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Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant genetic disease that is caused by a silent mutation of the LMNA gene encoding lamins A and C (lamin A/C). The G608G mutation generates a more accessible splicing donor site than does WT and produces an alternatively spliced product of LMNA called progerin, which is also expressed in normal aged cells. In this study, we determined that progerin binds directly to lamin A/C and induces profound nuclear aberrations. Given this observation, we performed a random screening of a chemical library and identified 3 compounds (JH1, JH4, and JH13) that efficiently block progerin-lamin A/C binding. These 3 chemicals, particularly JH4, alleviated nuclear deformation and reversed senescence markers characteristic of HGPS cells, including growth arrest and senescenceassociated β-gal (SA-β-gal) activity. We then used microarray-based analysis to demonstrate that JH4 is able to rescue defects of cell-cycle progression in both HGPS and aged cells. Furthermore, administration of JH4 to [Lmna.sup.C60SC/C60SC]-mutant mice, which phenocopy human HGPS, resulted in a marked improvement of several progeria phenotypes and an extended lifespan. Together, these findings indicate that specific inhibitors with the ability to block pathological progerin-lamin A/C binding may represent a promising strategy for improving lifespan and health in both HGPS and normal aging., Introduction Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare disease that recapitulates some aspects of physiological aging (1-5). Accordingly, a detailed understanding of the molecular mechanisms underlying HGPS may be [...]

In this paper, we present a theoretical study and a numerical simulation of various long wavelength top-illuminated p-i-n photodetectors in the frequency range of 2.5-60 GHz under high optical modulated power at 1.55-[[micro]meter] wavelength. The modeling includes a monodimensional Drift-Diffusion model for the device and takes into account the external circuit. We considered six InP/GaInAs/InP photodetectors especially designed to work at 2.5, 10, 20, 30, 40, and 60 GHz, respectively. For the one with the highest frequency, we intentionally sacrificed the quantum efficiency in order to compare them at the end with the results already obtained in the case of waveguide p-i-n photodetectors. The results show the maximum microwave-output power for each photodetector at its specific working frequency. Additionally, we present the effects of the modulation depth, the back illumination, and the wavelength 1.3 [[micro]meter]. Index Terms - Numerical analysis, optical interconnections, photodectors, p-i-n photodiodes, power transmission.

In this paper, the behavior under very high optical power of waveguide PIN photodetectors grown on InP substrate is simulated. The problem is solved using a pseudo-bidimensional Drift-Diffusion model which describes the electrical behavior of the device including the effects of the external circuit. The optical behavior of the device is analysed using FD 2D and 3D Beam Propagation Method. First, we present the optical behavior of the device when the illumination conditions change. Influence of device structure, spot width, spot position and injection angle on the quantum efficiency of the photodetector is so studied. Second, the whole modeling is validated using experimental results given in the literature. Three typical multimode structures which allow a high cut-off frequency as well as a good responsivity are then modeled and compared. The smaller one has a cut-off frequency of 75 GHz in small signal conditions and the main effect decreasing the microwave output signal when the optical input power increases is the carrier effect in the depletion region of the photodetector. The maximum microwave power of each photodetector is calculated in typical conditions of use.

The oxidizing ambient was built using high pressure H2O vapor at 550 °C. For the solid phase crystallization (SPC) polycrystalline silicon (poly-Si) that is annealed for 1 h at 2 MPa, the oxide thickness is about 150 Å. The oxide layer is approximately 90 Å above the original surface of the poly-Si and 60 Å below the original surface. The oxide layer is used as the first gate insulator layer of thin-film transistors (TFTs). The heating at 550 °C with 2 MPa H2O vapor increased the carrier mobility from 17.6 cm2/V s of the conventional SPC process to 30.4 cm2/V s, and it reduced the absolute value of the threshold voltage (Vth) from 4.13 to 3.62 V. The subthreshold swing also decreased from 0.72 to 0.60 V/decade. This improvement is attributed mainly to the reduction in defect density at the oxide/poly-Si interface and in the poly-Si film by the high pressure annealing (HPA) process. Since the realization of excellent performance at the oxide/poly-Si interface and in poly-Si depends on the defect density, the poly-Si having the thermal oxide formed by a combined process of SPC and HPA may be well suited for fabrication of poly-Si TFTs for flat panel displays such as active matrix organic light emitting diodes. [ABSTRACT FROM AUTHOR]

Abstract: A six-day static-renewal toxicity test was performed to determine the influences of cadmium on the development of embryos of soldatov''s catfish (Silurus soldatovi). The median lethal concentration (LC50) value and median effective concentration (EC50, i.e., the total adverse effects, including developmental defects and mortality) were calculated to be 2740 and 133μg/L, respectively, when cadmium was prepared in dilution water. The LC50 decreased to 266μg/L in a subsequent test one month later, thereby suggesting that the sensitivity of this fish to cadmium in the early life stage 1 [1] The early life stage terminology used here is defined by . Embryo, stage before hatching; pro-larva, stage between hatching and yolk sac resorption; larva, stage between yolk-stage resorption and juvenile morphology. was largely influenced by the quality of fertilized eggs, which is known to be dependent on the season. The mortality and total adverse effects showed a concentration-dependent relationship at dosages greater than 1000 or 10μg/L (p<0.05), respectively, at pro-larva stage (i.e., 144hpf) with dilution water. To compare the toxic effects of cadmium under field and experimental conditions, filtered river water was adopted as a solvent simultaneously compared with dilution water. No significant differences were observed in mortality rate, hatching rate and adverse effect prevalence between the two solvents. In comparison to previously published toxicity data for other fish, the pro-larva of soldatov''s catfish were less sensitive than established test fish in the early life stage. Therefore, the environmental risks would be overestimated when considering only existing toxicity data for other test fish. [Copyright &y& Elsevier]