Naresuan University Journal
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Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity.
No full textThe mechanisms by which melanoma and other cancer cells evade anti-tumor immunity remain incompletely understood. Here, we show that the growth of tumors formed by mutant Braf(V600E) mouse melanoma cells in an immunocompetent host requires their production of prostaglandin E2, which suppresses immunity and fuels tumor-promoting inflammation. Genetic ablation of cyclooxygenases (COX) or prostaglandin E synthases in Braf(V600E) mouse melanoma cells, as well as in Nras(G12D) melanoma or in breast or colorectal cancer cells, renders them susceptible to immune control and provokes a shift in the tumor inflammatory profile toward classic anti-cancer immune pathways. This mouse COX-dependent inflammatory signature is remarkably conserved in human cutaneous melanoma biopsies, arguing for COX activity as a driver of immune suppression across species. Pre-clinical data demonstrate that inhibition of COX synergizes with anti-PD-1 blockade in inducing eradication of tumors, implying that COX inhibitors could be useful adjuvants for immune-based therapies in cancer patients
Astrogliopathology in neurological, neurodevelopmental and psychiatric disorders.
No full textAstroglial cells represent a main element in the maintenance of homeostasis and providing defense to the brain. Consequently, their dysfunction underlies many, if not all, neurological, neurodevelopmental and neuropsychiatric disorders. General astrogliopathy is evident in diametrically opposing morpho-functional changes in astrocytes, i.e. their hypertrophy along with reactivity or atrophy with asthenia. Neurological disorders with astroglial participation can be genetic, of which Alexander disease is a primary sporadic astrogliopathy, environmentally caused, such as heavy metal encephalopathies, or neurodevelopmental in origin. Astroglia contribute to neurodegenerative processes seen in amyotrophic lateral sclerosis, Alzheimer's and Huntington's diseases. Furthermore, astroglia also play a role in major neuropsychiatric disorders, ranging from schizophrenia to depression, as well as in addictive disorders
Transport-Independent Protocols for Universal AER Communications
No full textThe emergence of Address-Event Representation (AER) as a general communications method across a large variety of neural devices suggests that they might be made interoperable. If there were a standard AER interface, systems could communicate using native AER signalling, allowing the construction of large-scale, real-time, heterogeneous neural systems. We propose a transport-agnostic AER protocol that permits direct bidirectional event communications between systems over Ethernet, and demonstrate practical implementations that connect a neuromimetic chip: SpiNNaker, both to standard host PCs and to real-time robotic systems. The protocol specifies a header and packet format that supports a variety of different possible packet types while coping with questions of data alignment, time sequencing, and packet compression. Such a model creates a flexible solution either for real-time communications between neural devices or for live spike I/O and visualisation in a host PC. With its standard physical layer and flexible protocol, the specification provides a prototype for AER protocol standardisation that is at once compatible with legacy systems and expressive enough for future very-large-scale neural systems
Too Big to Ignore? Hedge Fund Flow and Bond Yields
No full textThis paper investigates the information content of aggregate hedge fund flow and its predictive power with respect to bond yields. Dollar flows seem to capture the direct price impact, and percentage flows proxy for shifts in investor preferences. Dollar inflows to the largest 25% of funds predict decrease in Treasury bonds yields one month ahead, indicating that such funds may (temporarily) ''park'' new capital in safe bonds. Dollar outflows from these funds are followed by increasing yields of both government and corporate bonds, suggesting that funds liquidate their bond portfolios to meet their liquidity needs. Percentage outflow predicts decrease in Treasury bond yields, consistent with investor flight to safety. The strongest predictive power is associated with funds imposing short notice period prior to redemption
The Axl receptor tyrosine kinase is a discriminator of macrophage function in the inflamed lung.
