Co-determination and Innovation

This paper examines the effect of the German co-determination law of 1976 (MitbestG) on the innovative activity of German firms. Co-determination applies to firms with 2000 employees or more. Data from 1971-1976 and 1981-1990 on 148 firms are used to compare the number of patents granted to co-determined firms before and after the introduction of the law. Several control variables are applied and in particular, in order to avoid a possible bias from specific effects of firm size, we compare the co-determined firms with others before and after 1976. The results do not support the view that co-determination slows down technological progress and reduces innovativeness.co-determination, innovation, patents

Bridging the gap between academic responsibilities and practical application in logistics

The paper presents a model inspired by the success of innovative logistics programs that have enhanced the relevance of academic programs by developing closer ties with logistics and transportation practitioners. Discussion focuses on examples that illustrate implementation of the model. The intent is to provide a blueprint for academics to enhance cooperation at locations that do not currently have such programs in place

Surface modification of drugs for inhalation

In der vorliegenden Arbeit wird die Anwendung des „dry particle coating“ für die Oberflächenmodifizierung von mikronisiertem Salbutamolsulfat zur Inhalation beschrieben. Bei diesem Verfahren wird der Wirkstoff durch einen mechanischen Energieeintrag mit einem Hilfsstoff verbunden, um dadurch Veränderungen der Oberflächeneigenschaften zu erzielen. Der Einfluss der Oberflächenmodifizierung wurde sowohl für trägerfreie Pulverformulierungen als auch für suspensionsbasierte Dosieraerosole untersucht. Dazu wurden Co-Vermahlungen mit unterschiedlichen Konzentrationen an Glycerolmonostearat bzw. Magnesiumstearat in einer Luftstrahlmühle durchgeführt. Als Vergleich wurden physikalische Mischungen mittels Turbulamischer hergestellt. Die Proben wurden physiko-chemisch charakterisiert und das aerodynamische Verhalten der Pulver untersucht. Für die mit Glycerolmonostearat modifizierten Proben konnte kein verbessertes Dispergiervermögen festgestellt werden. Dahingegen konnte gezeigt werden, dass es durch die Co-Vermahlung mit Magnesiumstearat möglich ist, die Kohäsivität des Wirkstoffes zu reduzieren und dadurch das Dispergiervermögen zu verbessern. Die lungengängige Fraktion konnte infolgedessen, im Vergleich zum reinen Wirkstoff, mehr als verdoppelt werden. Untersuchungen zum Einfluss des Mischprozesses auf die Oberflächenmodifizierung mit Magnesiumstearat zeigten eine Verringerung der Feinpartikelfraktion bei längerer Mischdauer. Im Rahmen der physiko-chemischen Charakterisierung konnte für die co-vermahlenen Proben mit Magnesiumstearat eine diskontinuierliche Belegung der Wirkstoffoberfläche bzw. ein Nanocoating nachgewiesen werden. Außerdem wurde in dieser Arbeit die Verwendung von Nanopartikeln als sterische Abstandshalter zwischen den Wirkstoffpartikeln untersucht. Dazu wurde hydrophobes, hochdisperses Siliciumdioxid (Aerosil R 972) in unterschiedlichen Konzentrationen verwendet. Erneut erfolgte der Vergleich zwischen physikalischen Mischungen und den co-vermahlenen Proben. Es konnte für beide Herstellungsarten eine Verbesserung der aerodynamischen Eigenschaften, in Abhängigkeit von der verwendeten Aerosilkonzentration, gezeigt werden. Bereits bei einer Co-Vermahlung mit 2% (m/m) Aerosil R 972 übersteigen die Werte für die Feinpartikelfraktion mit 63% die der Turbulamischungen deutlich. Des Weiteren wurde ein Mechanofusionsgerät für die Oberflächen-modifizierung von Salbutamolsulfat mit Magnesiumstearat untersucht. Die Auswertung des statistischen Versuchsplans konnte einen signifikanten Einfluss der Umdrehungsgeschwindigkeit auf die Feinpartikelfraktion zeigen, sowie eine Wechselwirkung zwischen der Magnesiumstearatkonzentration und der Prozesszeit. Allerdings zeigte auch das reine Salbutamolsulfat nach der Prozessierung eine verbesserte Dispergierbarkeit. Im zweiten Teil der Arbeit wurden die co-vermahlenen Proben für die Herstellung suspensionsbasierter Dosieraerosole mit HFA 134a verwendet. Ziel war es hierbei, die veränderten Oberflächen-eigenschaften zu nutzen, um eine Stabilisierung der Suspension zu erhalten. Es konnte