Differential affinity of FLIP and procaspase 8 for FADD's DED binding surfaces regulates DISC assembly

Death receptor activation triggers recruitment of FADD, which via its death effector domain (DED) engages the DEDs of procaspase 8 and its inhibitor FLIP to form death-inducing signalling complexes (DISCs). The DEDs of FADD, FLIP and procaspase 8 interact with one another using two binding surfaces defined by α1/α4 and α2/α5 helices, respectively. Here we report that FLIP has preferential affinity for the α1/α4 surface of FADD, whereas procaspase 8 has preferential affinity for FADD's α2/α5 surface. These relative affinities contribute to FLIP being recruited to the DISC at comparable levels to procaspase 8 despite lower cellular expression. Additional studies, including assessment of DISC stoichiometry and functional assays, suggest that following death receptor recruitment, the FADD DED preferentially engages FLIP using its α1/α4 surface and procaspase 8 using its α2/α5 surface; these tripartite intermediates then interact via the α1/α4 surface of FLIP DED1 and the α2/α5 surface of procaspase 8 DED2.

The impact of accretion disc winds on the optical spectra of cataclysmic variables

Many high-state non-magnetic cataclysmic variables (CVs) exhibit blueshifted absorption or P-Cygni profiles associated with ultraviolet (UV) resonance lines. These features imply the existence of powerful accretion disc winds in CVs. Here, we use our Monte Carlo ionization and radiative transfer code to investigate whether disc wind models that produce realistic UV line profiles are also likely to generate observationally significant recombination line and continuum emission in the optical waveband. We also test whether outflows may be responsible for the single-peaked emission line profiles often seen in high-state CVs and for the weakness of the Balmer absorption edge (relative to simple models of optically thick accretion discs). We find that a standard disc wind model that is successful in reproducing the UV spectra of CVs also leaves a noticeable imprint on the optical spectrum, particularly for systems viewed at high inclination. The strongest optical wind-formed recombination lines are H alpha and He ii lambda 4686. We demonstrate that a higher density outflow model produces all the expected H and He lines and produces a recombination continuum that can fill in the Balmer jump at high inclinations. This model displays reasonable verisimilitude with the optical spectrum of RW Trianguli. No single-peaked emission is seen, although we observe a narrowing of the double-peaked emission lines from the base of the wind. Finally, we show that even denser models can produce a single-peaked H alpha line. On the basis of our results, we suggest that winds can modify, and perhaps even dominate, the line and continuum emission from CVs.

Determinants and heritability of intraocular pressure and cup-to-disc ratio in a defined older population.

PURPOSE:

To investigate the heritability of intraocular pressure (IOP) and cup-to-disc ratio (CDR) in an older well-defined population.

DESIGN:

Family-based cohort study.

PARTICIPANTS:

Through the population-based Salisbury Eye Evaluation study, we recruited 726 siblings (mean age, 74.7 years) in 284 sibships.

METHODS:

Intraocular pressure and CDR were measured bilaterally for all participants. The presence or absence of glaucoma was determined by a glaucoma specialist for all probands on the basis of visual field, optic nerve appearance, and history. The heritability of IOP was calculated as twice the residual between-sibling correlation of IOP using linear regression and generalized estimating equations after adjusting for age, gender, mean arterial pressure, race, self-reported diabetes status, and history of systemic steroid use. The heritability of CDR was calculated using the same model and adjustments as above, while also adjusting for IOP.

MAIN OUTCOME MEASURES:

Heritability and determinants of IOP and CDR, and impact of siblings' glaucoma status on IOP and CDR.

RESULTS:

We estimated the heritability to be 0.29 (95% confidence interval [CI], 0.12-0.46) for IOP and 0.56 (95% CI, 0.35-0.76) for CDR in this population. Mean IOP in siblings of glaucomatous probands was statistically significantly higher than in siblings of normal probands (mean difference, 1.02 mmHg; P = 0.017). The mean CDR in siblings of glaucomatous probands was 0.07 (or 19%) larger than in siblings of glaucoma suspect referrals (P = 0.045) and siblings of normal probands (P = 0.004).

