Assessing the assignation of public subsidies: Do the experts choose the most efficient R and D projects?

[spa] La implementación de un programa de subvenciones públicas a proyectos empresariales de I+D comporta establecer un sistema de selección de proyectos. Esta selección se enfrenta a problemas relevantes, como son la medición del posible rendimiento de los proyectos de I+D y la optimización del proceso de selección entre proyectos con múltiples y a veces incomparables medidas de resultados. Las agencias públicas utilizan mayoritariamente el método peer review que, aunque presenta ventajas, no está exento de críticas. En cambio, las empresas privadas con el objetivo de optimizar su inversión en I+D utilizan métodos más cuantitativos, como el Data Envelopment Análisis (DEA). En este trabajo se compara la actuación de los evaluadores de una agencia pública (peer review) con una metodología alternativa de selección de proyectos como es el DEA.

The geography of innovation: the effects of university research

Applied studies on the relationship between geography and technological innovation for United States, Germany, France and Italy have shown the positive effects that academic research exerts on the innovate output of firms at spatial level. The purpose of this paper is to look for new evidence on the possible effects of the university research for the case of Spain. To do so, within the framework of a Griliches-Jaffe knowledge production function, and using panel data and count models, the relationship between innovate inputs and patents, in the case of the Spanish regions is explored

Efficient photodynamic therapy of cancer using chemotherapeutic porphyrin-ruthenium metalla-cubes.

Two cationic octanuclear metalla-cubes [Ru(8)(η(6)-C(6)H(5)Me)(8)(tpp-H2)(2)(dhbq)(4)](8+) and [Ru(8)(η(6)-p-iPrC(6)H(4)Me)(8)(tpp-H2)(2)(dhbq)(4)](8+) were prepared and evaluated as dual photosensitizers and chemotherapeutics in cancer cells. In the dark, the complexes presented high cytotoxicity towards only melanoma and ovarian cancer cells. However, the complexes exhibited good phototoxicities toward all cancer cells (1μM concentration, LD(50)=2-7J/cm(2)), thus suggesting a dual synergistic effect with good properties of both the arene ruthenium chemotherapeutics and the porphyrin photosensitizers.

Efficient energy transfer from Si clusters to Er3+ in complex silicate glasses

We present an extensive study of the structural and optical emission properties in aluminum silicates and soda-lime silicates codoped with Si nanoclusters (Si-nc) and Er. Si excess of 5 and 15¿at.¿% and Er concentrations ranging from 2×1019 up to 6×1020¿cm¿3 were introduced by ion implantation. Thermal treatments at different temperatures were carried out before and after Er implantation. Structural characterization of the resulting structures was performed to obtain the layer composition and the size distribution of Si clusters. A comprehensive study has been carried out of the light emission as a function of the matrix characteristics, Si and Er contents, excitation wavelength, and power. Er emission at 1540¿nm has been detected in all coimplanted glasses, with similar intensities. We estimated lifetimes ranging from 2.5¿to¿12¿ms (depending on the Er dose and Si excess) and an effective excitation cross section of about 1×10¿17¿cm2 at low fluxes that decreases at high pump power. By quantifying the amount of Er ions excited through Si-nc we find a fraction of 10% of the total Er concentration. Upconversion coefficients of about 3×10¿18¿cm¿3¿s¿1 have been found for soda-lime glasses and one order of magnitude lower in aluminum silicates.

The geography of innovation: the effects of university research

Applied studies on the relationship between geography and technological innovation for United States, Germany, France and Italy have shown the positive effects that academic research exerts on the innovate output of firms at spatial level. The purpose of this paper is to look for new evidence on the possible effects of the university research for the case of Spain. To do so, within the framework of a Griliches-Jaffe knowledge production function, and using panel data and count models, the relationship between innovate inputs and patents, in the case of the Spanish regions is explored

Improving Reconstituted HDL Composition for Efficient Post-Ischemic Reduction of Ischemia Reperfusion Injury.

