Emergent collective chemotaxis without single-cell gradient sensing

Many eukaryotic cells chemotax, sensing and following chemical gradients. However, experiments have shown that even under conditions when single cells cannot chemotax, small clusters may still follow a gradient. This behavior has been observed in neural crest cells, in lymphocytes, and during border cell migration in Drosophila, but its origin remains puzzling. Here, we propose a new mechanism underlying this "collective guidance", and study a model based on this mechanism both analytically and computationally. Our approach posits that the contact inhibition of locomotion (CIL), where cells polarize away from cell-cell contact, is regulated by the chemoattractant. Individual cells must measure the mean attractant value, but need not measure its gradient, to give rise to directional motility for a cell cluster. We present analytic formulas for how cluster velocity and chemotactic index depend on the number and organization of cells in the cluster. The presence of strong orientation effects provides a simple test for our theory of collective guidance.Comment: Updated with additional simulations. Aspects of v1 of this paper about adaptation and amplification have been extended and turned into a separate paper, and removed from the current versio

Collective signal processing in cluster chemotaxis: roles of adaptation, amplification, and co-attraction in collective guidance

Single eukaryotic cells commonly sense and follow chemical gradients, performing chemotaxis. Recent experiments and theories, however, show that even when single cells do not chemotax, clusters of cells may, if their interactions are regulated by the chemoattractant. We study this general mechanism of "collective guidance" computationally with models that integrate stochastic dynamics for individual cells with biochemical reactions within the cells, and diffusion of chemical signals between the cells. We show that if clusters of cells use the well-known local excitation, global inhibition (LEGI) mechanism to sense chemoattractant gradients, the speed of the cell cluster becomes non-monotonic in the cluster's size - clusters either larger or smaller than an optimal size will have lower speed. We argue that the cell cluster speed is a crucial readout of how the cluster processes chemotactic signal; both amplification and adaptation will alter the behavior of cluster speed as a function of size. We also show that, contrary to the assumptions of earlier theories, collective guidance does not require persistent cell-cell contacts and strong short range adhesion to function. If cell-cell adhesion is absent, and the cluster cohesion is instead provided by a co-attraction mechanism, e.g. chemotaxis toward a secreted molecule, collective guidance may still function. However, new behaviors, such as cluster rotation, may also appear in this case. Together, the combination of co-attraction and adaptation allows for collective guidance that is robust to varying chemoattractant concentrations while not requiring strong cell-cell adhesion.Comment: This article extends some results previously presented in arXiv:1506.0669

Spatial Knowledge and Urban Planning (Editorial)

Urban planning is simultaneously shaped by and creates new (spatial) knowledge. The changes in planning culture that have taken place in the last decades - especially the so-called communicative turn in planning in the 1990s - have brought about an increased attention to a growing range of stakeholders of urban development, their interests, logics, and participation in planning as well as the negotiation processes between these stakeholders. However, while this has also been researched in breadth and depth, only scant attention has been paid to the knowledge (claims) of these stakeholders. In planning practice, knowledge, implicit and explicit, has been a highly relevant topic for quite some time: It is discussed how local knowledge can inform urban planning, how experimental knowledge on urban development can be generated in living labs, and what infrastructures can process "big data" and make it usable for planning, to name a few examples. With the thematic issue on "Spatial Knowledge and Urban Planning" we invited articles aiming at exploring the diverse understandings of (spatial) knowledge, and how knowledge influences planning and how planning itself constitutes processes of knowledge generation. The editorial gives a brief introduction to the general topic. Subsequently, abstracts of all articles illustrate what contents the issue has to offer and the specific contribution of each text is carved out. In the conclusion, common and recurring themes as well as remaining gaps and open questions at the interface of spatial knowledge and urban planning are discussed

Medical technology innovations - challenges for research, economic an health policy. Summary

