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Immer mehr Menschen fragen sich, ob die vorherrschende Wirtschaftswissenschaft Teil der Losung oder nicht sogar ein Teil des Problems ist. Angesichts von Klimakrise, steigendem Ressourcenverbrauch und vertiefter globaler Ungleichheit, scheint die Fokussierung der sogenannten „Mainstream-“ oder „Standard-Okonomik“ auf Wachstum, Marktfreiheiten und Effizienz zunehmend realitatsfern. Diese theoretische Verengung steht in eklatantem Widerspruch zu der Vielfalt an Forschungsparadigmen, welche die Wirtschaftswissenschaft in Ganze zu bieten hat. Das „Netzwerk Plurale Okonomik e.V.“ hat es sich zur Aufgabe gemacht, diese vielfaltigen okonomischen Ansatze im deutschsprachigen Raum zu fordern. Der Beitrag fasst die zentralen Kritikpunkte der Bewegung zusammen und zeigt neue Wege fur eine zukunftsfahige Wirtschafswissenschaft auf.

Inflammatory conditions are critically influenced by neuroimmune crosstalk. Cytokines and neurotrophic factors shape the responses of both nervous and immune systems. Although much progress has been made, most findings to date are based on expression of recombinant (tagged) proteins. The examination of receptor interactions by immunoprecipitation (IP) at endogenous levels provides further insight into the more subtle regulations of immune responses. Here, we present a comprehensive workflow and an optimized IP protocol that provide step-by-step instructions to investigate neurotrophin receptor p75NTR at endogenous, low abundance levels: from lysate preparation and confirmation of receptor expression to antibody validation and successful detection of protein-protein interactions. We employ human melanoma cell line A375 to validate specific antibodies and IP conditions, and apply these methods to explore p75NTR interactions in human leukemic plasmacytoid dendritic cell line PMDC05 detecting 14-3-3ϵ:p75NTR interaction in this cell type. With p75NTR as an exemplary protein, our approach provides a strategy to detect specific interaction partners even under endogenous, low abundance expression conditions.

We present a protocol for building, validating, and simulating models of signal transduction networks. These networks are challenging modeling targets due to the combinatorial complexity and sparse data, which have made it a major challenge even to formalize the current knowledge. To address this, the community has developed methods to model biomolecular reaction networks based on site dynamics. The strength of this approach is that reactions and states can be defined at variable resolution, which makes it possible to adapt the model resolution to the empirical data. This improves both scalability and accuracy, making it possible to formalize large models of signal transduction networks. Here, we present a method to build and validate large models of signal transduction networks. The workflow is based on rxncon, the reaction-contingency language. In a five-step process, we create a mechanistic network model, convert it into an executable Boolean model, use the Boolean model to evaluate and improve the network, and finally export the rxncon model into a rule-based format. We provide an introduction to the rxncon language and an annotated, step-by-step protocol for the workflow. Finally, we create a small model of the insulin signaling pathway to illustrate the protocol, together with some of the challenges-and some of their solutions-in modeling signal transduction.

National audience; Tests of legislative gatekeeping theories have been hampered by the absence of status quo estimates, making these tests vulnerable to selection bias. I overcome this problem with a novel data set on positions by private interests in Iowa, Nebraska, and Wisconsin because these states’ legislatures record organizations’ positions on lobbied bills irrespective of whether the bills receive floor consideration. This permits an estimation of the ideological locations of status quo policies for bills with and without floor consideration and in turn rigorous empirical tests of agenda-control theories. The data provide substantial evidence of partisan and nonpartisan gatekeeping and can adjudicate among the two models of gatekeeping in specific circumstances. In particular, they corroborate partisan gatekeeping in the Iowa House and the Wisconsin Assembly and cannot distinguish between the two accounts in the other chambers. Moreover, the results show that strong partisan institutions need not result in predominantly partisan gatekeeping.

We present a protocol for building, validating, and simulating models of signal transduction networks. These networks are challenging modeling targets due to the combinatorial complexity and sparse data, which have made it a major challenge even to formalize the current knowledge. To address this, the community has developed methods to model biomolecular reaction networks based on site dynamics. The strength of this approach is that reactions and states can be defined at variable resolution, which makes it possible to adapt the model resolution to the empirical data. This improves both scalability and accuracy, making it possible to formalize large models of signal transduction networks. Here, we present a method to build and validate large models of signal transduction networks. The workflow is based on rxncon, the reaction-contingency language. In a five-step process, we create a mechanistic network model, convert it into an executable Boolean model, use the Boolean model to evaluate and improve the network, and finally export the rxncon model into a rule-based format. We provide an introduction to the rxncon language and an annotated, step-by-step protocol for the workflow. Finally, we create a small model of the insulin signaling pathway to illustrate the protocol, together with some of the challenges-and some of their solutions-in modeling signal transduction.

