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Insbesondere in „reifen“ Innovationssystemen wie dem baden-wurttembergischen lassen sich in jungerer Zeit neue Innovationsformen, neue Akteure und Akteurskonstellationen beobachten, flankiert durch neue Instrumente der Innovationsunterstutzung. Vor dem Hintergrund einer weiterentwickelten Innovationssystemheuristik skizziert der vorliegende Beitrag diese neuen Entwicklungen in Baden-Wurttemberg. In exemplarischer Weise greift er charakteristische Innovationsakteure, Akteure aus der Forschungslandschaft, aus Bildung und Qualifizierung, ferner die intermediare Funktion von Mediatoren, gesellschaftliche Akteure sowie den Aspekt der Innovationsfinanzierung auf und zeigt aktuelle Tendenzen und Trends. Deutlich wird, dass sich das baden-wurttembergische Innovationssystem in den vergangenen Jahren bestandig weiterentwickelt und ausdifferenziert hat. Forschungsanstrengungen und Modernisierungsaktivitaten der Wirtschaft sowie die Gestaltung innovationsfreundlicher Politiken tragen zur Anpassungsfahigkeit des Systems bei und sind wesentliche Einflussfaktoren fur den anhaltenden Erfolg des Innovationssystems. Erganzt wird dies durch vielfaltige Neuerungen auf Akteurs‑, Institutionen- und Masnahmenebene. Es stellt sich die grundsatzliche Frage nach der Steuerungs- und Leistungsfahigkeit dieses komplexen Systems angesichts sich dynamisch verandernder globaler Umfeldbedingungen.

This deliverable summarises the outcomes of the second round of participatory workshops that took place in the period May-June 2019 at the premises of DESY and ALBA, close to the ELIXIR campus and in association with the MERIL conference in Lisbon. The report includes a synopsis of, first, suggestions for indicator selection and, second, further feedback on the IA framework as expressed by RI representatives during the workshops. Thereafter, it further specifies the long-lists of indicators and impact pathways as they were finalised subsequent to these workshops. Finally, it summarises the findings from a follow-up survey in which the (first and second round) workshop participants were asked to comment on and validate the finalised long-lists. Minutes and documentation from all workshops are appended to the report.

This report contains a critical literature review of the most common methodologies currently employed for the socio-economic impact assessment (IA) of research infrastructures (RIs). The review is intended to pave the way for the development of a conceptual framework IA model. There are a wide array of existing approaches and methods to assess the socio-economic impact of RI. While the majority of the reviewed approaches cover the main expected socio-economic impacts of RIs, such as the production of knowledge, human capital accumulation, increased innovation, productivity or effects on GDP, they differ in the way such impacts are measured, treated, and aggregated. Moreover, some of the reviewed methods are complementary, some are substitutes; some have broad applicability, while others are quite narrow in their scope and potential informative power. The review makes a systematic assessment based on six assessment criteria: reliability, validity, accuracy, cost/time needed, relevance for policy makers, relevance for RI managers. The review highlights that there is not a single methodological approach that can appropriately answer all the questions that a socio-economic IA addresses. Rather, a smart and rigorous combination of approaches can add value compared to existing methods.

Basically, complex systems are defined as a large number of autonomous entities in interaction, that create several levels of collective organization leading to emergent (and immergent) behavior. In short, complex systems are characterized by the observation that the whole is more than the sum of the parts (Aristotle). The aim of this paper is to address the issue of innovation systems in order to determine by how much they constitute complex systems.

