Naresuan University Journal
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Fitting transporter activities to cellular drug concentrations and fluxes: why the bumblebee can fly
No full textA recent paper in this journal argued that reported expression levels, kcat and Km for drug transporters could be used to estimate the likelihood that drug fluxes through Caco-2 cells could be accounted for solely by protein transporters. It was in fact concluded that if five such transporters contributed ‘randomly’ they could account for the flux of the most permeable drug tested (verapamil) 35% of the time. However, the values of permeability cited for verapamil were unusually high; this and other drugs have much lower permeabilities. Even for the claimed permeabilities, we found that a single ‘random’ transporter could account for the flux 42% of the time, and that two transporters can achieve 10 · 10−6 cm·s−1 90% of the time. Parameter optimisation methods show that even a single transporter can account for Caco-2 drug uptake of the most permeable drug. Overall, the proposal that ‘phospholipid bilayer diffusion (of drugs) is negligible’ is not disproved by the calculations of ‘likely’ transporter-based fluxes
Automating the Development of Metabolic Network Models
No full textAlthough substantial progress has been made in the automation of many areas of systems biology, from data processing and modelbuilding to experimentation, comparatively little work has been doneon integrated systems that combine all of these aspects. This paperpresents an active learning system, “Huginn”, that integrates experiment design and model revision in order to automate scientific reasoningabout Metabolic Network Models. We have validated our approach in asimulated environment using substantial test cases derived from a state-of-the-art model of yeast metabolism. We demonstrate that Huginn cannot only improve metabolic models, but that it is able to both solvea wider range of biochemical problems than previous methods, and toutilise a wider range of experiment types. Also, we show how design ofextended crucial experiments can be automated using Abductive LogicProgramming for the first time
“Representations of Moses Gaster (1856–1939) in Anglophone and Romanian Scholarship”
No full textThis article will analyze a selection of Anglophone and Romanian scholarship on Moses Gaster. Gaster (1856–1939) was an intellectual, bibliophile, rabbi, educator, and activist for Jewish emancipation and a national home in the geographical area of Palestine. The article is complemented by a thematically organized bibliography which brings together Anglophone and Romanian scholarship, and other material, such as newspaper articles. This work thus hopes to contribute to the closing of the gap between Anglophone and Romanian writing on Gaster. Whereas in Anglophone contexts Gaster is better remembered as an Anglo‑Jewish leader and an outspoken advocate of Zionism than for his literary scholarship, in Romania it seems to be the other way around. Gaster has, until recently, been remembered especially as a Romanian philologist and folklorist. This overview of the state of research also aims to contextualize my contribution, which focuses on Gaster’s scholarship and collection. I will argue that in order to evaluate Gaster’s significance, it is important to consider not only his wide‑ranging scholarly work and his political and communal involvements, but also his passion for collecting
Measurement of the cross section and limits on anomalous triple gauge couplings using final states with one lepton, missing transverse momentum, and two jets with the ATLAS detector at TeV
No full textControlled Synthesis of Nanoscopic Metal Cages
No full textHere we show an elegant and general route to the assembly of a giant {M12C24} cage from 12 palladium ions (M) and 24 heterometallic octanuclear coordination cages (C = {Cr7Ni-Py2}). The molecule is 8 nm in size, and the methods for its synthesis and characterization provide a basis for future developments at this scale
Advances and Concepts in Cervical Cancer Trials: A Road Map for the Future.
No full textOBJECTIVE: Cervical cancer is responsible for more than a quarter of a million deaths globally each year, mostly in developing countries, making therapeutic advances in all health care settings a top priority. The Gynecologic Cancer InterGroup (GCIG) is a worldwide collaboration of leading national research groups that develops and promotes multinational trials in gynecologic cancer. In recognition of the pressing need for action, the GCIG convened an international meeting with expert representation from the GCIG groups and selected large sites in low- and middle-income countries. METHODS: The focus was to develop a consensus on several concepts for future clinical trials, which would be developed and promoted by the GCIG and launched with major international participation. The first half of the meeting was devoted to a resume of the current state of the knowledge and identifying the gaps in need of new evidence, validating control arms for present and future clinical trials and identifying national and international barriers for studies of cervix cancers. The second half of the meeting was concerned with achieving consensus on a path forward. RESULTS AND CONCLUSIONS: There were 5 principal outcomes as follows: first, a proposal to expand fertility-preserving options with neoadjuvant chemotherapy; second, validation of the assessment of sentinel lymph nodes using minimally invasive surgery with an emphasis on identification and management of low-volume metastasis, such as isolated tumor cells and micrometastasis; third, evaluation of hypofractionation for palliative and curative radiation under the umbrella of the GCIG Cervix Cancer Research Network; fourth, adding to the advances in antiangiogenesis therapy in the setting of metastatic disease; and fifth, developing a maintenance study among women at high risk of relapse. The latter 2 systemic interventions could study PI3K (phosphatidylinositol-3-kinase) inhibitors, immunotherapy, anti-human papillomavirus approaches, or novel antiangiogenic agents/combinations