Recent studies find that idiosyncratic risk (IR)—the degree to which firm-specific returns are more volatile than aggregate market returns—has increased since the 1960s and attribute this to ...economy-wide factors such as the role of the IT revolution. Yet no innovation data is used in these studies. To gain further insights into the relationship between technology and IR, our aricle studies whether firms and industries that are more R&D intensive are in fact characterized by higher IR due to how innovation affects the uncertainty of expected future profits. While the industry-level results prove inconclusive, a clear relationship is found between firm-level R&D intensity and firm-level volatility of returns.
The mass storage challenge for the experiments at the Large Hadron Collider (LHC) is still nowadays a critical issue for the various Tier-1 computing centres and the Tier-0 centre involved in the ...custodial and analysis of the data produced by the experiments. In particular, the requirements for the tape mass storage systems are quite strong, amounting to about 15 PB of data produced annually that should be available for near-line access at any time. Besides the solutions already widely employed by the High Energy Physics community so far, INFN-CNAF has approched, in the last year, a solution based on the collaboration between the General Parallel File System (GPFS) and the Tivoli Storage Manager (TSM) by IBM and StoRM as Storage Resource Management (SRM) interface, developed at INFN. The new features available in GPFS version 3.2 allow in general to interface GPFS with any tape storage manager. We implemented such an interface for TSM, and we performed various performance studies on a prototype testbed system. The first StoRM/GPFS/TSM based system is already in production at CNAF for T1D1 Storage Class; it is used by the LHCb experiment. Currently we are performing new tests to exploit features implemented in the new versione of TSM 6.1. These features are focused in high performance and optimized access to the tape backend. We will describe the implementation of the interface and details of the prototype testbed for T1D0 SC and we will discuss the results of the LHCb production system.
This paper examines four models which might be used to account for variations in the number of producers who operate in a particular market over the lifetime of that market. Two of these are standard ...economics textbook models, one is a non-standard model and one is a textbook model derived from the literature on organizational ecology. The four models have several observable differences and this opens up the possibility of testing any one against the others. We apply these four models to 93 years of data on the population of domestic car producers in the US car industry. The salient feature of this population is the very large rise and fall in the number of firms operating in the very early years of the industry, a phenomena which seems hard to account for using any of the three textbook models that we consider here.
Demirel P. and Mazzucato M. The evolution of firm growth dynamics in the US pharmaceutical industry, Regional Studies. This paper studies the dynamics of firm growth and firm size distribution in the ...pharmaceutical industry from 1950 to 2003. Growth dynamics are studied in the context of how the size composition of firms changes, how innovation patterns change, and how location leads to growth differentials among US firms. It is found that the growth advantage of small pharmaceutical firms increases after the 1980s as small firms become more active in patenting and their patenting activities become more 'persistent'. Location is found to affect growth differences only for the most innovative firms (that is, for non-innovative firms, location does not matter).
Demirel P. et Mazzucato M. L'évolution de la dynamique de la croissance des entreprises dans l'industrie pharmaceutique aux Etats-Unis, Regional Studies. Cet article cherche à étudier la dynamique de la croissance des entreprises et de la distribution des entreprises par taille dans l'industrie pharmaceutique de 1950 jusqu'à 2003. On étudie la dynamique de la croissance pour déterminer comment la distribution des entreprises par taille évolue, comment la structure de l'innovation change, et comment la localisation entraîne des écarts de la croissance des entreprises aux Etats-Unis. Il s'avère que l'avantage des petites entreprises pharmaceutiques en termes de croissance augmente après les années 1980 au fur et à mesure que les petites entreprises obtiennent davantage de brevets et que le brevetage 'persiste'. Il s'avère que la localisation n'influe sur les écarts de croissance que pour les entreprises les plus innovatrices (c'est à dire que la localisation n'importe pas pour les entreprises qui ne sont pas innovatrices).