L’analyse que nous presentons ici est le fruit de l’experience de la cooperation franco-allemande en matiere de recherche. Elle reflete le vecu des chercheurs, directeurs de recherche et responsables de programmes de recherche bilateraux interroges par l’Institut Fraunhofer ISI dans le cadre de l’accompagnement des programmes bilateraux entre instituts Fraunhofer et Carnot (Zenker et al., 2013a), mandate par le ministere federal de la Recherche. La principale conclusion en est que le succes d’une cooperation bilaterale en matiere de recherche depend d’une maniere essentielle de facteurs individuels, institutionnels et politiques. En effet, la difficulte que pose la gestion d‘un financement conjoint, conjuguee aux differences culturelles, exige de la part des membres des equipes de recherche impliquees des capacites organisationnelles et manageriales prononcees, ainsi qu’une grande ouverture a l’autre, doublee d’une profonde tolerance, lorsqu’ils developpent une approche commune du projet pour le realiser au quotidien. Or ce qui semble a premiere vue un ‘surcroit de travail’ se revele en realite tres fructueux parce qu’il elargit l’acces a des infrastructures et a des savoirs existants, mene a une comprehension plus approfondie et plus intime des enjeux de l’interculturel, et favorise l’acces aux reseaux personnels des participants comme des marches dans le pays partenaire. Apres avoir rappele l’importance d’une intensification de la cooperation transfrontieres dans le domaine de la recherche, nous expliciterons les specificites inherentes a la cooperation franco-allemande, telles qu’elles sont apparues dans l’experience concrete des cooperations etudiees. Enfin, dans une analyse integrant les dimensions personnelles, institutionnelles et politiques ou societales, nous en presenterons les facteurs de succes comme les handicaps, et nous en tirerons quelques conclusions pour optimiser la cooperation bilaterale dans le domaine de la recherche.

Les PME industrielles allemandes sont reputees pour etre particulierement innovantes. Si elles pratiquent souvent la RD enfin, nous presenterons ses activites hors des frontieres, plus particulierement en France.

La presente contribution se propose d’analyser comment une region ou plus precisement les acteurs et les activites constituant l’environnement de la firme est percue par les firmes qui y sont situees, et si ces perceptions sont liees aux phenomenes d’innovation. Dans ce contexte, la question qui est posee est celle de l’existence – ou non – de comportements d’innovation et/ou de perceptions par les firmes qui caracterisent et distinguent les entreprises de differentes regions. L’analyse concerne un echantillon de petites et moyennes entreprises du secteur des services a forte intensite de connaissances localisees dans deux regions voisines appartenant a des contextes nationaux differents en Europe (Alsace et pays de Bade) et deux regions canadiennes (Bas-Saint-Laurent et Beauce au Quebec).

Purpose. Qualitative and quantitative determination of tear fluid components is of increasing interest in ophthalmology. Until now, for diagnosis and course control of some diseases of the anterior parts of the eye, different methods for tear fluid protein analysis are available. Results can be obtained by polyacrylamide gel electrophoresis (PAGE), immunochemistry, and high-performance liquid chromatography (HPLC). A new method for protein separation, identification and semi-quantitative determination on a chip-based micro-fluidic technique is used for the first time to investigate tear fluids. Methods. Normal human reflex tears were obtained by stimulation with China mint oil and collected using glass capillary tubes. A lab-on-a-chip technology (developed by Agilent Technologies, Waldbronn, Germany, in co-operation with Caliper Technologies, Mountain View, California, USA) was used for separation and semi-quantitative determination of tear proteins. Tear fluid was separated on the Agilent 2100 Bioanalyzer in combination with the Protein 200 LabChip kit and the dedicated protein assay software. Time and temperature of the incubation with sample buffer were varied, and the influence of these parameters on protein separation profiles was studied. Tear proteins were also analysed by PAGE, and the results obtained by both methods were compared. Results. The different proteins of tear fluid can be separated by the Agilent 2100 Bioanalyzer method in very short time. By this method, the molecular weight as well as the concentration of proteins can be determined. Data are automatically stored in digital format and can be retrieved and shared. Results of this technology were comparable with the protein pattern obtained by PAGE. It was confirmed by both methods that, depending on incubation time of tear fluid with sample buffer and on temperature, different protein pattern can be obtained from the tears of one specimen. Conclusion. Tear proteins – in contrast to serum or aqueous humour proteins – are very sensitive to changes in sample buffer temperature as well as incubation time with buffer. To obtain comparable results for tear fluid proteins, the sample buffer applied and the incubation time and temperature must be observed carefully. This can be demonstrated by both the new Agilent 2100 Bioanalyzer method and PAGE. These results are of importance when comparing tear fluid protein pattern for the diagnosis and course control of dry-eye syndrome and of other diseases of the anterior part of the eye.

