal, compared with the other bones. In summary, PTH therapy dramatically improved cancellous bone mass and architecture in both axial and appendicular sites.

Absorptiometry, Photon↗

Deliberate design of ligand architecture yields dramatic enhancement of metal ion affinity.

Evaluation of the malonamide substructure with respect to binding site preorganization and complementarity for lanthanide metal ions suggests a new ligand architecture specifically designed to enhance lanthanide ion affinity. Consideration of conformational reorganization, restricted bond rotation, and donor group orientation suggests that typical malonamide structures, for example, N,N,N'N'-tetrahexylpropane-1,3-diamide (1), N,N'-dibutyl-N,N'-dimethyl-2-tetradecylpropane-1,3-diamide (2), or N,N,N'N'-tetramethylpropane-1,3-diamide (6), are poorly organized for metal ion complexation. Molecular mechanics analyses show that the unfavorable enthalpic and entropic terms are eliminated by the use of the novel bicyclic architecture found in 3,9-diaza-3,9-dimethylbicyclo[4.4.0]decane-2,10-dione (7). Diamide 7 was prepared, and the X-ray crystal structure of the complex [Eu(7)(2)(NO(3))(3)] exhibits the same chelate conformation predicted by the molecular mechanics model. A hydrophobic derivative, 3,9-diaza-3,9-dioctylbicyclo[4.4.0]decane-2,10-dione (8), was prepared, and solvent extraction studies reveal that the preorganized architecture of 8 gives a dramatic enhancement in binding affinity, exhibiting Eu(3+) distribution coefficients that are 7 orders of magnitude larger than a typical malonamide ligand, 1.

Journal Article↗

Structural characterization of modular supramolecular architectures in solution.

Structures of modular supramolecular architectures consisting of a hexameric, diphenylethyne-linked porphyrin macrocyclic array and the corresponding host-guest complex formed by inclusion of a tripyridyl guest molecule were characterized in solution using high-angle X-ray scattering. Scattering measurements made to 6 A resolution coupled with pair distance function (PDF) analyses demonstrated that (1) the porphyrin architectures are not rigid but are distributed across a conformational ensemble with a mean diameter that is 1.5 A shorter than the diameter of a symmetric, energy-minimized model structure, (2) the conformational envelope has limits of 3 A positional dispersion and full rotational freedom for all six porphyrin groups, and (3) insertion of the tripyridyl guest molecule expands the diameter of the host conformer by 0.6 A and decreases the configurational dispersion by approximately 2-fold. These results validate the molecular design, provide a new measure of conformational ensembles in solution that cannot be obtained by other techniques, and establish a structural basis for understanding the photophysical and guest-hosting functions of the hexameric porphyrin architectures in liquids.

Journal Article↗

Room temperature fabrication of hollow ZnS and ZnO architectures by a sacrificial template route.

Hollow ZnS and ZnO architectures are fabricated by employing Zn(5)(CO(3))(2)(OH)(6) microspheres as the sacrificial template. Zn(5)(CO(3))(2)(OH)(6) microspheres can be effectively converted into the core/shell structured ZnO/ZnS composites (in the Na(2)S solution) and hollow ZnO architectures (in the KOH solution), by a spontaneous ion replacement reaction at room temperature. Removing the core by the KOH treatment of core/shell structured ZnO/ZnS, hollow ZnS spheres with different shell thicknesses can be effectively achieved. The obtained hollow ZnO architectures exhibit unique geometrical shapes, and their walls are composed of nanocrystals, which are connected to each other to form their hemispherical or circular shape. A possible formation process from Zn(5)(CO(3))(2)(OH)(6) microspheres to core/shell structured ZnO/ZnS composites is proposed by arresting a series of intermediate morphologies.

Journal Article↗

Characterization of architecture signals in proteins.

