The centrosome and cell proliferation

Centrosomes are frequently amplified in cancer cells. Increased numbers of centrosomes can give rise to multipolar spindles in mitosis, and thereby lead to the formation of aneuploid daughter cells. However, whether centrosome amplification is a cause or a consequence of cancer is unclear. In contrast, loss of a functional centrosome has been shown to lead to cell cycle arrest. In this review, the potential mechanisms underlying centrosome amplification and centrosome-dependent cell cycle regulation are discussed

Assembly of centrosomal proteins and microtubule organization depends on PCM-1

The protein PCM-1 localizes to cytoplasmic granules known as “centriolar satellites” that are partly enriched around the centrosome. We inhibited PCM-1 function using a variety of approaches: microinjection of antibodies into cultured cells, overexpression of a PCM-1 deletion mutant, and specific depletion of PCM-1 by siRNA. All approaches led to reduced targeting of centrin, pericentrin, and ninein to the centrosome. Similar effects were seen upon inhibition of dynactin by dynamitin, and after prolonged treatment of cells with the microtubule inhibitor nocodazole. Inhibition or depletion of PCM-1 function further disrupted the radial organization of microtubules without affecting microtubule nucleation. Loss of microtubule organization was also observed after centrin or ninein depletion. Our data suggest that PCM-1–containing centriolar satellites are involved in the microtubule- and dynactin-dependent recruitment of proteins to the centrosome, of which centrin and ninein are required for interphase microtubule organization

Co-constitutive Relationships in Modern Medicine: Körper-Werden um die Geburtsstunde der modernen Chemotherapie

Early modern chemotherapy made an enduring impact on the human body and on current practices of medical research. Contrary to the widespread myth that locates the origins of modern chemotherapy in the mind of man, this paper analyses its emergence from material assemblages comprising trypanosomes, dyestuffs, physicians, and nonhuman animals at the turn of the century. Anti-infective drugs were not the only bodies that arose from these complex meshworks – assemblages as bodies and bodies of assemblages shaped each other in “co-constitutive relationships” (Donna Haraway). Drawing on neo-materialist theory, this article cartographizes these productive assemblages on the basis of scientific papers by David Bruce and Paul Ehrlich/Kiyoshi Shiga. Finally, these texts are juxtaposed with an 1858 article by the missionary and physician David Livingstone to reflect on the contingency of the animal-human-relationship in medical science

Formal models of source reliability

The paper introduces, compares and contrasts formal models of source reliability proposed in the epistemology literature, in particular the prominent models of Bovens and Hartmann (2003) and Olsson (2011). All are Bayesian models seeking to provide normative guidance, yet they differ subtly in assumptions and resulting behavior. Models are evaluated both on conceptual grounds and through simulations, and the relationship between models is clarified. The simulations both show surprising similarities and highlight relevant differences between these models. Most importantly, however, our evaluations reveal that important normative concerns arguably remain unresolved. The philosophical implications of this for testimony are discussed