Cisplatin and four structurally related platinum(II) complexes were incubated with guanosine 5'-monophosphate (5'-GMP) in water at 37 degrees C. The adduct formation reactions were monitored with cation- and anion-exchange liquid chromatography/electrospray ionization mass spectrometry. In addition to mono- and bis-adducts of guanosine 5'-monophosphate with the platinum(II) complexes, other molecular species, presumably with a binuclear structure (two platinum(II) centres), were detected in the reaction mixtures, which have not been reported previously, indicating an unexpected complexity of adduct formation. Anion-exchange chromatography revealed the presence of isomers of two complexes which presumably result from the restricted rotation at the platinum-- N-7 (5'-GMP) bonds. All reaction products were characterized in both the positive and negative ion modes. Furthermore, preliminary kinetics and half-times of complex formation were investigated for cisplatin and two other platinum(II) complexes, monitoring the relative concentrations of free 5'-GMP and of mono- and bis-GMP adducts as a function of time (250 h) using an internal standard protocol with thymidine 5'-monophosphate.

Carboplatin (cis-diammine-1,1-cyclobutane-dicarboxylatoplatinum(II)) is the only cisplatin (cis-diammine-dichloroplatinum(II)) derivative currently available for the treatment of cancer worldwide. The higher stability of the carboxylate ligand compared to the coordinated chloride in cisplatin results in a reduced reactivity of the molecule. Capillary electrophoresis has been applied for investigating the adduct formation of carboplatin and analogues with nucleoside monophosphates, di- and trinucleotides. Adduct formation results in a significant shift of the absorption maximum to lower energy compared to free nucleotides. Therefore, characterization of the analytes was performed by UV additionally to NMR spectroscopy. A preference for GMP- and AMP-coordination was found. The ability of separating all four common nucleotides and their major platinum adducts in a single run demonstrates the suitability of CE for this kind of investigations.

Kinetics of the adduct formation of cisplatin and its hydrolysis products with 5′-GMP was investigated using capillary electrophoresis (CE) under ‘simulated physiological conditions’. Therefore, chloride ion and phosphate concentration as well as the pH were chosen comparable to intracellular conditions. Furthermore, the influence of the sulfur-containing α-amino acids l -methionine and l -cysteine on the kinetics of the adduct formation have been studied. Both amino acids increased the half-time of the reaction significantly but did not influence the formation of the major adduct cis-[Pt(NH3)2(N7-GMP)2]2−. The reaction products were separated using CE, and characterised using UV and NMR spectroscopy.

In this paper, we outline a general applicable matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS)-based strategy for the characterization of sodium borohydride-reduced peptidoglycan fragments (dimeric up to oligomeric fragments) derived from muramidase-digested murein. As an example, murein isolated from the cyanelles of the photoautotrophic Cyanophora paradoxa was selected. Separation of unreduced peptidoglycan fragments (generated by muramidase digestion) by gel filtration divided them into muropeptides according to their sizes (degree of polymerization). Afterwards, the pooled fractions were reduced by NaBH 4 and isolation of the individual peptidoglycan fragments was performed by reversed-phase high-performance liquid chromatography (RP HPLC), with a sodium- or potassium phosphate-containing water–methanol gradient giving the maximal separation efficiency. For determining the exact molecular masses of these individual components, MALDI MS proved to be the most sensitive mass spectrometric technique for these salt-containing samples. A desalting step based on a further HPLC step, using a water–acetonitrile–trifluoroacetic acid gradient turned out to be very helpful for the molecular mass determination, especially of large peptidoglycan fragments (molecular weight range >3500 Da), which were present in very small quantities, but were not absolutely necessary. In the negative ion, reflectron mode, we could achieve the best signal-to-noise ratio and a mass accuracy of −0.03 to +0.1% for deprotonated molecular ions. The combined results from negative (and positive ion) MALDI MS in the reflectron mode, gel chromatography, HPLC and amino acid/sugar analysis (on the total hydrolysate of the purified murein) allowed us to deduce the primary structure of dimeric up to tetrameric peptidoglycan fragments isolated from the cyanelle murein of C. paradoxa .

