969 resultados para Display Remarkable Potency


Relevância:

20.00% 20.00%

Publicador:

Resumo:

In recent years, many experimental and theoretical research groups worldwide have actively worked on demonstrating the use of liquid crystals (LCs) as adaptive lenses for image generation, waveform shaping, and non-mechanical focusing applications. In particular, important achievements have concerned the development of alternative solutions for 3D vision. This work focuses on the design and evaluation of the electro-optic response of a LC-based 2D/3D autostereoscopic display prototype. A strategy for achieving 2D/3D vision has been implemented with a cylindrical LC lens array placed in front of a display; this array acts as a lenticular sheet with a tunable focal length by electrically controlling the birefringence. The performance of the 2D/3D device was evaluated in terms of the angular luminance, image deflection, crosstalk, and 3D contrast within a simulated environment. These measurements were performed with characterization equipment for autostereoscopic 3D displays (angular resolution of 0.03 ).

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Vertical Alignment Nematics (VANs) displays are a form of LCDs in which the liquid crystals naturally align vertically to the glass substrates. In spite of their name, the liquid crystal (LC) director is never exactly vertical, rather it always show a small angle with the normal to the sample plane called tilt that may vary throughout the cell bulk. Its values are ultimately determined by the pretilt, defined as the tilt angle on the surfaces in the absence of voltage.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The three-dimensional wall-bounded open cavity may be considered as a simplified geometry found in industrial applications such as leading gear or slotted flats on the airplane. Understanding the three-dimensional complex flow structure that surrounds this particular geometry is therefore of major industrial interest. At the light of the remarkable former investigations in this kind of flows, enough evidences suggest that the lateral walls have a great influence on the flow features and hence on their instability modes. Nevertheless, even though there is a large body of literature on cavity flows, most of them are based on the assumption that the flow is two-dimensional and spanwise-periodic. The flow over realistic open cavity should be considered. This thesis presents an investigation of three-dimensional wall-bounded open cavity with geometric ratio 6:2:1. To this aim, three-dimensional Direct Numerical Simulation (DNS) and global linear instability have been performed. Linear instability analysis reveals that the onset of the first instability in this open cavity is around Recr 1080. The three-dimensional shear layer mode with a complex structure is shown to be the most unstable mode. I t is noteworthy that the flow pattern of this high-frequency shear layer mode is similar to the observed unstable oscillations in supercritical unstable case. DNS of the cavity flow carried out at different Reynolds number from steady state until a nonlinear saturated state is obtained. The comparison of time histories of kinetic energy presents a clearly dominant energetic mode which shifts between low-frequency and highfrequency oscillation. A complete flow patterns from subcritical cases to supercritical case has been put in evidence. The flow structure at the supercritical case Re=1100 resembles typical wake-shedding instability oscillations with a lateral motion existed in the subcritical cases. Also, This flow pattern is similar to the observations in experiments. In order to validate the linear instability analysis results, the topology of the composite flow fields reconstructed by linear superposition of a three-dimensional base flow and its leading three-dimensional global eigenmodes has been studied. The instantaneous wall streamlines of those composited flows display distinguish influence region of each eigenmode. Attention has been focused on the leading high-frequency shear layer mode; the composite flow fields have been fully recognized with respect to the downstream wave shedding. The three-dimensional shear layer mode is shown to give rise to a typical wake-shedding instability with a lateral motions occurring downstream which is in good agreement with the experiment results. Moreover, the spanwise-periodic, open cavity with the same length to depth ratio has been also studied. The most unstable linear mode is different from the real three-dimensional cavity flow, because of the existence of the side walls. Structure sensitivity of the unstable global mode is analyzed in the flow control context. The adjoint-based sensitivity analysis has been employed to localized the receptivity region, where the flow is more sensible to momentum forcing and mass injection. Because of the non-normality of the linearized Navier-Stokes equations, the direct and adjoint field has a large spatial separation. The strongest sensitivity region is locate in the upstream lip of the three-dimensional cavity. This numerical finding is in agreement with experimental observations. Finally, a prototype of passive flow control strategy is applied.