Moral imagination as the foundation of ethics

Floris van den Berg (1973) studeerde filosofie in Leiden en Utrecht en Japanologie. Naast zijn baan als programmamaker bij Studium Generale van de UU werkt hij aan een proefschrift in de moderne politieke filosofie. Hij is actief als vrijdenker en humanist. Ook heeft hij een academisch weblog: www.florismontis.nl.Universeel subjectivisme is een – tegen de tijdgeest in – universele ethische theorie. Door het vergroten van het domein van het Rawlsiaanse procedurele model van rechtvaardigheid ontwikkel ik een theorie die afwijkt van Rawls omdat het de notie van de Original Position oprekt en zodoende het model van rechtvaardigheid koppelt aan thema’s uit de toegepaste ethiek vanuit utilitaristisch perspectief zoals vooral ontwikkeld door Peter Singer. Universeel subjectivisme is gebaseerd op het idee dat vanuit de Original Position alle mogelijke vormen van leven kunnen worden gerealiseerd. Het vermogen tot lijden is het criterium voor ethische consideratie in dit model. Universeel subjectivisme is een gedachtenexperiment om de wereld te beleven vanuit elk mogelijk levend wezen. Het is een methode om de verschillende belangen met elkaar te harmoniseren. Universeel subjectivisme is een optimaliseringtheorie van de belangen van alle (in ieder geval zoveel mogelijk) levende wezens. Het model maakt het mogelijk om de belangen van diverse groepen te incorporeren in een coherente theorie, zoals de belangen van dieren, toekomstige generaties, internationale relaties, gehandicapten, immigranten etcetera. Zodoende komt tot uiting waar onrecht is en hoe het, in theorie althans, kan worden verworpen. Universeel subjectivisme is een niet-transcendente fundering van de ethiek en het doet geen beroep op noties van altruïsme

Electrochemical protein cleavage in a microfluidic cell for proteomics studies

Electrochemical protein digestion prior to mass spectrometric analysis is a purely instrumental approach to protein identification, offering reduced consumption of chemicals and shorter analysis times compared to the use of enzymes and chemical cleavage agents. Here we demonstrate the possibilities of site-specific peptide bond cleavage and disulphide bond reduction in a microfluidic electrochemical cell. The use of microfluidics in this context is beneficial for increased electrochemical cleavage yields, small sample volumes and the possibility of rapid on-line analysis, thereby providing a versatile tool for routine proteomics studies

Microbial diversity within the vicinity of the Antarctic Concordia Station - an analog for human exploration sites on Mars or the icy moons of Jupiter or Saturn

The extreme terrestrial environment of the Antarctic ice sheet serves as an excellent probing ground for the adaptation of extremotolerant microorganisms. To inhabit this hostile environment, microorganisms resist sub-zero temperatures, wide temperature fluctuations, high incidence of solar UV radiation, desiccation, and very low nutrient availability. Located on a 3200 meter-high plateau in Antarctica, the Concordia Station is a remote, isolated habitat, providing an ideal location to monitor the indigenous microbial diversity and human-associated bacterial dispersal on the surface snow. In this study, (ESA project No. AO-13-Concordia-23) surface snow was sampled monthly at three areas varying in proximity (10 m, 500 m, and 1 km) to the Concordia Station across two years (March 2015 to December 2016). Snow samples from the months January, March, May, July, September, and November of both years (n=33) were phylogenetically profiled via sequencing of the 16S rRNA gene to identify microbial presence and abundance with respect to seasonal changes and human activity. While harboring low microbial diversity, the surface snow samples were characterized by heterogeneous microbiomes. Interestingly, snow samples were found to have a core microbiome consisting of the genera Acinetobacter, Micrococcus, Delftia, Bacillus, Enhydrobacter, Cutibacterium, and Alcanivorax, which persisted regardless of the measured environmental factors and level of human activity. Ultimately, this study will further inform improvements or modifications to the existing techniques to interrogate the microbial ecology in extreme (sub-zero) environments as well as provide suggestions for future life-detection driven space missions

Do fatty lesions explain the effect of inflammation on new syndesmophytes in patients with radiographic axial spondyloarthritis? Results from the SIAS cohort and ASSERT trial

