The Use of Patents to Assess National Innovation Systems: Evidences from Spanish Biotechnology

Spain’s economy recorded a high rate of growth from the mid-1990s onwards. At the same time, the resources allocated to Research and Development (R&D) grew at a much faster pace than in other European Union (EU) countries. Spain’s growth recorded an average rate of 2.93% from the early 1990s to 2004. Over the same period, the average growth in the EU was 0.46%. This circumstance, together with several sound policy decisions implemented between 2004 and 2009, ushered in a “golden age of Spanish biotechnology”. In terms of the national patent licenses issued by the Spanish Patent and Trademark Office (SPTO) between 2004 and 2009, the number in biotechnology grew from 84 to 151. However, the current economic situation in Spain, along with a series of political decisions taken over the past two or three years to cut spending on R&D, predicts a sharp downturn in the performance of Spanish biotechnology. This scenario makes Spain one of the best places to study the successes and failures of the management of science and allows transfer this experience to the other international regions. We need to analyze the influence of political decisions as a major factor with a bearing on the quality of science. Using patents as an indicator of scientific development, this paper analyzes the evolution of the biotechnology sector in Spain and its relationship with scientific policy and the management of R&D

Implementing Parallel Differential Evolution on Spark

[Abstract] Metaheuristics are gaining increased attention as an efficient way of solving hard global optimization problems. Differential Evolution (DE) is one of the most popular algorithms in that class. However, its application to realistic problems results in excessive computation times. Therefore, several parallel DE schemes have been proposed, most of them focused on traditional parallel programming interfaces and infrastruc- tures. However, with the emergence of Cloud Computing, new program- ming models, like Spark, have appeared to suit with large-scale data processing on clouds. In this paper we investigate the applicability of Spark to develop parallel DE schemes to be executed in a distributed environment. Both the master-slave and the island-based DE schemes usually found in the literature have been implemented using Spark. The speedup and efficiency of all the implementations were evaluated on the Amazon Web Services (AWS) public cloud, concluding that the island- based solution is the best suited to the distributed nature of Spark. It achieves a good speedup versus the serial implementation, and shows a decent scalability when the number of nodes grows.[Resumen] Las metaheurísticas están recibiendo una atención creciente como técnica eficiente en la resolución de problemas difíciles de optimización global. Differential Evolution (DE) es una de las metaheurísticas más populares, sin embargo su aplicación en problemas reales deriva en tiempos de cómputo excesivos. Por ello se han realizado diferentes propuestas para la paralelización del DE, en su mayoría utilizando infraestructuras e interfaces de programación paralela tradicionales. Con la aparición de la computación en la nube también se han propuesto nuevos modelos de programación, como Spark, que permiten manejar el procesamiento de datos a gran escala en la nube. En este artículo investigamos la aplicabilidad de Spark en el desarrollo de implementaciones paralelas del DE para su ejecución en entornos distribuidos. Se han implementado tanto la aproximación master-slave como la basada en islas, que son las más comunes. También se han evaluado la aceleración y la eficiencia de todas las implementaciones usando el cloud público de Amazon (AWS, Amazon Web Services), concluyéndose que la implementación basada en islas es la más adecuada para el esquema de distribución usado por Spark. Esta implementación obtiene una buena aceleración en relación a la implementación serie y muestra una escalabilidad bastante buena cuando el número de nodos aumenta.[Resume] As metaheurísticas están recibindo unha atención a cada vez maior como técnica eficiente na resolución de problemas difíciles de optimización global. Differential Evolution (DE) é unha das metaheurísticas mais populares, ainda que a sua aplicación a problemas reais deriva en tempos de cómputo excesivos. É por iso que se propuxeron diferentes esquemas para a paralelización do DE, na sua maioría utilizando infraestruturas e interfaces de programación paralela tradicionais. Coa aparición da computación na nube tamén se propuxeron novos modelos de programación, como Spark, que permiten manexar o procesamento de datos a grande escala na nube. Neste artigo investigamos a aplicabilidade de Spark no desenvolvimento de implementacións paralelas do DE para a sua execución en contornas distribuidas. Implementáronse tanto a aproximación master-slave como a baseada en illas, que son as mais comúns. Tamén se avaliaron a aceleración e a eficiencia de todas as implementacións usando o cloud público de Amazon (AWS, Amazon Web Services), tirando como conclusión que a implementación baseada en illas é a mais acaida para o esquema de distribución usado por Spark. Esta implementación obtén unha boa aceleración en relación á implementación serie e amosa unha escalabilidade bastante boa cando o número de nos aumenta.Ministerio de Economía y Competitividad; DPI2014-55276-C5-2-RXunta de Galicia; GRC2013/055Xunta de Galicia; R2014/04

Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice

Technical Performance Reduces during the Extra-Time Period of Professional Soccer Match-Play

