986 resultados para vortex core structure
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El principal objetivo de este trabajo es aportar conocimiento para contestar la pregunta: ¿hasta que punto los ensayos en túnel aerodinámico pueden contribuir a determinar las características que afectan la respuesta dinámica de los aerogeneradores operando en terreno complejo?. Esta pregunta no es nueva, de hecho, el debate en la comunidad científica comenzó en el primer tercio del siglo pasado y aún está intensamente vivo. El método generalmente aceptado para enfrentar el mencionado problema consiste en analizar un caso de estudio determinado en el cual se aplican tanto ensayos a escala real como análisis computacionales y ensayos en túnel aerodinámico. Esto no es ni fácil ni barato. Esta es la razón por la cual desde el experimento de Askervein en 1988, los modelizadores del flujo atmosférico tuvieron que esperar hasta 2007 a que el experimento de Bolund fuese puesto en marcha con un despliegue de medios técnicos equivalentes (teniendo en cuenta la evolución de las tecnologías de sensores y computación). El problema contempla tantos aspectos que ambas experiencias fueron restringidas a condiciones de atmósfera neutra con efectos de Coriolis despreciables con objeto de reducir la complejidad. Este es el contexto en el que se ha desarrollado la presente tesis doctoral. La topología del flujo sobre la isla de Bolund ha sido estudiada mediante la reproducción del experimento de Bolund en los túneles aerodinámicos A9 y ACLA16 del IDR. Dos modelos de la isla de Bolund fueron fabricados a dos escalas, 1:230 y 1:115. El flujo de entrada en el túnel aerodinámico simulando la capa límite sin perturbar correspondía a régimen de transición (transitionally rough regime) y fue usado como situación de referencia. El modelo a escala 1:230 fue ensayado en el túnel A9 para determinar la presión sobre su superficie. La distribución del coeficiente de presión sobre la isla proporcionó una visualización y estimación de una región de desprendimiento sobre el pequeño acantilado situado al frente de la misma. Las medidas de presión instantánea con suficiente grado de resolución temporal pusieron de manifiesto la no estacionariedad en la región de desprendimiento. El modelo a escala 1:115 fue ensayado utilizando hilo caliente de tres componentes y un sistema de velocimetría por imágenes de partículas de dos componentes. El flujo fue caracterizado por el ratio de aceleración, el incremento normalizado de energía cinética turbulenta y los ángulos de inclinación y desviación horizontal. Los resultados a lo largo de la dirección 270°y alturas de 2 m y 5 m presentaron una gran similitud con los resultados a escala real del experimento de Bolund. Los perfiles verticales en las localizaciones de las torres meteorológicas mostraron un acuerdo significativo con los resultados a escala real. El análisis de los esfuerzos de Reynolds y el análisis espectral en las localizaciones de los mástiles meteorológicos presentaron niveles de acuerdo variados en ciertas posiciones, mientras que en otras presentaron claras diferencias. El mapeo horizontal del flujo, para una dirección de viento de 270°, permitió caracterizar el comportamiento de la burbuja intermitente de recirculación sobre el pequeño acantilado existente al frente de la isla así como de la región de relajación y de la capa de cortadura en la región corriente abajo de Bolund. Se realizaron medidas de velocidad con alta resolución espacial en planos perpendiculares a la dirección del flujo sin perturbar. Estas medidas permitieron detectar y caracterizar una estructura de flujo similar a un torbellino longitudinal con regiones con altos gradientes de velocidad y alta intensidad de turbulencia. Esta estructura de flujo es, sin duda, un reto para los modelos computacionales y puede considerarse un factor de riesgo para la operación de los aerogeneradores. Se obtuvieron y analizaron distribuciones espaciales de los esfuerzos de Reynolds mediante 3CHW y PIV. Este tipo de parámetros no constituyen parte de los resultados habituales en los ensayos en túnel sobre topografías y son muy útiles para los modelizadores que utilizan simulación de grades torbellinos (LES). Se proporciona una interpretación de los resultados obtenidos en el túnel aerodinámico en términos de utilidad para los diseñadores de parques eólicos. La evolución y variación de los parámetros del flujo a lo largo de líneas, planos y superficies han permitido identificar como estas propiedades del flujo podrían afectar la localización de los aerogeneradores y a la clasificación de emplazamientos. Los resultados presentados sugieren, bajo ciertas condiciones, la robustez de los ensayos en túnel para estudiar la topología sobre terreno complejo y su comparabilidad con otras técnicas de simulación, especialmente considerando el nivel de acuerdo del conjunto de resultados presentados con los resultados a escala real. De forma adicional, algunos de los parámetros del flujo obtenidos de las medidas en túnel son difícilmente determinables en ensayos a escala real o por medios computacionales, considerado el estado del arte. Este trabajo fue realizado como parte de las actividades subvencionadas por la Comisión Europea como dentro del proyecto FP7-PEOPLE-ITN-2008WAUDIT (Wind Resource Assessment Audit and Standardization) dentro de la FP7 Marie-Curie Initial Training Network y por el Ministerio Español de Economía y Competitividad dentro del proyecto ENE2012-36473, TURCO (Determinación en túnel aerodinámico de la distribución espacial de parámetros estadísticos de la turbulencia atmosférica sobre topografías complejas) del Plan Nacional de Investigación (Subprograma de investigación fundamental no orientada 2012). El informe se ha organizado en siete capítulos y un conjunto de anexos. En el primer capítulo se introduce el problema. En el capítulo dos se describen los medios experimentales utilizados. Seguidamente, en el capítulo tres, se analizan en detalle las condiciones de referencia del principal túnel aerodinámico utilizado en esta investigación. En el capítulo tres se presentan resultados de ensayos de presión superficial sobre un modelo de la isla. Los principales resultados del experimento de Bolund se reproducen en el capítulo cinco. En el capítulo seis se identifican diferentes estructuras del flujo sobre la isla y, finalmente, en el capitulo siete, se recogen las conclusiones y una propuesta de lineas de trabajo futuras. ABSTRACT The main objective of this work is to contribute to answer the question: to which extend can the wind tunnel testing contribute to determine the flow characteristics that affect the dynamic response of wind turbines operating in highly complex terrains?. This question is not new, indeed, the debate in the scientific community was opened in the first third of the past century and it is still intensely alive. The accepted approach to face this problem consists in analysing a given case study where full-scale tests, computational modelling and wind tunnel testing are applied to the same topography. This is neither easy nor cheap. This is is the reason why since the Askervein experience in 1988, the atmospheric flow modellers community had to wait till 2007 when the Bolund experiment was setup with a deployment of technical means equivalent (considering the evolution of the sensor and computing techniques). The problem is so manifold that both experiences were restricted to neutral conditions without Coriolis effects in order to reduce the complexity. This is the framework in which this PhD has been carried out. The flow topology over the Bolund Island has been studied by replicating the Bolund experiment in the IDR A9 and ACLA16 wind tunnels. Two mock-ups of the Bolund island were manufactured at two scales of 1:230 and 1:115. The in-flow in the empty wind tunnel simulating the incoming atmospheric boundary layer was in the transitionally rough regime and used as a reference case. The 1:230 model was tested in the A9 wind tunnel to measure surface pressure. The mapping of the pressure coefficient across the island gave a visualisation and estimation of a detachment region on the top of the escarpment in front of the island. Time resolved instantaneous pressure measurements illustrated the non-steadiness in the detachment region. The 1:115 model was tested using 3C hot-wires(HW) and 2C Particle Image Velocimetry(PIV). Measurements at met masts M3, M6, M7 and M8 and along Line 270°were taken to replicate the result of the Bolund experiment. The flow was characterised by the speed-up ratio, normalised increment of the turbulent kinetic energy, inclination angle and turning angle. Results along line 270°at heights of 2 m and 5 m compared very well with the full-scale results of the Bolund experiment. Vertical profiles at the met masts showed a significant agreement with the full-scale results. The analysis of the Reynolds stresses and the spectral analysis at the met mast locations gave a varied level of agreement at some locations while clear mismatch at others. The horizontal mapping of the flow field, for a 270°wind direction, allowed to characterise the behaviour of the intermittent recirculation bubble on top of the front escarpment followed by a relaxation region and the presence of a shear layer in the lee side of the island. Further detailed velocity measurements were taken at cross-flow planes over the island to study the flow structures on the island. A longitudinal vortex-like structure with high mean velocity gradients and high turbulent kinetic energy was characterised on the escarpment and evolving downstream. This flow structure is a challenge to the numerical models while posing a threat to wind farm designers when siting wind turbines. Spatial distribution of Reynold stresses were presented from 3C HW and PIV measurements. These values are not common results from usual wind tunnel measurements and very useful for modellers using large eddy simulation (LES). An interpretation of the wind tunnel results in terms of usefulness to wind farm designers is given. Evolution and variation of the flow parameters along measurement lines, planes and surfaces indicated how the flow field could affect wind turbine siting. Different flow properties were presented so compare the level of agreement to full-scale results and how this affected when characterising the site wind classes. The results presented suggest, under certain conditions, the robustness of the wind tunnel testing for studying flow topology over complex terrain and its capability to compare to other