A quantitative, property-based approach to protein sequence analysis is presented, grounded in Fourier analysis and signal-processing methodologies. The resulting tools are applied to four protein structure families. We demonstrate the existence of architecture-specific, large amplitude periodicities in amino acid properties encoded in the sequences of proteins. These signals, whose statistical significance we establish, occur at well-defined wavenumbers, but are expressed in different physical properties in the various proteins which fold to a common architecture. This result explains the long-known convergence of unrelated sequences to a common fold. It is further suggested that these results provide a physical basis for the experimental observation that unrelated sequences that adopt similar architectures fold with similar rates.

Amino Acid Sequence↗

Metastable gamma-MnS hierarchical architectures: synthesis, characterization, and growth mechanism.

Preparation of shape-controlled metastable gamma-MnS semiconductor nanocrystals has been achieved on a large scale through a simple solvothermal method in the presence of PVP. The key strategy is the use of sulfur powder as sulfur source in ethylene glycol (EG) solvent that also acted as a weak reducing agent. Reaction parameters such as reaction time and temperature are found to be important in controlling various hierarchical architectures, such as homogeneous semi-hollow core-shell, hollow nanospheres, and nanowires. Transmission electron microscopy observations indicate that these hierarchical architectures are formed mainly via Ostwald ripening. The optical absorption measurements reveal that these novel architectures exhibit remarkable shift of absorption peak during the course of structural compaction and grain growth.

Journal Article↗

The dramatic effect of architecture on the self-assembly of block copolymers at interfaces.

Dramatic morphological changes are observed in the Langmuir-Blodgett (LB) film assemblies of poly(ethylene glycol)-b-(styrene-r-benzocyclobutene) block copolymer (PEG-b-(S-r-BCB)) after intramolecular cross-linking of the S-r-BCB block to form a linear-nanoparticle structure. To isolate architectural effects and allow direct comparison, the linear block copolymer precursor and the linear-nanoparticle block copolymer resulting from selective intramolecular cross-linking of the BCB units were designed to have exactly the same molecular weight and chemical composition but different architecture. It was found that the effect of architecture is pronounced with these macromolecular isomers, which self-assemble into dramatically different surface aggregates. The linear block copolymer forms disklike surface assemblies over the range of compression states, while the linear-nanoparticle block copolymer exhibits long (>10 microm) wormlike aggregates whose length increases as a function of increasing cross-linking density. It is shown that the driving force behind the morphological change is a combination of the altered molecular geometry and the restricted degree of stretching of the nanoparticle block because of the intramolecular cross-linking. A modified approach to interpret the pi-A isotherm, which includes presence of the block copolymer aggregates, is also presented, while the surface rheological properties of the block copolymers at the air-water interface provide in-situ evidence of the aggregates' presence at the air-water interface.

Journal Article↗

Synthesis and characterization of variable-architecture thermosensitive polymers for complexation with DNA.

Copolymers of N-isopropylacrylamide with a fluorescent probe monomer were grafted to branched poly(ethyleneimine) to generate polycations that exhibited lower critical solution temperature (LCST) behavior. The structures of these polymers were confirmed by spectroscopy, and their phase transitions before and after complexation with DNA were followed using ultraviolet and fluorescence spectroscopy and light scattering. Interactions with DNA were investigated by ethidium bromide displacement assays, while temperature-induced changes in structure of both polymers and polymer-DNA complexes were evaluated by fluorescence spectroscopy, dynamic light scattering, laser Doppler anemometry, and atomic force microscopy (AFM) in water and buffer solutions. The results showed that changes in polymer architecture were mirrored by variations in the architectures of the complexes and that the overall effect of the temperature-mediated changes was dependent on the graft polymer architecture and content, as well as the solvent medium, concentrations, and stoichiometries of the complexes. Furthermore, AFM indicated subtle changes in polymer-DNA complexes at the microstructural level that could not be detected by light scattering techniques. Uniquely, variable-temperature aqueous-phase AFM was able to show that changes in the structures of these complexes were not uniform across a population of polymer-DNA condensates, with isolated complexes compacting above LCST even though the sample as a whole showed a tendency for aggregation of complexes above LCST over time. These results indicate that sample heterogeneities can be accentuated in responsive polymer--DNA complexes through LCST-mediated changes--a factor that is likely to be important in cellular uptake and nucleic acid transport.