gezeigt werden, dass die mit Glycerolmonostearat modifizierten Proben zu einer Verringerung der Sedimentations-geschwindigkeit führen und das Phänomen der Flockung aufweisen. Allerdings wirkt sich dies nicht positiv auf die Gleichförmigkeit der abgegebenen Dosis und die aerodynamischen Eigenschaften aus. Die Proben mit Magnesiumstearat zeigen hingegen eine geringe Erhöhung der Feinpartikelfraktion gegenüber dem reinen Wirkstoff und keine Unterschiede in der sich ausbildenden Sedimenthöhe. Der Anstieg der Feinpartikelfraktion wird auf veränderte Wechselwirkungen zwischen dem Treibmittel und den Partikeloberflächen durch die Prozessierung zurückgeführt. In dieser Arbeit konnte die Anwendung des „dry particle coating“ für pulmonale Darreichungsformen gezeigt werden. Da dieses Verfahren zahlreiche Vorteile gegenüber den bisherigen Methoden zur Oberflächenmodifizierung bietet, stellt es eine interessante und vielversprechende Alternative dar.A dry particle coating process for the surface modification of micronised salbutamol sulphate for inhalation was analysed. During this process high mechanical energy is applied to fuse drug and excipient together to achieve an alteration of surface properties. The influence of surface modification was investigated for carrier free powder formulations as well as for suspension-based pressurised metered dose inhalers. Therefore, co-milling with different concentrations of glycerol monstearate and magnesium stearate in an air jet mill was conducted. For comparison, physical mixtures were prepared with a Turbula blender. All samples were physico-chemically characterised and also the aerodynamic behaviour of the powder was analysed. The samples modified with glycerol monostearate did not show any improvement in powder de-agglomeration. However, co-milling with magnesium stearate reduces the cohesiveness of the drug and leads to an improvement in powder dispersibility. Consequently, the respirable fraction was more than doubled in comparison to pure drug substance. The influence of the mixing process on surface modification with magnesium stearate showed a reduction in fine partice fraction with longer mixing time. The physico-chemical characterisation of the samples co-milled with magnesium stearate showed a discontinuous surface coverage of the drug or a nanocoating. Furthermore, the application of nanoparticles as steric spacer between drug particles was investigated. For this, hydrophobic silicon dioxide (Aerosil R 972) was used in different concentrations. The co-milled samples were again compared with physical mixtures. An improvement of the aerodynamic behaviour for both processes depending on the Aerosil concentration could be shown. A concentration of only 2% (w/w) Aerosil R 972 for co-milling leads to a fine particle fraction of 63%. This exceeds by far the fine particle fraction measured for the blended samples. In addition, a mechanofusion system was used for surface modification with magnesium stearate. The analysis of a design of experiments’ study showed a significant influence of the rotational speed on the fine particle fraction as well as an interaction between magnesium stearate concentration and process time. However, also the pure drug substance showed an improved de-agglomeration after processing. In the second part of this study, the surface modified particles were used to prepare suspension-based pressurised metered dose inhaler in HFA 134a. The aim was to use the modified surface properties to stabilise the disperse system. It could be shown that the salbutamol sulphate particles modified with glycerol monostearate result in a reduction of sedimentation velocity and show flocculation. However, this has no positive influence on uniformity of delivered dose and the aerodynamic behaviour. The samples modified with magnesium stearate show a slight increase in fine particle fraction in comparison to pure drug substance and no differences in formed sediment height. The increase in fine particle fraction is assumed to be caused by different interactions between propellant and the particle surface after processing. In this study the application of dry particle coating for pulmonary dosage forms was shown. This process has several advantages compared to previous methods for surface modification and is, therefore, an interesting and promising alternative approach