Croissance des entreprises Innovation Industrie pharmaceutique
Demirel P. und Mazzucato M. Die Evolution der Wachstumsdynamik von Firmen in der pharmazeutischen Industrie der USA, Regional Studies. In diesem Beitrag untersuchen wir die Dynamik von Firmenwachstum und Firmengrößenverteilung in der pharmazeutischen Industrie im Zeitraum von 1950 bis 2003. Die Wachstumsdynamik wird im Kontext der Frage untersucht, wie sich die Größenzusammensetzung der Firmen ändert, wie sich die Innovationsabläufe ändern und wie der Standort zu Wachstumsdifferentialen zwischen Firmen in den USA führt. Wir stellen fest, dass der Wachstumsvorteil kleiner pharmazeutischer Firmen nach den achtziger Jahren zunimmt, da die kleineren Firmen bei der Patentierung aktiver und ihre Patentierungsaktivitäten beständiger werden. Der Standort wirkt sich hingegen nur bei den innovativsten Firmen auf Wachstumsdifferenzen aus (mit anderen Worten, bei nicht innovativen Firmen kommt es nicht auf den Standort an).
Firmenwachstum Innovation Pharmaindustrie
Demirel P. y Mazzucato M. La evolución de las dinámicas de crecimiento de empresas en la industria farmacéutica de los Estados Unidos, Regional Studies. En este artículo analizamos las dinámicas del crecimiento de empresas y la distribución del tamaño de las empresas en la industria farmacéutica de 1950 a 2003. Estudiamos las dinámicas de crecimiento en cuanto a cómo cambia la composición del tamaño de las empresas, cómo cambian los modelos de innovación y cómo lleva la ubicación a diferenciales de crecimiento entre empresas estadounidenses. Observamos que la ventaja de crecimiento de pequeños laboratorios farmacéuticos aumenta después de la década de los ochenta cuando las pequeñas empresas se vuelven más activas con las patentes y las actividades relacionadas con patentes son más 'persistentes'. Vemos que la ubicación afecta a las diferencias de crecimiento solamente en empresas más innovadoras (es decir, para las empresas no tan innovadoras la ubicación no importa).
Crecimiento de empresas Innovación Industria farmacéutica
Modern Grid middleware is built around components providing basic functionality, such as data storage, authentication, security, job management, resource monitoring and reservation. In this paper we ...describe the Computing Resource Execution and Management (CREAM) service. CREAM provides a Web service-based job execution and management capability for Grid systems; in particular, it is being used within the gLite middleware. CREAM exposes a Web service interface allowing conforming clients to submit and manage computational jobs to a Local Resource Management System. We developed a special component, called ICE (Interface to CREAM Environment) to integrate CREAM in gLite. ICE transfers job submissions and cancellations from the Workload Management System, allowing users to manage CREAM jobs from the gLite User Interface. This paper describes some recent studies aimed at assessing the performance and reliability of CREAM and ICE; those tests have been performed as part of the acceptance tests for integration of CREAM and ICE in gLite. We also discuss recent work towards enhancing CREAM with a BES and JSDL compliant interface.
An international grid has been built in Europe during the past years in the framework of various EC-funded projects to support the growth of e-Science. After several years of work spent to increase ...the scale of the infrastructure, to expand the user community and improve the availability of the services delivered, effort is now concentrating on the creation of a new organizational model, capable of fulfilling the vision of a sustainable European grid infrastructure. The European Grid Initiative (EGI) is the proposed framework to seamlessly link at a global level the European national grid e-Infrastructures operated by the National Grid Initiatives and European International Research Organizations, and based on a European Unified Middleware Distribution, which will be the result of a joint effort of various European grid Middleware Consortia. This paper describes the requirements that EGI addresses, the actors contributing to its foundation, the offering and the organizational structure that constitute the EGI business model.
