Wirtschaftliche Evolution aus systemtheoretischer Perspektive

In der Dissertation von Peter Rassidakis, Diplom Volkswirt aus Marburg, wird unter Verwendung des systemtheoretischen Instrumentariums aufgezeigt, wie sich Evolution als ein Prozess der Vielfaltsstei-gerung in unterschiedlichen Systemen vollzieht. Nach einer Darstellung grundlegender systemtheoretischer Überlegungen werden zunächst individuelle Evolutionsprozesse betrachtet. Individuen sind aus systemtheoretischer Perspektive operativ geschlos-sene Systeme und können durch eine autopoietische Reproduktion ihres Bewusstseins ihre Vielfalt steigern. Sie nehmen dabei Reize aus der Umwelt wahr, die zur Aufdeckung von unbewussten Inkom-petenzen führen und Lernprozesse auslösen können, die sich auf mehreren Lernebenen abspielen. Individuen agieren im Rahmen sozialer Systeme, in denen sie eingebunden sind und ihre Kommunikationen reproduziert werden. Soziale Systeme nehmen ihre Umwelt über ihre partizipierenden Individuen wahr und besitzen eine eigene Wissensbasis, die ein emergentes Produkt des Wissens und der Kompetenzen ihrer Akteure ist. Insbesondere sind Unternehmenssysteme dargestellt worden, die mit Hilfe ihrer Strukturen und Regeln unterschiedliche Kommunikationen zulassen bzw. fördern oder aber verbieten. Es wurden zentrale Kriterien herausgestellt, die den Wissensaufbau und die Wissensdurchsetzung innerhalb von Unternehmenssystemen unterstützen können. In einem weiteren Schritt der Untersuchung werden Wirtschaftssysteme betrachtet. Ihr Hauptmerkmal sind die Form der Interaktion durch Zahlungen sowie ihr wertschöpfender Operationsmodus. Diese können anhand unterschiedlicher systemischer Abgrenzungskriterien in Teilsysteme wie bspw. funktionale Systeme, Märkte oder Industrien differenziert werden. Wirtschaftssysteme können ebenfalls Evo-lutionsprozesse durchlaufen. Sie steigern dadurch ihre Fähigkeiten, mit gegenwärtigen und zukünftigen Knappheiten umzugehen. Die Notwendigkeit der Evolution - in Form der Integration neuen Wissens in den Wertschöpfungsprozess - wird hauptsächlich durch den abnehmenden Grenznutzen von Innova-tionen begründet. Für den Prozess wirtschaftlicher Evolution stellen sich technologische Pfadabhängig-keiten sowie sozio-ökonomischer Faktoren als äußerst bedeutsam heraus. Abschließend wird die Rolle wirtschaftlicher Evolution für übergeordnete gesellschaftliche Systeme sowie die Bedeutung von Interaktionen zwischen gesellschaftlichen Teilsystemen für die Erzeugung und Diffusion von Wissen untersucht. Ein besonderer Fokus wird dabei auf die strukturelle Kopplung der Systeme der Wissenschaft und der Wirtschaft gelegt, wobei sich gesamtgesellschaftliche sowie system-spezifische Normen und Regeln aufzeigen lassen, die den Wissenstransfer zwischen diesen Systemen beeinflussen können. Vor dem Hintergrund der prinzipiellen Schwierigkeit, Erfahrungswissen zu übertragen, wird die besondere Rolle individuellen Handelns für diesen Prozess herausgestellt. Der systemtheoretische Ansatz zeigt auf, dass der Versuch einer Erklärung evolutiver Prozesse abhängig von der Abgrenzung ist, die ein Beobachter vornimmt. Die Wahrnehmung, der Aufbau und die Selektion von Wissen erfolgen somit innerhalb von Grenzen, die je nach systemischem Blickwinkel in einem System selbst oder in seiner Umwelt anzusiedeln sind. Dadurch lässt sich wirtschaftliche Evolution als eine Abfolge bestimmter Interaktionen zwischen psychischen, unternehmerischen und wirtschaftlichen Systemen untersuchen

Von “Inländern” und “Barbaren”. Identitäts- und Alteritätskonzepte bei Ilse Aichinger und Konstantinos Kavafis

In their texts Ilse Aichinger and Konstantinos Kavafis adopt a perspective from which the conceptions of identity and otherness can be questioned and their interrelationship reconsidered. The binary opposition between “Us” and the “Other” is thus undermined and its dimension as a discursive construction becomes apparent. Both Aichinger and Kavafis do not focus on the “Other” when writing about “Barbarians”; they rather question the conception of “Us”. The subversive value of these texts lies in this very questioning of a homogeneous and clearly drawn conception of identity

«Verweile nicht bei den Hellenen, vernimm dich zu Byzanz». Facetten der Griechenlandsehnsucht in deutschsprachigen literarischen Reiseberichten des 19. und angehenden 20. Jahrhunderts: [«Linger not among the Greeks, betake yourself to Byzantium». Aspects of the nostalgia for Ancient Greece in German travel literature of the 19th and early 20th centuries]

