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Results are presented from the optimal operation of a fully automated robotic liquid handling station where parallel experiments are performed for calibrating a kinetic fermentation model. To increase the robustness against uncertainties and/or wrong assumptions about the parameter values, an iterative calibration and experiment design approach is adopted. Its implementation yields a stepwise reduction of parameter uncertainties together with an adaptive redesign of reactor feeding strategies whenever new measurement information is available. The case study considers the adaptive optimal design of 4 parallel fed-batch strategies implemented in 8 mini-bioreactors. Details are given on the size and complexity of the problem and the challenges related to calibration of over-parameterized models and scarce and non-informative measurement data. It is shown how methods for parameter identifiability analysis and numerical regularization can be used for monitoring the progress of the experimental campaigns in terms of generated information regarding parameters and selection of the best fitting parameter subset.

Recent research on the professionalization of psychology at the end of the nineteenth century shows how objects of knowledge which appear illegitimate to us today shaped the institutionalization of disciplines. The veridical or telepathic hallucination was one of these objects, constituting a field both of division and exchange between nascent psychology and disciplines known as ‘psychic sciences’ in France, and ‘psychical research’ in the Anglo-American context. In France, Leon Marillier (1862–1901) was the main protagonist in discussions concerning the concept of the veridical hallucination, which gave rise to criticisms by mental specialists and psychopathologists. After all, not only were these hallucinations supposed to occur in healthy subjects, but they also failed to correspond to the Esquirolian definition of hallucinations through being corroborated by their representation of external, objective events.

We show how to efficiently compute A-optimal experimental designs, which are formulated in terms of the minimization of the trace of the covariance matrix of the underlying regression process, using quasi-Newton sequential quadratic programming methods. In particular, we introduce a modification of the problem that leads to significantly faster convergence. To derive this modification, we model each iteration in terms of an initial experimental design that is to be improved, and show that the absolute condition number of the model problem grows without bounds as the quality of the initial design improves. As a remedy, we devise a preconditioner that ensures that the absolute condition number will instead stay uniformly bounded. Using numerical experiments, we study the effect of this reformulation on relevant cases of the general problem class, and find that it leads to significant improvements in both stability and convergence behavior.

ZusammenfassungJohannes Rohbeck: Aufklärung und Geschichte. Über eine praktische Geschichtsphilosophie der Zukunft, Akademie Verlag, Berlin 2010, 247 S.

AbstractJohann Friedrich Wilhelm Jerusalem's Betrachtungen ber die vornehmsten Wahrheiten der Religionwas a bestseller of the German Enlightenment, although it is a theological book. In this article, his Betrachtungenis treated as a text that tries to synthesize the newly established philosophy of history with more or less traditional theological patterns. Jerusalem uses the argument of universal development and progress in history to demonstrate the evidence of divine providence. His book thus resembles Gotthold Ephraim Lessing's Erziehung des Menschengeschlechts, which it may have influenced. The main purpose of Jerusalem is to calm and pacify the individual's soul. He wants to prove that the individual's life fits into the general order of history, which is also the purpose of profane philosophy of history in German Enlightenment. Jerusalem's neological philosophy of history provides new answers to the problem of evil after the decline of a metaphysical theodicy in the tradition of Leibniz.