The medical technology sector is characterised by a pronounced innovative strength, high knowledge intensity and social relevance due to its contributions to the health care of the population. In Germany, the situation of this future-oriented sector can be characterised as good overall: The scientific-technical basis of medical technology research and development (R&D) is internationally outstanding in many areas. As an industry, German medical technology manufacturers are very well positioned and occupy a leading place on the world market alongside the USA and Japan. Despite this favourable starting position, the industry faces a number of challenges resulting from intensifying international competition, the internationalisation of production and distribution structures and the changing conditions in the health care sector. Subject and objective of the study The promotion of medical technology and the creation of the most favourable framework conditions possible also pose considerable challenges for the public sector: In addition to taking into account the complex requirements for the promotion of this markedly heterogeneous cross-sectional technology, it must be noted that medical technology falls within the sphere of responsibility of both research, economic and health policy. The innovation policy problem here is to coordinate the partly synergetic, but also partly divergent objectives, measures and instruments of the respective policy fields in such a way that favourable framework conditions are created for the development and clinical application of medical technology innovations. The aim of the policy benchmarking was to analyse, with regard to medical technology at the interfaces between research, economic and health policy, which demands on research policy for medical technology arise from health and economic policy objectives and strategies, through which mechanisms, procedures and instruments this situation could be taken into account in practice or is taken into account in order to create goal conflicts. To this end, to identify good practice examples of successful medical technology funding in two countries that are also successful in medical technology (Great Britain and Switzerland) and to examine the extent to which these examples can be transferred to the situation in Germany, and on this basis to develop options for action for a successful innovation policy from a research policy perspective in medical technology in Germany

Future coastal population growth and exposure to sea-level rise and coastal flooding - A global assessment

Coastal zones are exposed to a range of coastal hazards including sea-level rise with its related effects. At the same time, they are more densely populated than the hinterland and exhibit higher rates of population growth and urbanisation. As this trend is expected to continue into the future, we investigate how coastal populations will be affected by such impacts at global and regional scales by the years 2030 and 2060. Starting frombaseline population estimates for the year 2000, we assess future population change in the low-elevation coastal zone and trends in exposure to 100-year coastal floods based on four different sea-level and socio-economic scenarios. Our method accounts for differential growth of coastal areas against the land-locked hinterland and for trends of urbanisation and expansive urban growth, as currently observed, but does not explicitly consider possible displacement or out-migration due to factors such as sea-level rise.We combine spatially explicit estimates of the baseline population with demographic data in order to derive scenario-driven projections of coastal population development. Our scenarios show that the number of people living in the low-elevation coastal zone, as well as the number of people exposed to flooding from 1-in-100 year storm surge events, is highest in Asia. China, India, Bangladesh, Indonesia and Viet Nam are estimated to have the highest total coastal population exposure in the baseline year and this ranking is expected to remain largely unchanged in the future. However, Africa is expected to experience the highest rates of population growth and urbanisation in the coastal zone, particularly in Egypt and sub-Saharan countries in Western and Eastern Africa. The results highlight countries and regions with a high degree of exposure to coastal flooding and help identifying regions where policies and adaptive planning for building resilient coastal communities are not only desirable but essential. Furthermore, we identify needs for further research and scope for improvement in this kind of scenario-based exposure analysis

A disulfide bridge in the calcium binding site of a polyester hydrolase increases its thermal stability and activity against polyethylene terephthalate

Elevated reaction temperatures are crucial for the efficient enzymatic degradation of polyethylene terephthalate (PET). A disulfide bridge was introduced to the polyester hydrolase TfCut2 to substitute its calcium binding site. The melting point of the resulting variant increased to 94.7°C (wild-type TfCut2: 69.8 °C) and its half-inactivation temperature to 84.6 °C (TfCut2: 67.3 °C). The variant D204C-E253C-D174R obtained by introducing further mutations at vicinal residues showed a temperature optimum between 75 and 80 °C compared to 65 and 70 °C of the wild-type enzyme. The variant caused a weight loss of PET films of 25.0 +/- 0.8% (TfCut2: 0.3 +/-0.1%) at 70 °C after a reaction time of 48 h. The results demonstrate that a highly efficient and calcium-independent thermostable polyester hydrolase can be obtained by replacing its calcium binding site with a disulfide bridge