Innovationsverhalten und Schutzrechtnutzung deutscher Aktiengesellschaften

Die vorliegende Arbeit beschäftigt sich mit diversen Apekten der Schutzrechtnutzung von westdeutschen Aktiengesellschaften des verarbeitenden Gewerbes in Deutschland. Drei Fragen werden explizit untersucht: 1. Wirken Gesetzesänderungen im Patentrecht signifikant auf die Anmeldepraxis der betrachteten Unternehmen oder bleibt diese hiervon nahezu unberührt? 2. Welche Determinanten beeinflussen das Nutzungsverhalten im Bereich Gebrauchsmuster? 3. Durch welche Faktoren wird die Entscheidung getrieben, Lizenzen an Schutzrechten zu erwerben oder selbst zu generieren? Die genannten Aspekte werden mit Hilfe mikroökonomischer Verfahren untersucht, denen ein cross-sektoraler Datensatz für die Zeit von 1972 - 1994 zugrunde liegt. Die Ergebnisse legen nahe, dass Änderungen im Patentrecht nicht nur weit reichende Auswirkungen auf das Anmeldeverfahren der Unternehmen haben, sondern darüber hinaus auch die Erfolgswahrscheinlichkeit einer Erteilung beeinflusst wird. Des Weiteren kann gezeigt werden, dass nur wenige Determinanten im Bereich Gebrauchsmuster identifiziert werden können, welche die Nutzung dieses Schutzrechtes systematisch zu erklären in der Lage sind. Hier unterscheiden sich die Ergebnisse stark gegenüber denen der klassischen Patentforschung. Letztlich konnte ermittelt werden, dass die vorherrschende Meinung, in Zeiten wachsenden Wettbewerbsdruck müssen Unternehmen Innovationen sowohl selbst generieren als auch fremd beziehen, in einem cross-sektorealen Panel nicht durchweg Bestätigung findet. Vielmehr hängt diese Entscheidung stark von der jeweiligen Branchenzugehörigkeit ab

MiR-146a Upregulation of Phagocytosis in Human Macrophages

Sjögrens Syndrome (SjS) is an autoimmune disease that attacks exocrine glands such as salivary and lacrimal glands resulting in severe dryness of the mouth and eyes. Previous studies have linked increased microRNA-146a (miR-146a) expression in peripheral blood mononuclear cells in SjS patients compared to healthy controls. MicroRNAs (miRNAs), small non-coding RNA molecules that post-transcriptionally regulate gene expression, are known to play key regulatory roles in immune responses and have been implicated in a growing number of autoimmune disorders. Further investigation into the role of increased miR-146a expression in SjS revealed links to several immune functions including phagocytosis.Our goal was to further examine the relationship between miR-146a expression and the rate of phagocytosis in human macrophages by using apoptotic human cells as a phagocytic target. We hypothesized that upregulation of miR-146a would increase phagocytic activity of differentiated THP-1 human monocytes. To quantify phagocytic activity, a pH-sensitive fluorescent dye (pHrodo) was used to indicate the E. coli or apoptotic Jurkats that had been phagocytosed. THP-1 cells were transfected with miR-146a and differentiated into macrophages. Phagocytic activity was observed by incubating fluorescently labeled E.coli or apoptotic Jurkat cells with miR-146a transfected and mock transfected THP-1 cells for 2-4 hours. Fluorescence intensity was quantified using a fluorescent plate reader (E. coli) and microscopy (apoptotic Jurkats). MiR-146a-transfected THP-1 cells exhibited significantly increased phagocytic activity of fluorescently labeled E. coli (P\u3c0.001) and apoptotic Jurkats. Knockdown of TRAF6, a gene target of miR-146a, did not impact the phagocytic activity. MiR-146a appears to upregulate phagocytic activity in human THP-1 cells through an unknown mechanism. Further studies are in progress to determine the mechanism by which miR-146a upregulates phagocytosis

Computational Studies on the Relation Between Macromolecular Dynamics and Protein Binding and Function

