Das Paradigma des kritischen Realismus

Der Kritische Realismus („Critical Realism“) ist seit Ian G. Barbours grundlegenden Issues in Science and Religion (1966) erkenntnistheoretisches Paradigma zentraler Ansätze im angelsächsischen Gespräch zwischen Theologie und Naturwissenschaften geworden; neben Barbour selbst sind hier insbesondere Arthur Peacocke und John Polkinghorne zu nennen.

Neural correlate of spatial presence in an arousing and noninteractive virtual reality: an EEG and psychophysiology study

Using electroencephalography (EEG), psychophysiology, and psychometric measures, this is the first study which investigated the neurophysiological underpinnings of spatial presence. Spatial presence is considered a sense of being physically situated within a spatial environment portrayed by a medium (e.g., television, virtual reality). Twelve healthy children and 11 healthy adolescents were watching different virtual roller coaster scenarios. During a control session, the roller coaster cab drove through a horizontal roundabout track. The following realistic roller coaster rides consisted of spectacular ups, downs, and loops. Low-resolution brain electromagnetic tomography (LORETA) and event-related desynchronization (ERD) were used to analyze the EEG data. As expected, we found that, compared to the control condition, experiencing a virtual roller coaster ride evoked in both groups strong SP experiences, increased electrodermal reactions, and activations in parietal brain areas known to be involved in spatial navigation. In addition, brain areas that receive homeostatic afferents from somatic and visceral sensations of the body were strongly activated. Most interesting, children (as compared to adolescents) reported higher spatial presence experiences and demonstrated a different frontal activation pattern. While adolescents showed increased activation in prefrontal areas known to be involved in the control of executive functions, children demonstrated a decreased activity in these brain regions. Interestingly, recent neuroanatomical and neurophysiological studies have shown that the frontal brain continues to develop to adult status well into adolescence. Thus, the result of our study implies that the increased spatial presence experience in children may result from the not fully developed control functions of the frontal cortex.

Developmental self-construction and -configuration of functional neocortical neuronal networks.

The prenatal development of neural circuits must provide sufficient configuration to support at least a set of core postnatal behaviors. Although knowledge of various genetic and cellular aspects of development is accumulating rapidly, there is less systematic understanding of how these various processes play together in order to construct such functional networks. Here we make some steps toward such understanding by demonstrating through detailed simulations how a competitive co-operative ('winner-take-all', WTA) network architecture can arise by development from a single precursor cell. This precursor is granted a simplified gene regulatory network that directs cell mitosis, differentiation, migration, neurite outgrowth and synaptogenesis. Once initial axonal connection patterns are established, their synaptic weights undergo homeostatic unsupervised learning that is shaped by wave-like input patterns. We demonstrate how this autonomous genetically directed developmental sequence can give rise to self-calibrated WTA networks, and compare our simulation results with biological data.

Evidence of an association between sleep and levodopa-induced dyskinesia in an animal model of Parkinson's disease.

Levodopa-induced dyskinesia (LID) represents a major challenge for clinicians treating patients affected by Parkinson's disease (PD). Although levodopa is the most effective treatment for PD, the remodeling effects induced by disease progression and the pharmacologic treatment itself cause a narrowing of the therapeutic window because of the development of LID. Although animal models of PD provide strong evidence that striatal plasticity underlies the development of dyskinetic movements, the pathogenesis of LID is not entirely understood. In recent years, slow homeostatic adjustment of intrinsic excitability occurring during sleep has been considered fundamental for network stabilization by gradually modifying plasticity thresholds. So far, how sleep affects on LID has not been investigated. Therefore, we measured synaptic downscaling across sleep episodes in a parkinsonian animal model showing dyskinetic movements similar to LID. Our electrophysiological, molecular, and behavioral results are consistent with an impaired synaptic homeostasis during sleep in animals showing dyskinesia. Accordingly, sleep deprivation causes an anticipation and worsening of LID supporting a link between sleep and the development of LID.

WIPI-dependent autophagy during neutrophil differentiation of NB4 acute promyelocytic leukemia cells.