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Uno de los capítulos más interesantes del gótico europeo lo constituyen las bóvedas sexpartitas, sin lugar a dudas una de las bóvedas más singulares jamás creadas dentro de este estilo. Las primeras bóvedas góticas, en cruce de ojivas y de planta cuadrada, limitaban su uso a espacios relativamente pequeños, pero ante la necesidad de cubrir espacios de considerables dimensiones, apareció una nueva bóveda de características muy peculiares; la sexpartita. Esta bóveda en cruce de ojivas está reforzada por el centro con un arco paralelo a los arcos fajones que la divide por la mitad y que fragmenta el arco formero en dos, creando una pareja de ventanales en cada lado. La sencilla superficie en bóveda de arista, en el origen de las bóvedas de crucería, se complica extraordinariamente creando una volumetría de gran complejidad con seis cuarteles de plementería y con seis apoyos de distinto tamaño, cuatros esquineros y dos centrales más pequeños. Las dificultades que implica la construcción de este tipo de bóvedas explican quizás su abandono prematuro y la vuelta a la bóveda de crucería simple, ahora de tramos rectangulares. No obstante, a pesar de su corta existencia, la bóveda sexpartita fue la gran protagonista de los inicios del gótico y con ella se llevaron a cabo importantes abovedamientos, desde Inglaterra hasta Rumanía. La disciplina de la Historia de la Construcción se vio extraordinariamente favorecida por los estudios realizados en el siglo XIX, sin embargo su investigación se abandona durante el siglo XX para ser recuperada recientemente. Viollet-le-Duc, a finales del s. XIX, hace una sucinta explicación de este tipo de bóvedas. También Auguste Choisy, más tarde, dedica unas páginas a la bóveda sexpartita francesa; desde entonces, este tema, ha merecido escasísimas referencias en los estudios posteriores. Esta investigación se enmarca en este contexto y pretende poner de manifiesto los conocimientos geométricos y constructivos que hicieron posible la realización de las bóvedas sexpartitas europeas. Para ello se ha llevado a cabo la investigación de las principales bóvedas en Europa occidental; Francia, España, Inglaterra, Alemania, Suiza e Italia. Su estudio comparativo nos ha permitido poner de manifiesto sus características constructivas comunes y aquellos aspectos propios de cada país, así como algunos de los canales de comunicación que permitieron la expansión de esta arquitectura. Las nuevas tecnologías de medición, el escáner láser, la estación total, la fotogrametría, etc., han supuesto una revolución para la documentación y restauración del Patrimonio y un salto cualitativo formidable para el análisis de las bóvedas góticas, permitiendo estudios de la arquitectura histórica hasta ahora inabordables. Para realizar el análisis de las bóvedas sexpartitas europeas se ha llevado a cabo un levantamiento exhaustivo de las mismas, lo que ha permitido definir su despiece, obteniendo la forma de la talla de cada uno de los elementos constructivos que la componen; jarjas, dovelas, claves y plementería. La obtención de estos datos nos ha permitido abordar un profundo estudio de su estereotomía y construcción, aportando datos inéditos hasta el momento. Por otro lado se ha llevado a cabo la detección y catalogación de las principales bóvedas sexpartitas que aún se conservan en Europa. Los estudios realizados nos permiten afirmar que la bóveda sexpartita surge en Francia en la segunda mitad del siglo XII, utilizándose en las principales catedrales francesas, como Notre Dame de Paris, Bourges o Laon. A comienzos del siglo XIII cae en desuso en Francia y comienza su expansión por el resto de Europa, donde se abandona medio siglo después, desapareciendo definitivamente del gótico europeo. Mientras que los ejemplos que datan del siglo XII muestran soluciones escasamente desarrolladas y propias del románico, las bóvedas construidas en el siglo XIII muestran soluciones enormemente complejas, con grandes jarjamentos e inteligentes estrategias constructivas y geométricas que permiten la simplificación de sus estructuras auxiliares y una mayor libertad en su diseño. Estas bóvedas son el reflejo del desarrollo de la estereotomía gótica en sus comienzos por lo que su estudio nos ha permitido conocer el desarrollo y la evolución del gótico primitivo en Europa. ABSTRACT One of the most interesting chapters of European Gothic is the sexpartite vault, without doubt one of the most remarkable vaults ever created within this style. The first Gothic vaults, with crossed ribs on a square base, were restricted to relatively small areas, but a new vault, with very particular characteristics emerged to address the need to cover spaces of considerable size; the sexpartite vault. This cross-ribbed