Austrian and German intellectuals were often disappointed when visiting contemporary Greece. This article examines various aspects of this tension between expectation and disappointment, as recorded in travel literature dating from the mid-nineteenth to the early twentieth century. It focuses on the nostalgia for Ancient Greece and its disillusionment due to the immense temporal distance. It also examines the portrayal of the landscape as a guarantee of continuity, in order to overcome this disappointment. To this Ancient-centered nostalgia this article juxtaposes one of a different kind, this time related to the Byzantine tradition. This nostalgia can be found in the German and Austrian travel literature that describes visits to Greek monasteries, especially on the Athos peninsula, and reaches its peak in the mystical overtones of travellers’ accounts in the twentieth century

Differential proteomic analysis of the reactivated p53 via Nutlin-3a, in 3 different types of human lymphomas

Purpose: The identification and quantification of protein expression levels of nutlin-3A-induced p53 stabilization and activation in human lymphoma. Methods: The Isotope Coded Protein Label (ICPL) technique was followed by nano-Liquid Chromatography coupled on-line with Mass Spectrometry (nLC-MS/MS). Results: Reliable identification & differential quantitative determination of human lymphoma proteome profile, revealing alterations in the HSPs relative expression levels

Deciphering the role of autophagy and exosomes in human lymphoma

The orchestrated homeostatic action of autophagy and exosome biogenesis provides a potential causal relation with lymphomagenesis. This study aims to characterize the differently expressed proteins associated with both above-mentioned pathways, as well as to explore their potential implication in therapeutic response controlling lymphomagenesis via N3a-induced re-activated p53 in different lymphoma subtypes

Immunoreactivity of CD99 in Non-Hodgkin's Lymphoma: Unexpected Frequent Expression in ALK-positive Anaplastic Large Cell Lymphoma

To verify the spectrum of CD99-expressing lymphoid malignancy, an immunohistochemical study for CD99 was carried out in 182 cases of non-Hodgkin's lymphoma, including 21 lymphoblastic lymphomas, 11 small lymphocytic lymphomas, 9 mantle cell lymphomas, 12 follicular lymphomas, 37 diffuse large B cell lymphomas, 18 Burkitt's lymphomas, 28 NK/T-cell lymphomas, 8 angioimmunoblastic T-cell lymphomas, 23 peripheral T-cell lymphomas, unspecified, and 15 systemic anaplastic large cell lymphomas. CD99 was positive in all T-lymphoblastic lymphomas and in 60% of B-lymphoblastic lymphomas. Majority of T and NK cell lymphomas were negative for CD99, except anaplastic large cell lymphomas (ALCLs). Eight of 15 cases (54%) of ALCLs reacted with anti CD99 antibody. Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive. Of the mature B-cell lymphomas, 5.4% (2/37) of diffuse large B cell lymphomas and 11.1% (2/18) of Burkitt's lymphomas expressed CD99. In conclusion, CD99 is infrequently expressed in mature B and T cell lymphomas, except ALK-positive ALCL. High expression of CD99 in ALK-positive ALCL is unexpected finding and its biologic and clinical significances have yet to be clarified

Treatment strategies for Hodgkin lymphoma recurring following autologous hematopoietic stem cell transplantation

Hodgkin lymphoma (HL) represents one of the great success stories in hematology going from a uniformly fatal disease, to one that is curable in the vast majority of cases. Despite this success, some patients experience relapse. To address this unmet need a variety of agents, classes of drugs, and strategies have demonstrated activity in HL recurring after autologous hematopoietic stem cell transplantation. These include chemotherapeutics (gemcitabine-based combinations, bendamustine), histone deacetylase (HDAC) inhibitors (panobinostat), immunomodulatory agents (lenalidomide), mTOR inhiobitors (everolimus), monoclonal antibodies (rituximab), and antibody-drug conjugates (brentuximab vedotin) as well the potential of long-term disease control via allogeneic transplantation. Such advances reflect our increased understanding of the biology of HL and hold promise for continued improved outcomes for those suffering with this condition

mTOR signaling is activated by FLT3 kinase and promotes survival of FLT3-mutated acute myeloid leukemia cells

Activating mutations of the FLT3 gene mediate leukemogenesis, at least in part, through activation of PI3K/AKT. The mammalian target of rapamycin (mTOR)-Raptor signaling pathway is known to act downstream of AKT. Here we show that the mTOR effectors, 4EBP1, p70S6K and rpS6, are highly activated in cultured and primary FLT3-mutated acute myeloid leukemia (AML) cells. Introduction of FLT3-ITD expressing constitutively activated FLT3 kinase further activates mTOR and its downstream effectors in BaF3 cells. We also found that mTOR signaling contributes to tumor cell survival, as demonstrated by pharmacologic inhibition of PI3K/AKT/mTOR, or total silencing of the mTOR gene. Furthermore, inhibition of FLT3 kinase results in downregulation of mTOR signaling associated with decreased survival of FLT3-mutated AML cells. These findings suggest that mTOR signaling operates downstream of activated FLT3 kinase thus contributing to tumor cell survival, and may represent a promising therapeutic target for AML patients with mutated-FLT3

