Finite Minds and Open Minds

One of the most persistent complaints about Peter Klein’s infinitism involves the finite mind objection: given that we are finite, how can we ever handle an infinite series of reasons? Klein’s answer has been that we need not actually produce an infinite series; it is enough that such a series be available to us. In this paper a different reply is presented through the reconstruction of epistemic justification as a trade-off. In acting as responsible agents, we are striking a balance between the number of reasons that we can handle and the level of precision that we want our beliefs to have. If we are unable or unwilling to manage a large number of reasons, then we have to pay the price in terms of justificatory inexactitude and thereby of accepting relatively untrustworthy beliefs. As well as being intuitively attractive, this idea of a trade-off is warranted by the mathematics of epistemic justification, understood as involving probabilistic relations

Unlocking the full evolutionary potential of artificial metalloenzymes through direct metal-protein coordination: A review of recent advances for catalyst development

Generation of artificial metalloenzymes (ArMs) has gained much inspiration from the general understanding of natural metalloenzymes. Over the last decade, a multitude of methods generating transition metal-protein hybrids have been developed and many of these new-to-nature constructs catalyse reactions previously reserved for the realm of synthetic chemistry. This perspective will focus on ArMs incorporating 4d and 5d transition metals. It aims to summarise the significant advances made to date and asks whether there are chemical strategies, used in nature to optimise metal catalysts, that have yet to be fully recognised in the synthetic enzyme world, particularly whether artificial enzymes produced to date fully take advantage of the structural and energetic context provided by the protein. Further, the argument is put forward that, based on precedence, in the majority of naturally evolved metalloenzymes the direct coordination bonding between the metal and the protein scaffold is integral to catalysis. Therefore, the protein can attenuate metal activity by positioning ligand atoms in the form of amino acids, as well as making non-covalent contributions to catalysis, through intermolecular interactions that pre-organise substrates and stabilise transition states. This highlights the often neglected but crucial element of natural systems that is the energetic contribution towards activating metal centres through protein fold energy. Finally, general principles needed for a different approach to the formation of ArMs are set out, utilising direct coordination inspired by the activation of an organometallic cofactor upon protein binding. This methodology, observed in nature, delivers true interdependence between metal and protein. When combined with the ability to efficiently evolve enzymes, new problems in catalysis could be addressed in a faster and more specific manner than with simpler small molecule catalysts.</jats:p

Versuch einer Bestandsaufnahme: Kai Mikkonens Studie zur Narratologie des Comics

Kai Mikkonen: The Narratology of Comic Art. New York / London 2017 (= Routledge Advances in Comics Studies Bd. 3). 312 S. GBP 110.00. ISBN 978-1-138-22155-

Benign Infinity

According to infinitism, all justification comes from an infinite series of reasons. Peter Klein defends infinitism as the correct solution to the regress problem by rejecting two alternative solutions: foundationalism and coherentism. I focus on Klein's argument against foundationalism, which relies on the premise that there is no justification without meta-justification. This premise is incompatible with dogmatic foundationalism as defended by Michael Huemer and Time Pryor. It does not, however, conflict with non-dogmatic foundationalism. Whereas dogmatic foundationalism rejects the need for any form of meta-justification, non-dogmatic foundationalism merely rejects Laurence BonJour's claim that meta-justification must come from beliefs. Unlike its dogmatic counterpart, non-dogmatic foundationalism can allow for basic beliefs to receive meta-justification from non-doxastic sources such as experiences and memories. Construed thus, non-dogmatic foundationalism is compatible with Klein's principle that there is no justification without meta-justification. I conclude that Klein's rejection of foundationalism. fails. Nevertheless, I agree with Klein that when in response to a skeptical challenge we engage in the activity of defending our beliefs, the number of reasons we can give is at least in principle infinite. I argue that this type of infinity is benign because, when we continue to give reasons, we will eventually merely repeat previously stated reasons. Consequently, I reject Klein's claim that the more reasons we give the more we increase the justification of our beliefs

Introduction.: Narrating Reality in Comics

Introduction to the Special Issue by the Guest Editor

Einleitung.: Wirklichkeit erzählen im Comic

Einleitung der Gastherausgeber/in des Themenheft

MFGE8 does not influence chorio-retinal homeostasis or choroidal neovascularization in vivo

Purpose: Milk fat globule-epidermal growth factor-factor VIII (MFGE8) is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization. The prevalence of two single nucleotide polymorphisms (SNP) in MFGE8 was studied in two exsudative or “wet” Age-related Macular Degeneration (AMD) groups and two corresponding control groups. We studied the effect of MFGE8 deficiency on retinal homeostasis with age and on choroidal neovascularization (CNV) in mice. Methods: The distribution of the SNP (rs4945 and rs1878326) of MFGE8 was analyzed in two groups of patients with “wet” AMD and their age-matched controls from Germany and France. MFGE8-expressing cells were identified in Mfge8+/− mice expressing ß-galactosidase. Aged Mfge8+/− and Mfge8−/− mice were studied by funduscopy, histology, electron microscopy, scanning electron microscopy of vascular corrosion casts of the choroid, and after laser-induced CNV. Results: rs1878326 was associated with AMD in the French and German group. The Mfge8 promoter is highly active in photoreceptors but not in retinal pigment epithelium cells. Mfge8−/− mice did not differ from controls in terms of fundus appearance, photoreceptor cell layers, choroidal architecture or laser-induced CNV. In contrast, the Bruch's membrane (BM) was slightly but significantly thicker in Mfge8−/− mice as compared to controls. Conclusions: Despite a reproducible minor increase of rs1878326 in AMD patients and a very modest increase in BM in Mfge8−/− mice, our data suggests that MFGE8 dysfunction does not play a critical role in the pathogenesis of AMD

Health-related quality of life in glioma patients in China

<p>Abstract</p> <p>Background</p> <p>Health-related quality of life (HRQOL) has been increasingly emphasized in cancer patients. There are no reports comparing baseline HRQOL of different subgroups of glioma patients prior to surgery.</p> <p>Methods</p> <p>HRQOL assessments by the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0), the Mini-Mental State Examination and Karnofsky Performance Status were obtained from glioma patients prior to surgery.</p> <p>Results</p> <p>Ninety-two pathologically confirmed glioma patients were recruited. There were 84.8% patients with emotional impairment, 75% with social and cognitive impairment, 70.7% with physical impairment, and 50% with role impairment. Eighty-two percent of patients reported fatigue symptoms, 72.8% reported pain, 50% reported appetite loss, 39.1% reported insomnia, and 36.9% reported nausea/vomiting, whereas other symptoms (dyspnea, diarrhea, constipation) in the QLQ-C30 were reported by fewer than 30% of patients. Fatigue and pain symptoms and all "functioning" scales were strongly correlated with global health status/quality of life (QoL). Fatigue was strongly related to all functioning scales, pain, appetite loss, and global health status/QoL. No difference in baseline HRQOL prior to surgery was reported between females and males, among different lesion locations, or between normal- and abnormal-cognition subgroups of glioma patients. Age, KPS, WHO grade, and tumor recurrence significantly affected HRQOL in glioma patients.</p> <p>Conclusions</p> <p>These data provided the baseline HRQOL in glioma patients prior to surgery in China. Most pre-surgery glioma patients indicated emotional, social, cognitive, physical, and role impairment. Fatigue, pain, appetite loss, insomnia, and nausea/vomiting were common in these patients. The fatigue and pain symptoms and all types of functioning strongly affected global health status/QoL. Old age, worse performance status, WHO grade IV and tumor recurrence had deleterious effects on HRQOL.</p