Gremlin1 preferentially binds to Bone Morphogenetic Protein-2 (BMP-2) and BMP-4 over BMP-7

Gremlin (Grem1) is a member of the DAN family of secreted bone morphogenetic protein (BMP) antagonists. Bone morphogenetic protein-7 (BMP-7) mediates protective effects during renal fibrosis-associated with diabetes and other renal diseases. The pathogenic mechanism of Grem1 during DN has been suggested to be binding and inhibition of BMP-7. However, the precise interactions between Grem1, BMP-7 and other BMPs have not been accurately defined. Here we show the affinity of Grem1 for BMP-7 is lower than that of BMP-2 and BMP-4, using a combination of surface plasmon resonance and cell culture techniques. Using kidney proximal tubule cells and HEK-293 cell Smad1/5/8 phosphorylation and BMP-dependent gene expression as readout, Grem1 consistently demonstrated a higher affinity for BMP-2>4>7. Cell-associated Grem1 did not inhibit BMP-2 or BMP-4 mediated signalling, suggesting that Grem1-BMP-2 binding occurred in solution, preventing BMP receptor activation. These data suggest that Grem1 preferentially binds to BMP-2 and this may be the dominant complex in a disease situation where levels of Grem1 and BMPs are elevated.

INTERPLAY OF CAF2 SUBSTRATE ROUGHENING AND FILM DEPOSITION RATE ON RADIATIVE SCATTERING OF SURFACE-PLASMON POLARITONS FROM AG FILMS

The radiative decay of surface plasmon polaritons has been investigated in an attempt to characterize the surface roughness of Ag films prepared under different conditions. The polaritons were excited by the method of attenuated total reflection of light. The films were deposited on the face of a 60-degrees BK-7 glass prism at a rate that was deliberately fixed in two different ranges (centred on 0.1 and 10 nm s-1) and in some cases a CaF2 underlayer was used to roughen the film surfaces. The intensity of the scattered light emitted from the opposite face of the films was measured as a function of direction for each using the same sensitivity scale and was correlated with the preparation of the film. It was found that on nominally smooth substrates fast-deposited thinner films give out more light and are deduced to have greater short wavelength (300-600 nm) roughness amplitude. There is also evidence for long wavelenth (7 mum) periodic roughness due to the prism substrate itself. On CaF2 roughened surfaces the light output from the films is further increased and the peak intensity is backward directed with respect to the exciting laser beam direction. Here roughness on a lateral scale of 350 nm is responsible. Also, elastic scattering of surface plasmon polaritons at grain boundaries reduces the light output from fast deposited, small grain, films on CaF2 roughened surfaces. Overall, a consistent picture of roughness induced radiative polariton decay emerges for all cases studied.

DEPENDENCE OF LIGHT OUTPUT FROM NOMINALLY SMOOTH AL-OX-AU TUNNEL-JUNCTIONS ON ELECTRODE MORPHOLOGY

The light output from nominally smooth Al-Ox-Au tunnel junctions is observed to be substantially independent of the deposition rate of the Au film electrode. Films deposited quickly (2 nm s-1) and those deposited slowly (0.16 nm s-1) have similar spectral dependences and intensities. (This is in contrast to roughened films where those deposited quickly give out less light, especially towards the blue end of the spectrum.) The behaviour can be interpreted in terms of the ratio l(ph)/l(em) where l(ph) and l(em) are the mean free paths of surface plasmons between external photon emissions and internal electromagnetic absorptions respectively. Once l(ph)/l(em) exceeds 100, as it does on smooth films, grain size has little further effect on the spectral shape of the light output. In fast-deposited films there are two compensating effects on the output intensity: grain boundary scattering decreases it and greater surface roughness increases it.

FAST MODE SURFACE-PLASMON DAMPING ON TUNNEL JUNCTION STRUCTURES

Using a prism-air gap-sample (Otto) configuration we have optically excited surface plasmon polaritons at the Ag-air interface of passive Al-Al oxide-Ag tunnel junction structures at wavelength 632.8 nm. It is found that the internal damping of this excitation is more than a factor of 2 greater for samples with a very thin (approximately 15 nm) Ag electrode than for samples with a thicker (approximately 40 nm) Ag electrode. This observation is explained by the fact that the fields of the surface plasmon polariton penetrate more substantially into the lossy Al base electrode when the Ag top electrode is very thin.

CHARACTERIZATION OF THE AU SURFACE-STRUCTURE OF AL-L-AU LIGHT-EMITTING TUNNEL-JUNCTIONS

Visible light is emitted from the Au-air interface of Al-I-Au thin-film tunnel junctions (deposited over a thin layer of CaF2 on glass) as a result of the decay of surface plasmon polaritons (SPPs). We show the surface topography of such a Au film and relate its large-scale features to the outcoupling of fast SPP's to photons. The absence of short-scale roughness features is explained by thier disappearance through surface diffusion. To confirm this a controlled sequence of 5-nm, 20-ms scanning tunneling microscope (STM) W tip crashes has been used to produce indentations 3 nm deep with a lateral dimension of 5-7 nm on a Au crystal in air at room temperature. Four sequences of indentations were drawn in the form of a square box. Right from the start, feature decay is observed and over a period of 2 h a succession of images shows that the structure disappears into the background as a result of surface diffusion. The surface diffusion constant is estimated to be 10(-18) cm2 s-1. The lack of light output via slow mode SPPs is an inevitable consequence of surface annealing.

Optimizing the efficiency of the sub-map technique for large-scale simultaneous localization and mapping

A technique for optimizing the efficiency of the sub-map method for large-scale simultaneous localization and mapping (SLAM) is proposed. It optimizes the benefits of the sub-map technique to improve the accuracy and consistency of an extended Kalman filter (EKF)-based SLAM. Error models were developed and engaged to investigate some of the outstanding issues in employing the sub-map technique in SLAM. Such issues include the size (distance) of an optimal sub-map, the acceptable error effect caused by the process noise covariance on the predictions and estimations made within a sub-map, when to terminate an existing sub-map and start a new one and the magnitude of the process noise covariance that could produce such an effect. Numerical results obtained from the study and an error-correcting process were engaged to optimize the accuracy and convergence of the Invariant Information Local Sub-map Filter previously proposed. Applying this technique to the EKF-based SLAM algorithm (a) reduces the computational burden of maintaining the global map estimates and (b) simplifies transformation complexities and data association ambiguities usually experienced in fusing sub-maps together. A Monte Carlo analysis of the system is presented as a means of demonstrating the consistency and efficacy of the proposed technique.