The dose‐related effects of systemically administered rhIGF‐I and rhIGF‐I/IGFBP‐3 were monitored in the osteopenic rat skeleton at three different sites with cancellous bone: distal femoral metaphysis, epiphysis, and lumbar vertebral bodies. At the age of 16 weeks, rats were bilaterally ovariectomized (OVX) or sham operated (sham) and 8 weeks later divided into the control groups (sham OVX), and OVX groups treated with different doses of rhIGF‐I or rhIGF‐I/IGFBP‐3 for 8 weeks. Fluorescent bone markers were given 9 and 2 days before necropsy. In addition, changes in designated bone sites as a result of ovariectomy alone were evaluated 8 and 16 weeks after surgery. High bone resorption, which dominates the postovariectomy remodeling process, resulted in a loss of cancellous bone at all measured sites. The highest trabecular bone loss was measured in the metaphyses (40%), compared with 22% in the lumbar vertebrae and 16% in the epiphyses. After 8 weeks of treatment with 7.5 mg/kg of rhIGF‐I/IGFBP‐3, bone formation rates were increased at all sites measured. Increased trabecular thickness was observed at the epiphyses and in the lumbar vertebral bodies. Increased bone resorption was restricted to the metaphyses of the rats that received the highest dose of rhIGF‐I or rhIGF‐I/IGFBP‐3. Both formulations of rhIGF‐I increased longitudinal bone growth similarly. This experiment demonstrates site‐specific differences in cancellous bone reactions following ovariectomy. Epyphyses showed some advantages for cancellous bone histomorphometry over metaphyses and lumbar vertebral bodies. The data presented confirm the potential of rhIGF‐I/IGFBP‐3 complex to promote the bone formation process at various bone sites in osteoporotic rat skeleton.

A diagonal polyacrylamide-dodecyl sulfate gel electrophoresis procedure is described. Its utility is related to the use of the reagent methyl-4-mercaptobutyrimidate as a protein-protein crosslinking reagent. Crosslinking with this reagent occurs through the formation of intermolecular disulfide bonds. Oxidized proteins are separated in one dimension by electrophoresis under non-reducing conditions and in the second dimension under reducing conditions. All proteins except those derived from crosslinked species fall on a diagonal. Methods are described for the identification of the separated monomeric components of crosslinked species. The technique has been applied to the 30S ribosomal subunit of Escherichia coli, and the new crosslinked dimer, S4-S13, has been identified.

Yeast chromatin, isolated by a rapid procedure contains in addition to histones H2A, H2B, H3 and H4 a fifth major basic protein. This fifth polypeptide is not an intrinsic component of the nucleosome structure. It has properties of both histone and nonhistone proteins and might represent an early form of histone H1 and of high mobility group nonhistone proteins of higher eukaryotes.

Es ist kein Geheimnis, daß Friedrich Nietzsche ein in der Bonner (und Leipziger) Schule Friedrich Ritschls solide ausgebildeter Philologe gewesen ist, der das Geschäft der Philologie ein Jahrzehnt lang professionell ausgeübt hat. Seltsam einig scheint sich die ansonsten außerordentlich heterogene literaturwissenschaftliche und philosophische Nietzsche-Forschung bislang freilich darin gewesen zu sein, daß Nietzsche diese philologische Prägung schon sehr früh zu transformieren und bald gänzlich abzustreifen gesucht habe. Die Philologie, so die herrschende Meinung, habe Nietzsche – wie sich etwa in den Aufzeichnungen zur unvollendet gebliebenen Unzeitgemäßen Betrachtung Wir Philologen(1874/75) zeige – als eine schulmeisterliche, aber nicht zur wahren Menschheitserziehung befähigende, engstirnig auf kleinteilige Kärnerarbeit und einseitig aufs klassische Altertum fixierte Disziplin für zu leicht befunden, um weiter für seine großen Pläne in Betracht zu kommen. Schon mit seiner Geburt der Tragödie(1872) habe sich Nietzsche bewußt aus der philologischen Zunft verabschiedet, die seinen denkerischen Entgrenzungswillen folgerichtig mit akademischer Ächtung bestraft habe.

In der deutschsprachigen Forschungslandschaft scheint die Zeit der großen säkularisationstheoretischen Entwürfe vorbei zu sein. Unter Philosophen und Soziologen dominieren strukturale und funktionalistische Betrachtungsweisen gesellschaftlicher Ausdifferenzierungsprozesse, die die Frage nach dem Herkommen und nach unserem Verhältnis zu diesem Herkommen sorgfältig vermeiden. Das ist wohl kein Zufall, sondern dürfte in Zeiten knapper finanzieller Ressourcen der sicherste Weg sein, jedem Positionsbezug auszuweichen, denn wer weiß, ob nicht der für die Mittelvergabe zuständige Ministerialdirigent oder Stiftungsrat den Glauben hegt, die heutigen okzidentalen Werte hätten im Kern christlich oder aber antichristlich zu sein.