In the context of ongoing criticisms of the lack of pluralism in economics, the present article aims to discuss the development of ‘heterodox’ economics since the 1970s. Following Lakatos’s concept of scientific research programs (srp), and concentrating on the situation in Germany, the article will discuss classifications of economics, and will specify the understanding of diversity in the light of ‘axiomatic variations’ of the economic mainstream. This will form the basis for the subsequent description of the development of heterodoxy in Germany, with special reference to the founding of new universities and the reform movements in the 1970s. It can be shown that the heterodox scene flourished in this period, but that this pluralization remained fragmented and short-lived; by the 1980s at the latest heterodoxy was again on its way to marginalization. The history of heterodoxy in Germany thus presents itself as an unequal ‘battle of the paradigms,’ and can only be told as the story of a failure.

Chronic granulomatous disease (CGD) is an inherited immunodeficiency, caused by the inability of neutrophils to produce functional NADPH oxidase required for fighting microbial infections. The X-linked form of CGD (X-CGD), which is due to mutations in the CYBB (gp91phox) gene, a component of NADPH oxidase, accounts for about two-thirds of CGD cases. We derived induced pluripotent stem cells (iPSCs) from X-CGD patient keratinocytes using a Flp recombinase excisable lentiviral reprogramming vector. For restoring gp91phox function, we applied two strategies: transposon-mediated bacterial artificial chromosome (BAC) transgenesis and gene targeting using vectors with a fixed 5′ homology arm (HA) of 8 kb and 3′HA varying in size from 30 to 80 kb. High efficiency of homologous recombination (up to 22%) was observed with increased size of the 3′HA. Both, BAC transgenesis and gene targeting resulted in functional restoration of the gp91phox measured by an oxidase activity assay in X-CGD iPSCs differentiated into the myeloid lineage. In conclusion, we delivered an important milestone towards the use of genetically corrected autologous cells for the treatment of X-CGD and monogenic diseases in general.

Do bipartisan contributions by corporations and trade associations reflect strategic considerations or ideological moderation? In this paper, I leverage lobbying disclosures in Iowa, Nebraska, and Wisconsin to provide a new measure of ideology that allows me to adjudicate between the two accounts. These states' legislatures permit or require lobbyists to declare their principals' positions on lobbied bills. I combine these data with roll call votes to estimate the ideal points of legislators and private interests in the same ideological space. I find that the revealed preferences of most corporations and trade groups are more conservative than what would be implied by their contribution behavior. The discrepancies are particularly acute for high-level contributors. This shows that a moderate contribution record need not imply moderation in policy preferences. Thus, such interests may not reduce polarization overall. Further, the divergence between contribution and position-taking behavior indicates that many business interests employ sophisticated strategies to influence public officials whom they disagree with.

SUMMARYCladding through laser metal deposition is a promising application of additive manufacturing. On the one hand, industrial robots are increasingly used in cladding because they provide wide wrist reorientation, which enables manufacturing of complex geometries. On the other hand, limitations in robot dynamics may prevent cladding of sharp edges and large objects. To overcome these issues, this paper aims at exploiting the residual degrees of freedom granted by the cladding process for the optimization of the deposition orientation. The proposed method optimizes the robot head orientation along a predefined path while coping with kino-dynamic constraints as well as process constraints. Experimental tests and results are reported and used to validate the approach.

In the context of ongoing criticisms of the lack of pluralism in economics, the present article aims to discuss the development of ‘heterodox’ economics since the 1970s. Following Lakatos’s concept of scientific research programs (srp), and concentrating on the situation in Germany, the article will discuss classifications of economics, and will specify the understanding of diversity in the light of ‘axiomatic variations’ of the economic mainstream. This will form the basis for the subsequent description of the development of heterodoxy in Germany, with special reference to the founding of new universities and the reform movements in the 1970s. It can be shown that the heterodox scene flourished in this period, but that this pluralization remained fragmented and short-lived; by the 1980s at the latest heterodoxy was again on its way to marginalization. The history of heterodoxy in Germany thus presents itself as an unequal ‘battle of the paradigms,’ and can only be told as the story of a failure....