CONCLUSIONS:

In this elderly population, we found CDR to be highly heritable and IOP to be moderately heritable. On average, siblings of glaucoma patients had higher IOPs and larger CDRs than siblings of nonglaucomatous probands.

ALMA Observations of a Gap and a Ring in the Protoplanetary Disk around TW Hya

We report the first detection of a gap and a ring in dust continuum emission from the protoplanetary disk around TW Hya, using the Atacama Large Millimeter/Submillimeter Array. The gap and ring are located at 25 and 41 AU from the central star, respectively, and are associated with the CO snowline at ~ 30AU. The gap width and depth are 15AU at the maximum and 23% at the minimum, respectively, regarding that the observations are limited to an angular resolution of ~ 15AU. In addition, we detect a decrement in CO line emission down to ~ 10AU, indicating freeze-out of gas-phase CO onto grain surfaces and possible subsequent surface reactions to form larger molecules. According to theoretical studies, the gap could be caused by gravitational interaction between the disk gas and a planet with a mass less than super-Neptune (2 Neptune mass), or result from destruction of large dust aggregates due to the sintering of CO ice.

First Detection of Gas-phase Methanol in a Protoplanetary Disk

The first detection of gas-phase methanol in a protoplanetary disk (TW Hya) is presented. In addition to being one of the largest molecules detected in disks to date, methanol is also the first disk organic molecule with an unambiguous ice chemistry origin. The stacked methanol emission, as observed with the Atacama Large Millimeter/submillimeter Array, is spectrally resolved and detected across six velocity channels (>3σ), reaching a peak signal-to-noise of 5.5σ, with the kinematic pattern expected for TW Hya. Using an appropriate disk model, a fractional abundance of 3 x 10^-12 – 4 x 10^-11 (with respect to H₂) reproduces the stacked line profile and channel maps, with the favored abundance dependent upon the assumed vertical location (midplane versus molecular layer). The peak emission is offset from the source position, suggesting that the methanol emission has a ring-like morphology: the analysis here suggests it peaks at ≈30 au, reaching a column density ≈3–6 x 10¹² cm⁻². In the case of TW Hya, the larger (up to millimeter-sized) grains, residing in the inner 50 au, may thus host the bulk of the disk ice reservoir. The successful detection of cold gas-phase methanol in a protoplanetary disk implies that the products of ice chemistry can be explored in disks, opening a window into studying complex organic chemistry during planetary system formation.

Fiber optic sensors for the biomechanical study of the intervertebral disc

O presente trabalho teve como objetivo principal estudar o comportamento mecânico do disco intervertebral recorrendo a sensores em fibra ótica. Na expetativa de efetuar o melhor enquadramento do tema foi efetuada uma revisão exaustiva das várias configurações de sensores em fibra ótica que têm vindo a ser utilizadas em aplicações biomédicas e biomecânicas, nomeadamente para medição de temperatura, deformação, força e pressão. Nesse âmbito, procurou-se destacar as potencialidades dos sensores em fibra ótica e apresentá-los como uma tecnologia alternativa ou até de substituição das tecnologias associadas a sensores convencionais. Tendo em vista a aplicação de sensores em fibra ótica no estudo do comportamento do disco intervertebral efetuou-se também uma revisão exaustiva da coluna vertebral e, particularmente, do conceito de unidade funcional. A par de uma descrição anatómica e funcional centrada no disco intervertebral, vértebras adjacentes e ligamentos espinais foram ainda destacadas as suas propriedades mecânicas e descritos os procedimentos mais usuais no estudo dessas propriedades. A componente experimental do presente trabalho descreve um conjunto de experiências efetuadas com unidades funcionais cadavéricas utilizando sensores convencionais e sensores em fibra ótica com vista à medição da deformação do disco intervertebral sob cargas compressivas uniaxiais. Inclui ainda a medição in vivo da pressão intradiscal num disco lombar de uma ovelha sob efeito de anestesia. Para esse efeito utilizou-se um sensor comercial em fibra ótica e desenvolveu-se a respetiva unidade de interrogação. Finalmente apresenta-se os resultados da investigação em curso que tem como objetivo propor e desenvolver protótipos de sensores em fibra ótica para aplicações biomédicas e biomecânicas. Nesse sentido, são apresentadas duas soluções de sensores interferométricos para medição da pressão em fluídos corporais.