BACKGROUND: New evidence shows that high density lipoproteins (HDL) have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL) offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion injury (IRI). However, basic rHDL composition is limited to apolipoprotein AI (apoAI) and phospholipids; addition of bioactive compound may enhance its beneficial effects. OBJECTIVE: The aim of this study was to investigate the role of rHDL in post-ischemic model, and to analyze the potential impact of sphingosine-1-phosphate (S1P) in rHDL formulations. METHODS AND RESULTS: The impact of HDL on IRI was investigated using complementary in vivo, ex vivo and in vitro IRI models. Acute post-ischemic treatment with native HDL significantly reduced infarct size and cell death in the ex vivo, isolated heart (Langendorff) model and the in vivo model (-48%, p<0.01). Treatment with rHDL of basic formulation (apoAI + phospholipids) had a non-significant impact on cell death in vitro and on the infarct size ex vivo and in vivo. In contrast, rHDL containing S1P had a highly significant, protective influence ex vivo, and in vivo (-50%, p<0.01). This impact was comparable with the effects observed with native HDL. Pro-survival signaling proteins, Akt, STAT3 and ERK1/2 were similarly activated by HDL and rHDL containing S1P both in vitro (isolated cardiomyocytes) and in vivo. CONCLUSION: HDL afford protection against IRI in a clinically relevant model (post-ischemia). rHDL is significantly protective if supplemented with S1P. The protective impact of HDL appears to target directly the cardiomyocyte.

Assessing the assignation of public subsidies: Do the experts choose the most efficient R and D projects?

[spa] La implementación de un programa de subvenciones públicas a proyectos empresariales de I+D comporta establecer un sistema de selección de proyectos. Esta selección se enfrenta a problemas relevantes, como son la medición del posible rendimiento de los proyectos de I+D y la optimización del proceso de selección entre proyectos con múltiples y a veces incomparables medidas de resultados. Las agencias públicas utilizan mayoritariamente el método peer review que, aunque presenta ventajas, no está exento de críticas. En cambio, las empresas privadas con el objetivo de optimizar su inversión en I+D utilizan métodos más cuantitativos, como el Data Envelopment Análisis (DEA). En este trabajo se compara la actuación de los evaluadores de una agencia pública (peer review) con una metodología alternativa de selección de proyectos como es el DEA.

Ownership structure and innovation: Is there a real link?

This work focuses on the study of the relationship between ownership and control structure of the company and its innovative activity. Its aim consists of analysing the role that may be played by determinants within the company related to ownership structure when the decision to incur research and development activities is taken as well as on the output of this innovate process. Among these determinants we may think of issues such as who owns the firm and how the control of decision-making is distributed, the nature of this control and the level of concentration of ownership, among others. The study is carried out for the year 2001 using a representative sample of Spanish manufacturing industries.

A regulatory network for the efficient control of transgene expression.

BACKGROUND: Expression of heterologous genes in mammalian cells or organisms for therapeutic or experimental purposes often requires tight control of transgene expression. Specifically, the following criteria should be met: no background gene activity in the off-state, high gene expression in the on-state, regulated expression over an extended period, and multiple switching between on- and off-states. METHODS: Here, we describe a genetic switch system for controlled transgene transcription using chimeric repressor and activator proteins functioning in a novel regulatory network. In the off-state, the target transgene is actively silenced by a chimeric protein consisting of multimerized eukaryotic transcriptional repression domains fused to the DNA-binding tetracycline repressor. In the on-state, the inducer drug doxycycline affects both the derepression of the target gene promoter and activation by the GAL4-VP16 transactivator, which in turn is under the control of an autoregulatory feedback loop. RESULTS: The hallmark of this new system is the efficient transgene silencing in the off-state, as demonstrated by the tightly controlled expression of the highly cytotoxic diphtheria toxin A gene. Addition of the inducer drug allows robust activation of transgene expression. In stably transfected cells, this control is still observed after months of repeated cycling between the repressed and activated states of the target genes. CONCLUSIONS: This system permits tight long-term regulation when stably introduced into cell lines. The underlying principles of this network system should have general applications in biotechnology and gene therapy.

Cell therapies for tendons: old cell choice for modern innovation.

