Lifespan extension and increased resistance to environmental stressors by N-Acetyl-L-Cysteine in Caenorhabditis elegans

OBJECTIVE: This study was performed to determine the effect of N-acetyl-L-cysteine, a modified sulfur-containing amino acid that acts as a strong cellular antioxidant, on the response to environmental stressors and on aging in C. elegans. METHOD: The survival of worms under oxidative stress conditions induced by paraquat was evaluated with and without in vivo N-acetyl-L-cysteine treatment. The effect of N-acetyl-L-cysteine on the response to other environmental stressors, including heat stress and ultraviolet irradiation (UV), was also monitored. To investigate the effect on aging, we examined changes in lifespan, fertility, and expression of age-related biomarkers in C. elegans after N-acetyl-L-cysteine treatment. RESULTS: Dietary N-acetyl-L-cysteine supplementation significantly increased resistance to oxidative stress, heat stress, and UV irradiation in C. elegans. In addition, N-acetyl-L-cysteine supplementation significantly extended both the mean and maximum lifespan of C. elegans. The mean lifespan was extended by up to 30.5% with 5 mM N-acetyl-L-cysteine treatment, and the maximum lifespan was increased by 8 days. N-acetyl-L-cysteine supplementation also increased the total number of progeny produced and extended the gravid period of C. elegans. The green fluorescent protein reporter assay revealed that expression of the stress-responsive genes, sod-3 and hsp-16.2, increased significantly following N-acetyl-L-cysteine treatment. CONCLUSION: N-acetyl-L-cysteine supplementation confers a longevity phenotype in C. elegans, possibly through increased resistance to environmental stressors

Interactive media server with media synchronized raid storage system

We propose an efficient placement algorithm and per-disk prefetching method to effectively support interactive operations in the media server. Our placement policy is incorporated with an encoder having a special bitcount control scheme that repeatedly tunes quantization parameters to adjust the bitcounts of video frames. This encoder can generate coded frames whose sizes are synchronized with the RAID stripe size, so that when various fast-forward levels are accessed we can reduce the seek and rotational latency and enhance the disk throughput of each disk in the RAID system. In the experimental results, the proposed placement policy and bitrate control scheme can significantly improve the average service time, which can enlarge the capacity of the interactive media server

Structure and spectral features of H+(H2O)(7): Eigen versus Zundel forms

The two dimensional (2D) to three dimensional (3D) transition for the protonated water cluster has been controversial, in particular, for H+(H2O)(7). For H+(H2O)(7) the 3D structure is predicted to be lower in energy than the 2D structure at most levels of theory without zero-point energy (ZPE) correction. On the other hand, with ZPE correction it is predicted to be either 2D or 3D depending on the calculational levels. Although the ZPE correction favors the 3D structure at the level of coupled cluster theory with singles, doubles, and perturbative triples excitations [CCSD(T)] using the aug-cc-pVDZ basis set, the result based on the anharmonic zero-point vibrational energy correction favors the 2D structure. Therefore, the authors investigated the energies based on the complete basis set limit scheme (which we devised in an unbiased way) at the resolution of the identity approximation Moller-Plesset second order perturbation theory and CCSD(T) levels, and found that the 2D structure has the lowest energy for H+(H2O)(7) [though nearly isoenergetic to the 3D structure for D+(D2O)(7)]. This structure has the Zundel-type configuration, but it shows the quantum probabilistic distribution including some of the Eigen-type configuration. The vibrational spectra of MP2/aug-cc-pVDZ calculations and Car-Parrinello molecular dynamics simulations, taking into account the thermal and dynamic effects, show that the 2D Zundel-type form is in good agreement with experiments. (c) 2006 American Institute of Physics.open353

Elevated intracellular cAMP exacerbates vulnerability to oxidative stress in optic nerve head astrocytes.