modelling techniques especially from the level of agreement between the different data sets presented. Additionally, some flow parameters obtained from wind tunnel measurements would have been quite difficult to be measured at full-scale or by computational means considering the state of the art. This work was carried out as a part of the activities supported by the EC as part of the FP7- PEOPLE-ITN-2008 WAUDIT project (Wind Resource Assessment Audit and Standardization) within the FP7 Marie-Curie Initial Training Network and by the Spanish Ministerio de Economía y Competitividad, within the framework of the ENE2012-36473, TURCO project (Determination of the Spatial Distribution of Statistic Parameters of Flow Turbulence over Complex Topographies in Wind Tunnel) belonging to the Spanish National Program of Research (Subprograma de investigación fundamental no orientada 2012). The report is organised in seven chapters and a collection of annexes. In chapter one, the problem is introduced. In chapter two the experimental setup is described. Following, in chapter three, the inflow conditions of the main wind tunnel used in this piece of research are analysed in detail. In chapter three, preliminary pressure tests results on a model of the island are presented. The main results from the Bolund experiment are replicated in chapter five. In chapter six, an identification of specific flow strutures over the island is presented and, finally, in chapter seven, conclusions and lines for future works related to the presented one are included.
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En el presente trabajo se ha realizado un estudio sobre el comportamiento dinámico de vórtices magnéticos en su aplicación en osciladores de espín-torque. A partir de los modelos matemáticos elaborados en [4] sobre estos osciladores de espín-torque, se han simulado y estudiado usando MATLAB, entre otras herramientas, para tratar de verificar su concordancia con el comportamiento físico observado en el laboratorio. Es importante señalar que el estudio tiene en cuenta la dinámica no lineal, esencial para describir correctamente un sistema oscilante en la práctica. El análisis matemático del sistema que describe la órbita del núcleo de un vórtice magnético sometido a la acción de un campo magnético externo oscilatorio, muestra la posibilidad de la existencia de hasta tres soluciones especiales, según la geometría del dot y el valor del campo magnético de excitación, tanto de su frecuencia como de su amplitud. Estas soluciones corresponden a estados estacionarios del vórtice caracterizados como una órbita circular, aunque en el caso de existir tres equilibrios uno de ellos es inestable. El modelo matemático ha sido estudiado y analizado para reproducir los resultados obtenidos en [4] y adicionalmente se ha implementado el caso de la energía potencial del vórtice con el término no lineal distinto de [4] (con una constante β negativa). Los resultados obtenidos bajo esta suposición muestran una cierta disparidad respecto al caso de β positiva y reflejan la existencia de comportamientos muy diferentes. En la dinámica del vórtice bajo la suposición de β negativa también surgen bifurcaciones de pliegue (fold-over) en la trayectoria del núcleo del vórtice: siempre se obtienen tres equilibrios a bajas frecuencias y aparecen a veces dos intervalos con tres equilibrios en lugar de uno solo, a diferencia del caso de β positiva. El comportamiento del núcleo del vórtice sigue un proceso de histéresis en ambos casos, cuando se dan ciertas condiciones. ABSTRACT. This work is a study about the dynamic behaviour of magnetic vortex in its application in spin-torque oscillators. Starting from mathematical models developed in [4] on this subject, a further analysis has been performed using MATLAB to simulate the behaviour of vortex-based spin-torque oscillators as different relevant parameters vary. The main aim of the study is to check if the obtained results can explain the observed physical behaviour, and an important observation is that fully nonlinear effects are taken into consideration. The mathematical analysis of the system that describes the orbit of the vortex core under the influence of an external oscillatory magnetic field shows that there are up to three possible special solutions depending on the dot geometry and the magnetic driving field value, both on its amplitude as well as its frequency. These solutions correspond to a stable circular orbit of the vortex core, but when the system has three solutions one of them is unstable. This mathematical model has been analyzed and studied to reproduce the results obtained in [4] and, additionally, the effect of a negative value of the nonlinear part of the vortex potential (constant β). Results derived from this assumption exhibit certain differences with respect to the case of a positive constant (β) and reflect the existence of very different patterns. Vortex dynamics under the supposition of a negative β also yield fold-over bifurcations in the trajectory of the vortex core: there are always three solutions at low frequencies and there may be two different intervals with three solutions as opposed to the case of positive β. The vortex core follows a hysteresis process in both cases, when certain conditions are met.