Although tissue engineering and cell therapies are becoming realistic approaches for medical therapeutics, it is likely that musculoskeletal applications will be among the first to benefit on a large scale. Cell sources for tissue engineering and cell therapies for tendon pathologies are reviewed with an emphasis on small defect tendon injuries as seen in the hand which could adapt well to injectable cell administration. Specifically, cell sources including tenocytes, tendon sheath fibroblasts, bone marrow or adipose-derived stem cells, amniotic cells, placenta cells and platelet-derivatives have been proposed to enhance tendon regeneration. The associated advantages and disadvantages for these different strategies will be discussed and evolving regulatory requirements for cellular therapies will also be addressed. Human progenitor tenocytes, along with their clinical cell banking potential, will be presented as an alternative cell source solution. Similar cell banking techniques have already been described with other progenitor cell types in the 1950's for vaccine production, and these "old" cell types incite potentially interesting therapeutic options that could be improved with modern innovation for tendon regeneration and repair.

Road Use Tax Fund Efficiency Report, January 2012

In the November 2011 report issued by the Governor’s Transportation 2020 Citizen Advisory Commission (CAC), the commission recommended the Iowa Department of Transportation (DOT), at least annually, convene meetings with the cities and counties to review the operation, maintenance and improvement of Iowa’s public roadway system to identify ways to jointly increase efficiency. In response to this recommendation, Gov. Branstad directed the Iowa DOT to begin this effort immediately with a target of identifying $50 million of efficiency savings that can be captured from the $1.2 billion of Road Use Tax Funds (RUTF) provided to the Iowa DOT, cities and counties to administer, maintain and improve the public roadway system. This would build upon past joint and individual actions that have reduced administrative costs and resulted in increased funding for system improvements. Efficiency actions should be quantified, measured and reported to the public on a regular basis. Beyond the discussion of identifying funding solutions to our road and bridge needs, it is critical that all jurisdictions that own, maintain and improve the nation’s road and bridge systems demonstrate to the public these funds are utilized in the most efficient and effective manner. This requires continual innovation in all aspects of transportation planning, design, construction and maintenance - done in a transparent manner to clearly demonstrate to the public how their funds are being utilized. The Iowa DOT has identified 13 efficiency measures separated into two distinct categories – Program Efficiencies and Partnership Efficiencies. The total value of the efficiency measures is $50 million. Many of the efficiency items will need input, refinement and partnership from cities, counties, other local jurisdictions, and stakeholder interest groups. The Iowa DOT has begun meetings with many of these groups to help identify potential efficiency measures and strategies for moving forward. These partnerships and discussions will continue through implementation of the efficiency measures. Dependent on the measures identified, additional action may be required by the legislature, Iowa Transportation Commission, and/or other bodies to implement the action. In addition, a formal process will be developed to quantify, measure and report the results of actions taken on a regular basis.

Granulocyte-macrophage colony-stimulating factor elicits bone marrow-derived cells that promote efficient colonic mucosal healing.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy is effective in treating some Crohn's disease (CD) patients and protects mice from colitis induced by dextran sulfate sodium (DSS) administration. However, its mechanisms of action remain elusive. We hypothesized that GM-CSF affects intestinal mucosal repair. METHODS: DSS colitic mice were treated with daily pegylated GM-CSF or saline and clinical, histological, and inflammatory parameters were kinetically evaluated. Further, the role of bone marrow-derived cells in the impact of GM-CSF therapy on DSS colitis was addressed using cell transfers. RESULTS: GM-CSF therapy reduced clinical signs of colitis and the release of inflammatory mediators. GM-CSF therapy improved mucosal repair, with faster ulcer reepithelialization, accelerated hyperproliferative response of epithelial cells in ulcer-adjacent crypts, and lower colonoscopic ulceration scores in GM-CSF-administered mice relative to untreated mice. We observed that GM-CSF-induced promotion of mucosal repair is timely associated with a reduction in neutrophil numbers and increased accumulation of CD11b(+) monocytic cells in colon tissues. Importantly, transfer of splenic GM-CSF-induced CD11b(+) myeloid cells into DSS-exposed mice improved colitis, and lethally irradiated GM-CSF receptor-deficient mice reconstituted with wildtype bone marrow cells were protected from DSS-induced colitis upon GM-CSF therapy. Lastly, GM-CSF-induced CD11b(+) myeloid cells were shown to promote in vitro wound repair. CONCLUSIONS: Our study shows that GM-CSF-dependent stimulation of bone marrow-derived cells during DSS-induced colitis accelerates colonic tissue repair. These data provide a putative mechanism for the observed beneficial effects of GM-CSF therapy in Crohn's disease.