Barriers to the establishment of new key technologies. Summary

Germany is considered innovative and, in a global comparison, excellent in basic research and technology development. Germany is strong in its traditional markets, such as mechanical and vehicle engineering or electrical engineering. However, Germany also has problems when it comes to the rapid and broad implementation of the innovative ideas and results of research and development in concrete applications, especially for the establishment of new, future-oriented key technologies. The diffusion of applications resulting from new key technologies on the market also often confronts companies and entrepreneurs with blockades that are difficult or almost impossible to overcome. Subject and objective of the study The objective of the project "Blockades in the Establishment of New Key Technologies" was to investigate the existing innovation barriers in Germany that block or impede the establishment of new key technologies and the creation of German lead markets or the replacement of traditional export technologies by new key technologies. However, factors that have a particularly beneficial effect should also be identified. On this basis, specific technologies or markets were identified where Germany has not yet exhausted its diffusion and market potential or has been particularly successful in doing so. Finally, by analysing the factors to which these deficits or successes could be attributed, possibilities for political influence were elicited that could contribute to the removal of existing blockades and the promotion of positive factors. The project used a combined approach of a cross-technology innovation system analysis and three technology-specific, in-depth case studies to investigate specific key technologies. The innovation system approach was based on a comprehensive literature and data analysis and provided a research grid for the three case studies. In doing so, the innovation system analysis primarily aimed at capturing and structuring the central inhibiting and facilitating factors, which were specifically investigated and evaluated in the case studies. The case studies selected were Nanoelectronics as a cross-sectional technology, wind energy as an application technology, MP3 players and mini beamers as applications and product innovations respectively. Within the framework of these case studies, several expert interviews were conducted with relevant stakeholders in each case, as well as a workshop in the German Bundestag in Berlin with representatives from science, business and politics. The results of the three case studies were harmonised via the research grid in order to finally compare the identified blockages and derived measures or options for action on a generalised basis. In doing so, blockades were related to suitable measures and possible contributions for involved actors were identified, by means of which the dismantling of existing blockades and the establishment of new key technologies could be supported

Effect of Tris, MOPS, and phosphate buffers on the hydrolysis of polyethylene terephthalate films by polyester hydrolases

The enzymatic degradation of polyethylene terephthalate (PET) occurs at mild reaction conditions and may find applications in environmentally friendly plastic waste recycling processes. The hydrolytic activity of the homologous polyester hydrolases LC cutinase (LCC) from a compost metagenome and TfCut2 from Thermobifida fusca KW3 against PET films was strongly influenced by the reaction medium buffers tris(hydroxymethyl)aminomethane (Tris), 3-(N-morpholino)propanesulfonic acid (MOPS), and sodium phosphate. LCC showed the highest initial hydrolysis rate of PET films in 0.2 M Tris, while the rate of TfCut2 was 2.1-fold lower at this buffer concentration. At a Tris concentration of 1 M, the hydrolysis rate of LCC decreased by more than 90% and of TfCut2 by about 80%. In 0.2 M MOPS or sodium phosphate buffer, no significant differences in the maximum initial hydrolysis rates of PET films by both enzymes were detected. When the concentration of MOPS was increased to 1 M, the hydrolysis rate of LCC decreased by about 90%. The activity of TfCut2 remained low compared to the increasing hydrolysis rates observed at higher concentrations of sodium phosphate buffer. In contrast, the activity of LCC did not change at different concentrations of this buffer. An inhibition study suggested a competitive inhibition of TfCut2 and LCC by Tris and MOPS. Molecular docking showed that Tris and MOPS interfered with the binding of the polymeric substrate in a groove located at the protein surface. A comparison of the Ki values and the average binding energies indicated MOPS as the stronger inhibitor of the both enzymes

Changes in the composition of marine and sea-ice diatoms derived from sedimentary ancient DNA of the eastern Fram Strait over the past 30 000 years