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Centrosome duplication and separation are of central importance for cell division. Here we provide a detailed account of this dynamic process in Dictyostelium. Centrosome behavior was monitored in living cells using a γ-tubulin–green fluorescent protein construct and correlated with morphological changes at the ultrastructural level. All aspects of the duplication and separation process of this centrosome are unusual when compared with, e.g., vertebrate cells. In interphase the Dictyostelium centrosome is a box-shaped structure comprised of three major layers, surrounded by an amorphous corona from which microtubules emerge. Structural duplication takes place during prophase, as opposed to G1/S in vertebrate cells. The three layers of the box-shaped core structure increase in size. The surrounding corona is lost, an event accompanied by a decrease in signal intensity of γ-tubulin–green fluorescent protein at the centrosome and the breakdown of the interphase microtubule system. At the prophase/prometaphase transition the separation into two mitotic centrosomes takes place via an intriguing lengthwise splitting process where the two outer layers of the prophase centrosome peel away from each other and become the mitotic centrosomes. Spindle microtubules are now nucleated from surfaces that previously were buried inside the interphase centrosome. Finally, at the end of telophase, the mitotic centrosomes fold in such a way that the microtubule-nucleating surface remains on the outside of the organelle. Thus in each cell cycle the centrosome undergoes an apparent inside-out/outside-in reversal of its layered structure.
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Symbiotic bacteria of the genus Rhizobium synthesize lipo-chitooligosaccharides, called Nod factors (NFs), which act as morphogenic signal molecules on legume hosts. The common nodABC genes, present in all Rhizobium species, are required for the synthesis of the core structure of NFs. NodC is an N-acetylglucosaminyltransferase, and NodB is a chitooligosaccharide deacetylase; NodA is involved in N-acylation of the aminosugar backbone. Specific nod genes are involved in diverse NF substitutions that confer plant specificity. We transferred to R. tropici, a broad host-range tropical symbiont, the ability to nodulate alfalfa, by introducing nod genes of R. meliloti. In addition to the specific nodL and nodFE genes, the common nodABC genes of R. meliloti were required for infection and nodulation of alfalfa. Purified NFs of the R. tropici hybrid strain, which contained chitin tetramers and were partly N-acylated with unsaturated C16 fatty acids, were able to elicit nodule formation on alfalfa. Inactivation of the R. meliloti nodABC genes suppressed the ability of the NFs to nodulate alfalfa. Studies of NFs from nodA, nodB, nodC, and nodI mutants indicate that (i) NodA of R. meliloti, in contrast to NodA of R. tropici, is able to transfer unsaturated C16 fatty acids onto the chitin backbone and (ii) NodC of R. meliloti specifies the synthesis of chitin tetramers. These results show that allelic variation of the common nodABC genes is a genetic mechanism that plays an important role in signaling variation and in the control of host range.
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Escherichia coli DnaK acts as a molecular chaperone through its ATP-regulated binding and release of polypeptide substrates. Overexpressing a C-terminal fragment (CTF) of DnaK (Gly-384 to Lys-638) containing the polypeptide substrate binding domain is lethal in wild-type E. coli. This dominant-negative phenotype may result from the nonproductive binding of CTF to cellular polypeptide targets of DnaK. Mutations affecting DnaK substrate binding were identified by selecting noncytotoxic CTF mutants followed by in vitro screening. The clustering of such mutations in the three-dimensional structure of CTF suggests the model that loops L1,2 and L4,5 form a rigid core structure critical for interactions with substrate.