Film thickness in a ball-on-disc contact lubricated with greases, bleed oils and base oils

Three different lubricating greases and their bleed and base oils were compared in terms of film thickness in a ball-on-disc test rig through optical interferometry. The theoretical values calculated according to Hamrock's equation are in close agreement with the base oil film thickness measurements, which validates the selected experimental methodology. The grease and bleed oil film thickness under fully flooded lubrication conditions presented quite similar behaviour and levels. Therefore, the grease film thickness under full film conditions might be predicted using their bleed oil properties, namely the viscosity and pressure-viscosity coefficient. The base and bleed oil lubricant parameter LP are proportional to the measured film thickness. A relationship between grease and the corresponding bleed oil film thickness was evidenced.

Une nouvelle méthode de détection du glaucome par la mesure de l'asymétrie interoculaire : l’asymétrie du rapport de la surface neurorétinienne sur la surface du disque optique ou rim area to disc area asymmetry ratio (RADAAR)

Cette thèse constitue à la fois un apport de nature clinique et technologique dans l’approche diagnostique du glaucome. Plus précisément, nous nous proposons d’étudier une nouvelle façon de détecter le glaucome par la mesure de l’asymétrie du rapport de la surface de l’anneau neurorétinien et de la surface de la papille ou du disque optique ou rim to disc area asymmetry ratio (RADAAR). Pour atteindre cet objectif, nous avons recours à une base de données composée d’une population subdivisée en 4 différents groupes de diagnostic (normal, glaucome possible, glaucome probable et glaucome définitif). Les mesures du RADAAR sont calculées de différentes façons à partir des paramètres stéréométriques de la tête du nerf optique des sujets, produits par la microscopie confocale à balayage laser (Heidelberg Retina Tomograph (HRT) (Heidelberg Engineering, Germany)). Nous procédons à une analyse de données grâce au logiciel SPSS où nous mettons en exergue la distribution du RADAAR dans les différentes populations, sa validité et son utilité dans le dépistage du glaucome. Nous enrôlons donc 523 sujets dans cette étude avec 82 sujets atteints de glaucome définitif. La moyenne d’âge est de 62 ans. Il y a plus de femmes que d’hommes et plus de Caucasiens que d’Africains Caribéens. Nous trouvons que la distribution de la mesure du RADAAR est différente des sujets d’un groupe de diagnostic à l’autre. En termes de performance, la sensibilité de la mesure du RADAAR est très basse c'est-à-dire que sa capacité de détecter la maladie est basse. En revanche la mesure du RADAAR est plus spécifique c'est-à-dire que sa capacité d’identifier les sujets exempts de la maladie est plus grande. Elle tendrait à être aussi plus performante chez les Africains Caribéens que chez les Caucasiens. De même, elle serait plus sensible chez les hommes que chez les femmes. La mesure du RADAAR est utile si on l’associe à une autre méthode de diagnostic comme l’analyse de Régression de Moorfields (MRA) incluse dans le logiciel du HRT3 spécialement lors de la détection du glaucome dans la population à haut risque. En définitive, nous déterminons que la mesure du RADAAR se veut un outil d’aide au diagnostic. Elle est particulièrement intéressante dans le contexte de dépistage de glaucome.

Automatic Optic Disc Boundary Extraction from Color Fundus Images

Efficient optic disc segmentation is an important task in automated retinal screening. For the same reason optic disc detection is fundamental for medical references and is important for the retinal image analysis application. The most difficult problem of optic disc extraction is to locate the region of interest. Moreover it is a time consuming task. This paper tries to overcome this barrier by presenting an automated method for optic disc boundary extraction using Fuzzy C Means combined with thresholding. The discs determined by the new method agree relatively well with those determined by the experts. The present method has been validated on a data set of 110 colour fundus images from DRION database, and has obtained promising results. The performance of the system is evaluated using the difference in horizontal and vertical diameters of the obtained disc boundary and that of the ground truth obtained from two expert ophthalmologists. For the 25 test images selected from the 110 colour fundus images, the Pearson correlation of the ground truth diameters with the detected diameters by the new method are 0.946 and 0.958 and, 0.94 and 0.974 respectively. From the scatter plot, it is shown that the ground truth and detected diameters have a high positive correlation. This computerized analysis of optic disc is very useful for the diagnosis of retinal diseases

Sinera en disc.