Collective irrationality

Kollektive Irrationalität durchdringt alle Bereiche des sozialen Lebens. Von der Herdenbildung an Börsen zur politischen Polarisierung und sogar bis in die epistemische Gemeinschaft der Wissenschaft misslingt es Gruppen, die optimalen Mittel zu wählen, um ihre Ziele zu erreichen. Der Begriff der kollektiven Rationalität lässt sich präzise fassen durch eine Analyse der Argumente, die seine Zuschreibung rechtfertigen. Dazu ist es erforderlich, die Entscheidungsumgebung, die ablaufenden sozialen Prozesse und die relevanten normativen Standards zu erfassen, wozu sich insbesondere agentenbasierte Modellierung und Simulationen eignen. Diese Methode wird auf zwei Fallstudien angewendet, jeweils eines aus dem Bereich der theoretischen und eines aus dem der praktischen Rationalität. Die erste Fallstudie beschreibt die Entstehung sogenannter \textit{unpopular social norms}, also solcher sozialer Normen, die dem Interesse der überwiegenden Mehrheit der Gruppe zuwiderlaufen. Die Analyse eines entsprechenden Modells, in dem begrenzt rationale Akteure mit eingeschränkter Information versuchen, eine optimale Norm zu wählen, zeigt, dass der zugrundeliegende Prozess zwar ineffiziente Normen generieren kann, häufig jedoch effiziente Ergebnisse liefert. Das unmittelbare Urteil der kollektiven Irrationalität muss daher zurückgewiesen werden. In der zweiten Fallstudie wird der Einfluss strategischen Verhaltens in einer Gruppe von Agenten, die Informationen aggregieren, untersucht. Simulationen unterstützen die These, dass es keine universell optimale epistemische Strategie gibt: Agenten, die unter idealen Bedingungen erfolgreich sind, unterliegen im Falle strategischer Einflüsse konkurrierenden Agenten, die wiederum unter idealen Bedingungen suboptimale Ergebnisse erzielen. Eine evolutionäre Analyse des Modells belegt darüber hinaus, dass nichtepistmisch motiviertes Verhalten unter einem wengistens teilweise auf epistemischen Werten basierenden Belohnungssystem zurückgedrängt wird, ohne jedoch vollständig zu verschwinden. Die Verwendung agentenbasierter Modellierung und Simulation lässt sich insbesondere durch die epistemischen Eigenschaften der Methode rechtfertigen. Anders als Computersimulationen im Allgemeinen sind Modelle epistemisch transparent, das heißt nicht opak. Sie können außerdem unter den richtigen Bedingungen auch Bestätigung liefern. Gepaart mit der großen Flexibilität in der Modellierung handelt es sich daher ABM um ein wertvolles Werkzeug für ingenieursmäßig betriebene Philosophie. Dieser Ansatz strebt konkrete Lösungen für spezifische philosophische Probleme an, ohne vorher die Rechtfertigung einer fundamentalen Theorie zu fordern. Philosophische Probleme sind real und allgegenwärtig und verlangen daher Lösungen; die obigen Untersuchungen schlagen solche Lösungen vor

Red Y2O3:Eu-Based Electroluminescent Device Prepared by Atomic Layer Deposition for Transparent Display Applications

Y2O3:Eu is a promising red-emitting phosphor owing to its high luminance efficiency, chemical stability, and non-toxicity. Although Y2O3:Eu thin films can be prepared by various deposition methods, most of them require high processing temperatures in order to obtain a crystalline structure. In this work, we report on the fabrication of red Y2O3:Eu thin film phosphors and multilayer structure Y2O3:Eu-based electroluminescent devices by atomic layer deposition at 300 °C. The structural and optical properties of the phosphor films were investigated using X-ray diffraction and photoluminescence measurements, respectively, whereas the performance of the fabricated device was evaluated using electroluminescence measurements. X-ray diffraction measurements show a polycrystalline structure of the films whereas photoluminescence shows emission above 570 nm. Red electroluminescent devices with a luminance up to 40 cd/m2 at a driving frequency of 1 kHz and an efficiency of 0.28 Lm/W were achieved

Centrosome proteins form an insoluble perinuclear matrix during muscle cell differentiation

<p>Abstract</p> <p>Background</p> <p>Muscle fibres are formed by elongation and fusion of myoblasts into myotubes. During this differentiation process, the cytoskeleton is reorganized, and proteins of the centrosome re-localize to the surface of the nucleus. The exact timing of this event, and the underlying molecular mechanisms are still poorly understood.</p> <p>Results</p> <p>We performed studies on mouse myoblast cell lines that were induced to differentiate in culture, to characterize the early events of centrosome protein re-localization. We demonstrate that this re-localization occurs already at the single cell stage, prior to fusion into myotubes. Centrosome proteins that accumulate at the nuclear surface form an insoluble matrix that can be reversibly disassembled if isolated nuclei are exposed to mitotic cytoplasm from Xenopus egg extract. Our microscopy data suggest that this perinuclear matrix of centrosome proteins consists of a system of interconnected fibrils.</p> <p>Conclusion</p> <p>Our data provide new insights into the reorganization of centrosome proteins during muscular differentiation, at the structural and biochemical level. Because we observe that centrosome protein re-localization occurs early during differentiation, we believe that it is of functional importance for the reorganization of the cytoskeleton in the differentiation process.</p