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Although rRNA has a conserved core structure, its size varies by more than 2000 bases between eubacteria and vertebrates, mostly due to the size variation of discrete variable regions. Previous studies have shown that insertion of foreign sequences into some of these variable regions has little effect on rRNA function. These properties make rRNA a potentially very advantageous vehicle to carry other RNA moieties with biological activity, such as "antisense RNAs." We have explored this possibility by inserting antisense RNAs targeted against one essential and two nonessential genes into a site within a variable region in the Tetrahymena thermophila large subunit rRNA gene. Expression of each of the three genes tested can be drastically reduced or eliminated in transformed T. thermophila lines containing these altered rRNAs. In addition, we found that only antisense rRNAs containing RNA sequences complementary to the 5' untranslated region of the targeted mRNA were effective. Lines containing antisense rRNAs targeted against either of the nonessential genes grow well, indicating that the altered rRNAs fulfill their functions within the ribosome. Since functional rRNA is extremely abundant and stable and comes into direct contact with translated mRNAs, it may prove to be an unparalleled vehicle for enhancing the activity of functional RNAs that act on mRNAs.
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The central structural feature of natural proteins is a tightly packed and highly ordered hydrophobic core. If some measure of exquisite, native-like core packing is necessary for enzymatic function, this would constitute a significant obstacle to the development of novel enzymes, either by design or by natural or experimental evolution. To test the minimum requirements for a core to provide sufficient structural integrity for enzymatic activity, we have produced mutants of the ribonuclease barnase in which 12 of the 13 core residues have together been randomly replaced by hydrophobic alternatives. Using a sensitive biological screen, we find that a strikingly high proportion of these mutants (23%) retain enzymatic activity in vivo. Further substitution at the 13th core position shows that a similar proportion of completely random hydrophobic cores supports enzyme function. Of the active mutants produced, several have no wild-type core residues. These results imply that hydrophobicity is nearly a sufficient criterion for the construction of a functional core and, in conjunction with previous studies, that refinement of a crudely functional core entails more stringent sequence constraints than does the initial attainment of crude core function. Since attainment of crude function is the critical initial step in evolutionary innovation, the relatively scant requirements contributed by the hydrophobic core would greatly reduce the initial hurdle on the evolutionary pathway to novel enzymes. Similarly, experimental development of novel functional proteins might be simplified by limiting core design to mere specification of hydrophobicity and using iterative mutation-selection to optimize core structure.
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Human transcription initiation factor TFIID is composed of the TATA-binding polypeptide (TBP) and at least 13 TBP-associated factors (TAFs) that collectively or individually are involved in activator-dependent transcription. To investigate protein-protein interactions involved in TFIID assembly and in TAF-mediated activator functions, we have cloned and expressed cDNAs encoding human TAFII80 and TAFII31. Coimmunoprecipitation assays showed that TAFII80 interacted with TAFII250, TAFII31, TAFII20, and TBP, but not with TAFII55. Similar assays showed that TAFII80 interacted with TFIIE alpha and with TFIIF alpha (RAP74) but not with TFIIB, TFIIE beta, or TFIIF beta (RAP30). Further studies with TAFII80 mutations revealed three distinct interaction domains which fall within regions conserved in human TAFII80, Drosophila TAFII60, and yeast TAFII60. The N terminus of TAFII80 (residues 1-100) interacts with both TAFII31 and TAFII20, while two C-terminal regions are involved, respectively, in interactions with TAFII250 and TFIIF alpha (RAP74) (residues 203-276) and with TBP and TFIIE alpha (residues 377-505). The interactions between TAFII80 and general factors TFIIE alpha and TFIIF alpha (RAP74) could be important for recruitment of GTFs during activator-dependent transcription. Because TAFs 80, 31, and 20 show sequence similarities to histones H4, H3, and H2B, as well as some parallel interactions, this subset of TAFs may form a related core structure within TFIID.
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Mycobacterium tuberculosis, the primary agent of tuberculosis, must acquire iron from the host to cause infection. To do so, it releases high-affinity iron-binding siderophores called exochelins. Exochelins are thought to transfer iron to another type of high-affinity iron-binding molecule in the bacterial cell wall, mycobactins, for subsequent utilization by the bacterium. In this paper, we describe the purification of exochelins of M. tuberculosis and their characterization by mass spectrometry. Exochelins comprise a family of molecules whose most abundant species range in mass from 744 to 800 Da in the neutral Fe(3+)-loaded state. The molecules form two 14-Da-increment series, one saturated and the other unsaturated, with the increments reflecting different numbers of CH2 groups on a side chain. These series further subdivide into serine- or threonine-containing species. The virulent M. tuberculosis Erdman strain and the avirulent M. tuberculosis H37Ra strain produce a similar set of exochelins. Based on a comparison of their tandem mass spectra, exochelins share a common core structure with mycobactins. However, exochelins are smaller than mycobactins due to a shorter alkyl side chain, and the side chain of exochelins terminates in a methyl ester. These differences render exochelins more polar than the lipophilic mycobactins and hence soluble in the aqueous extracellular milieu of the bacterium in which they bind iron in the host.
