GMEM: Generalized Memory Management for Peripheral Devices

This paper presents GMEM, generalized memory management, for peripheral devices. GMEM provides OS support for centralized memory management of both CPU and devices. GMEM provides a high-level interface that decouples MMU-specific functions. Device drivers can thus attach themselves to a process's address space and let the OS take charge of their memory management. This eliminates the need for device drivers to "reinvent the wheel" and allows them to benefit from general memory optimizations integrated by GMEM. Furthermore, GMEM internally coordinates all attached devices within each virtual address space. This drastically improves user-level programmability, since programmers can use a single address space within their program, even when operating across the CPU and multiple devices. A case study on device drivers demonstrates these benefits. A GMEM-based IOMMU driver eliminates around seven hundred lines of code and obtains 54% higher network receive throughput utilizing 32% less CPU compared to the state-of-the-art. In addition, the GMEM-based driver of a simulated GPU takes less than 70 lines of code, excluding its MMU functions.Comment: Finished before Weixi left Rice and submitted to ASPLOS'2

Effects of a Standardized Phenolic-Enriched Maple Syrup Extract on β-Amyloid Aggregation, Neuroinflammation in Microglial and Neuronal Cells, and β-Amyloid Induced Neurotoxicity in \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e

Published data supports the neuroprotective effects of several phenolic-containing natural products, including certain fruit, berries, spices, nuts, green tea, and olive oil. However, limited data are available for phenolic-containing plant-derived natural sweeteners including maple syrup. Herein, we investigated the neuroprotective effects of a chemically standardized phenolic-enriched maple syrup extract (MSX) using a combination of biophysical, in vitro, and in vivo studies. Based on biophysical data (Thioflavin T assay, transmission electron microscopy, circular dichroism, dynamic light scattering, and zeta potential), MSX reduced amyloid β1−42 peptide (Aβ1−42) fibrillation in a concentration-dependent manner (50–500 μg/mL) with similar effects as the neuroprotective polyphenol, resveratrol, at its highest test concentration (63.5 % at 500 μg/mL vs. 77.3 % at 50 μg/mL, respectively). MSX (100 μg/mL) decreased H2O2-induced oxidative stress (16.1 % decrease in ROS levels compared to control), and down-regulated the production of lipopolysaccharide (LPS)-stimulated inflammatory markers (22.1, 19.9, 74.8, and 87.6 % decrease in NOS, IL-6, PGE2, and TNFα levels, respectively, compared to control) in murine BV-2 microglial cells. Moreover, in a non-contact co-culture cell model, differentiated human SH-SY5Y neuronal cells were exposed to conditioned media from BV-2 cells treated with MSX (100 μg/mL) and LPS or LPS alone. MSX-BV-2 media increased SH-SY5Y cell viability by 13.8 % compared to media collected from LPS-BV-2 treated cells. Also, MSX (10 μg/mL) showed protective effects against Aβ1−42 induced neurotoxicity and paralysis in Caenorhabditis elegans in vivo. These data support the potential neuroprotective effects of MSX warranting further studies on this natural product

Anti-glycation and anti-oxidative effects of a phenolic-enriched maple syrup extract and its protective effects on normal human colon cells

Oxidative stress and free radical generation accelerate the formation of advanced glycation endproducts (AGEs) which are linked to several chronic diseases. Published data suggest that phenolic-rich plant foods, show promise as natural anti-AGEs agents due to their anti-oxidation capacities. A phenolic-enriched maple syrup extract (MSX) has previously been reported to show anti-inflammatory and neuroprotective effects but its anti-AGE effects remain unknown. Therefore, herein, we investigated the anti-glycation and anti-oxidation effects of MSX using biochemical and biophysical methods. MSX (500 μg mL−1) reduced the formation of AGEs by 40% in the bovine serum albumin (BSA)–fructose assay and by 30% in the BSA–methylglyoxal (MGO) assay. MSX also inhibited the formation of crosslinks typically seen in the late stage of glycation. Circular dichroism and differential scanning calorimeter analyses demonstrated that MSX maintained the structure of BSA during glycation. In the anti-oxidant assays, MSX (61.7 μg mL−1) scavenged 50% of free radicals (DPPH assay) and reduced free radical generation by 20% during the glycation process (electron paramagnetic resonance time scan). In addition, the intracellular levels of hydrogen peroxide induced reactive oxygen species were reduced by 27–58% with MSX (50–200 μg mL−1) in normal/non-tumorigenic human colon CCD-18Co cells. Moreover, in AGEs and MGO challenged CCD-18Co cells, higher cellular viabilities and rapid extracellular signal-regulated kinase (ERK) phosphorylation were observed in MSX treated cells, indicating its protective effects against AGEs-induced cytotoxicity. Overall, this study supports the biological effects of MSX, and warrants further investigation of its potential as a dietary agent against diseases mediated by oxidative stress and inflammation

Performance measurement of cross-culture supply chain partnership: a case study in the Chinese automotive industry

This study explores a performance measurement system for a dynamic supply chain partnership in a cross-cultural context. An initial framework is constructed by reviewing the existing literature, followed by an in-depth case study in the Chinese automotive industry, where the framework is refined to address the multi-cultural setting. A performance measurement, system which includes the relationship strategy and operational measurement criteria for a supply chain partnership, has been developed. The relationship strategy contains elements of strategy orientation, management style, interdependence, mutual organisational characteristics and common goals. The operational measurement criteria consist of commitment, trust, communication behaviour, information sharing, participation decision, quality, production performance, delivery, cost, supplier strength, attitude, compromise and loyalty. The last three operational measurement criteria are found to be particularly relevant to the cross-cultural feature. While existing studies tend to focus on either specific measures or individual organisations, this paper for the first time proposes a comprehensive framework to measure the performance of supply chain partnerships. The cross-cultural perspective provides a further unique view on how a performance measurement system can be responsive to the dynamics in practice