The Fram Strait is an area with a relatively low and irregular distribution of diatom microfossils in surface sediments, and thus microfossil records are scarce, rarely exceed the Holocene, and contain sparse information about past richness and taxonomic composition. These attributes make the Fram Strait an ideal study site to test the utility of sedimentary ancient DNA (sedaDNA) metabarcoding. Amplifying a short, partial rbcL marker from samples of sediment core MSM05/5-712-2 resulted in 95.7 % of our sequences being assigned to diatoms across 18 different families, with 38.6 % of them being resolved to species and 25.8 % to genus level. Independent replicates show a high similarity of PCR products, especially in the oldest samples. Diatom sedaDNA richness is highest in the Late Weichselian and lowest in Mid- and Late Holocene samples. Taxonomic composition is dominated by cold-water and sea-ice-associated diatoms and suggests several reorganisations – after the Last Glacial Maximum, after the Younger Dryas, and after the Early and after the Mid-Holocene. Different sequences assigned to, amongst others, Chaetoceros socialis indicate the detectability of intra-specific diversity using sedaDNA. We detect no clear pattern between our diatom sedaDNA record and the previously published IP25 record of this core, although proportions of pennate diatoms increase with higher IP25 concentrations and proportions of Nitzschia cf. frigida exceeding 2 % of the assemblage point towards past sea-ice presence

Medizintechnische Innovationen – Herausforderungen für die Forschungs-, Gesundheits- und Wirtschaftspolitik. Politikbenchmarking