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Tau filaments are the pathological hallmark of >20 neurodegenerative diseases including Alzheimer's disease, Pick's disease, and progressive supranuclear palsy. In the adult human brain, six isoforms of tau are expressed that differ by presence or absence of the second of the four semiconserved repeats. As a consequence, half of the tau isoforms have three repeats (3R tau), whereas the other half has four repeats (4R tau). Site-directed spin labeling of recombinant tau in conjunction with electron paramagnetic resonance spectroscopy was used to obtain structural insights into tau filaments. The studies showed that the filaments of 4R tau and 3R tau share a highly ordered core structure in the third repeat with parallel, in-register arrangement of beta-strands. This structure in 3R and 4R is conserved regardless of whether full-length isoforms (htau40 and htau23) or truncated constructs (K18 and K19) are used. When mixed, 3R tau and 4R tau coassembled into heterogeneous filaments. Hence, these findings indicate that there are at least three compositionally distinct types of filaments: homogeneous 3R tau, homogeneous 4R tau, and heterogeneous 3R/4R tau. In vitro experiments show that the seeded filament growth, a prerequisite for tau spreading in tissue culture and brain, is crucially dependent on the isoform composition of individual seeds. Seeds of 3R tau and 3R/4R tau recruit both types of isoforms whereas seeds of 4R tau can recruit 4R tau, but not 3R tau, establishing an asymmetric barrier. Conformational templating of 4R tau onto 3R tau seeds eliminates this barrier, giving rise to a new type of tau filament. Conformational studies at the molecular level of tau filaments were done using Double electron-electron resonance spectroscopy, which allows the determination of distances between pairs of spin labels. These studies revealed structural differences between filaments of 3R tau and 4R tau. Furthermore, they indicated that 4R tau assumed the conformation of 3R tau when templated on 3R tau seeds. Our measurements have also provided insights into the heterogeneity of tau filament structure. Conformational differences due to variation in filament composition and seeding properties of tau filaments have shown that they are structurally polymorphic in nature. This structural polymorphism of tau filaments has widespread implications in understanding and treatment of neurodegenerative diseases.
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The core structure of a dislocation complex in SiGe/Si system composed of a perfect 60degrees dislocation and an extended 60 dislocation has been revealed at atomic level. This is attained by applying the image deconvolution technique in combination with dynamical diffraction effect correction to an image taken with a 200 kV field-emission high-resolution electron microscope. The possible configuration of the dislocation complex is analyzed and their Burgers vectors are determined. (C) 2003 Elsevier B.V. All rights reserved.
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A cellulose/xyloglucan framework is considered to form the basis for the mechanical properties of primary plant cell walls and hence to have a major influence on the biomechanical properties of growing, fleshy plant tissues. In this study, structural variants of xyloglucan have been investigated as components of composites with bacterial cellulose as a simplified model for the cellulose/xyloglucan framework of primary plant cell walls. Evidence for molecular binding to cellulose with perturbation of cellulose crystallinity was found for all xyloglucan types. High molecular mass samples gave homogeneous centimeter-scale composites with extensive cross-linking of cellulose with xyloglucan. Lower molecular mass xyloglucans gave heterogeneous composites having a range of microscopic structures with little, if any, cross-linking. Xyloglucans with reduced levels of galactose substitution had evidence of self-association, competitive with cellulose binding. At comparable molecular mass, fucose substitution resulted in a modest promotion of microscopic features characteristic of primary cell walls. Taken together, the data are evidence that galactose substitution of the xyloglucan core structure is a major determinant of cellulose composite formation and properties, with additional fucose substitution acting as a secondary modulator. These conclusions are consistent with reported structural and mechanical properties of Arabidopsis mutants lacking specific facose and/or galactose residues.
