Sociobiology, universal Darwinism and their transcendence: An investigation of the history, philosophy and critique of Darwinian paradigms, especially gene-Darwinism, process-Darwinism, and their types of reductionism towards a theory of the evolution of evolutionary processes, evolutionary freedom and ecological idealism

Based on a review of different Darwinian paradigms, particularly sociobiology, this work, both, historically and philosophically, develops a metaphysic of gene-Darwinism and process-Darwinism, and then criticises and transcends these Darwinian paradigms in order to achieve a truly evolutionary theory of evolution. Part I introduces essential aspects of current sociobiology as the original challenge to this investigation. The claim of some sociobiologists that ethics should become biologized in a gene-egoistic way, is shown to be tied to certain biological views, which ethically lead to problematic results. In part II a historical investigation into sociobiology and Darwinism in general provides us, as historical epistemology', with a deeper understanding of the structure and background of these approaches. Gene-Darwinism, which presently dominates sociobiology and is linked to Dawkins' selfish gene view of evolution, is compared to Darwin's Darwinism and the evolutionary' synthesis and becomes defined more strictly. An account of the external history of Darwinism and its subparadigms shows how cultural intellectual presuppositions, like Malthusianism or the Newtonian concept of the unchangeable laws of nature, also influenced biological theory' construction. In part III universal 'process-Darwinism' is elaborated based on the historical interaction of Darwinism with non-biological subject areas. Building blocks for this are found in psychology, the theory of science and economics. Additionally, a metaphysical argument for the universality of process- Darwinism, linked to Hume's and Popper's problem of induction, is proposed. In part IV gene-Darwinism and process-Darwinism are criticised. Gene-Darwinism—despite its merits—is challenged as being one-sided in advocating 'gene-atomism', 'germ-line reductionism' and 'process-monism'. My alternative proposals develop and try to unify different criticisms often found. In respect of gene-atomism I advocate a many-level approach, opposing the necessary radical selfishness of single genes. I develop the concept of higher-level genes, propose a concept of systemic selection, which may stabilise group properties, without relying on permanent group selection and extend the applicability of a certain group selectionist model generally to small open groups. Proposals of mine linked to the critique of germ-line reductionism are: 'exformation', phenotypes as evolutionary factors and a field theoretic understanding of causa formalis (resembling Aristotelian hylemorphism). Finally the process-monism of gene-Darwinism, process-Darwinism and, if defined strictly, Darwinism in general is criticised. 1 argue that our ontology and ethics would be improved by replacing the Newtoman-Paleyian deist metaphor of an eternal and unchangeable law of nature, which lies at tire very heart of Darwinism, by a truly evolutionary understanding of evolution where new processes may gain a certain autonomy. All this results in a view that I call 'ecological idealism', which, although still very much based on Darwinism, clearly transcends a Darwinian world view

Atmospheric Circulation Response to Short-Term Arctic Warming in an Idealized Model

Recent Arctic sea ice loss in fall has been posited to drive midlatitude circulation changes into winter and even spring. Past work has shown that sea ice loss can indeed trigger a weakening of the stratospheric polar vortex, which can lead to delayed surface weather changes. But the mechanisms of such changes and their relevant time scales have remained unclear. This study uses large ensembles of idealized GCM simulations to identify how and over what time scales the atmospheric circulation responds to short-term surface heat flux changes in high latitudes. The ensemble-mean response of the atmospheric circulation is approximately linear in the amplitude of the surface forcing. It is also insensitive to whether the forcing is zonally asymmetric or symmetric, that is, whether stationary waves are generated or not. The circulation response can be decomposed into a rapid thermal response and a slower dynamic adjustment. The adjustment arises through weakening of vertical wave activity fluxes from the troposphere into the stratosphere in response to polar warming, a mechanism that differs from sudden stratospheric warmings yet still results in a weakened stratospheric circulation. The stratospheric response is delayed and persists for about 2 months because the thermal response of the stratosphere is slow compared with that of the troposphere. The delayed stratospheric response feeds back onto the troposphere, but the tropospheric effects are weak compared with natural variability. The general pathway for the delayed response appears to be relatively independent of the atmospheric background state at the time of the anomalous surface forcing