vault is reinforced in the centre by an arch that runs parallel to the transverse arches, divides the vault in half and splits the wall arch in two, creating a pair of windows, one on each side. The simple groin vault surface, the source of ribbed vaults, was greatly complicated creating a highly complex volume with six sections of severies and with six supports of different sizes, four on the corners and two smaller central ones. The construction difficulties involved in building this type of vault may explain its premature abandonment and a return to the simple cross-ribbed vault, now in rectangular sections. However, despite its brief existence, the sexpartite vault was the great protagonist of the beginnings of Gothic architecture and important vaulting was built using this system from England to Romania. Studies undertaken in the 19th century helped the History of Construction as a discipline tremendously. Research was abandoned during the twentieth century however, and has only recently been taken up again. Towards the end of the 19th century, Viollet-le-Duc gave a brief description of this type of vault. Later, Auguste de Choisy also devoted some pages to the French sexpartite vault; since then, later studies have made very few references to it. Against this background, this research now attempts to bring to light the knowledge of geometry and construction that made the construction of the European sexpartite vault possible. To this end, the main vaults in Western Europe - France, Spain, England, Germany, Switzerland and Italy, have been studied. By making a comparative study we have been able to reveal the common construction features and those that are specific to each country, as well as some of the channels of communication that enabled this architecture to spread. New measuring technologies, the laser scanner, total station, photogrammetry, etc., have given rise to a revolution in heritage documentation and restoration, as well as facilitating a huge qualitative leap for the analysis of Gothic vaults, enabling studies of historical architecture that until now were inaccessible. A comprehensive survey was carried out to be able to analyse European sexpartite vaults. We could thus create an exploded view, which enabled us to obtain the form of each of the elements; tas-de-charges, voussoirs, keystones and severies. The data gathered provided previously unknown facts that enabled us to make an in-depth study of stereotomy and construction. Furthermore, the main sexpartite vaults still preserved in Europe have been identified and categorised. The studies undertaken allowed us to affirm that the sexpartite vault appeared in France in the second half of the twelfth century, being used in the main French cathedrals, such as Notre Dame de Paris, Bourges or Laon. At the beginning of the thirteenth century it fell into disuse in France and began to expand throughout the rest of Europe, where it was abandoned half a century later, disappearing from European Gothic for good. While the examples dating back to the 12th century display poorly developed solutions more characteristic of the Romanesque, the vaults built in the 13th century reveal enormously complex solutions, with large tas-de-charges and intelligent construction and geometric strategies that allowed auxiliary support structures to be simplified, and gave more freedom to design. These vaults reflect the beginnings of Gothic stereotomy and by studying them we have been able to learn more about the development and evolution of Early Gothic architecture in Europe.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Tree nut allergies are considered an important health issue in developed countries. To comply with the regulations on food labeling, reliable allergen detection methods are required. In this work we isolated almond-specific recombinant antibody fragments (scFv) from a commercial phage display library bypassing the use of live animals, hence being consistent with the latest policies on animal welfare. To this end an iterative selection procedure employing the Tomlinson I phage display library and a crude almond protein extract was carried out. Two different almond-specific scFv (named PD1F6 and PD2C9) were isolated after two rounds of biopanning, and an indirect phage ELISA was implemented to detect the presence of almond protein in foodstuffs. The isolated scFvs demonstrated to be highly specific and allowed detection of 40 ng mL?1 and 100 ng mL?1 of raw and roasted almond protein, respectively. The practical detection limit of the assay in almond spiked food products was 0.1 mg g?1 (110e120 ppm). The developed indirect phage ELISA was validated by analysis of 92 commercial food products, showing good correlation with the results obtained by a previously developed real-time PCR method for the detection of almond in foodstuffs. The selected phage clones can be affinity maturated to improve their sensitivity and genetically engineered to be employed in different assay formats.