A MicroRNA-7 Binding Site Polymorphism in HOXB5 Leads to Differential Gene Expression in Bladder Cancer

PURPOSE: To investigate the biological function of HOXB5 in human bladder cancer and explore whether the HOXB5 3'-UTR SNP (1010A/G), which is located within the microRNA-7 binding site, was correlated with clinical features of bladder cancer. METHODS: Expression of HOXB5 in 35 human bladder cancer tissues and 8 cell lines were examined using real-time PCR and immunohistochemistry. Next, we explored the biological function of HOXB5 in vitro using cell proliferation, migration and colony formation assays. Using bioinformatics, a SNP (1010A/G) was found located within the microRNA-7 binding site in the 3'-UTR of HOXB5. Real-time PCR was used to test HOXB5 expression affected by different alleles. Finally, multivariate logistic regression analysis was used to determine the relationship between SNP (1010A/G) frequency and clinical features in 391 cases. RESULTS: HOXB5 was frequently over-expressed both in bladder cancer tissues and cell lines. Inhibition of HOXB5 suppressed the oncogenic function of cancer cells. Next, we demonstrated that a SNP (1010A/G), located within the microRNA-7 binding site in the 3'-UTR of HOXB5, could affect HOXB5 expression in bladder cancer mainly by differential binding activity of microRNA-7 and SNP-related mRNA stability. Finally, we also showed the frequency of 1010G genotype was higher in cancer group compared to normal controls and correlated with the risk of high grade and high stage. CONCLUSION: HOXB5 is overexpressed in bladder cancer. A miRNA-binding SNP (1010A/G) located within 3'-UTR of HOXB5 is associated with gene expression and may be a promising prognostic factor for bladder cancer

Modular construction of mammalian gene circuits using TALE transcriptional repressors

An important goal of synthetic biology is the rational design and predictable implementation of synthetic gene circuits using standardized and interchangeable parts. However, engineering of complex circuits in mammalian cells is currently limited by the availability of well-characterized and orthogonal transcriptional repressors. Here, we introduce a library of 26 reversible transcription activator–like effector repressors (TALERs) that bind newly designed hybrid promoters and exert transcriptional repression through steric hindrance of key transcriptional initiation elements. We demonstrate that using the input-output transfer curves of our TALERs enables accurate prediction of the behavior of modularly assembled TALER cascade and switch circuits. We also show that TALER switches using feedback regulation exhibit improved accuracy for microRNA-based HeLa cancer cell classification versus HEK293 cells. Our TALER library is a valuable toolkit for modular engineering of synthetic circuits, enabling programmable manipulation of mammalian cells and helping elucidate design principles of coupled transcriptional and microRNA-mediated post-transcriptional regulation.National Institutes of Health (U.S.) (Grant 5R01CA155320-04)National Institutes of Health (U.S.) (Grant P50GM098792)National Institutes of Health (U.S.) (Grant 1R01CA173712-01

A Novel NAD Signaling Mechanism in Axon Degeneration and its Relationship to Innate Immunity.

Axon degeneration represents a pathological feature of many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease where axons die before the neuronal soma, and axonopathies, such as Charcot-Marie-Tooth disease and hereditary spastic paraplegia. Over the last two decades, it has slowly emerged that a central signaling pathway forms the basis of this process in many circumstances. This is an axonal NAD-related signaling mechanism mainly regulated by the two key proteins with opposing roles: the NAD-synthesizing enzyme NMNAT2, and SARM1, a protein with NADase and related activities. The crosstalk between the axon survival factor NMNAT2 and pro-degenerative factor SARM1 has been extensively characterized and plays an essential role in maintaining the axon integrity. This pathway can be activated in necroptosis and in genetic, toxic or metabolic disorders, physical injury and neuroinflammation, all leading to axon pathology. SARM1 is also known to be involved in regulating innate immunity, potentially linking axon degeneration to the response to pathogens and intercellular signaling. Understanding this NAD-related signaling mechanism enhances our understanding of the process of axon degeneration and enables a path to the development of drugs for a wide range of neurodegenerative diseases

Effectiveness of Ferric Salts to Remove Low Levels of Dosed Copper from NOM-Containing Natural Water

Water utilities dose copper in drinking water systems to inhibit/kill microorganisms including algae. Under conditions observed in the systems, the majority of dosed copper is reported to be in dissolved forms of Cu-NOM and inorganic compounds. High concentrations (40 mg/L) of ferric salts are reported to be able to remove large amounts of copper. However, the fate of dissolved copper when a small amount of ferric salts (<2 mg/L) is present in natural water or in the distribution pipes when they are released from the corroded iron pipes are not known. The current paper investigates the mechanisms behind the dissolved copper removal in NOM-containing bulk water. When copper was dosed from 250–800 mg-Cu/L, relatively high solubility was demonstrated in Mundaring water, with dissolved copper increased from 250–720 mg-Cu/L. Both ferric chloride and ferric hydroxide were found to have a considerable ability to remove dissolved copper while the former showed higher capacity. Ferric chloride showed a linear relationship with copper removal (R2=0.99) and the removal by ferric hydroxide showed excellent agreement with either the Freundlich (R2=0.98) or Langmuir (R2=0.99) adsorption isotherm