Members of the WD-repeat protein interacting with phosphoinositides (WIPI) family are phosphatidylinositol 3-phosphate (PI3P) effectors that are essential for the formation of autophagosomes. Autophagosomes, unique double-membraned organelles, are characteristic for autophagy, a bulk degradation mechanism with cytoprotective and homeostatic function. Both, WIPI-1 and WIPI-2 are aberrantly expressed in several solid tumors, linking these genes to carcinogenesis. We now found that the expression of WIPI-1 was significantly reduced in a large cohort of 98 primary acute myeloid leukemia (AML) patient samples (complex karyotypes; t(8;21); t(15,17); inv(16)). In contrast, the expression of WIPI-2 was only reduced in acute promyelocytic leukemia (APL), a distinct subtype of AML (t(15,17)). As AML cells are blocked in their differentiation, we tested if the expression levels of WIPI-1 and WIPI-2 increase during all-trans retinoic acid (ATRA)-induced neutrophil differentiation of APL. According to the higher WIPI-1 expression in granulocytes compared with immature blast cells, WIPI-1 but not WIPI-2 expression was significantly induced during neutrophil differentiation of NB4 APL cells. Interestingly, the induction of WIPI-1 expression was dependent on the transcription factor PU.1, a master regulator of myelopoiesis, supporting our notion that WIPI-1 expression is reduced in AML patients lacking proper PU-1 activity. Further, knocking down WIPI-1 in NB4 cells markedly attenuated the autophagic flux and significantly reduced neutrophil differentiation. This result was also achieved by knocking down WIPI-2, suggesting that both WIPI-1 and WIPI-2 are functionally required and not redundant in mediating the PI3P signal at the onset of autophagy in NB4 cells. In line with these data, downregulation of PI3KC3 (hVPS34), which generates PI3P upstream of WIPIs, also inhibited neutrophil differentiation. In conclusion, we demonstrate that both WIPI-1 and WIPI-2 are required for the PI3P-dependent autophagic activity during neutrophil differentiation, and that PU.1-dependent WIPI-1 expression is significantly repressed in primary AML patient samples and that the induction of autophagic flux is associated with neutrophil differentiation of APL cells.

Are We Sims? How Computer Simulations Represent and What this Means for the Simulation Argument

N. Bostrom’s simulation argument and two additional assumptions imply that we are likely to live in a computer simulation. The argument is based upon the following assumption about the workings of realistic brain simulations: The hardware of a computer on which a brain simulation is run bears a close analogy to the brain itself. To inquire whether this is so, I analyze how computer simulations trace processes in their targets. I describe simulations as fictional, mathematical, pictorial, and material models. Even though the computer hardware does provide a material model of the target, this does not suffice to underwrite the simulation argument because the ways in which parts of the computer hardware interact during simulations do not resemble the ways in which neurons interact in the brain. Further, there are computer simulations of all kinds of systems, and it would be unreasonable to infer that some computers display consciousness just because they simulate brains rather than, say, galaxies.

Good just isn't Good Enough: Humean Chances and Boltzmannian Statistical Physics

Statistical physicists assume a probability distribution over micro-states to explain thermodynamic behavior. The question of this paper is whether these probabilities are part of a best system and can thus be interpreted as Humean chances. I consider two Boltzmannian accounts of the Second Law, viz.\ a globalist and a localist one. In both cases, the probabilities fail to be chances because they have rivals that are roughly equally good. I conclude with the diagnosis that well-defined micro-probabilities under-estimate the robust character of explanations in statistical physics.

"Und sehe, daß wir nichts wissen können"? Grenzen des Wissens und ihre Vermessung

Unsere Gesellschaft schmückt sich gerne mit dem Prädikat der Wissensgesellschaft. Statistiken, denen zufolge sich das Wissen alle paar Jahre verdoppelt, legitimieren diese Bezeichnung ein Stück weit. Die Suche nach neuem Wissen stösst aber auch immer wieder an Grenzen. Bestimmte Themen wie die ersten Anfänge unseres Universums scheinen sich dem erkennenden Zugriff des Menschen hartnäckig zu entziehen. Wie steht es dann mit unserem Wissensdrang? Können wir alles wissen oder stossen wir irgendwann an Erkenntnisgrenzen, die wir nicht überschreiten können? Wenn ja, warum gibt es solche Grenzen? Wie lassen sich diese Grenzen klassifizieren und bestimmen? Und können wir überhaupt wissen, wo diese Grenzen verlaufen? Die Untersuchung von menschlichen Wissensansprüchen ist seit Sokrates eine zentrale Aufgabe der Philosophie. Ziel des Vortrags ist es daher, aus philosophischer Perspektive über die Grenzen des Wissens nachzudenken. Dabei soll einmal erklärt werden, warum Wissen Grenzen hat und wie wir diese Grenzen zum Gegenstand kritischer Reflexion machen können. Zum anderen soll vorgeführt werden, wie sich Wissensgrenzen im Zusammenspiel einzelwissenschaftlicher Erkenntnis und philosophischer Reflexion bestimmen lassen und welche Schwierigkeiten sich dabei auftun.

