The practical philosophy of T. H. Green: an idealistic conception of liberal politics

As a critical advocate of the philosophy of Enlightenment, Thomas Hill Green (1836-1882) reconsidered the development of the empiricist and naturalistic philosophies of the seventeenth and eighteenth centuries and held that their development was connected in intricate ways to various quite specific issues arising in nineteenth-century British society. In order to respond to these issues, he established a comprehensive framework of philosophical thought as the foundation for his practical activities. In this framework, the core argument focuses on the relationship between consciousness and action. However, though Green’s philosophy has been widely investigated, no study has, as yet, focused exclusively on Green’s practical philosophy, and in particular his idea of the ethical citizen. This thesis undertakes this task and argues firstly that viewing the relationship between consciousness and action as the nexus of the human condition, Green’s practical philosophy is a coherent and consistent philosophical system which includes metaphysics; moral and ethical theory; and social and political theory. I then go on to argue that, by virtue of his philosophical system, Green founded political activity on the basis of metaphysical and moral ideas, on the one side, but on the other side, provided politics with a deep raison d’être; that is, to maintain and to provide the equality of opportunity for individuals by means of state power. Finally, I argue that while Green accordingly established a justification for state action, the nature of such state action relates closely to the self-government of individual citizens. Hence, Green’s practical philosophy provides an ethical theory of politics which underpins an important legacy for contemporary liberal political philosophy

Incorporating air density into a Gaussian process wind turbine power curve model for improving fitting accuracy

A power curve conventionally represents the relationship between hub height wind speed and wind turbine power output. Power curves facilitate the prediction of power production at a site and are also useful in identifying the significant changes in turbine performance which can be vital for condition monitoring. However, their accuracy is significantly influenced by changes in air density, mainly when the turbine is operating below rated power. A Gaussian process (GP) is a nonparametric machine learning approach useful for power curve fitting. Critical analysis of temperature correction is essential for improving the accuracy of wind turbine power curves. The conventional approach is to correct the data for air density before it is binned to provide a power curve, as described in the IEC standard. In this paper, four different possible approaches of air density correction and its effect on GP power curve fitting model accuracy are explored to identify whether the traditional IEC approach used for air density correction is most effective when estimating power curves using a GP. Finding the most accurate air density compensation approach is necessary to minimize GP model uncertainty

HMDB: a knowledgebase for the human metabolome

The Human Metabolome Database (HMDB, http://www.hmdb.ca) is a richly annotated resource that is designed to address the broad needs of biochemists, clinical chemists, physicians, medical geneticists, nutritionists and members of the metabolomics community. Since its first release in 2007, the HMDB has been used to facilitate the research for nearly 100 published studies in metabolomics, clinical biochemistry and systems biology. The most recent release of HMDB (version 2.0) has been significantly expanded and enhanced over the previous release (version 1.0). In particular, the number of fully annotated metabolite entries has grown from 2180 to more than 6800 (a 300% increase), while the number of metabolites with biofluid or tissue concentration data has grown by a factor of five (from 883 to 4413). Similarly, the number of purified compounds with reference to NMR, LC-MS and GC-MS spectra has more than doubled (from 380 to more than 790 compounds). In addition to this significant expansion in database size, many new database searching tools and new data content has been added or enhanced. These include better algorithms for spectral searching and matching, more powerful chemical substructure searches, faster text searching software, as well as dedicated pathway searching tools and customized, clickable metabolic maps. Changes to the user-interface have also been implemented to accommodate future expansion and to make database navigation much easier. These improvements should make the HMDB much more useful to a much wider community of users

Exome and genome sequencing of nasopharynx cancer identifies NF-κB pathway activating mutations

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Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Effects of Frame Action on Seismic Performance of Gusset Plate Connections in Buckling-restrained Braced Frames