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Retrocyclin-1, a 0-defensin, protects target cells from human immunodeficiency virus, type 1 (HIV-1) by preventing viral entry. To delineate its mechanism, we conducted fusion assays between susceptible target cells and effector cells that expressed HIV-1 Env. Retrocyclin-1 (4 mu M) completely blocked fusion mediated by HIV-1 Envs that used CXCR4 or CCR5 but had little effect on cell fusion mediated by HIV-2 and simian immunodeficiency virus Envs. Retrocyclin-1 inhibited HIV-1 Env-mediated fusion without impairing the lateral mobility of CD4, and it inhibited the fusion of CD4-deficient cells with cells bearing CD4-independent HIV-1 Env. Thus, it could act without cross-linking membrane proteins or inhibiting gp120-CD4 interactions. Retrocyclin-1 acted late in the HIV-1 Env fusion cascade but prior to 6-helix bundle formation. Surface plasmon resonance experiments revealed that retrocyclin bound the ectodomain of gp41 with high affinity in a glycan-independent manner and that it bound selectively to the gp41 C-terminal heptad repeat. Native-PAGE, enzyme-linked immunosorbent assay, and CD spectroscopic analyses all revealed that retrocyclin-1 prevented 6-helix bundle formation. This mode of action, although novel for an innate effector molecule, resembles the mechanism of peptidic entry inhibitors based on portions of the gp41 sequence.
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The poor retention and efficacy of instilled drops as a means of delivering drugs to the ophthalmic environment is well-recognised. The potential value of contact lenses as a means of ophthalmic drug delivery, and consequent improvement of pre-corneal retention is one obvious route to the development of a more effective ocular delivery system. Furthermore, the increasing availability and clinical use of daily disposable contact lenses provides the platform for the development of viable single-day use drug delivery devices based on existing materials and lenses. In order to provide a basis for the effective design of such devices, a systematic understanding of the factors affecting the interaction of individual drugs with the lens matrix is required. Because a large number of potential structural variables are involved, it is necessary to achieve some rationalisation of the parameters and physicochemical properties (such as molecular weight, charge, partition coefficients) that influence drug interactions. Ophthalmic dyes and structurally related compounds based on the same core structure were used to investigate these various factors and the way in which they can be used in concert to design effective release systems for structurally different drugs. Initial studies of passive diffusional release form a necessary precursor to the investigation of the features of the ocular environment that over-ride this simple behaviour. Commercially available contact lenses of differing structural classifications were used to study factors affecting the uptake of the surrogate actives and their release under 'passive' conditions. The interaction between active and lens material shows considerable and complex structure dependence, which is not simply related to equilibrium water content. The structure of the polymer matrix itself was found to have the dominant controlling influence on active uptake; hydrophobic interaction with the ophthalmic dye playing a major role. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
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Eyewall replacement cycle (ERC) is frequently observed during the evolution of intensifying Tropical Cyclones (TCs). Although intensely studied in recent years, the underlying mechanisms of ERC are still poorly understood, and the forecast of ERC remains a great challenge. To advance our understanding of ERC and provide insights in improvement of numerical forecast of ERC, a series of numerical simulations is performed to investigate ERCs in TC-like vortices on a f-plane. The simulated ERCs possess key features similar to those observed in real TCs including the formation of a secondary tangential wind maximum associated with the outer eyewall. The Sawyer-Eliassen equation and tangential momentum budget analyses are performed to diagnose the mechanisms underlying the secondary eyewall formation (SEF) and ERC. Our diagnoses reveal crucial roles of outer rainband heating in governing the formation and development of the secondary tangential wind maximum and demonstrate that the outer rainband convection must reach a critical strength relative to the eyewall before SEF and the subsequent ERC can occur. A positive feedback among low-level convection, acceleration of tangential winds in the boundary layer, and surface evaporation that leads to the development of ERC and a mechanism for the demise of inner eyewall that involves interaction between the transverse circulations induced by eyewall and outer rainband convection are proposed. The tangential momentum budget indicates that the net tendency of tangential wind is a small residual resultant from a large cancellation between tendencies induced by the resolved and sub-grid scale (SGS) processes. The large SGS contribution to the tangential wind budget explains different characteristics of ERC shown in previous numerical studies and poses a great challenge for a timely correct forecast of ERC. The sensitivity experiments show that ERCs are strongly subjected to model physics, vortex radial structure and background wind. The impact of model physics on ERC can be well understood with the interaction among eyewall/outer rainband heating, radilal inflow in the boundary layer, surface layer turbulent processes, and shallow convection in the moat. However, further investigations are needed to fully understand the exhibited sensitivities of ERC to vortex radial structure and background wind.