Whole-genome informed circulating tumor DNA analysis by multiplex digital PCR for disease monitoring in B-cell lymphomas: a proof-of-concept study

IntroductionAnalyzing liquid biopsies for tumor-specific aberrations can facilitate detection of measurable residual disease (MRD) during treatment and at follow-up. In this study, we assessed the clinical potential of using whole-genome sequencing (WGS) of lymphomas at diagnosis to identify patient-specific structural (SVs) and single nucleotide variants (SNVs) to enable longitudinal, multi-targeted droplet digital PCR analysis (ddPCR) of cell-free DNA (cfDNA).MethodsIn 9 patients with B-cell lymphoma (diffuse large B-cell lymphoma and follicular lymphoma), comprehensive genomic profiling at diagnosis was performed by 30X WGS of paired tumor and normal specimens. Patient-specific multiplex ddPCR (m-ddPCR) assays were designed for simultaneous detection of multiple SNVs, indels and/or SVs, with a detection sensitivity of 0.0025% for SV assays and 0.02% for SNVs/indel assays. M-ddPCR was applied to analyze cfDNA isolated from serially collected plasma at clinically critical timepoints during primary and/or relapse treatment and at follow-up.ResultsA total of 164 SNVs/indels were identified by WGS including 30 variants known to be functionally relevant in lymphoma pathogenesis. The most frequently mutated genes included KMT2D, PIM1, SOCS1 and BCL2. WGS analysis further identified recurrent SVs including t(14;18)(q32;q21) (IGH::BCL2), and t(6;14)(p25;q32) (IGH::IRF4). Plasma analysis at diagnosis showed positive circulating tumor DNA (ctDNA) levels in 88% of patients and the ctDNA burden correlated with baseline clinical parameters (LDH and sedimentation rate, p-value <0.01). While clearance of ctDNA levels after primary treatment cycle 1 was observed in 3/6 patients, all patients analyzed at final evaluation of primary treatment showed negative ctDNA, hence correlating with PET-CT imaging. One patient with positive ctDNA at interim also displayed detectable ctDNA (average variant allele frequency (VAF) 6.9%) in the follow-up plasma sample collected 2 years after final evaluation of primary treatment and 25 weeks before clinical manifestation of relapse.ConclusionIn summary, we demonstrate that multi-targeted cfDNA analysis, using a combination of SNVs/indels and SVs candidates identified by WGS analysis, provides a sensitive tool for MRD monitoring and can detect lymphoma relapse earlier than clinical manifestation

Expression and prognostic significance of cox-2 and p-53 in hodgkin lymphomas: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Cyclooxygenase (cox) is the rate-limiting enzyme, which catalyzes the conversion of arachidonic acid into prostaglandins and contributes to the inflammatory process. Cyclooxygenase-2 (cox-2), which is one of the two isoforms, plays a role in tumor progression and carcinogenesis. p53 contributes to apoptosis, DNA renewal and cell cycle. Studies concerning the relationship of cox-2 and p53 expressions and carcinogenesis are available, but the association between cox-2 and p53 in Hodgkin lymphoma (HL) is not exactly known.</p> <p>In our study, we examined the association of cox-2 and p53 expression, with age, stage, histopathological subtype, and survival in HL. We also examined correlation between cox-2 and p53 expression.</p> <p>Methods</p> <p>Cox-2 and p53 expressions in Hodgkin-Reed Sternberg cells (HRS) were examined in 54 patients with HL depending on cox-2 expression, stained cases were classified as positive, and unstained cases as negative. Nuclear staining of HRS cells with p53 was evaluated as positive. The classifications of positivity were as follows: negative if<10%; (1+) if 10-25%; (2+) if 25-50%; (3+) if 50-75%, (4+) if >75%.</p> <p>Results</p> <p>Cox-2 and p53 expressions were found in 49 (80%) and 29 (46%) patients, respectively. There were differences between histological subtypes according to cox-2 expression (p = 0.012). Mixed cellular (MC) and nodular sclerosing (NS) subtypes were seen most of the patients and cox-2 expression was evaluated mostly in the mixed cellular subtype.</p> <p>There were no statistically significant relationships between p53 and the histopathological subtypes; or between p53, cox-2 and the factors including stage, age and survival; or between p53 and cox-2 expression (p > 0.05).</p> <p>Conclusion</p> <p>Considering the significant relationship between the cox-2 expression and the subtypes of HL, cox-2 expression is higher in MC and NS subtypes. However the difference between these two subtypes was not significant. This submission must be advocated by studies with large series</p