No full textMuch of the biology surrounding macrophage functional specificity has arisen through examining inflammation-induced polarizing signals, but this also occurs in homeostasis, requiring tissue-specific environmental triggers that influence macrophage phenotype and function. The TAM receptor family of receptor tyrosine kinases (Tyro3, Axl and MerTK) mediates the non-inflammatory removal of apoptotic cells by phagocytes through the bridging phosphatidylserine-binding molecules growth arrest-specific 6 (Gas6) or Protein S. We show that one such TAM receptor (Axl) is exclusively expressed on mouse airway macrophages, but not interstitial macrophages and other lung leukocytes, under homeostatic conditions and is constitutively ligated to Gas6. Axl expression is potently induced by granulocyte-macrophage colony-stimulating factor expressed in the healthy and inflamed airway, and by type I interferon or Toll-like receptor-3 stimulation on human and mouse macrophages, indicating potential involvement of Axl in apoptotic cell removal under inflammatory conditions. Indeed, an absence of Axl does not cause sterile inflammation in health, but leads to exaggerated lung inflammatory disease upon influenza infection. These data imply that Axl allows specific identification of airway macrophages, and that its expression is critical for macrophage functional compartmentalization in the airspaces or lung interstitium. We propose that this may be a critical feature to prevent excessive inflammation because of secondary necrosis of apoptotic cells that have not been cleared by efferocytosis.Mucosal Immunology advance online publication, 21 January 2015; doi:10.1038/mi.2014.129
Automated Data-Driven Approaches to Evaluating and Interpreting Water Quality Time Series Data from Water Distribution Systems
No full textWater distribution networks are not inert transport systems. The high-quality water produced at water treatment works is subject to a variety of complex and interacting physical, chemical, and biological interactions within these highly variable, high-surface reactors. In particular, the aging and deteriorating asset condition in water distribution systems can result in a degradation of water quality delivered to the customer, often experienced as discoloration caused by increasing amounts of fine particulate matter. Here, it is proposed that by assessing measured turbidity over time, in particular its correlation with local hydraulics, an assessment of change in risk of fouling can be obtained and asset deterioration inferred. This paper presents a methodology for pairwise monitoring of a hydraulic parameter (flow or pressure) and turbidity using wavelet-based semblance analysis-a novel methodology from another domain, which is applied for the first time to water quality data in distribution systems. It is suggested and subsequently explored through case studies that an increasing (anti) correlation of the turbidity with the (pressure) flow diurnal cycle will be indicative of increasing fouling risk. This can be further supported through evaluation of the rate and magnitude of drift and through assessment of the change in magnitude of the daily turbidity profile. The composite of these approaches is applied to an extensive data set from a United Kingdom distribution system revealing the effectiveness of the analysis preflushing and postflushing (reducing discoloration events by 64-89%). With increasing proliferation of monitoring devices and real-time data acquisition the potential for online systems and well-informed proactive management is apparent. (C) 2015 American Society of Civil Engineers
Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases.
No full textThe similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD
Effect of polymer concentration on electrospinning of hydroxypropyl-β-cyclodextrins/PEO nanofibres
No full textElectrospinning is a versatile method for making nanofibres from polymer solution. Hydroxypropyl-β-cyclodextrin (HP-β-CD) is electrospun from aqueous solution by blending with non-toxic, biocompatible, synthetic polymer poly(ethylene oxide) (PEO). The aqueous solutions containing 70:30 HP-β-CD/PEO polymer blend with 8 wt.% concentration was electrospun to study the effects of process parameters on fibre morphology. Electrospinning was carried out at variable feed rate, applied voltage and working distance to see the effect on process stability and fibre diameter. Scanning electron microscope (SEM) images revealed that increasing feed rate, applied voltage and working distance promote bead formation in the fibre. The average diameter of the nanofibres was measured by using ImageJ software. The ultimate objective of this research is to optimize the electrospinning parameters to obtain bead-free HP-β-CD/PEO nanofibres. It is found that the fibre diameter increases with increasing feed rate and applied voltage. In contrast, the diameter of the fibres decreases with increasing working distance to a certain level. Further increases of working distance produces beads in the fibres. A feed rate of 0.5-1.0 ml/h, a working distance of 10-14cm and an applied voltage of 5-7kV have been found to produce smooth HP-β-CD/PEO nanofibres