Platelet adhesion to von Willebrand factor (VWF) activates alpha IIb beta 3, a prerequisite for thrombus formation. However, it is unclear whether the primary VWF receptor, glycoprotein (GP) Ib-IX-V, ...mediates alpha IIb beta 3 activation directly or through other signaling proteins physically associated with it (eg, FcR gamma-chain), possibly with the contribution of other agonist receptors and of VWF signaling through alpha IIb beta 3. To resolve this question, human and GP Ibalpha transgenic mouse platelets were plated on dimeric VWF A1 domain (dA1VWF), which engages only GP Ib-IX-V, in the presence of inhibitors of other agonist receptors. Platelet adhesion to dA1VWF induced Src kinase-dependent tyrosine phosphorylation of the FcR gamma-chain and the adapter molecule, ADAP, and triggered intracellular Ca(2+) oscillations and alpha IIb beta 3 activation. Inhibition of Ca(2+) oscillations with BAPTA-AM prevented alpha IIb beta 3 activation but not tyrosine phosphorylation. Pharmacologic inhibition of protein kinase C (PKC) or phosphatidylinositol 3-kinase (PI 3-kinase) prevented alpha IIb beta 3 activation but not Ca(2+) oscillations. Inhibition of Src with 2 distinct compounds blocked all responses downstream of GP Ib-IX-V under static or flow conditions. However, dA1VWF-induced responses were reduced only slightly in GP Ibalpha transgenic platelets lacking FcR gamma-chain. These data establish that GP Ib-IX-V itself can signal to activate alpha IIb beta 3, through sequential actions of Src kinases, Ca(2+) oscillations, and PI 3-kinase/PKC.
We have obtained evidence that selective inhibition of high affinity thrombin-binding sites located in the amino-terminal domain of the membrane glycoprotein (GP) Ib alpha results in impaired ...platelet activation, as shown by abrogation or reduction of the following responses induced in normal platelets by exposure to less than 1 nM alpha-thrombin: (i) increase in intracellular ionized calcium concentration (Ca2+i), (ii) release of dense granule content, (iii) binding of fibrinogen, (iv) aggregation. An anti-GP Ib monoclonal antibody, LJ-Ib 10, which does not inhibit von Willebrand factor binding to platelets, obliterated the high affinity alpha-thrombin-binding sites on normal platelets. Isotherms of alpha-thrombin binding to normal platelets treated with saturating amounts of the antibody were virtually identical to those obtained with platelets from a patient with classical Bernard-Soulier syndrome. In parallel with decreased binding of the agonist, this antibody caused 50% inhibition of the maximal extent of platelet aggregation and 90% inhibition of ATP release induced by 0.3 nM alpha-thrombin. By inhibiting alpha-thrombin binding to GP Ib, the antibody prevented the activation of platelets exposed to low concentrations of the agonist, as demonstrated by abrogation of the increase in intraplatelet ionized calcium concentration induced in control platelets by 0.18 nM alpha-thrombin; under these conditions, fibrinogen binding was inhibited by 84%. Therefore, there is a correlation between occupancy of the high affinity sites for alpha-thrombin on GP Ib alpha and platelet activation, secretion, and aggregation, suggesting that GP Ib alpha is part of an alpha-thrombin receptor relevant for platelet function.
Background and Objectives Ex vivo peripheral blood progenitor cell (PBPC) expansion has been proposed as a strategy to increase the number of haematopoietic progenitors available for cell ...transplantation. We have expanded CD34+ cells from PBPCs obtained from four patients with haematological malignancies and one patient with an Ewing's sarcoma.
Materials and Methods Cells were expanded in the Dideco ‘Pluricell system’. After 12 days in culture, we evaluated cell phenotype, total nucleated cells, CD34+ fold increase, cell apoptosis and colony assay of expanded cells. Cell engraftment has been evaluated by transplanting two groups of irradiated non‐obese diabetic/severe combined immunodeficient (NOD‐SCID) mice with expanded and non‐expanded cell populations.
Results Total nucleated cells and CD34+ cells increased 59·5 and 4·0 times, respectively. The expanded cells were mainly constituted of myeloid and megakaryocytic cells. A significant increase in the number of colony‐forming unit–granulocyte macrophage (CFU‐GM) was observed in the CFU assay. Ten mice transplanted with expanded cells showed a best overall survival (80%) compared to 10 mice transplanted with non‐expanded cells (20%). Human CD45+ cells were detected by flow cytometry and polymerase chain reaction in bone marrow and spleen of transplanted animals. The relative low engraftment level obtained with the expanded cells suggests a loss of SCID repopulating cells maybe due to cell differentiation during expansion.
Conclusions We have demonstrated the feasibility of the ex vivo expansion of mobilized PBPCs from cancer patients, evidencing a clonal expansion of CFUs and the ability of the expanded cells to engraft the bone marrow and spleen of immunosuppressed mice. The differentiation of the CD34+ stem cell compartment could be further minimized by ameliorating the expansion conditions.
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