A methodology of a sensitivity analysis in dem experiments

In this publication a sensitivity analysis for DEM modelparameters with respect to the pile- and the oedometer experiment is described. The analysis is performed with Sobol’ indices. Since the huge computational effort of the corresponding DEM models different metamodels are used to determine these indices. The (RSM) metamodels are established by using Latin Hypercube sampling points. A three-dimensional ansatz for the determination of the angle of repose as well as the algorithm of a force-controlled plate is described in order to get results for the pile- and the oedometer experiment

Impact of size, shape and composition on piezoelectric effects and the electronic properties of InGaAs/GaAs quantum dots

The strain fields in and around self-organized In(Ga)As/GaAs quantum dots (QD) sensitively depend on QD geometry, average InGaAs composition and the In/Ga distribution profile. Piezoelectric fields of varying size are one result of these strain fields. We study systematically a large variety of realistic QD geometries and composition profiles, and calculate the linear and quadratic parts of the piezoelectric field. The balance of the two orders depends strongly on the QD shape and composition. For pyramidal InAs QDs with sharp interfaces a strong dominance of the second order fields is found. Upon annealing the first order terms become dominant, resulting in a reordering of the electron p- and d-states and a reorientation of the hole wavefunctions

Zellbiologische Effekte aktivierter Gerinnungsfaktoren auf Tumorzellen

Ein prokoagulatorischer Status ist ein typisches Symptom von Tumorerkrankungen und deren Progression und geht mit der Entwicklung tiefer Venenthrombosen sowie maligner Ergüsse einher, in denen Gerinnungsfaktoren nachgewiesen werden können. Die raumfordernden Ergüsse führen je nach Lokalisation und Umfang des Ergusses zu Brust- oder Abdominalschmerzen, Atemnot, Husten, Erbrechen, Verdauungsstörungen, Anorexie und Kachexie, Nausea sowie einer eingeschränkten Beweglichkeit, und senken die Lebensqualität der Betroffenen erheblich. Die Therapieoptionen sind spärlich, oft bleibt nur eine wiederholte Punktion der rasch rezidivierenden Ergüsse. In der vorliegenden Arbeit wurde der Einfluss von PAR-Agonisten (Thrombin, SFLLRN, Faktor Xa, SLIGKV) auf die Proliferation, das Ansprechen auf Zytostatika, die Epitheliale-mesenchymale Transition (EMT) und daraus folgende Änderungen im Migrationsverhalten von Tumorzellen untersucht. Ziel war es, das Verständnis der Rolle von Gerinnungsfaktoren im Ergussmilieu und im Rahmen des Metastasierungsprozesses weiter aufzuklären, um möglichen Therapieansätzen mit Gerinnungsinhibitoren den Boden zu bereiten. 107 Ergüsse aus klinisch notwendigen Punktionen wurden gesammelt, die enthaltenen Zellen isoliert und kultiviert sowie die Ergüsse nach Geschlecht und Diagnose zum Zeitpunkt des Ergusses in maligne und benigne Ergüsse charakterisiert. In einer koagulometrischen Untersuchung an 72 Ergüssen konnten alle Gerinnungsfaktoren der extrinsischen Kaskade (Faktor II, V, VII, X, Fibrinogen, Protein C, Antithrombin III) im Erguss nachgewiesen werden. Die klinischen Marker für ein aktiviertes Gerinnungssystem, D-Dimere und F1+2 Fragmente, waren deutlich erhöht. In einem chromogenen Aktivitätsassay konnten nur geringe Aktivitäten Faktor IIa und Faktor Xa im Erguss nachgewiesen werden. Die Ergebnisse zeigten ein deutlich aktiviertes Gerinnungssystem in benignen und malignen Ergüssen, was die Frage nach deren Einfluss auf die im Erguss enthaltenen Tumorzellen aufwirft. Die aus Ergüssen isolierten Tumorzellen exprimierten membranständige PAR-1 und PAR-2 Rezeptoren, über die Thrombin und Faktor Xa zellbiologische Effekte vermitteln können. Auf der als Modellzellen eingesetzten humanen Pankreaskarzinom-Zelllinie PANC-1, der humanen monozytären Tumorzelllinie THP-1 und der nicht-tumorigenen humanen pankreatischen Epithelzelllinie HPDE konnten PAR-1 und PAR-2 Rezeptoren in unterschiedlicher Dichte nachgewiesen werden. HPDE und PANC-1 Zellen zeigten darüber hinaus eine starke intrazelluläre, granuläre Expression beider Rezeptoren. Eine Supplementierung des Kulturmediums von THP-1 Zellen mit 10 % (v/v) Erguss führte bei 60 getesteten Ergüssen im Mittel zu einer Hemmung des Zellwachstums in unbehandelten und mit Carboplatin oder Doxorubicin behandelten Zellen. Ergüsse weiblicher Patientinnen mit benigner Diagnose oder gastrointestinaler Krebserkrankung führten teilweise zu deutlich erhöhten Zellzahlen in unbehandelten und mit Zytostatikum behandelten Ansätzen, was einer Resistenz entspricht. Höhere FII Aktivitäten im Erguss korrelierten mit einer Hemmung des Zellwachstums in unbehandelten und mit Carboplatin behandelten Zellen. Stimulation der THP-1 Zellen mit PAR-Agonisten führte zu einer Hemmung des Zellwachstums sowie einer Chemoresistenz gegen Carboplatin und Doxorubicin. Die Stimulation mit PAR-Agonisten zeigte keinen konzentrationsabhängigen Einfluss auf das Zellwachstum von PANC-1 Zellen sowie das Ansprechen der Zellen auf Zytostatika. Eine Supplementierung des Kulturmediums von PANC-1 Zellen mit 10 % (v/v) Erguss führte bei den 10 getesteten Ergüssen im Mittel ebenfalls zu einer Hemmung des Zellwachstums. Die Hemmung von im Erguss enthaltenen