The X-linked histone demethylase UTX has a pivotal role in cellular and developmental processes including embryogenesis, hematopoiesis and cancer. UTX removes di- and trimethyl groups on histone H3 lysine 27, thereby regulating gene expression. But there is growing evidence that UTX displays biological functions independent of its histone demethylase activity. To elucidate these novel functions, it is of great interest to define subcellular localizations of UTX. Here we show for the first time that native UTX is primarily localized in the cytoplasm whereas ectopic GFP and Flag-tagged UTX display nuclear and cytoplasmic localization. While its epigenetic function is exerted in the nucleus, its cytoplasmic localization points to a novel function.

The metabolic modelling community has established the gold standard for bottom-up systems biology with reconstruction, validation and simulation of mechanistic genome-scale models. Similar methods have not been established for signal transduction networks, where the representation of complexes and internal states leads to scalability issues in both model formulation and execution. While rule- and agent-based methods allow efficient model definition and execution, respectively, model parametrisation introduces an additional layer of uncertainty due to the sparsity of reliably measured parameters. Here, we present a scalable method for parameter-free simulation of mechanistic signal transduction networks. It is based on rxncon and uses a bipartite Boolean logic with separate update rules for reactions and states. Using two generic update rules, we enable translation of any rxncon model into a unique Boolean model, which can be used for network validation and simulation—allowing the prediction of system-level function directly from molecular mechanistic data. Through scalable model definition and simulation, and the independence of quantitative parameters, it opens up for simulation and validation of mechanistic genome-scale models of signal transduction networks., Modelling: signal transduction at the genome scale Mechanistic models are like road maps—they help us understand how signals travel through cells and guide cellular decisions. We developed a method to turn these models executable at the genome scale, and show that this method can explain and predict cellular physiology directly from molecular mechanisms. The bottom line is that the regulatory structure of the network is encoded in the molecular mechanisms, and we capture this knowledge in two generic update rules. These can be used to assemble molecular mechanisms, LEGO-brick style, into a functional model—without parametrisation or model fitting. This makes it possible to use the method for network validation and simulation of systems that are far too large to be parametrised, opening the door to genome-scale mechanistic models of cellular signal transduction.

What are the ideological positions of private interests? Valid measurements of interest group and legislator preferences on the same scale enable a closer examination of the role of private interests in the legislative process. In this paper, I exploit lobbying disclosure requirements in Iowa, Nebraska, and Wisconsin to provide a new measure of interest group ideology. These states' legislatures either permit or require lobbyists to declare their principals' positions on lobbied bills. I combine these data with roll call votes and candidate survey responses to estimate, via an item-response model, the ideal points of legislators and interest groups in the same space. Although the interest groups' position-based ideal points correlate strongly with contribution-based measures, there is more extremism in the former, which is primarily driven by conservative-leaning groups. In addition to providing a new measure of interest group ideology, the analysis suggests that private interests, including corporations and trade groups, cannot be ruled out as a source of partisan polarization.

What is the nature of agenda control in legislatures? Tests of canonical theories of gatekeeping have been limited to analyses of bills that make it through committees and are sent to the floor, making these tests vulnerable to selection bias. I overcome this problem with a novel dataset drawn from three US state legislatures (Iowa, Nebraska and Wisconsin) that record interest groups' positions on the bills on which they lobby lawmakers. This permits an estimation of the ideological locations of status quo policies for bills that die in legislative committees, and in turn rigorous empirical tests of agenda control theories. Unsurprisingly, I find that many bills are introduced even though they are very likely to die in committee, suggesting either uncertainty or pure position-taking by sponsors. The data provide substantial evidence of legislative gatekeeping, but can only adjudicate among different theories of gatekeeping in specific circumstances. Specifically, they corroborate partisan gatekeeping in the Iowa House and the Wisconsin Assembly, but cannot distinguish between partisan and non-partisan accounts in the Iowa Senate, the Wisconsin Senate, or the Nebraska Legislature.