Die Medizintechnikbranche zeichnet sich durch ausgeprägte Innovationskraft, hohe Wissensintensität und gesellschaftliche Relevanz aufgrund ihrer Beiträge zur Gesundheitsversorgung der Bevölkerung aus. In Deutschland kann die Situation dieser Zukunftsbranche insgesamt als gut charakterisiert werden: Die wissenschaftlich-technische Basis der medizintechnischen Forschung und Entwicklung (FuE) ist in vielen Bereichen international herausragend. Als Branche sind die deutschen Medizintechnikhersteller sehr gut positioniert und nehmen neben den USA und Japan einen führenden Platz auf dem Weltmarkt ein. Trotz dieser günstigen Ausgangsposition steht die Branche vor einer Reihe von Herausforderungen, die sich aus dem sich verschärfenden internationalen Wettbewerb, der Internationalisierung der Produktions- und Vertriebsstrukturen und den sich verändernden Bedingungen im Gesundheitswesen ergeben. Gegenstand und Ziel der Untersuchung Die Förderung der Medizintechnik und die Gestaltung möglichst günstiger Rahmenbedingungen stellt auch die öffentliche Hand vor erhebliche Herausforderungen: Neben der Berücksichtigung der komplexen Anforderungen an die Förderung dieser ausgesprochen heterogenen Querschnittstechnologie ist zu beachten, dass die Medizintechnik in den Zuständigkeitsbereich sowohl der Forschungs-, der Wirtschafts- und der Gesundheitspolitik fällt. Dabei besteht die innovationspolitische Problemstellung darin, die teilweise synergetischen, teilweise aber auch divergierenden Zielsetzungen, Maßnahmen und Instrumente der jeweiligen Politikfelder so aufeinander abzustimmen, dass günstige Rahmenbedingungen für die Entwicklung und klinische Anwendung von medizintechnischen Innovationen geschaffen werden. Ziel des Politikbenchmarking war es, mit Blick auf die Medizintechnik an den Schnittstellen zwischen Forschungs-, Wirtschafts- und Gesundheitspolitik zu analysieren, welche Anforderungen sich an die Forschungspolitik für die Medizintechnik aus gesundheits- und wirtschaftspolitischen Zielsetzungen und Strategien ergeben, durch welche Mechanismen, Prozeduren und Instrumente dieser Situation in der Praxis Rechnung getragen werden könnte bzw. getragen wird, um Zielkonflikte aufzulösen und Synergien zu nutzen, zu diesem Zweck Good-Practice-Beispiele für erfolgreiche Medizintechnikförderung in zwei ebenfalls in der Medizintechnik erfolgreichen Ländern (Großbritannien und Schweiz) zu identifizieren und zu überprüfen, inwieweit diese Beispiele auf die Verhältnisse in Deutschland übertragbar sind, und auf dieser Basis Handlungsoptionen für eine erfolgreiche Innovationspolitik aus forschungspolitischer Sicht in der Medizintechnik in Deutschland zu entwickeln. INHALT ZUSAMMENFASSUNG 5 I. EINLEITUNG 19 1. Thematischer Hintergrund 19 2. Ziele und Vorgehensweise 21 3. Aufbau der Studie 23 4. Danksagungen 25 II. PROBLEMORIENTIERTE BESTANDSAUFNAHME 27 1. Medizintechnik: wichtige Branchenkennzahlen 27 2. Medizintechnikstandort Deutschland: Stärken- und Schwächenanalyse 37 2.1 Stärken 37 2.2 Chancen 45 2.3 Schwächen 51 2.4 Risiken 58 III. INNOVATIONSPOLITIK – KONZEPTIONELLE GRUNDLAGEN UND GOVERNANCEPRINZIPIEN 63 1. Innovationsforschung aus systemischer Perspektive 63 2. Governance von Innovationspolitik 67 2.1 Innovationspolitische Interventionsmöglichkeiten 67 2.2 »Good Governance« in der Innovationspolitik 75 IV. FORSCHUNGS- UND INNOVATIONSPOLITIK IN INTERNATIONALER PERSPEKTIVE 79 1. Auswahl und Vorgehen 79 2. Fallbeispiel Großbritannien 81 2.1 Rahmenbedingungen und Strukturen 81 2.2 Forschungs- und innovationspolitische Strategieentwicklung 92 3. Fallbeispiel Schweiz 106 3.1 Rahmenbedingungen und Strukturen 106 3.2 Forschungs- und innovationspolitische Strategieentwicklung 116 4. Fazit 123 4.1 Vergleichende Gegenüberstellung der Rahmenbedingungen 123 4.2 Förderung der Medizintechnik im Vergleich 127 4.3 Schlussfolgerungen für die Medizintechnikförderung in Deutschland 128 V. ANSATZPUNKTE FÜR EINE INNOVATIONSFÖRDERNDE MEDIZINTECHNIKPOLITIK IN DEUTSCHLAND 131 1. Auswahl und Vorgehen 131 2. Forschungs- und Innovationspolitik des Bundes im Bereich der Medizintechnik 133 2.1 Forschungs- und innovationspolitische Strategieentwicklung 135 2.2 Bewertungen 141 3. Zulassung von Medizinprodukten 146 3.1 Bedeutung von Zulassungen im Innovationsprozess 146 3.2 Zulassungsverfahren für Medizinprodukte 147 3.3 Ansatzpunkte zur Verringerung von Hemmnissen bei der Zulassung von Medizinprodukten 152 4. Nachhaltige Integration von Medizintechnik-KMU in Innovationsnetzwerke 172 4.1 Ausgangssituation und Problemstellung 172 4.2 Kooperation KMU und FuE-Institute zur Stärkung der technologischen Wettbewerbsfähigkeit 174 4.3 Innovative Finanzierungs- und Kooperationsmodelle als Mittel der Markterschließung und Kundenbindung 204 VI. RESÜMEE UND HANDLUNGSOPTIONEN 221 1. Vorbemerkung 221 2. Ansatzpunkte für eine Stärkung der Medizintechnik in Deutschland 222 VII. LITERATUR 233 VIII. ANHANG 245 1. Tabellenverzeichnis 245 2. Abbildungsverzeichnis 246 3. Abkürzungsverzeichnis 246 4. Gesprächspartner 252 5. Das deutsche Gesundheitssystem: Organisationsstruktur und Akteurslandschaft 254 5.1 Gesundheitssystem: orientierender Überblick 254 5.2 Bundesebene 257 5.3 Länderebene 259 5.4 Korporatistische Ebene in der gesetzlichen Krankenversicherung und Selbstverwaltung 260 5.5 Weitere Gesundheitsakteure 267 6. Tabellen 26