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Molecular and biochemical mechanisms that modulate the production of eumelanin or pheomelanin pigments involve the opposing effects of two intercellular signaling molecules, α-melanocyte stimulating hormone (MSH) and agouti signal protein (ASP). ASP is an antagonist of MSH signaling through the melanocyte-specific MSH receptor, although its mechanism(s) of action is controversial. We previously have reported significant down-regulation of all known melanogenic genes during the eumelanin to pheomelanin switch in murine hair follicle melanocytes and in cultured melanocytes treated with recombinant ASP. To identify factors that might be involved in the switch to pheomelanogenesis, we screened ASP-treated melanocytes by using differential display and identified three up-regulated genes: a DNA replication control protein, a basic helix–loop–helix transcription factor, and a novel gene. We have simultaneously identified six down-regulated genes in ASP-treated melanocytes; two of those encode tyrosinase and TRP2, melanogenic genes known to be down-regulated during pheomelanogenesis, which provide good internal controls for this approach. These results suggest that there are complex mechanisms involved in the switch to pheomelanin production, and that these modulated genes might be involved in the pleiotropic changes seen in yellow mice, including the change in coat color.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Interleukin 3-dependent murine 32D cells do not detectably express members of the ErbB receptor family and do not proliferate in response to known ligands for these receptors. 32D transfectants were generated expressing human ErbB4 alone (32D.E4) or with ErbB2 (32D.E2/E4). Epidermal growth factor (EGF), neuregulin 1-β (NRG1-β), betacellulin (BTC), transforming growth factor-α (TGF-α), heparin binding-EGF (HB-EGF), and amphiregulin were analyzed for their ability to mediate mitogenesis in these transfectants. 32D.E4 responded mitogenically to NRG1-β and BTC. Surprisingly, EGF also induced significant DNA synthesis and TGF-α was negligibly mitogenic on 32D.E4 cells, whereas HB-EGF and amphiregulin were inactive. Although coexpression of ErbB2 with ErbB4 in 32D.E2/E4 cells did not significantly alter DNA synthesis in response to NRG1-β or BTC, it greatly enhanced mitogenesis elicited by EGF and TGF-α and unmasked the ability of HB-EGF to induce proliferation. EGF-related ligands that exhibited potent mitogenic activity on 32D.E2/E4 cells at low concentrations induced adherence, morphological alterations, and up-regulation of the Mac-1 integrin and FcγRII/III at higher concentrations. While 125I-EGF could be specifically crosslinked to both 32D.E4 and 32D.E2/E4 cells, its crosslinking capacity was greatly enhanced in the cotransfected cells. The ability of the various ligands to mediate proliferation and/or adhesion in the two transfectants correlated with their capacity to induce substrate tyrosine phosphorylation and to initiate and sustain activation of mitogen-activated protein kinase. We conclude that the ability of ErbB4 to mediate signal transduction through EGF-like ligands is broader than previously assumed and can be profoundly altered by the concomitant expression of ErbB2.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

A systematic screen termed the allelic message display (AMD) was developed for the hunting of imprinted genes. In AMD, differential display PCR is adopted to image allelic expression status of multiple polymorphic transcripts in two parental mouse strains, reciprocal F1 hybrids and pooled backcross progenies. From the displayed patterns, paternally and maternally expressed transcripts can be unequivocally identified. The effectiveness of AMD screening was clearly demonstrated by the identification of a paternally expressed gene Impact on mouse chromosome 18, the predicted product of which belongs to the YCR59c/yigZ hypothetical protein family composed of yeast and bacterial proteins with currently unknown function. In contrast with previous screening methods necessitating positional cloning efforts or generation of parthenogenetic embryos, this approach requires nothing particular but appropriately crossed mice and can be readily applied to any tissues at various developmental stages. Hence, AMD would considerably accelerate the identification of imprinted genes playing pivotal roles in mammalian development and the pathogenesis of various diseases.