Mesenchymal stromal cells (MSC) and factors secreted by them are essential components of the hematopoietic stem cell (HSC) niche within the bone marrow microenvironment. It has been shown that the extracellular matrix (ECM) can influence HSC-supportive potential of MSC and is a prerequisite for the proper signaling of morphogens. Therefore, we aimed at the identification of ECM components and candidate morphogens capable of enhancing the expression of HSC-supportive proteins in human MSC, namely, angiopoietin-1 (Ang-1) and stromal cell-derived factor 1 (SDF-1). For this purpose, highly sensitive secreted dual reporter constructs for Ang-1 and SDF-1 were established. These newly designed dual reporter systems enable continuous monitoring of the Ang-1 and SDF-1 promoter activity in an immortalized human MSC line cultured on ECM/morphogen microarrays. Reporter arrays showed that Ang-1 and SDF-1 expression can be induced by different ECM/morphogen combinations. In addition, continuous monitoring of promoter activity allows delineating time-dependent effects of the ECM and morphogens. Thus, we identified that collagen I and vitronectin in combination with Wnt3a favored SDF-1 expression over time, while only transiently inducing the expression of Ang-1. Taken together, the newly developed reporter systems allow for the monitoring of Ang-1 and SDF-1 promoter activity induced by morphogens and the ECM in a combinatorial and high-throughput manner. This technology might therefore be helpful to optimize culture conditions, which favor the activity of MSC as feeder cells for various types of stem and progenitor cells.

Nachstehend wird die Universitatsentwicklung in Deutschland einschlieslich der Rahmenbedingungen skizziert, soweit dies im Rahmen dieser Arbeit notwendig erschien. Fur das historische Verstandnis wird dazu anfanglich auch auf die Entwicklungen ab Etablierung der Universitaten im 19. Jahrhundert Bezug genommen.

Die Geschichte der Wirtschaftswissenschaften zeigt sehr unterschiedliche Wurzeln: Wahrend die Okonomik in Grosbritannien beispielsweise (moral-) philosophische Ursprunge aufweist, aufgrund des britischen College-Systems aber immer auch die Nahe zu naturwissenschaftlichen Disziplinen wahrte, hatte sich die deutsche Wirtschaftswissenschaft als Kameralismus aus der Rechtswissenschaft entwickelt, mit der sie lange die staatswissenschaftlichen Fakultaten an deutschen Universitaten teilte. Die verschiedenen Ursprunge mogen ein Teil der Erklarung sein, weshalb sich die Wirtschaftswissenschaft bis ins 20. Jahrhundert hinein methodisch-paradigmatisch recht unterschiedlich entwickelte: Wahrend die englische Politische Okonomik spatestens mit David Ricardo zu einer deduktiv-reduktionistischen Disziplin wurde, deren methodologische Individualisierung mit den Ansatzen von Stanley Jevons und Alfred Marshall eine gewisse Zwangslaufigkeit hatte, stellte sich die deutschsprachige Wirtschaftswissenschaft in Form der dominanten „Historischen Schule“ als eine induktiv-historisch argumentierende Disziplin dar, die keine praskriptiven Erklarungsmodelle anstrebte, sondern auf das je zeitlich-geopolitisch spezifische Verstehen ausgerichtet war.

Im Folgenden soll der Entwicklung der heterodoxen Okonomik innerhalb der deutschen universitaren Wirtschaftswissenschaft im Rahmen einer Bourdieuʼschen Feldanalyse nachgegangen werden. Dazu werden zunachst einmal der Bourdieuʼsche Ansatz skizziert und dogmenhistorisch die paradigmatische Entwicklung der Volkwirtschaftslehre in Deutschland vor dem Hintergrund der institutionellen Universitatsentwicklung dargelegt, woraus dann Hypothesen fur eine Pluralisierungsprognose abgeleitet werden. Diese Prognose soll anschliesend detailliert mit der tatsachlichen Entwicklung abgeglichen werden. Danach bleibt zu fragen, wie sich das zu konstatierende Ergebnis auf der Grundlage einer Feldanalyse erklaren und bewerten lasst.

Im Folgenden soll die personelle und paradigmatische Entwicklung der Wirtschaftswissenschaften – beides lasst sich naturlich nicht voneinander trennen – an zwei ausgewahlten Fachbereichen an deutschen Universitaten genauer untersucht und einander gegenuber gestellt werden. Im Zentrum des Erkenntnisinteresses stehen einerseits die konkreten Umstande der personellen Aufstellung und paradigmatischen Ausrichtung der Volkswirtschaftslehre unter den Bedingungen der Studentenbewegung und der universitaren Reformpolitik ab den 1960er Jahren – also die Berufungspolitik -, andererseits die qualitativ-inhaltliche und quantitative Entwicklung der Fachbereiche wahrend der letzten 50 Jahre und die Rahmenbedingungen der Reproduktion und Rekrutierung unter sich wandelnden Vorstellungen von den Aufgaben der Wissenschaft, der effektiven Steuerung einer Universitat und informellen Institutionalisierung von Wissenschaftsstandards.