Thrombin und Faktor Xa blieb ohne Einfluss auf das Zellwachstum was eine Rolle der Gerinnungsinhibitoren am proliferationsinhibierenden Effekt ausschließt. Abschließend wurde der Einfluss von PAR-Agonisten auf die EMT untersucht. PAR-Agonisten zeigten in HPDE und PANC-1 Zellen keinen transkriptionellen Einfluss auf die Expression der EMT-assoziierten Proteine E-Cadherin, Vimentin, N-Cadherin, L1CAM, Slug und Snail, aber induzierten eine Delokalisierung von membranständigem E-Cadherin ins Zytosol, eine Auflösung von Zellkontakten sowie eine spindelförmige Morphologie. Diese zellbiologischen Veränderungen führten zu einer erhöhten Migrationsfähigkeit sowohl der nicht-tumorigenen HPDE Zellen als auch der in der EMT weit fortgeschrittenen Karzinomzelllinie PANC-1. Die Ergebnisse dieser Arbeit belegen eine tumorfördernde Wirkung von Gerinnungsfaktoren auf tumorigene und nicht-tumorigene Zellen und leisten somit einen Beitrag zum Verständnis der Rolle der Gerinnungsfaktoren im Ergussmilieu und im Rahmen von Metastasierungsprozessen. Dies zeigt die Notwendigkeit einer antikoagulatorischen Therapie in Tumorpatienten oder zur Tumorprophylaxe.A procoagulant state accompanied by deep vein thrombosis and development of expansive effusions containing coagulation factors are well known matters in cancer patients during the progression of the disease. Patients suffer from chest and abdominal pain, dyspnoea, cough, digestive disorders, vomiting, anorexia and cachexia, nausea, limited mobility resulting in a reduced quality of life. Until now therapeutical options are poor besides repetitive puncture and pleurodesis. In order to elucidate the role of coagulation factors on growth, chemosensitivity, epithelial-mesenchymal transition (EMT) and cell migration of cancer cells within effusions, 108 effusions from clinically necessary punctures were collected and characterized in terms of gender and diagnosis at the date of puncture (malignant vs. benign; gynaecological, lung and gastroenterological cancers). After separating the cells from the effusions all coagulation factors of the extrinsic cascade (factor II, V, VII, X, fibrinogen) were detected at low concentrations whereas clinical markers for an activated coagulation system such as D-dimer fragments and prothrombin fragment 1.2 were significantly elevated. Thrombin and factor Xa showed almost no activity in a chromogenic assay. These findings indicate a highly activated coagulation system within the effusions without significant differences between gender and diagnosis. Tumour cells isolated from the effusions expressed PAR-1 and PAR-2 receptors that were membrane-bound but mainly localized in the cytosol. PAR-1 and PAR-2 are relevant for protease signalling and influence on the cell biology. Owing to the low proliferative activity and contamination with fibroblasts these cells were not suitable for further experiments. The alternatively used cell lines HPDE (non-tumorigenic human pancreatic duct epithelial cells), PANC-1 (human pancreatic cancer) and THP-1 (human acute monocytic leukaemia) showed variable PAR-1 and PAR-2 surface expression, and HPDE and PANC-1 cells showed a marked cytosolic expression of both receptors, too. Culture medium supplemented with 10 % (v/v) effusion fluid inhibited THP-1 cell growth and improved response to Carboplatin and doxorubicin treatment. Moreover, benign effusions and effusions from gastroenterological cancers of female patients lead to a concomitant slightly developed chemoresistance against carboplatin and doxorubicin and increased cell growth. Elevated thrombin levels within the effusions correlated with improved response to carboplatin and increased cell growth. Stimulation of THP-1 cells with PAR-agonists resulted in a PAR-1 mediated marginal inhibition of cell proliferation and a distinct chemoresistance against carboplatin and doxorubicin while PAR-2 agonist led to a chemoresistance against doxorubicin. PANC-1 cells showed no concentration-dependent response to PAR-1 and PAR-2 agonists with respect to cell proliferation and response to cytostatic drugs. However, culture of PANC-1 cells in medium supplemented with 10 % (v/v) effusion fluid inhibited cell growth. Co-incubation with Lepirudin (thrombin inhibitor) or Rivaroxaban (factor Xa inhibitor) had no influence on cell growth indicating that other factors in the effusions beside coagulation factors are responsible for the growth inhibitory effect. Finally, PAR agonists showed no transcriptional influence on EMT-associated marker proteins E-cadherin, Vimentin, N-cadherin, L1CAM, Slug and Snail in HPDE and PANC-1 cells but induced delocalisation of membrane-bound E-cadherin into the cytosol. Along with this delocalisation a dissolving of cell-cell junctions and a spindle-shaped cell morphology was observed in both cell lines. These cell biological changes could be associated with an increased cell migration in both non-tumorigenic HPDE cells and tumorigenic PANC-1 cells. In summary, these results revealed a distinct tumour progressive potential of coagulation factors on tumorigenic and even non-tumorigenic cells and contribute to the understanding of their role during tumorigenesis and metastasis. They suggest also the need of anticoagulant treatment of tumour patients and in tumour prophylactic treatment

