Simone Weil : a study in moral psychology and observations on religious life

At the heart of this thesis is the work of Simone Weil; at its centre is a critique of Iris Murdoch's The Sovereignty of Good . Murdoch was greatly inspired by Simone Weil and also wrote in the tradition of Anglo-Saxon philosophy; a thorough critique of her book therefore provides an opportunity to discuss critical concepts in Weil's work in a context meaningful to philosophers in the analytic tradition. I demonstrate the prima facie implausibility of Murdoch's portrayal of a moral agent as a psychologically isolated rather than socially situated human being; I then critique her views by appealing both to psychological evidence and to insights owing to linguistic philosophy. I show, in contrast, that on Well's conception humans are socially and politically situated thinking beings endowed with a faculty of attention and capable of consent. I further show how Weil's view of human relationships acknowledges the harm and isolation that people can experience, and only experience, as social beings, and which are constitutive of the phenomenon that she calls "affliction". As an experience of the lack of a referring context, affliction cannot be either acknowledged or named. The insight of linguistic philosophy that meaning is tied to context proves helpful to understanding this. Finally, I extend the notion of context beyond the social and argue for a four-stage schematism in the thought of Simone Weil; this schematism begins with the individual, passes on to the social world, then to the natural world viewed as necessity, and then to Go

Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0

Genome-scale metabolic models (GEMs) have been widely used for quantitative exploration of the relation between genotype and phenotype. Streamlined integration of enzyme constraints and proteomics data into such models was first enabled by the GECKO toolbox, allowing the study of phenotypes constrained by protein limitations. Here, we upgrade the toolbox in order to enhance models with enzyme and proteomics constraints for any organism with a compatible GEM reconstruction. With this, enzyme-constrained models for the budding yeasts Saccharomyces cerevisiae, Yarrowia lipolytica and Kluyveromyces marxianus are generated to study their long-term adaptation to several stress factors by incorporation of proteomics data. Predictions reveal that upregulation and high saturation of enzymes in amino acid metabolism are common across organisms and conditions, suggesting the relevance of metabolic robustness in contrast to optimal protein utilization as a cellular objective for microbial growth under stress and nutrient-limited conditions. The functionality of GECKO is expanded with an automated framework for continuous and version-controlled update of enzyme-constrained GEMs, also producing such models for Escherichia coli and Homo sapiens. In this work, we facilitate the utilization of enzyme-constrained GEMs in basic science, metabolic engineering and synthetic biology purposes

Hidden Epidemic of Macrolide-resistant Pneumococci

Community-acquired respiratory tract infections (RTIs) account for a substantial proportion of outpatient antimicrobial drug prescriptions worldwide. Concern over the emergence of multidrug resistance in pneumococci has largely been focused on penicillin-resistant Streptococcus pneumoniae. Macrolide antimicrobial drugs have been widely used to empirically treat community-acquired RTIs because of their efficacy in treating both common and atypical respiratory pathogens, including S. pneumoniae. However, increased macrolide use has been associated with a global increase in pneumococcal resistance, which is leading to concern over the continued clinical efficacy of the macrolides to treat community-acquired RTIs. We provide an overview of macrolide-resistant S. pneumoniae and assess the impact of this resistance on the empiric treatment of community-acquired RTIs

Hallmarks of Aromatase Inhibitor Drug Resistance Revealed by Epigenetic Profiling in Breast Cancer

Aromatase inhibitors are the major first-line treatment of estrogen receptor-positive breast cancer, but resistance to treatment is common. To date, no biomarkers have been validated clinically to guide subsequent therapy in these patients. In this study, we mapped the genome-wide chromatin-binding profiles of estrogen receptor alpha (ER alpha), along with the epigenetic modifications H3K4me3 and H3K27me3, that are responsible for determining gene transcription (n = 12). Differential binding patterns of ER alpha, H3K4me3, and H3K27me3 were enriched between patients with good or poor outcomes after aromatase inhibition. ER alpha and H3K27me3 patterns were validated in an additional independent set of breast cancer cases (n = 10). We coupled these patterns to array-based proximal gene expression and progression-free survival data derived from a further independent cohort of 72 aromatase inhibitor-treated patients. Through this approach, we determined that the ER alpha and H3K27me3 profiles predicted the treatment outcomes for first-line aromatase inhibitors. In contrast, the H3K4me3 pattern identified was not similarly informative. The classification potential of these genes was only partially preserved in a cohort of 101 patients who received first-line tamoxifen treatment, suggesting some treatment selectivity in patient classification. (C) 2013 AACR

