A revised perspective on innovation policy for renewal of mature economies – Historical evidence from finance and telecommunications in Sweden 1980–1990

What is the role of innovation policy for accomplishing renewal of mature industries in Western economies? Drawing upon an unusually rich dataset spanning 9752 digitized archival documents, we categorize and code decisions taken by policymakers on several levels while also mapping and quantifying the strategic activities of both entrant firms and incumbent monopolists over a decade. Our data concerns two empirical cases from Sweden during the time period 1980–1990: the financial sector and the telecommunications sector. In both industries, a combination of technological and institutional upheaval came into motion during this time period which in turn fueled the revitalization of the Swedish economy in the subsequent decades. Our findings show that Swedish policymakers in both cases consistently acted in order to promote the emergence of more competition and de novo entrant firms at the expense of established monopolies. The paper quantifies and documents this process while also highlighting several enabling conditions. In conclusion, the results indicate that successful innovation policy in mature economies is largely a matter of strategically dealing with resourceful vested interest groups, alignment of expectations, and removing resistance to industrial renewal

The RhoA GEF Syx Is a Target of Rnd3 and Regulated via a Raf1-Like Ubiquitin-Related Domain

Background: Rnd3 (RhoE) protein belongs to the unique branch of Rho family GTPases that has low intrinsic GTPase activity and consequently remains constitutively active [1,2]. The current consensus is that Rnd1 and Rnd3 function as important antagonists of RhoA signaling primarily by activating the ubiquitous p190 RhoGAP [3], but not by inhibiting the ROCK family kinases. Methodology/Principal Findings: Rnd3 is abundant in mouse embryonic stem (mES) cells and in an unbiased two-step affinity purification screen we identified a new Rnd3 target, termed synectin-binding RhoA exchange factor (Syx), by mass spectrometry. The Syx interaction with Rnd3 does not occur through the Syx DH domain but utilizes a region similar to the classic Raf1 Ras-binding domain (RBD), and most closely related to those in RGS12 and RGS14. We show that Syx behaves as a genuine effector of Rnd3 (and perhaps Rnd1), with binding characteristics similar to p190-RhoGAP. Morpholinooligonucleotide knockdown of Syx in zebrafish at the one cell stage resulted in embryos with shortened anterior-posterior body axis: this phenotype was effectively rescued by introducing mouse Syx1b mRNA. A Rnd3-binding defective mutant of Syx1b mutated in the RBD (E164A/R165D) was more potent in rescuing the embryonic defects than wild-type Syx1b, showing that Rnd3 negatively regulates Syx activity in vivo. Conclusions/Significance: This study uncovers a well defined Rnd3 effector Syx which is widely expressed and directl

VEGF and Angiopoietin-1 Exert Opposing Effects on Cell Junctions by Regulating the Rho GEF Syx

Vascular endothelial growth factor (VEGF) and Ang1 (Angiopoietin-1) have opposing effects on vascular permeability, but the molecular basis of these effects is not fully known. We report in this paper that VEGF and Ang1 regulate endothelial cell (EC) junctions by determining the localization of the RhoA-specific guanine nucleotide exchange factor Syx. Syx was recruited to junctions by members of the Crumbs polarity complex and promoted junction integrity by activating Diaphanous. VEGF caused translocation of Syx from cell junctions, promoting junction disassembly, whereas Ang1 maintained Syx at the junctions, inducing junction stabilization. The VEGF-induced translocation of Syx from EC junctions was caused by PKD1 (protein kinase D1)-mediated phosphorylation of Syx at Ser806, which reduced Syx association to its junctional anchors. In support of the pivotal role of Syx in regulating EC junctions, syx−/− mice had defective junctions, resulting in vascular leakiness, edema, and impaired heart function