Acrylamides↗

Biological evaluation of polyester dendrimer: poly(ethylene oxide) "bow-tie" hybrids with tunable molecular weight and architecture.

High molecular weight (MW) polymers have shown promise in terms of improving the properties and the efficacy of low MW therapeutics. However, new systems that are highly biocompatible, are biodegradable, have well-defined MW, and have multiple functional groups for drug attachment are still needed. The biological evaluation of a library of eight polyester dendrimer-poly(ethylene oxide) (PEO) bow-tie hybrids is described here. The group of evaluated polymers was designed to include a range of MWs (from 20000 to 160000) and architectures with the number of PEO arms ranging from two to eight. In vitro experiments revealed that the polymers were nontoxic to cells and were degraded to lower MW species at pH 7.4 and pH 5.0. Biodistribution studies with (125)I-radiolabeled polymers showed that the high MW carriers (>40000) exhibited long circulation half-lives. Comparison of the renal clearances for the four-arm versus eight-arm polymers indicated that the more branched polymers were excreted more slowly into the urine, a result attributed to their decreased flexibility. Due to their essentially linear architecture that does not provide for good isolation of the iodinated phenolic moieties, the polymers with "two arms" were rapidly taken up by the liver. The biodistributions of two long-circulating high MW polymers in mice bearing subcutaneous B16F10 tumors were evaluated, and high levels of tumor accumulation were observed. These new carriers are therefore promising for applications in drug delivery and are also useful for improving our understanding of the effect of polymer architecture on pharmacokinetic properties.

Animals↗

A role for SSeCKS, a major protein kinase C substrate with tumour suppressor activity, in cytoskeletal architecture, formation of migratory processes, and cell migration during embryogenesis.

SSeCKS is a major protein kinase C substrate which has tumour suppressor activity in models of src- and ras-induced oncogenic transformation. The mitogenic regulatory activity of SSeCKS is likely manifested by its ability to bind key signalling proteins such as protein kinases C and A and calmodulin, and to control actin-based cytoskeletal architecture. Rat SSeCKS shares extensive homology with human Gravin, an autoantigen in myasthenia gravis that encodes kinase scaffolding functions and whose expression pattern in fibroblasts and nerves suggests a role in cell motility. Here, we analyse the expression of SSeCKS and Gravin in rodent and human fibroblast and epithelial cell lines using antibodies specific or crossreactive for SSeCKS or Gravin. SSeCKS expression was then analysed in developing mouse embryos and in adult tissues. In the foetal mouse, early SSeCKS protein expression (E10-11) is focused in the loose mesenchyme, luminal surface of the neural tube, notochord, early heart and pericardium, urogenital ridge, and dorsal and ventral sections of limb buds. In later stages (E12-14), SSeCKS is widely expressed in mesenchymal cells but is absent in the spinal ganglia. By E15, SSeCKS expression is ubiquitous, although the staining pattern varies from being striated within smooth muscle sarcomeres to filamentous in mesenchymal and select epithelial cells. In the adult mouse, SSeCKS staining is relatively ubiquitous, with highest expression in the gonads, smooth and cardiac muscle, lung, brain and heart. High expression is also detected in fibroblasts and nerve fibres as well as in more specialized cells such as glomerular mesangial cells and testicular Sertoli cells. SSeCKS expression in the rat testes correlates with the induction of puberty, and in mature mouse spermatozoa, SSeCKS is found in peripheral acrosome membranes and in a helix-like winding pattern within the midsection. Periodic enrichments of SSeCKS are found in sperm midsections and in developing axons, suggesting a role in architectural infrastructure. As with Gravin, high SSeCKS expression is absent in most epithelial cells; however, in contrast to Gravin, SSeCKS is expressed in Purkinje cells, cardiac muscle, macrophages and hepatic stellate cells, indicating overlapping yet distinct patterns of tissue expression in the SSeCKS/Gravin family. The data suggest roles for SSeCKS in the control of cytoskeletal and tissue architecture, formation of migratory processes and cell migration during embryogenesis.

