Naresuan University Journal
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Caveolae and signalling in cancer.
No full textIt has been over 20 years since the discovery that caveolar lipid rafts function as signalling organelles. Lipid rafts create plasma membrane heterogeneity, and caveolae are the most extensively studied subset of lipid rafts. A newly emerging paradigm is that changes in caveolae also generate tumour metabolic heterogeneity. Altered caveolae create a catabolic tumour microenvironment, which supports oxidative mitochondrial metabolism in cancer cells and which contributes to dismal survival rates for cancer patients. In this Review, we discuss the role of caveolae in tumour progression, with a special emphasis on their metabolic and cell signalling effects, and their capacity to transform the tumour microenvironment
Meta-analysis of Expression of Hepatic Organic Anion Transporting Polypeptide (OATP) Transporters in Cellular Systems Relative to Human Liver Tissue
No full textOrganic anion transporting polypeptide (OATP)1B1, OATP1B3 and OATP2B1 transporters play an important role in hepatic drug disposition. Recently, an increasing number of studies have reported proteomic expression data for OATP transporters. However, systematic analysis and understanding of the actual differences in OATP expression between liver tissue and commonly used cellular systems is lacking. In the current study, meta-analysis was performed to assess the protein expression of OATP transporters reported in hepatocytes relative to liver tissue and identify any potential correlations in transporter expression levels in the same individual. OATP1B1 was identified as the most abundant uptake transporter at 5.9 ± 8.3, 5.8 ± 3.3 and 4.2 ± 1.7 fmol/μg protein in liver tissue, sandwich-cultured human hepatocytes (SCHH) and cryopreserved suspended hepatocytes, respectively. The rank order in average expression in liver tissue and cellular systems was OATP1B1 > OATP1B3 ≈ OATP2B1. Abundance levels of the OATP transporters investigated were not significantly different between liver and cellular systems, with the exception of OATP2B1 expression in SCHH relative to liver tissue. Analysis of OATP1B1, OATP1B3 and OATP2B1 liver expression data in the same individuals (n = 86) identified weak (OATP1B1/OATP2B1) to moderate (OATP1B3/OATP2B1) significant correlations. A significant weak correlation was noted between OATP1B1 abundance and age of human donors, whereas expression of the OATPs investigated was independent of sex. Implications of the current analysis on the in vitro-in vivo extrapolation of transporter-mediated drug disposition using physiologically-based pharmacokinetic models are discussed
Voltage control of PV-rich LV networks: OLTC-fitted transformer and capacitor banks
No full textDue to the increasing adoption of domestic photovoltaic (PV) systems, the use of technologies such as on-load tap changer (OLTC)-fitted transformers, capacitor banks, and remote monitoring are being considered to mitigate voltage issues, particularly in European-style low voltage (LV) networks. Depending on the control strategy, however, the effects on customer voltages and control actions (e.g., tap changes or capacitor switching) can vary significantly. This work presents a framework to assess the performance of different OLTC-based control strategies in terms of voltage compliance with the standard BS EN50160 and the number of control actions. Three control strategies are proposed: constant set-point (CSC), time-based (TBC) and remote monitoring-based (RMC). A week-long Monte Carlo analysis is carried out considering a real UK LV network, three-phase power flows, different PV penetrations and seasonality. Results show that the TBC outperforms the CSC but at the expense of more tap changes. Due to the enhanced visibility, the RMC significantly increases the PV hosting capacity whilst limiting tap operations. Finally, when feeders have contrasting voltage issues, capacitor banks are found to provide additional flexibility and allow higher PV penetrations. These findings are expected to help the industry determining the benefits from OLTC-based solutions in future LV networks
Crystal structure of X-prolyl aminopeptidase from Caenorhabditis elegans: A cytosolic enzyme with a di-nuclear active site.
No full textEukaryotic aminopeptidase P1 (APP1), also known as X-prolyl aminopeptidase (XPNPEP1) in human tissues, is a cytosolic exopeptidase that preferentially removes amino acids from the N-terminus of peptides possessing a penultimate N-terminal proline residue. The enzyme has an important role in the catabolism of proline containing peptides since peptide bonds adjacent to the imino acid proline are resistant to cleavage by most peptidases. We show that recombinant and catalytically active Caenorhabditis elegans APP-1 is a dimer that uses dinuclear zinc at the active site and, for the first time, we provide structural information for a eukaryotic APP-1 in complex with the inhibitor, apstatin. Our analysis reveals that C. elegans APP-1 shares similar mode of substrate binding and a common catalytic mechanism with other known X-prolyl aminopeptidases
Statistical top-down approach for energy loss estimation in distribution systems
No full textThis work proposes a statistical top-down methodology for energy loss estimation in medium voltage (MV) distribution systems. A statistical model is used to adjust the load parameters (i.e., ZIP coefficients) of the aggregated load allocated to each secondary transformer along the MV feeder. This adjustment process also results in the estimation of the corresponding energy losses. The information required by the proposed methodology is limited to the feeder topology, conductors, rated capacity of the transformers, and the voltage and power measurements at the primary substation during the period of analysis. If available, additional information from meters installed along the feeder can be used to improve the estimation. To illustrate the approach, a real Brazilian 13.8kV feeder is used. The results, compared with other methodologies available in the literature, demonstrate the benefits of the proposed methodology