Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system

Growth inhibitory proteins in the central nervous system (CNS) block axon growth and regeneration by signaling to Rho, an intracellular GTPase. It is not known how CNS trauma affects the expression and activation of RhoA. Here we detect GTP-bound RhoA in spinal cord homogenates and report that spinal cord injury (SCI) in both rats and mice activates RhoA over 10-fold in the absence of changes in RhoA expression. In situ Rho-GTP detection revealed that both neurons and glial cells showed Rho activation at SCI lesion sites. Application of a Rho antagonist (C3–05) reversed Rho activation and reduced the number of TUNEL-labeled cells by ∼50% in both injured mouse and rat, showing a role for activated Rho in cell death after CNS injury. Next, we examined the role of the p75 neurotrophin receptor (p75NTR) in Rho signaling. After SCI, an up-regulation of p75NTR was detected by Western blot and observed in both neurons and glia. Treatment with C3–05 blocked the increase in p75NTR expression. Experiments with p75NTR-null mutant mice showed that immediate Rho activation after SCI is p75NTR dependent. Our results indicate that blocking overactivation of Rho after SCI protects cells from p75NTR-dependent apoptosis

The conduction band absorption spectrum of interdiffused InGaAs/GaAs quantum dot infrared photodetectors

We report on a theoretical study of the relationship between interdiffusion and the conduction bandoptical absorption of In(Ga)As/GaAs quantum dots.Quantum dot geometries are progressively interdiffused based on Fick’s model and the quantum dot strain, band structure and optical absorption cross-section are calculated numerically. Quantifying the effects of interdiffusion on quantum dotoptical absorption is important for applications that utilize post-growth techniques such as selective area intermixing.Thanks are due to the Australian Research Council for the financial support of this research

Effect of GaP strain compensation layers on rapid thermally annealed InGaAs∕GaAs quantum dot infrared photodetectors grown by metal-organic chemical-vapor deposition

The effect of GaP strain compensation layers was investigated on ten-layer InGaAs∕GaAsquantum dot infrared photodetectors(QDIPs) grown by metal-organic chemical-vapor deposition. Compared with the normal QDIP structure, the insertion of GaP has led to a narrowed spectral linewidth and slightly improved detector performance. A more significant influence of GaP was observed after the structure was annealed at various temperatures. While a similar amount of wavelength tuning was obtained, the GaPQDIPs exhibited much less degradation in device characteristics with increasing annealing temperature.The financial support from Australian Research Council is acknowledged

Effects of rapid thermal annealing on device characteristics of InGaAs/GaAs quantum dot infrared photodetectors

In this work, rapid thermal annealing was performed on InGaAs/GaAs quantum dot infrared photodetectors (QDIPs) at different temperatures. The photoluminescence showed a blueshifted spectrum in comparison with the as-grown sample when the annealing temperature was higher than 700 °C, as a result of thermal interdiffusion of the quantum dots (QDs). Correspondingly, the spectral response from the annealed QDIP exhibited a redshift. At the higher annealing temperature of 800 °C, in addition to the largely redshifted photoresponse peak of 7.4 µm (compared with the 6.1 µm of the as-grown QDIP), a high energy peak at 5.6 µm (220 meV) was also observed, leading to a broad spectrum linewidth of 40%. This is due to the large interdiffusion effect which could greatly vary the composition of the QDs and thus increase the relative optical absorption intensity at higher energy. The other important detector characteristics such as dark current, peak responsivity, and detectivity were also measured. It was found that the overall device performance was not affected by low annealing temperature, however, for high annealing temperature, some degradation in device detectivity (but not responsivity) was observed. This is a consequence of increased dark current due to defect formation and increased ground state energy. © 2006 American Institute of Physic

Unexpected short- and medium-range atomic structure of sputtered amorphous silicon upon thermal annealing

We investigate the structure of magnetron-sputtered (MS) amorphous silicon(a-Si) prepared under standard deposition conditions and compare this to pure ion-implanted (II) a-Si. The structure of both films is characterized in their as-prepared and thermally annealed states. Significant differences are observed in short- and medium-range order following thermal annealing. Whereas II a-Si undergoes structural relaxation toward a continuous random network, MS a-Si exhibits little change. Cross-sectional transmission electron microscopy reveals the presence of nanopores in the MS film consistent with reduced mass-density. Therefore, the short- and medium-range order of annealed, MS a-Si is tentatively attributed to these pores

A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury.

Multiple lines of evidence have validated the Rho pathway as important in controlling the neuronal response to growth inhibitory proteins after central nervous system (CNS) injury. A drug called BA-210 (trademarked as Cethrin(®)) blocks activation of Rho and has shown promise in pre-clinical animal studies in being used to treat spinal cord injury (SCI). This is a report of a Phase I/IIa clinical study designed to test the safety and tolerability of the drug, and the neurological status of patients following the administration of a single dose of BA-210 applied during surgery following acute SCI. Patients with thoracic (T2-T12) or cervical (C4-T1) SCI were sequentially recruited for this dose-ranging (0.3 mg to 9 mg Cethrin), multi-center study of 48 patients with complete American Spinal Injury Association assessment (ASIA) A. Vital signs; clinical laboratory tests; computed tomography (CT) scans of the spine, head, and abdomen; magnetic resonance imaging (MRI) of the spine, and ASIA assessment were performed in the pre-study period and in follow-up periods out to 1 year after treatment. The treatment-emergent adverse events that were reported were typical for a population of acute SCI patients, and no serious adverse events were attributed to the drug. The pharmacokinetic analysis showed low levels of systemic exposure to the drug, and there was high inter-patient variability. Changes in ASIA motor scores from baseline were low across all dose groups in thoracic patients (1.8±5.1) and larger in cervical patients (18.6±19.3). The largest change in motor score was observed in the cervical patients treated with 3 mg of Cethrin in whom a 27.3±13.3 point improvement in ASIA motor score at 12 months was observed. Approximately 6% of thoracic patients converted from ASIA A to ASIA C or D compared to 31% of cervical patients and 66% for the 3-mg cervical cohort. Although the patient numbers are small, the observed motor recovery in this open-label trial suggests that BA-210 may increase neurological recovery after complete SCI. Further clinical trials with Cethrin in SCI patients are planned, to establish evidence of efficacy

In-plane coupling of light from InP-based photonic crystal band-edge lasers into single-mode waveguides

In this paper, we analyze the coupling of light from photonic-crystal band-edge lasers into single-mode waveguides. Both active and passive devices lie in the same plane and coupling of light is achieved by using parabolic and nanotapers in InP based epitaxial structures. Two- and three-dimensional finite-difference time-domain methods are employed to analyze these devices. Coupling efficiencies higher than 80% can be obtained with parabolic couplers. We also present laser configurations that can reduce multiwavelength coupling of light into single-mode waveguides, using structures that are similar to coupled cavity Fabry-Pérot lasers