Controlling angiogenesis : Functional studies of angiomotin

The expansion of a blood circulatory network by the process of angiogenesis is essential for embryonic as well as postnatal growth. Deregulated blood vessel formation may also negatively contribute to the pathogenesis of diseases, e.g. cancer and diabetic retinopathy. Furthermore, compounds that interfere with angiogenesis signalling pathways have shown great promise when used in clinical trials for patients suffering from cancer or macular degeneration. The formation of a functional blood vessel involves several distinct steps. Cells of the vessel wall, i.e. endothelial cells, extend filopodia that sense pro-angiogenic signals and direct migration and the formation of the vessel network. Circulation is established when two endothelial sprouts fuse and form a continuous lumen. Angiomotin has previously been implicated to play a role in endothelial migration and to be a possible target for anti-angiogenic therapy. The aim of this thesis was to investigate the biological role of angiomotin during vascular development and to elucidate the signalling pathways involved. In this thesis it is demonstrated that the angiomotin gene is expressed as two isoforms with distinct functions. The shorter isoform, p80-angiomotin, is expressed during the migratory phase of retinal angiogenesis, whereas the other isoform, p130-angiomotin, is expressed during and after vessel maturation. In vitro, these isoforms exhibit opposite functions. For instance, p80-angiomotin promotes cell migration whereas p130-angiomotin promotes actin fibre formation and cell contacts. It is further shown that p80-angiomotin expression removes p130-angiomotin from cell junctions resulting in a migratory switch. The angiomotin signalling pathway was analysed by identifying binding proteins by two different approaches, peptide pull down and yeast two-hybrid screening. Data are presented demonstrating that the PDZ-binding domain of angiomotin binds to a polarity protein complex as well as to a Rho-GEF, which has previously been shown to mediate endothelial cell migration. These findings argue that angiomotin acts as a scaffold for proteins regulating cell polarity and GTPase activity. The biological role of angiomotin during mouse and zebrafish embryogenesis was also studied. Genetic ablation of angiomotin in the mouse results in vascular defects in the intersomitic region as well as dilated vessels in the brain and embryonic lethality after E11. Furthermore, knockdown of angiomotin in zebrafish impaired the migration of intersegmental vessels and caused dilation of vessels in the brain, confirming the phenotype found in the mouse. It is further shown that angiomotin deficient endothelial cells have an intact proliferative response to VEGF but exhibit defects in migration. Taken together, these data indicate that angiomotin is essential for normal embryonic vessel formation and that it may affect directional cell migration by controlling cell polarity and GTPase activity

Svensk dataspelsutveckling, 1960–1995 : Transkript av ett vittnesseminarium vid Tekniska museet i Stockholm den 12 december 2007

 The witness seminar ”Svensk dataspelsutveckling, 1960–1995” was held at Tekniska museet [the National Museum of Science and Technology] in Stockholm on December 12, 2007 and was led by Mirko Ernkvist. The participants were Swedes that had been involved in the development of computer games during this period. The development process of several pioneering computer games were discussed from the perspective of the developers themselves. These games included: a demonstration game on the Saab manufactured computer D2 (1960–61), Stugan (1978), Space Action (1983), Fairlight (1985), Time Zero (1985), several games by Team17 (1990–) and Backpacker (1995). Computer game development efforts were initiated early in the Swedish history of computing, even by international comparisons. The first known Swedish game with moving graphics was a demonstration game for D2 displayed on an oscilloscope from the early 1960s. When computers became more widespread among Swedish universities, game development efforts soon followed. The first Swedish adventure game, “Stugan” was released in 1978 on the computers at Stockholm Datacentral, QZ. Subsequently, the introduction of home computers in Sweden in the early 1980s enabled more widespread Swedish game development efforts. Many Swedish game developers from this time were self-learned, but several were also involved in some of the computer groups that emerged during this time. These groups cracked, compressed, modified and traded computer games and created demos. The cracker and demo culture of the 1980s provided an environment of learning, socialization, and competition for many Swedish game developers. England that had a more established computer game industry during the 1980s provided opportunities for some of the Swedish game developers. The game “Fairlight” by a Swedish developer was published by an English game company and another Swedish game developer was one of the founders of the English game company Team17. Other Swedish game development projects discussed such as “Space Action”, “Time Zero” and “Backpacker” had Swedish companies as publishers

Svensk dataspelsutveckling, 1960–1995 : Transkript av ett vittnesseminarium vid Tekniska museet i Stockholm den 12 december 2007

 The witness seminar ”Svensk dataspelsutveckling, 1960–1995” was held at Tekniska museet [the National Museum of Science and Technology] in Stockholm on December 12, 2007 and was led by Mirko Ernkvist. The participants were Swedes that had been involved in the development of computer games during this period. The development process of several pioneering computer games were discussed from the perspective of the developers themselves. These games included: a demonstration game on the Saab manufactured computer D2 (1960–61), Stugan (1978), Space Action (1983), Fairlight (1985), Time Zero (1985), several games by Team17 (1990–) and Backpacker (1995). Computer game development efforts were initiated early in the Swedish history of computing, even by international comparisons. The first known Swedish game with moving graphics was a demonstration game for D2 displayed on an oscilloscope from the early 1960s. When computers became more widespread among Swedish universities, game development efforts soon followed. The first Swedish adventure game, “Stugan” was released in 1978 on the computers at Stockholm Datacentral, QZ. Subsequently, the introduction of home computers in Sweden in the early 1980s enabled more widespread Swedish game development efforts. Many Swedish game developers from this time were self-learned, but several were also involved in some of the computer groups that emerged during this time. These groups cracked, compressed, modified and traded computer games and created demos. The cracker and demo culture of the 1980s provided an environment of learning, socialization, and competition for many Swedish game developers. England that had a more established computer game industry during the 1980s provided opportunities for some of the Swedish game developers. The game “Fairlight” by a Swedish developer was published by an English game company and another Swedish game developer was one of the founders of the English game company Team17. Other Swedish game development projects discussed such as “Space Action”, “Time Zero” and “Backpacker” had Swedish companies as publishers