En lengua catalana

A rotating disc voltammetry study of the 1,8-dihydroxyanthraquinone mediated reduction of colloidal indigo

Colloidal indigo is reduced to an aqueous solution of leuco-indigo in a mediated two-electron process converting the water-insoluble dye into the water-soluble leuco form. The colloidal dye does not interact directly with the electrode surface, and to employ an electrochemical process for this reduction, the redox mediator 1,8-dihydroxyanthraquinone (1,8-DHAQ) is used to transfer electrons from the electrode to the dye. The mediated reduction process is investigated at a (500-kHz ultrasound-assisted) rotating disc electrode, and the quantitative analysis of voltammetric data is attempted employing the Digisim numerical simulation software package. At the most effective temperature, 353 K, the diffusion coefficient for 1,8-DHAQ is (0.84 +/- 0.08)x10(-9) m(2) s(-1), and it is shown that an apparently kinetically controlled reaction between the reduced form of the mediator and the colloidal indigo occurs within the diffusion layer at the electrode surface. The apparent bimolecular rate constant k (app)=3 mol m(-3) s(-1) for the rate law d[leuco-indigo]/dt = k(app) x [mediator] x [indigo] is determined and attributed to a mediator diffusion controlled dissolution of the colloid particles. The average particle size and the number of molecules per particles are estimated from the apparent bimolecular rate constant and confirmed by scanning electron microscopy.

Electrochemical characterisation and anodic stripping voltammetry at mesoporous platinum rotating disc electrodes

Using the technique of liquid crystal templating a rotating disc electrode (RDE) was modified with a high surface area mesoporous platinum film. The surface area of the electrode was characterised by acid voltammetry, and found to be very high (ca. 86 cm(2)). Acid characterisation of the electrode produced distorted voltammograms was interpreted as being due to the extremely large surface area which produced a combination of effects such as localised pH change within the pore environment and also ohmic drop effects. Acid voltammetry in the presence of two different types of surfactant, namely Tween 20 and Triton X-100, suggested antifouling properties associated with the mesoporous deposit. Further analysis of the modified electrode using a redox couple in solution showed typical RDE behaviour although extra capacitive currents were observed due to the large surface area of the electrode. The phenomenon of underpotential deposition was exploited for the purpose of anodic stripping voltammetry and results were compared with data collected for microelectrodes. Underpotential deposition of metal ions at the mesoporous RDE was found to be similar to that at conventional platinum electrodes and mesoporous microelectrodes although the rate of surface coverage was found to be slower at a mesoporous RDE. It was found that a mesoporous RDE forms a suitable system for quantification of silver ions in solution.

Measurement of the epicycle frequency in the Galactic disc and initial velocities of open clusters

A new method to measure the epicycle frequency kappa in the Galactic disc is presented. We make use of the large data base on open clusters completed by our group to derive the observed velocity vector (amplitude and direction) of the clusters in the Galactic plane. In the epicycle approximation, this velocity is equal to the circular velocity given by the rotation curve, plus a residual or perturbation velocity, of which the direction rotates as a function of time with the frequency kappa. Due to the non-random direction of the perturbation velocity at the birth time of the clusters, a plot of the present-day direction angle of this velocity as a function of the age of the clusters reveals systematic trends from which the epicycle frequency can be obtained. Our analysis considers that the Galactic potential is mainly axis-symmetric, or in other words, that the effect of the spiral arms on the Galactic orbits is small; in this sense, our results do not depend on any specific model of the spiral structure. The values of kappa that we obtain provide constraints on the rotation velocity of the in particular, V(0) is found to be 230 +/- 15 km s(-1) even if the scale (R(0) = 7.5 kpc) of the Galaxy is adopted. The measured kappa at the solar radius is 43 +/- 5 km s(-1) kpc(-1). The distribution of initial velocities of open clusters is discussed.