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The brain vesicular monoamine transporter (VMAT2) pumps monoamine neurotransmitters and Parkinsonism-inducing dopamine neurotoxins such as 1-methyl-4-phenyl-phenypyridinium (MPP+) from neuronal cytoplasm into synaptic vesicles, from which amphetamines cause their release. Amphetamines and MPP+ each also act at nonvesicular sites, providing current uncertainties about the contributions of vesicular actions to their in vivo effects. To assess vesicular contributions to amphetamine-induced locomotion, amphetamine-induced reward, and sequestration and resistance to dopaminergic neurotoxins, we have constructed transgenic VMAT2 knockout mice. Heterozygous VMAT2 knockouts are viable into adult life and display VMAT2 levels one-half that of wild-type values, accompanied by smaller changes in monoaminergic markers, heart rate, and blood pressure. Weight gain, fertility, habituation, passive avoidance, and locomotor activities are similar to wild-type littermates. In these heterozygotes, amphetamine produces enhanced locomotion but diminished behavioral reward, as measured by conditioned place preference. Administration of the MPP+ precursor N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to heterozygotes produces more than twice the dopamine cell losses found in wild-type mice. These mice provide novel information about the contributions of synaptic vesicular actions of monoaminergic drugs and neurotoxins and suggest that intact synaptic vesicle function may contribute more to amphetamine-conditioned reward than to amphetamine-induced locomotion.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Catalytic antibodies have shown great promise for catalyzing a tremendously diverse set of natural and unnatural chemical transformations. However, few catalytic antibodies have efficiencies that approach those of natural enzymes. In principle, random mutagenesis procedures such as phage display could be used to improve the catalytic activities of existing antibodies; however, these studies have been hampered by difficulties in the recombinant expression of antibodies. Here, we have grafted the antigen binding loops from a murine-derived catalytic antibody, 17E8, onto a human antibody framework in an effort to overcome difficulties associated with recombinant expression and phage display of this antibody. “Humanized” 17E8 retained similar catalytic and hapten binding properties as the murine antibody while levels of functional Fab displayed on phage were 200-fold higher than for a murine variable region/human constant region chimeric Fab. This construct was used to prepare combinatorial libraries. Affinity panning of these resulted in the selection of variants with 2- to 8-fold improvements in binding affinity for a phosphonate transition-state analog. Surprisingly, none of the affinity-matured variants was more catalytically active than the parent antibody and some were significantly less active. By contrast, a weaker binding variant was identified with 2-fold greater catalytic activity and incorporation of a single substitution (Tyr-100aH → Asn) from this variant into the parent antibody led to a 5-fold increase in catalytic efficiency. Thus, phage display methods can be readily used to optimize binding of catalytic antibodies to transition-state analogs, and when used in conjunction with limited screening for catalysis can identify variants with higher catalytic efficiencies.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

ETS transcription factors play important roles in hematopoiesis, angiogenesis, and organogenesis during murine development. The ETS genes also have a role in neoplasia, for example in Ewing’s sarcomas and retrovirally induced cancers. The ETS genes encode transcription factors that bind to specific DNA sequences and activate transcription of various cellular and viral genes. To isolate novel ETS target genes, we used two approaches. In the first approach, we isolated genes by the RNA differential display technique. Previously, we have shown that the overexpression of ETS1 and ETS2 genes effects transformation of NIH 3T3 cells and specific transformants produce high levels of the ETS proteins. To isolate ETS1 and ETS2 responsive genes in these transformed cells, we prepared RNA from ETS1, ETS2 transformants, and normal NIH 3T3 cell lines and converted it into cDNA. This cDNA was amplified by PCR and displayed on sequencing gels. The differentially displayed bands were subcloned into plasmid vectors. By Northern blot analysis, several clones showed differential patterns of mRNA expression in the NIH 3T3-, ETS1-, and ETS2-expressing cell lines. Sixteen clones were analyzed by DNA sequence analysis, and 13 of them appeared to be unique because their DNA sequences did not match with any of the known genes present in the gene bank. Three known genes were found to be identical to the CArG box binding factor, phospholipase A2-activating protein, and early growth response 1 (Egr1) genes. In the second approach, to isolate ETS target promoters directly, we performed ETS1 binding with MboI-cleaved genomic DNA in the presence of a specific mAb followed by whole genome PCR. The immune complex-bound ETS binding sites containing DNA fragments were amplified and subcloned into pBluescript and subjected to DNA sequence and computer analysis. We found that, of a large number of clones isolated, 43 represented unique sequences not previously identified. Three clones turned out to contain regulatory sequences derived from human serglycin, preproapolipoprotein C II, and Egr1 genes. The ETS binding sites derived from these three regulatory sequences showed specific binding with recombinant ETS proteins. Of interest, Egr1 was identified by both of these techniques, suggesting strongly that it is indeed an ETS target gene.