The new coaxial fine wire deposition optic presents reduced weight (~10 kg without fiber and wire feed) and has extended functionality. The optical components are designed for wavelengths of 450 – 550 nm and 890 – 1100 nm. The head is prepared for the processing of even thin wires down to 100 μm in diameter. The new system is equipped with an integrated mini camera, sensors and interfaces to control units and networks. As a result the new head exhibits potential to produce very precise metallic structures as low as 200 - 300 μm. Suitable materials are steel, titanium, nickel and cobalt base alloys as well as materials on the basis of copper.

Mesenchymal stromal cells (MSC) are an important component of the bone marrow microenvironment. Notch ligands expressed by MSC are known to play a regulatory role for hematopoietic stem and progenitor cells (HSPC) and in support of bone marrow homeostasis. While the role of Notch signaling in HSPC, their progeny, and MSC has been relatively well studied, little is known about the Notch-independent regulatory impact of Notch ligands on MSC themselves. In the present study, we used genetically engineered bone marrow-derived human MSC to study the function role of Jagged-1 and the Jagged-1 intracellular domain (JICD) with regard to the interaction with HSPC. We demonstrate that Jagged-1 in human MSC undergoes cleavage to produce an intracellular domain that translocates into the nucleus. JICD but not Jagged-1 overexpression was associated with an increased expression of stromal cell-derived factor-1. Short-term co-culture (7 days) of HSPC with JICD-overexpressing MSC, but not with Jagged-1-overexpressing MSC, led to increased proliferation of CD34(+) progenitors. In contrast, long-term co-culture of HSPC with Jagged-1-overexpressing MSC (up to 6 weeks) led to a significantly better support of cobblestone area-forming cells and long-term culture-initiating cells (LTC-ICs) compared with JICD-overexpressing MSC. Taken together, results of this study indicate that full-length Jagged-1 and JICD have differential effects on MSC and on their interaction with HSPC ex-vivo. JICD-overexpressing MSC induce proliferation of HSPCs in short-term culture at the expense of immature precursors (LTC-ICs), whereas Jagged-1 overexpressing MSC favor LTC-IC formation.

Laser-based additive manufacturing (AM) technologies such as laser metal deposition have been introduced in various fields of applications. Laser metal deposition is not only used for the fabrication of complete new parts but also for the purpose of repair and redesign. Therefore, weld beads with dimensions above 1 mm were mostly used in the past. In some cases, bead widths can even exceed 10 mm or more. However, the build-up of filigree parts by means of submillimeter structures has gained interest during the last several years. Fabrication of structures with small dimensions requires different process modifications along the process chain. This includes not only general process strategies but also adjusted system components. The changed process yields material deposition of varying geometries possibly used in aerospace, space, medical technology, and microtooling. Additionally, it can also be used in the repair of worn or damaged microparts. In this paper, the aforementioned process modifications are shown and demonstrated. In addition, high-speed process observations are discussed and, finally, the fabricated parts are analyzed. The latter includes nondestructive and also destructive methods. Based on the combination of changed process elements, a stable laser-based AM procedure is presented, which is already in production.

The melanoma cell adhesion molecule defines mesenchymal stromal cells in the human bone marrow that regenerate bone and establish a hematopoietic microenvironment in vivo. The role of the melanoma cell adhesion molecule in primary human mesenchymal stromal cells and the maintenance of hematopoietic stem and progenitor cells during ex vivo culture has not yet been demonstrated. We applied RNA interference or ectopic overexpression of the melanoma cell adhesion molecule in human mesenchymal stromal cells to evaluate the effect of the melanoma cell adhesion molecule on their proliferation and differentiation as well as its influence on co-cultivated hematopoietic stem and progenitor cells. Knockdown and overexpression of the melanoma cell adhesion molecule affected several characteristics of human mesenchymal stromal cells related to osteogenic differentiation, proliferation, and migration. Furthermore, knockdown of the melanoma cell adhesion molecule in human mesenchymal stromal cells stimulated the proliferation of hematopoietic stem and progenitor cells, and strongly reduced the formation of long-term culture-initiating cells. In contrast, melanoma cell adhesion molecule-overexpressing human mesenchymal stromal cells provided a supportive microenvironment for hematopoietic stem and progenitor cells. Expression of the melanoma cell adhesion molecule increased the adhesion of hematopoietic stem and progenitor cells to human mesenchymal stromal cells and their migration beneath the monolayer of human mesenchymal stromal cells. Our results demonstrate that the expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells determines their fate and regulates the maintenance of hematopoietic stem and progenitor cells through direct cell-cell contact.