Atmospheric Circulation Response to Short-Term Arctic Warming in an Idealized Model

Recent Arctic sea ice loss in fall has been posited to drive midlatitude circulation changes into winter and even spring. Past work has shown that sea ice loss can indeed trigger a weakening of the stratospheric polar vortex, which can lead to delayed surface weather changes. But the mechanisms of such changes and their relevant time scales have remained unclear. This study uses large ensembles of idealized GCM simulations to identify how and over what time scales the atmospheric circulation responds to short-term surface heat flux changes in high latitudes. The ensemble-mean response of the atmospheric circulation is approximately linear in the amplitude of the surface forcing. It is also insensitive to whether the forcing is zonally asymmetric or symmetric, that is, whether stationary waves are generated or not. The circulation response can be decomposed into a rapid thermal response and a slower dynamic adjustment. The adjustment arises through weakening of vertical wave activity fluxes from the troposphere into the stratosphere in response to polar warming, a mechanism that differs from sudden stratospheric warmings yet still results in a weakened stratospheric circulation. The stratospheric response is delayed and persists for about 2 months because the thermal response of the stratosphere is slow compared with that of the troposphere. The delayed stratospheric response feeds back onto the troposphere, but the tropospheric effects are weak compared with natural variability. The general pathway for the delayed response appears to be relatively independent of the atmospheric background state at the time of the anomalous surface forcing