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Molting or ecdysis is the most fundamentally important process in arthropod life history, because shedding of the exoskeleton is an absolute prerequisite for growth and metamorphosis. Although the hormonal mechanisms driving ecdysis in insects have been studied extensively, nothing is known about these processes in crustaceans. During late premolt and during ecdysis in the crab Carcinus maenas, we observed a precise and reproducible surge in hemolymph hyperglycemic hormone (CHH) levels, which was over 100-fold greater than levels seen in intermolt animals. The source of this hormone surge was not from the eyestalk neurosecretory tissues but from previously undescribed endocrine cells (paraneurons), in defined areas of the foregut and hindgut. During premolt (the only time when CHH is expressed by these tissues), the gut is the largest endocrine tissue in the crab. The CHH surge, which is a result of an unusual, almost complete discharge of the contents of the gut endocrine cell, regulates water and ion uptake during molting, thus allowing the swelling necessary for successful ecdysis and the subsequent increase in size during postmolt. This study defines an endocrine brain/gut axis in the arthropods. We propose that the ionoregulatory process controlled by CHH may be common to arthropods, in that, for insects, a similar mechanism seems to be involved in antidiuresis. It also seems likely that a cascade of very precisely coordinated release of (neuro) hormones controls ecdysis.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Efforts to increase the potency of transcriptional activators are generally unsuccessful because poor expression of activators in mammalian cells limits their delivery to target promoters. Here we report that the effectiveness of chimeric activators can be dramatically improved by expressing them as noncovalent tetrameric bundles. Bundled activation domains are much more effective at activating a reporter gene than simple monomeric activators, presumably because, at similar expression levels, up to 4 times as many the activation domains are delivered to the target promoter. These bundled activation domains are also more effective than proteins in which activation domains are tandemly reiterated in the same polypeptide chain, because such proteins are very poorly expressed and therefore not delivered effectively. These observations suggest that there is a threshold number of activation domains that must be bound to a promoter for activation, above which promoter activity is simply a function of the number of activators bound. We show that bundling can be exploited practically to enhance the sensitivity of mammalian two-hybrid assays, enabling detection of weak interactions or those between poorly expressed proteins. Bundling also dramatically improves the performance of a small-molecule-regulated gene expression system when the expression level of regulatory protein is limiting, a situation that may be encountered in gene therapy applications.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Activation of gene transcription in eukaryotes requires the cooperative assembly of an initiation complex containing many protein subunits. The necessity that these components contact each other and the promoter/enhancer in defined ways suggests that their spatial arrangement might influence the activation response. Indeed, growing evidence indicates that DNA architecture can profoundly affect transcriptional potency. Much less is known about the influence of protein architecture on transcriptional activation. Here, we examine the architectural dependence of activator function through the analysis of matched pairs of AP-1•DNA complexes differing only in their orientation. Mutation of a critical Arg residue in the basic-leucine zipper domain of either Fos or Jun yielded single point-mutant heterodimers that bind DNA in a single defined orientation, as determined directly by native chemical ligation/affinity cleavage; by contrast, the corresponding wild-type protein binds DNA as a roughly equal mixture of two isomeric orientations, which are related by subunit interchange. The stereochemistry of the point-mutant heterodimers could be switched by inversion of a C•G base pair in the center of the AP-1 site, thus providing access to both fixed orientational isomers. Yeast reporter gene assays consistently revealed that one orientational isomer activates transcription at least 10-fold more strongly than the other. These results suggest that protein architecture, especially the spatial relationship of the activation domain to the promoter, can exert a powerful influence on activator potency.