Glaucoma is characterized by a progressive loss of retinal ganglion cells and their axons, but the underlying biological basis for the accompanying neurodegeneration is not known. Accumulating evidence indicates that structural and functional abnormalities of astrocytes within the optic nerve head (ONH) have a role. However, whether the activation of cyclic adenosine 3',5'-monophosphate (cAMP) signaling pathway is associated with astrocyte dysfunction in the ONH remains unknown. We report here that the cAMP/protein kinase A (PKA) pathway is critical to ONH astrocyte dysfunction, leading to caspase-3 activation and cell death via the AKT/Bim/Bax signaling pathway. Furthermore, elevated intracellular cAMP exacerbates vulnerability to oxidative stress in ONH astrocytes, and this may contribute to axonal damage in glaucomatous neurodegeneration. Inhibition of intracellular cAMP/PKA signaling activation protects ONH astrocytes by increasing AKT phosphorylation against oxidative stress. These results strongly indicate that activation of cAMP/PKA pathway has an important role in astrocyte dysfunction, and suggest that modulating cAMP/PKA pathway has therapeutic potential for glaucomatous ONH degeneration

Influence of cultivation parameters or supplement on product qualities and culture performances during perfusion

Perfusion processes have been developed with technological advances in single-use bioreactor and cell retention device. Perfusion has advantages such as high cell density culture in compact facilities and media change or culture parameter shifts for protein production with desired qualities. Single use bioreactor (200L or 1000L) with ATF System was used for the clinical production. For the process development, the scale-down model was established with lab-scale (2L) bioreactor with ATF2. A recombinant CHO cell line producing a fusion protein was cultivated using in-house serum-free media. Influence of insulin (0~3mg/L) on qualities was investigated in the established perfusion process using in-house serum-free medium and 2L scale-down model. The results showed that low concentration of insulin enhanced O-glycosylation and -2 charged N-glycan of fusion protein. Temperature (30~34oC) conditions, under no addition of insulin, were investigated to evaluate effect on qualities. High temperature enhanced O-glycosylation and -2 charged N-glycan of fusion protein. To evaluate interaction among culture parameters (Temperature, pH, and Dissolved Oxygen) in the perfusion process, Central Composite Inscribed (CCI) was selected as design of experiment. 20 perfusion cultures were carried out in the 2L scale-down model. The results showed each parameter and interactions among parameters had an effect on qualities and culture performances

A Hybrid Approach Based on Variational Mode Decomposition for Analyzing and Predicting Urban Travel Speed

Predicting travel speeds on urban road networks is a challenging subject due to its uncertainty stemming from travel demand, geometric condition, traffic signals, and other exogenous factors. This uncertainty appears as nonlinearity, nonstationarity, and volatility in traffic data, and it also creates a spatiotemporal heterogeneity of link travel speed by interacting with neighbor links. In this study, we propose a hybrid model using variational mode decomposition (VMD) to investigate and mitigate the uncertainty of urban travel speeds. The VMD allows the travel speed data to be divided into orthogonal and oscillatory sub-signals, called modes. The regular components are extracted as the low-frequency modes, and the irregular components presenting uncertainty are transformed into a combination of modes, which is more predictable than the original uncertainty. For the prediction, the VMD decomposes the travel speed data into modes, and these modes are predicted and summed to represent the predicted travel speed. The evaluation results on urban road networks show that, the proposed hybrid model outperforms the benchmark models both in the congested and in the overall conditions. The improvement in performance increases significantly over specific link-days, which generally are hard to predict. To explain the significant variance of the prediction performance according to each link and each day, the correlation analysis between the properties of modes and the performance of the model are conducted. The results on correlation analysis show that the more variance of nondaily pattern is explained through the modes, the easier it was to predict the speed. Based on the results, discussions on the interpretation on the correlation analysis and future research are presented. Document type: Articl

An Annular Array MPT for Enhanced Generation of Omnidirectional SH Waves in a Plate

If guided wave transducers are fabricated in an annular array type, the excitation and measurement of target guided wave modes could be considerably enhanced (see, e.g., [1]). Accordingly, various annular array transducers have been developed, including those generating omnidirectional Lamb waves in a plate. Here, we newly consider an annular array type MPT (magnetostrictive patch transducer) to generate enhanced SH (shear-horizontal) waves in a plate. This annular array MPT is based on our earlier development of an omnidirectional SH wave MPT [2]. For wave field analysis by the annular array SH wave MPT, the strain response in a plate due to wave excitation by the MPT is calculated by using the Green’s function approach [3]. Using the analysis, an optimal configuration of the annular array MPT which can maximize the transducer output at the given frequency is determined. For the validation of numerical predictions, a series of experiments with varying frequencies were carried out and the numerical results were found to be in good agreement with the experimental results