A Kinase Anchor Proteins↗

Acclimation response of spring wheat in a free-air CO(2) enrichment (FACE) atmosphere with variable soil nitrogen regimes. 3. Canopy architecture and gas exchange.

The response of whole-canopy net CO(2) exchange rate (CER) and canopy architecture to CO(2) enrichment and N stress during 1996 and 1997 for open-field-grown wheat ecosystem (Triticum aestivum L. cv. Yecora Rojo) are described. Every Control (C) and FACE (F) CO(2) treatment (defined as ambient and ambient +200 mumol mol(-1), respectively) contained a Low- and High-N treatment. Low-N treatments constituted initial soil content amended with supplemental nitrogen applied at a rate of 70 kg N ha(-1) (1996) and 15 kg N ha(-1) (1997), whereas High-N treatments were supplemented with 350 kg N ha(-1) (1996 and 1997). Elevated CO(2) enhanced season-long carbon accumulation by 8% and 16% under Low-N and High-N, respectively. N-stress reduced season-long carbon accumulation 14% under ambient CO(2), but by as much as 22% under CO(2) enrichment. Averaging both years, green plant area index (GPAI) peaked approximately 76 days after planting at 7.13 for FH, 6.00 for CH, 3.89 for FL, and 3.89 for CL treatments. Leaf tip angle distribution (LTA) indicated that Low-N canopies were more erectophile than those of High-N canopies: 48 degrees for FH, 52 degrees for CH, and 58 degrees for both FL and CL treatments. Temporal trends in canopy greenness indicated a decrease in leaf chlorophyll content from the flag to flag-2 leaves of 25% for FH, 28% for CH, 17% for CL, and 33% for FL during 1997. These results indicate that significant modifications of canopy architecture occurs in response to both CO(2) and N-stress. Optimization of canopy architecture may serve as a mechanism to diminish CO(2) and N-stress effects on CER.

Journal Article↗

Considerations on the astroglial architecture and the columnar organization of the cerebral cortex.

Present knowledge on astroglial roles in brain organization and function indicates that these cells can regulate the extracellular ionic composition and modulate neuronal activity. In this regard, the "panglial synctium" formed by electrically and chemically coupled stellate astrocytes ("general mammalian" architecture) is believed to provide an intracellular pathway for the redistribution of ions and molecules within the cerebral cortex. Long astroglial interlaminar processes ("primate-specific" architecture) that run parallel to apical dendrites in the cerebral cortex of primates, may provide additional properties to the glial participation in cortical physiology and function. Since these processes are exclusively present within the primate order, functional models of cortical computations for these species should incorporate the astroglial interlaminar architecture in addition to the panglial synctium. This study analyzes possible implications of interlaminar astroglial processes, for the regulation of the extracellular ionic composition and segregation of functional columns in the cerebral cortex.

Animals↗

On the incomplete architecture of human ontogeny. Selection, optimization, and compensation as foundation of developmental theory.

Drawing on both evolutionary and ontogenetic perspectives, the basic biological-genetic and social-cultural architecture of human development is outlined. Three principles are involved. First, evolutionary selection pressure predicts a negative age correlation, and therefore, genome-based plasticity and biological potential decrease with age. Second, for growth aspects of human development to extend further into the life span, culture-based resources are required at ever-increasing levels. Third, because of age-related losses in biological plasticity, the efficiency of culture is reduced as life span development unfolds. Joint application of these principles suggests that the life span architecture becomes more and more incomplete with age. Degree of completeness can be defined as the ratio between gains and losses in functioning. Two examples illustrate the implications of the life span architecture proposed. The first is a general theory of development involving the orchestration of 3 component processes: selection, optimization, and compensation. The second considers the task of completing the life course in the sense of achieving a positive balance between gains and losses for all age levels. This goal is increasingly more difficult to attain as human development is extended into advanced old age.

Adolescent↗