本研究主要為探討消能支撐構架中梁柱效應對接合板耐震行為，測試在構架效應下，接合板在受梁、柱之開合效應下端部應力集中之影響，提出一等效支撐概念，設計接合板在構架運動之受力及斜撐軸力下所需之尺寸。並為瞭解與AISC-LRFD(2005)接合板設計方法之差異，設計五組接合板試體，分別使用於五組實尺寸一層樓之消能支撐構架試驗。其中試體一及二為利用單接合板將消能支撐與構架接合，試體三至五採用雙接合板將消能支撐與構架接合，並且為了測試接合板端部側邊加勁板對接合板端部的影響，於試體一及三之接合板試體端部加入側邊加勁板。五組試體中，除了其中一組為依照AISC-LRFD(2005)設計方式而得之單接合板在試驗時發生挫屈外，其餘四組試體於試驗後其行為良好，並由試驗觀察出，構架梁柱之開合效應，對接合板端部會因應力集中造成可觀的應變量，但加了側邊加勁板後，應變量即可降低，而單接合板與雙接合板在接合板與梁、柱界面比較上，單接合板之應變較雙接合板來得高。本研究並利用非線性有限元素分析程式ABAQUS(2005)，針對五組試驗構架進行模擬與分析，可預測五組試驗構架之整體行為。而經由實驗與有限元素分析之結果，可知本研究所提出之等效支撐模型確實可以準確預測接合板在構架梁柱效應下之受力，進而驗證本研究所提出之接合板設計方法。The present study of this thesis is focus on the seismic performance of a gusset plate subjected to frame action in Buckling-Restrained Braced Frames (BRBF). In order to test the stress concentration effects on gusset palte edges induced by frame action, an equivalent sturt model was proposed to estimate the frame action forces on a gusset plate, and a new design criteria by considering frame action and brace action simultanesly was proposed. In order to interpret the difference of each design methods, i.e. the AISC design method, or the design method by considering frame action presented in this thesis, a totally five full-scale, one story BRBF was tested to investigate the seismic performace of gusset plates under frame action. Single gusset plates was used in Specimen 1 and 2, dual gusset plates was used in Specimen 3 to 5, and edge stiffeners was applied on the gusset plate edges in specimen 1 and 3, so as to identify the contribution of edge stiffeners on gusset plate edges. One of gusset plates in five specimens was buckled after test, which was designed using AISC method, and the others gusset plates, which was designed using the theoretical formula presented from this study, was all fine. From the test observation, the edge of gusset plates will suffer large stains by frame action, but the applying of edge stiffeners can reduce the maginitude of normal strains effectively on the edge of gusset plates, and it seems true that single gusset plates will suffer larger frame action compared with dual gussets. Besides the test results, nonlinear FEM program ABAQUS was used to simulate the responses of specimen. This study describes the detailed analytical model and the modeling techniques, such as material model, boundary conditions, initial imperfections. The cyclic base shear versus the story drift relationships obtained from the test and FEM analytical results are quite agreeable. The analytical result confirm that the magnitude of frame action forces on a gusset plate can be accurately simulated. And baed on the theortical formula presented in this thesis, the edge stresses can also be accurately predicted when compared with FEM analytical results, so as to confirm the proposed design method in this thesis

Effect of polyvalencies of glycotopes on the binding of a lectin from the edible mushroom, Agaricus bisporus.

Agaricus bisporus agglutinin (ABA) isolated from edible mushroom has a potent anti-proliferative effect on malignant colon cells with considerable therapeutic potential as an anti-neoplastic agent. Since previous studies on the structural requirement for binding were limited to molecular or submolecular levels of Galbeta1-3GalNAc (T; Thomsen-Friedenreich disaccharide glycotope; where Gal represents D-galactopyranose and GalNAc represents 2-acetamido-2-deoxy-D-galactopyranose) and its derivatives, the binding properties of ABA were further investigated using our collection of glycans by enzyme-linked lectinosorbent assay and lectin-glycan inhibition assay. The results indicate that polyvalent Galbeta1-related glycotopes, GalNAcalpha1-Ser/Thr (Tn), and their cryptoforms, are the most potent factor for ABA binding. They were up to 5.5x10(5) and 4.7x10(6) times more active than monomeric T and GalNAc respectively. The affinity of ABA for ligands can be ranked as: multivalent T (alpha) (Galbeta1-3GalNAcalpha1-), Tn and I / II (Galbeta1-3GlcNac/Galbeta1-4GlcNAc, where GlcNAc represents 2-acetamido-2-deoxy-D-glucopyranose)>>>>monomeric T (alpha) and Tn > I >>GalNAc>>> II, L (Galbeta1-4Glc, where Glc represents D-glucopyranose) and Gal (inactive). These specific binding features of ABA establish the importance of affinity enhancement by high-density polyvalent (versus multiantennary I / II) glycotopes and facilitate our understanding of the lectin receptor recognition events relevant to its biological activities