Carbon Neutral Aviation

The aviation industry can become carbon neutral by CO2 recycling into synthetic kerosene using renewable energy. As an example we take CO2 emissions from Tata Steel in the Netherlands as well as Schiphol Airport’s kerosene consumption

Adiposity and metabolic syndrome analyzed from physique and body composition

メタボリックシンドローム(MS)の診断基準の適否を検討する目的で、40～50代男性86名(平均年齢51.2±5.2歳)をウエスト周囲径(W)≧85cmかつ内臓脂肪面積(V)≧100cm^2をA群、V<100cm^2をB群、W<85cmかつV≧100m^2をC群、V<100cm^2をD群に分類し、以下の検討をした。結果は1)MSはA群に33.3%、B群に13.3%存在した。危険因子(血圧高値、高脂血症・高血糖)が2以上はC群に25%、D群に2.8%含まれていた。2)A群:C群の比較では(1)体重・BMI・Wに有意差を認め、C群はBMIでは非肥満症であった。(2)上肢の筋肉量/脂肪量比(M/F比)、全身脂肪量に対する下肢脂肪量(F比)ともに有意差を認めなかった。しかし、C群:D群の比較ではこれらは有意に低値を示した(各3.2±0.9:4.4±1.6,28.9±4.4:34.4±6.9,P<0.01)。(3)V・皮下脂肪面積(S)・S/V・血圧・血液値に有意差を認めなかった。従って、1)A群とC群は身体組成的には差異はなく、D群と比較しM/F比、F比の低値が特徴的である。2)WではMSの診断基準外でも、内臓脂肪蓄積を伴い他のリスクも合併する"MS型"が存在すると考えられた。 / In order to review the propriety of diagnosis criteria of metabolic syndrome (MS), 86 males (40～50 generations, average age: 51.2±5.2) were classified to following four groups (A group: waist circumference (W)≧85cm and visceral fat area (V)≧100cm^2, B group: (W)≧85cm and V<100cm^2, C group: (W)<85cm, (V)≧100cm^2, D group: (W)<85cm, (V)<100cm^2.), and the following were reviewed. As the results, 1) MS was 33.3% in A group, and 13.3% in B group. Subjects with more than 2 of 3 risk factors (high blood pressure/hyperlipidemia/hyperglycemia) were included in C group as 25%, and in D group as 2.8%. 2) (1) Significant difference was recognized between A group and C groups in weight, BMI and (W), but C group was non-adiposity judged from BMI. (2) Between A group and C groups, the significant difference was not recognized in "Rate of muscle quantity to fat quantity in upper extremity (M/F rate)" and "Rate of fat quantity in lower extremities to whole body fat quantity (F rate)". In D group, these were significantly low values (M/F rate: A=2.9±1.8, C=3.2±0.9, D=4.4±1.6, P<0.05 ; F rate: A=28.9±5.9, C=28.9±4.4, D=34.4±6.9, P<0.05). (3) Between A group and C groups, the significant difference was not recognized in V (cm^2), subcutaneous fat (S) (cm^2), S/V, blood pressure, and blood analysis, respectively. From the above, 1) Although there was no difference of body composition between A group and C group, low values of M/F rate and F rate are characteristic to them in comparison with D group. 2) Even if (W) is out of the diagnosis criteria of MS, it was thought that there were "MS type" subjects with visceral adiposity and other risk factors

Hallmarks of Aromatase Inhibitor Drug Resistance Revealed by Epigenetic Profiling in Breast Cancer

Aromatase inhibitors are the major first-line treatment of estrogen receptor-positive breast cancer, but resistance to treatment is common. To date, no biomarkers have been validated clinically to guide subsequent therapy in these patients. In this study, we mapped the genome-wide chromatin-binding profiles of estrogen receptor alpha (ER alpha), along with the epigenetic modifications H3K4me3 and H3K27me3, that are responsible for determining gene transcription (n = 12). Differential binding patterns of ER alpha, H3K4me3, and H3K27me3 were enriched between patients with good or poor outcomes after aromatase inhibition. ER alpha and H3K27me3 patterns were validated in an additional independent set of breast cancer cases (n = 10). We coupled these patterns to array-based proximal gene expression and progression-free survival data derived from a further independent cohort of 72 aromatase inhibitor-treated patients. Through this approach, we determined that the ER alpha and H3K27me3 profiles predicted the treatment outcomes for first-line aromatase inhibitors. In contrast, the H3K4me3 pattern identified was not similarly informative. The classification potential of these genes was only partially preserved in a cohort of 101 patients who received first-line tamoxifen treatment, suggesting some treatment selectivity in patient classification. (C) 2013 AACR