Modulation of allergic immune responses by using adequate adjuvants is a promising concept for future immunotherapy of type I hypersensitivity. In the present study, recombinant Bet v 1 (rBet v 1, the major birch pollen allergen) was conjugated to cross-linked crystalline surface layer proteins (SL) derived from Gram-positive eubacteria. T cell lines (TCL) and clones (TCC) were established from peripheral blood of birch pollen-allergic patients. TCL and TCC were induced either using rBet v 1 alone or rBet v 1/SL conjugates (rBet v 1/SL) as initial antigen stimulus. Cytokine production after re-stimulation with rBet v 1 was investigated. TCL initiated with rBet v 1/SL showed significantly increased IFN-gamma production as compared to rBet v 1 -selected TCL. TCC were established from TCL of five patients. As expected, the majority of CD4+ TCC induced by rBet v 1 (55%) displayed a Th2-like pattern of cytokine production. However, only 21% of Bet v 1-specific TCC isolated from TCL established with the Bet v 1/SL revealed this phenotype. The majority of SL-specific TCC (80%) belonged to the Th1 phenotype. In cultures of peripheral blood mononuclear cells, both, SL and Bet v 1/SL (but not rBet v 1) stimulated the production of high levels of IL-12, a pivotal mediator of Th1 responses. Moreover, stimulation of rBet v 1-induced TCC with rBet v 1/SL led to an increased IFN-gamma production. This effect could be reversed by neutralizing anti-IL-12 mAb. Together these results indicate an adjuvant effect of SL mediated by IL-12. Our results indicate that bacterial components, such as SL, displaying adjuvant effects may be suitable for immunotherapeutical vaccines for type I allergy.

A strategy for the primary stucture characterization of reduced peptidoglycan trimers derived from muramidase-digested murein (e.g. isolated from the cyanelles of Cyanophora paradoxa) is outlined. First, muropeptides are separated by gel filtration according to their size (degree of cross-linking). This step is followed by reduction with sodium borohydride and reversed-phase high-performance liquid chromatography (HPLC). Trimeric and oligomeric compounds (molecular weight range 2500–4500 Da), in particular, are present in small quantities and therefore sophisticated methods for characterization are required due to the biological importance of these components. For determining moecular weight with high accuracy, positive-ion plasma desorption mass spectrometry (PDMS) proves to be a well-suited analytical method with sufficient sensitivity (medium picomole range) and mass accuracy (±0.04%). Based on combined data from PDMS, gel chromatography, HPLC and amino acid and amino sugar analyses, the primary structure of peptidoglycan trimeric compounds could be determined unambiguously.

The peptidoglycan layer surrounding the photosynthetic organelles (cyanelles) of the protist Cyanophora paradoxa is thought to be a relic of their cyanobacterial ancestors. The separation of muropeptides by gel filtration and reverse-phase high-performance liquid chromatography revealed four different muropeptide monomers. A number of muropeptides were identical in retention behavior to muropeptides of Escherichia coli, while others had remarkably long retention times with respect to their sizes, as indicated by gel filtration. Molecular mass determination by plasma desorption and matrix-assisted laser desorption ionization mass spectrometry showed that these unusual muropeptides had molecular masses greater by 112 Da or a multiple thereof than those of ones common to both species. Fast atom bombardment-tandem mass spectrometry of these reduced muropeptide monomers allowed the localization of the modification to D-glutamic acid. High-resolution fast atom bombardment-mass spectrometry and amino acid analysis revealed N-acetylputrescine to be the substituent (E. Pittenauer, E. R. Schmid, G. Allmaier, B. Pfanzagl, W. Löffelhardt, C. Quintela, M. A. de Pedro, and W. Stanek, Biol. Mass Spectrom. 22:524-536, 1993). In addition to the 4 monomers already known, 8 dimers, 11 trimers, and 6 tetramers were characterized. An average glycan chain length of 51 disaccharide units was determined by the transfer of [U-14C]galactose to the terminal N-acetylglucosamine residues of cyanelle peptidoglycan. The muropeptide pattern is discussed with respect to peptidoglycan biosynthesis and processing.

The undeniable importance of knowledge and innovation in modern economies justifies the increasing interest that scholars are taking in studying knowledge-intensive business services (KIBS). Since the mid 1990s, there has been a significant increase in the attention paid to KIBS and their role and functions in innovation systems (Illeris, 1991; Miles et al. 1995; den Hertog, 2000; Strambach, 2001; Muller and Zenker, 2001; Wood, 2002a; Tether, 2005). In general terms, the activity of KIBS can be mainly described as the provision of knowledge-intensive inputs to the business process of other organizations, private as well as public sector clients. In more precise terms, Miles et al. (1995, p. 18) define KIBS as “services that involve economic activities which are intended to result in the creation, accumulation or dissemination of knowledge.” Den Hertog (2000, p. 505) emphasizes professional knowledge as basic for KIBS’ professional activities, “i.e. knowledge or expertise related to a specific (technical) discipline or (technical) functional-domain to supply intermediate products and services that are knowledge-based”, while Bettencourt et al. (2002, pp. 100–1) focus on the accumulation, creation, and dissemination of knowledge “for the purpose of developing a customized service or product solution to satisfy the client’s needs.”