Computational methods can help to better understand and analyze the interaction of proteins and their binding partners. This interaction is influenced by many factors, including specific sequence variants, the dynamics and electrostatics of the proteins, as well as further physicochemical properties of the corresponding binding partners. A detailed investigation of these different, and often complicated, properties helps to better understand the functionality of proteins, for which the interaction with other molecules plays a crucial role. The work presented here provides new methodologies, implemented in webservers and software, which assist during the analysis of proteins. Furthermore, in an application case, computational methods and analyses in combination with experimental results were used to detect a specific interaction network of proteins. The new ProSAT+ webserver enables the visualization of protein sequence annotations in the context of the three–dimensional protein structure and contains additional options for visualizing and sharing protein annotations. The sequence information allows an easy, but extensive analysis of proteins. The functionality of the ProSAT+ webserver can be integrated into other webservers, which was done in the case of the two other webservers for the analysis of protein binding pockets described here. A tool for the LigDig webserver was developed that provides the comparison of protein binding pockets by the alignment and visualization of the binding pockets based on an existing algorithm. The new TRAPP webserver assists in the analysis of protein binding pocket dynamics. The existing TRAPP software was used, and a user web interface was implemented to simplify the usability. Additional new functionalities were also developed, such as the visualization of protein sequence conservation in context of all other TRAPP results in the three–dimensional structure. This allows the detection of conserved or non–conserved regions inside the binding pocket, which might influence the dynamics of the pocket. This newly gained information can be used during the process of designing selective inhibitors. During the protein disaggregation process, members from different classes of the so-called J–protein (HSP40) co–chaperones play a crucial role. The synergetic application of different computational methods and experiments enabled the detection of an interclass specific J–protein interaction and indicated that the interaction evolved to enable a high efficiency in the disaggregation process. The resulting data of performed protein domain docking simulations required an update of the standard clustering workflow. This new methodology can be applied for protein docking in cases that have problems with multiple, weakly specific interaction sites. The work presented here facilitates in many ways the analysis of proteins, including their structure and sequence features, as well as, their dynamics and interactions with their binding partners. The new methods are provided as webservers and therefore are accessible, and easy to use for all researchers. This can assist in many research projects and provide relevant information. The analyses of the J–proteins improved the knowledge about their biological role and functionality, and therefore provide an important contribution for a better understanding of the overall protein disaggregation process

SENSAÇÕES CORPÓREO-ESPACIAIS E A FAZEDURA DE “MAPAS SENSACIONAIS”: um relato de experiência

O presente texto aborda alguns desdobramentos e reflexões acerca de práticas desenvolvidas na oficina Geografia Experimental do Corpo, – cujo intuito é propiciar ao participante um percurso sensório – espacial sem o uso da visão. Com isso visa-se produzir e discutir “mapas sensacionais” a partir desse percurso. Tal oficina teve início em de práticas relacionadas à iniciação cartografia com turmas do 5º ano do fundamental de uma escola estadual localizada no município de Florianópolis – SC, alcançando outras dimensões fora da escola. Com base no material produzido nessa oficina discorre-se sobre as suas possibilidades e limitações, bem como brevemente, seus processos de formação e evolução. Partindo desse contexto de formação e prática em educação, busca-se pensar sobre dois pontos que se sobressaem no processo da oficina: a questão da relação do visível (olhar) e do corpo com espaço; e as cartografias oriundas dessa relação, em um contexto de experiência em educação na área de Geografia. Em paralelo a essas reflexões, analisa-se essa proposta de oficina considerando-a como uma ferramenta prática que tenta fazer com que algo nos passe, buscando uma aproximação ao conceito de experiência em Jorge Larrosa, e que se relaciona com um modo de fazer e pensar cartografia

SUPPLY CHAIN INTEGRATION IN THE FOOD AND CONSUMER GOODS INDUSTRIES

The interorganizational structures necessary to implement and achieve the logistical performance improvements identified in the Efficient Consumer Response (ECR) initiative and related supply chain management concepts are difficult to develop. Firms continue to struggle to implement integrated programs and techniques, particularly with respect to changing operating structures, relationships, and mindsets to facilitate true supply chain integration. This research explores the logistical strategies and structures used by selected food and consumer goods firms to integrate their supply chains. It illustrates effective integration strategies and identifies critical success factors and barriers to successful ECR implementation. A framework is used to guide managers in developing the competencies essential to integrating the supply chain and to establishing the relationships necessary to operate in an ECR environment. The framework, entitled Supply Chain 2000, depicts supply chain value creation as achieving synchronization and coordination across four critical supply chain flows: product/service; market accommodation; information; and cash.Industrial Organization,

Bending the Chain: The Surprising Challenge of Integrating Purchasing and Logistics

Over the last several decades, supply chain (SC) professionals have focused on performance issues that have emerged from a lack of commercial/business alignment with supply chain operations. Significant improvements have been made, and systemic processes (IBP—integrated business planning—and S&OP—sales and operations planning) have been developed to drive a fully integrated business. As business integration has continued to improve, the biggest SC opportunities have shifted. Every year, the University of Tennessee’s Global Supply Chain Institute networks with hundreds of companies, requesting information on emerging supply chain issues. Our recent research shows that one of the greatest business integration opportunities is found within the traditional supply chain functions themselves. (“We have met the enemy and he is us!”). Specifically, we believe a major strategic integration opportunity exists between purchasing and logistics, and failing to capitalize on this opportunity is very clearly causing many firms to miss important opportunities to create value