Experimenting and modeling: sharp distinctions, integration or just a mess?

At first sight, experimenting and modeling form two distinct modes of scientific inquiry. This spurs philosophical debates about how the distinction should be drawn (e.g. Morgan 2005, Winsberg 2009, Parker 2009). But much scientific practice casts serious doubts on the idea that the distinction makes much sense. There are two worries. First, the practices of modeling and experimenting are often intertwined in intricate ways because much modeling involves experimenting, and the interpretation of many experiments relies upon models. Second, there are borderline cases that seem to blur the distinction between experiment and model (if there is any). My talk tries to defend the philosophical project of distinguishing models from experiment and to advance the related philosophical debate. I begin with providing a minimalist framework of conceptualizing experimenting and modeling and their mutual relationships. The methods are conceptualized as different types of activities that are characterized by a primary goal, respectively. The minimalist framwork, which should be uncontroversial, suffices to accommodate the first worry. I address the second worry by suggesting several ways how to conceptualize the distinction in a more flexible way. I make a concrete suggestion of how the distinction may be drawn. I use examples from the history of science to argue my case. The talk concentrates and models and experiments, but I will comment on simulations too.

The Age of the Universe and its Measurement

Current wisdom in cosmology has it that the Universe is about 13.8 billions year old. Statements about the age of the Universe are not just difficult to confirm, but also carry a lot of presuppositions. The aim of this talk is to make explicit these presuppositions, to discuss their significance and to trace the implications for an emipirical investigation of the age of the Universe.

Wissen wir, was wir nicht wissen können?

«Was kann ich wissen?» – Für Immanuel Kant ist das eine der Grundfragen der Philosophie. Wie können wir sie heute beantworten? Und warum ist sie wichtig?

Short communication: Timing of first milking affects serotonin (5-HT) concentrations

Hormonal signals differentially regulate the timing of parturition, as well lactogenesis and, potentially, colostrum formation in the mammary gland. Non-neuronal serotonin (5-HT) is a homeostatic regulator of the mammary gland. In the current study, we manipulated the timing of first milking to investigate its effects on serum 5-HT and calcium concentrations in the maternal and calf circulation, as well as in colostrum. Twenty-three cows were randomly assigned to a control (CON; n=10) group, milked for the first time at 4h postcalving, or a treatment (TRT; n=13) group, milked for the first time approximately 1 d before calving in addition to 4h postcalving. Maternal blood samples were collected for 4 d precalving, 3 times daily, and 1 blood sample was taken 4h postcalving. Calf blood samples were collected 4 (before first colostrum feeding) and 12h after birth, and at 3 wk of age. Calves from both treatments were fed colostrum from their respective mothers. Serum 5-HT concentrations were greater in CON cows and decreased significantly in TRT cows after milking was initiated precalving (951 vs. 524 ± 111 ng/mL, respectively). Cow serum calcium concentrations were affected by time, beginning to decrease 1 d precalving until 4h postcalving, but this drop in serum calcium was more pronounced in TRT cows. Serum 5-HT and calcium concentrations were negatively correlated (r=-0.57) for the CON cows and positively correlated (r=0.6) for the TRT cows. Maternal calcium and 5-HT decreased similarly due to precalving milking. Calcium and 5-HT concentrations were greater in colostrum collected from TRT cows milked precalving. Overall, calves had higher circulating 5-HT concentrations than cows, and calves born to TRT cows had increased 5-HT concentrations compared with the CON. Precalving milking could affect 5-HT synthesis within the mammary gland and therefore affect maternal 5-HT and calcium concentrations. Further research is needed in ruminants to assess the extent of 5-HT placental transfer, its role on pre- and postnatal development of the calf, the importance of its presence in colostrum, and potential long-term effects on calf health