OBJECTIVES: To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. METHODS: Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) cohort and ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial were assessed at T0, T1 (SIAS: 1 year; ASSERT: 24 weeks) and T2 (2 years). Syndesmophytes assessed in each vertebral corner by whole spine low-dose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 were considered present if seen by two of two readers. Inflammation (T0) and fat deposition (T0 and T1) on MRI were present if seen by ≥2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). Vertebral corners showing fat deposition or a syndesmophyte at baseline were ignored. Mediation analysis was applied to determine what proportion of the total effect of inflammation on syndesmophyte formation could be explained via the path of intermediate fat deposition. RESULTS: Forty-nine SIAS patients (with 2667 vertebral corners) and 168 ASSERT patients (with 2918 vertebral corners) were analysed. The presence of inflammation at T0 increased the probability of a new syndesmophyte in the same vertebral corner at T2 by 9.3%. Of this total effect, 0.2% (2% (0.2 of 9.3) of the total effect) went via intermediate new fat deposition. In ASSERT, the total effect was 7.3%, of which 0.8% (10% of the total effect) went via new fat deposition. CONCLUSION: In r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition

Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma

Summary: The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort of SHH (Sonic Hedgehog), group 3, and group 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence and resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second profile showed enrichment for DNA damage, as well as apoptotic and neuronal signaling. Integrative analysis demonstrated that heterogeneous transcriptional input converges on these protein-signaling profiles: all SHH and a subset of group 3 patients exhibited the MYC-like protein-signaling profile; the majority of the other group 3 subset and group 4 patients displayed the DNA damage/apoptotic/neuronal signaling profile. Functional analysis of enriched pathways highlighted cell-cycle progression and protein synthesis as therapeutic targets for MYC-like medulloblastoma. : Using peptide phosphorylation profiling, Zomerman et al. identify two medulloblastoma phosphoprotein-signaling profiles that have prognostic value and are potentially targetable. They find that these profiles extend across transcriptome-based subgroup borders. This suggests that diverse genetic information converges on common protein-signaling pathways and highlights protein-signaling as a unique information layer. Keywords: medulloblastoma, protein-signaling, protein synthesis, MYC, TP53, proteome, phosphoproteom

プレゼンテーション演習

平成26年8月5日にお茶の水女子大学で行われた「三大学連携 機関リポジトリ研修会」におけるプレゼンテーション資

A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke

The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations. METHODS We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points. RESULTS The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P=0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81). CONCLUSIONS In a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups

Modulations of Neuroendocrine Stress Responses During Confinement in Antarctica and the Role of Hypobaric Hypoxia

The Antarctic continent is an environment of extreme conditions. Only few research stations exist that are occupied throughout the year. The German station Neumayer III and the French-Italian Concordia station are such research platforms and human outposts. The seasonal shifts of complete daylight (summer) to complete darkness (winter) as well as massive changes in outside temperatures (down to -80 degrees C at Concordia) during winter result in complete confinement of the crews from the outside world. In addition, the crew at Concordia is subjected to hypobaric hypoxia of similar to 650 hPa as the station is situated at high altitude (3,233 m). We studied three expedition crews at Neumayer Ill (sea level) (n = 16) and two at Concordia (high altitude) (n = 15) to determine the effects of hypobaric hypoxia on hormonal/metabolic stress parameters [endocannabinoids (ECs), catecholamines, and glucocorticoids] and evaluated the psychological stress over a period of 11 months including winter confinement. In the Neumayer III (sea level) crew, EC and n-acylethanolamide (NAE) concentrations increased significantly already at the beginning of the deployment (p < 0.001) whereas catecholamines and cortisol remained unaffected. Over the year, ECs and NAEs stayed elevated and fluctuated before slowly decreasing till the end of the deployment. The classical stress hormones showed small increases in the last third of deployment. By contrast, at Concordia (high altitude), norepinephrine concentrations increased significantly at the beginning (p < 0.001) which was paralleled by low EC levels. Prior to the second half of deployment, norepinephrine declined constantly to end on a low plateau level, whereas then the EC concentrations increased significantly in this second period during the overwintering (p < 0.001). Psychometric data showed no significant changes in the crews at either station. These findings demonstrate that exposition of healthy humans to the physically challenging extreme environment of Antarctica (i) has a distinct modulating effect on stress responses. Additionally, (ii) acute high altitude/hypobaric hypoxia at the beginning seem to trigger catecholamine release that downregulates the EC response. These results (iii) are not associated with psychological stress