It is often argued that multinational enterprises (MNEs) act space-less in the global economy and that they are an essential mechanism in the internationalization of the transfer of knowledge and technologies. The existence of international inner-organizational learning and synergy effects distinguishes MNEs from market-based exchange relationships and national companies (The Oxford Handbook of Innovation, 2005). With their knowledge accumulating and processing capacities, MNEs can use product, production, distribution, and development competences, which they accumulated in their homeland and in all other socio-cultural and institutional contexts where branch plants are located. In this respect, MNEs can combine the advantages of globally-coordinated product and production strategies with the advantages of local proximity and specific locational factors (Management International Review 40:127–148, 2000).

In the literature devoted to interrelations between innovative firms and economic transition, only little attention has been paid to the influence of regional determinants. In line with the current academic and political debates on the role of regions for competitiveness and economic development, the aim of this paper is to provide some insights on innovation activities from a regional perspective. The investigation deals primarily with a Hungarian region: West Transdanubia. More precisely, the analysis focuses on firm behaviours and characteristics with regards to innovation and cooperation, determining remarkable facts on an empirical basis. This in turn enables a typology of regional firms to be established which may be helpful for innovation policy in West Transdanubia. The paper is organised as follows. The first section reviews the background of the analysis, addressing the concept of innovation systems and economic changes from a regional perspective. The second section, concentrating on manufacturing firms, contrasts innovation and co-operation patterns in West Transdanubia with two other central European regions (Saxony and Slovenia) allowing the introduction of comparative elements into the investigation. The third section examines the innovation and co-operation activities of manufacturing and business service firms in West Transdanubia. Finally, concluding comments explore policy implications, insisting notably on the current and future importance of regional innovation capacities.

The debate about whether small or large firms are more innovative, and whether size is a useful criterion for distinguishing the differences in the intensity and kind of innovative activity is not a recent phenomenon. It can be traced back to the pioneering work of Schumpeter, who in his early work emphasised the risk-taking behaviour of pioneer entrepreneurs in enhancing the supply of innovative solutions (Schumpeter 1911). He later argued that large firms can devote more resources to systematic research and development (R&D) and are therefore more innovative than small firms due to scale advantages (Schumpeter 1942). These two hypotheses were summarised by Freeman in the models of entrepreneurial innovation (Mark I) and of large-firm managed innovation (Mark II) (Freeman 1982).

In the light of globalisation, increasing industrial specialisation, and growing competitive pressure, innovative developments and processes have reached a level of primary importance. New products and processes, as well as organisational and societal innovations, contribute to firms’, regions’, and nations’ competitiveness. Considering innovative processes on a regional level provides insights into space-specific economic, historical, socio-political and cultural factors which form the background of industrial innovation processes. The region in which innovating firms are located represents their "home base" and here interactive relationships lead to the development of specific innovation patterns.

The binding behaviour as well as the time-dependent reaction of five platinum(II) complexes with 5'-GMP have been investigated by capillary electrophoresis under simulated physiological conditions referred to chloride concentration, pH and temperature. Different amine ligands influenced the binding properties towards 5'-GMP and resulted in different half-times of the overall reaction. Complexes with bidentate ligands reacted faster with the monophosphate compared to complexes with monodentate ligands. Complexes consisting of two monodentate hydroxyethylamine ligands reacted very slowly owing to a competitive intramolecular reaction of the hydroxyethyl residues, which was proven by NMR investigations. Reducing the number of hydroxyethyl residues increased the half-times of the reactions. Moreover, the major adducts formed with 5'-GMP were identified by MALDI-MS analysis.

cis-Diamminedichloroplatinum(II) (cisplatin) is applied against different kinds of cancer although toxic side effects are known. Screening systems for alternative compounds with higher effectiveness but minimizing toxic side effects are required. We investigated the adduct formation of cisplatin with nucleoside monophosphates, di- and trinucleotides. Capillary electrophoretic separations were performed in a sodium phosphate buffer using an instrument equipped with a diode array detector. Adduct formation results in a significant shift of λmax to lower energy compared to free nucleotides. Therefore, UV spectra are an important tool for peak identification. We could separate and identify all four common nucleotides and their major platinum adducts in a single run demonstrating the suitability of CE for these kinds of investigations. Furthermore, kinetic studies of these reactions are performed.

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