Stochastic Modeling of Hybrid Cache Systems

In recent years, there is an increasing demand of big memory systems so to perform large scale data analytics. Since DRAM memories are expensive, some researchers are suggesting to use other memory systems such as non-volatile memory (NVM) technology to build large-memory computing systems. However, whether the NVM technology can be a viable alternative (either economically and technically) to DRAM remains an open question. To answer this question, it is important to consider how to design a memory system from a "system perspective", that is, incorporating different performance characteristics and price ratios from hybrid memory devices. This paper presents an analytical model of a "hybrid page cache system" so to understand the diverse design space and performance impact of a hybrid cache system. We consider (1) various architectural choices, (2) design strategies, and (3) configuration of different memory devices. Using this model, we provide guidelines on how to design hybrid page cache to reach a good trade-off between high system throughput (in I/O per sec or IOPS) and fast cache reactivity which is defined by the time to fill the cache. We also show how one can configure the DRAM capacity and NVM capacity under a fixed budget. We pick PCM as an example for NVM and conduct numerical analysis. Our analysis indicates that incorporating PCM in a page cache system significantly improves the system performance, and it also shows larger benefit to allocate more PCM in page cache in some cases. Besides, for the common setting of performance-price ratio of PCM, "flat architecture" offers as a better choice, but "layered architecture" outperforms if PCM write performance can be significantly improved in the future.Comment: 14 pages; mascots 201

PINK1 Protects Against Gentamicin-Induced Sensory Hair Cell Damage: Possible Relation to Induction of Autophagy and Inhibition of p53 Signal Pathway

Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) is a gatekeeper of mitochondrial quality control. The present study was aimed to examine whether PINK1 possesses a protective function against gentamicin (GM)-induced sensory hair cell (HC) damage in vitro. The formation of parkin particles (a marker revealing the activation of PINK1 pathway which is a substrate of PINK1 and could signal depolarized mitochondria for clearance) and autophagy were determined by immunofluorescence staining. The expressions of PINK1, LC3B, cleaved-caspase 3 and p53 were measured by Western blotting. The levels of reactive oxygen species (ROS) and apoptosis were respectively evaluated by DCFH-DA staining, Annexin V Apoptosis Detection Kit and TUNEL staining. Cell viability was tested by a CCK8 kit. We found that treatment of 400 μM GM elicited the formation of ROS, which, in turn, led to PINK1 degradation, parkin recruitment, autophagy formation, an increase of p53 and cleaved-caspase 3 in HEI-OC1 cells and murine HCs. In contrast, co-treatment with ROS scavenger N-acetyl-L-cysteine (NAC) inhibited parkin recruitment, alleviated autophagy and p53 pathway-related damaged-cell elimination. Moreover, PINK1 interference contributed to a decrease of autophagy but an increase of p53 level in HEI-OC1 cells in response to GM stimulus. Findings from this work indicate that PINK1 alleviates the GM-elicited ototoxicity via induction of autophagy and resistance the increase of p53 in HCs

An automatic system for multidimensional integrated protein chromatography

An automatic system for multidimensional integrated protein chromatography was designed for simultaneous separation of multiple proteins from complex mixtures, such as human plasma and tissue lysates. This computer-controlled system integrates several chromatographic columns that work independently or cooperatively with one another to achieve efficient high throughputs. The pipelines can be automatically switched either to another column or to a collection container for each UV-detected elution fraction. Environmental contamination is avoided due to the closed fluid paths and elimination of manual column change. This novel system was successfully used for simultaneous preparation of five proteins from the precipitate of human plasma fraction IV (fraction IV). The system involved gel filtration, ion exchange, hydrophobic interaction, and heparin affinity chromatography. Human serum albumin (HSA), transferrin (TO, antithrombin-III (AT-III), alpha 1-antitrypsin (alpha 1-AT), and haptoglobin (Hp) were purified within 3 h. The following recovery and purity were achieved: 95% (RSD, 2.8%) and 95% for HSA, 80% (RSD, 2.0%) and 99% for Tf, 70% (RSD, 2.1%) and 99% for AT-III, 65% (RSD, 2.0%) and 94% for alpha 1-AT, and 50% (RSD, 1.0%) and 90% for Hp. The results demonstrate that this novel multidimensional integrated chromatography system is capable of simultaneously separating multiple protein products from the same raw material with high yield and purity and it has the potential for a wide range of multi-step chromatography separation processes. (c) 2010 Elsevier B.V. All rights reserved