Interpretation of primary care physicians' attitude regarding rotavirus immunisation using diffusion of innovation theories.

To evaluate primary care physicians' attitude towards implementation of rotavirus (RV) immunisation into the Swiss immunisation schedule, an eight-question internet-based questionnaire was sent to the 3799 subscribers of InfoVac, a nationwide web-based expert network on immunisation issues, which reaches >95% of paediatricians and smaller proportions of other primary care physicians. Five demographic variables were also inquired. Descriptive statistics and multivariate analyses for the main outcome "acceptance of routine RV immunisation" and other variables were performed. Diffusion of innovation theory was used for data assessment. Nine-hundred seventy-seven questionnaires were returned (26%). Fifty percent of participants were paediatricians. Routine RV immunisation was supported by 146 participants (15%; so called early adopters), dismissed by 620 (64%), leaving 211 (21%) undecided. However, when asked whether they would recommend RV vaccination to parents if it were officially recommended by the federal authorities and reimbursed, 467 (48.5%; so called early majority) agreed to recommend RV immunisation. Multivariate analysis revealed that physicians who would immunise their own child (OR: 5.1; 95% CI: 4.1-6.3), hospital-based physicians (OR: 1.6; 95% CI: 1.1-2.3) and physicians from the French (OR: 1.6; 95% CI: 1.2-2.3) and Italian speaking areas of Switzerland (OR: 2.5; 95% CI: 1.1-5.8) were more likely to support RV immunisation. Diffusion of innovation theory predicts a >80% implementation if approximately 50% of a given population support an innovation. Introduction of RV immunisation in Switzerland is likely to be successful, if (i) the federal authorities issue an official recommendation and (ii) costs are covered by basic health care insurance.

Accurate and efficient simulation of multiphase flow in a heterogeneous reservoir by using error estimate and control in the multiscale finite-volume framework

The multiscale finite-volume (MSFV) method is designed to reduce the computational cost of elliptic and parabolic problems with highly heterogeneous anisotropic coefficients. The reduction is achieved by splitting the original global problem into a set of local problems (with approximate local boundary conditions) coupled by a coarse global problem. It has been shown recently that the numerical errors in MSFV results can be reduced systematically with an iterative procedure that provides a conservative velocity field after any iteration step. The iterative MSFV (i-MSFV) method can be obtained with an improved (smoothed) multiscale solution to enhance the localization conditions, with a Krylov subspace method [e.g., the generalized-minimal-residual (GMRES) algorithm] preconditioned by the MSFV system, or with a combination of both. In a multiphase-flow system, a balance between accuracy and computational efficiency should be achieved by finding a minimum number of i-MSFV iterations (on pressure), which is necessary to achieve the desired accuracy in the saturation solution. In this work, we extend the i-MSFV method to sequential implicit simulation of time-dependent problems. To control the error of the coupled saturation/pressure system, we analyze the transport error caused by an approximate velocity field. We then propose an error-control strategy on the basis of the residual of the pressure equation. At the beginning of simulation, the pressure solution is iterated until a specified accuracy is achieved. To minimize the number of iterations in a multiphase-flow problem, the solution at the previous timestep is used to improve the localization assumption at the current timestep. Additional iterations are used only when the residual becomes larger than a specified threshold value. Numerical results show that only a few iterations on average are necessary to improve the MSFV results significantly, even for very challenging problems. Therefore, the proposed adaptive strategy yields efficient and accurate simulation of multiphase flow in heterogeneous porous media.