Despite the importance of extra-time in determining progression in specific soccer tournament matches, few studies have profiled the demands of 120-minutes of soccer match-play. With a specific focus on the extra-time period, and using a within-match approach, we examined the influence of prolonged durations of professional soccer match-play on markers of technical (i.e., skilled) performance. In 18 matches involving professional European teams played between 2010 and 2014, this retrospective study quantified the technical actions observed during eight 15-minute epochs (E1: 00:00–14:59 min, E2: 15:00-29:59 min, E3: 30:00-44:59 min, E4: 45:00-59:59 min, E5: 60:00-74:59 min, E6: 75:00-89:59 min, E7: 90:00-104:59 min, E8: 105:00-119:59 min). Analysis of players who completed the demands of the full 120 min of match-play revealed that the cumulative number of successful passes observed during E8 (61±23) was lower than E1-4 (E1: 88±23, P=0.001; E2: 77±21, P=0.005; E3: 79±18, P=0.001; E4: 80±21, P=0.001) and E7 (73±20, P=0.002). Similarly, the total number of passes made in E8 (71±25) was reduced when compared to E1 (102±22, P=0.001), E3 (91±19, P=0.002), E4 (93±22, P≤0.0005) and E7 (84±20, P=0.001). The cumulative number of successful dribbles reduced in E8 (9±4) when compared to E1 (14±4, P=0.001) and E3 (12±4, P≤0.0005) and the total time the ball was in play was less in E8 (504±61 s) compared to E1 (598±70 s, P≤0.0005). These results demonstrate that match-specific factors reduced particular indices of technical performance in the second half of extra-time. Interventions that seek to maintain skilled performance throughout extra-time warrant further investigation

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Association of common variants in JAK2 gene with reduced risk of metabolic syndrome and related disorders

<p>Abstract</p> <p>Background</p> <p>Disturbances in leptin and insulin signaling pathways are related to obesity and metabolic syndrome (MS) with increased risk of diabetes and cardiovascular disease. Janus kinase 2 (JAK2) is a tyrosine kinase involved in the activation of mechanisms that mediate leptin and insulin actions. We conducted a population cross-sectional study to explore the association between two common variants in JAK2 gene and MS related traits in 724 Argentinean healthy male subjects.</p> <p>Methods</p> <p>A total of 724 unrelated men aged 37.11 ± 10.91 yr were included in a cross-sectional study. Physical examination, anthropometric measurements and biochemical analysis were determined by a standardized protocol. rs7849191 and rs3780378 were genotyped. Analyses were done separately for each SNP and followed up by haplotype analysis.</p> <p>Results</p> <p>rs7849191 and rs3780378 were both associated with reduced risk of MS [p = 0.005; OR (95%CI) = 0.52 (0.33-0.80) and p = 0.006; OR (95% CI) = 0.59 (0.40-0.86) respectively, assuming a dominant model]. rs3780378 T allele was associated with triglyceridemia values under 150 mg/dl [p = 0.007; OR (95%CI) = 0.610 (0.429-0.868)] and TT carriers showed lower triglycerides (p = 0.017), triglycerides/HDL-C ratio (p = 0.022) and lipid accumulation product (p = 0.007) compared to allele C carriers. The two-SNPs-haplotype analysis was consistent with single locus analysis.</p> <p>Conclusions</p> <p>It was found for the first time, significant associations of JAK2 common variants and related haplotypes with reduced risk of MS. These findings could be explained by the role of JAK2 in insulin and/or leptin signaling.</p

Extracting Axial Depth and Trajectory Trend Using Astigmatism, Gaussian Fitting, and CNNs for Protein Tracking

Accurate analysis of vesicle trafficking in live cells is challenging for a number of reasons: varying appearance, complex protein movement patterns, and imaging conditions. To allow fast image acquisition, we study how employing an astigmatism can be utilized for obtaining additional information that could make tracking more robust. We present two approaches for measuring the z position of individual vesicles. Firstly, Gaussian curve fitting with CNN-based denoising is applied to infer the absolute depth around the focal plane of each localized protein. We demonstrate that adding denoising yields more accurate estimation of depth while preserving the overall structure of the localized proteins. Secondly, we investigate if we can predict using a custom CNN architecture the axial trajectory trend. We demonstrate that this method performs well on calibration beads data without the need for denoising. By incorporating the obtained depth information into a trajectory analysis, we demonstrate the potential improvement in vesicle tracking

The assessment of neuromuscular fatigue during 120 min of simulated soccer exercise

Purpose This investigation examined the development of neuromuscular fatigue during a simulated soccer match incorporating a period of extra time (ET) and the reliability of these responses on repeated test occasions. Methods Ten male amateur football players completed a 120 min soccer match simulation (SMS). Before, at half time (HT), full time (FT), and following a period of ET, twitch responses to supramaximal femoral nerve and transcranial magnetic stimulation (TMS) were obtained from the knee-extensors to measure neuromuscular fatigue. Within 7 days of the first SMS, a second 120 min SMS was performed by eight of the original ten participants to assess the reliability of the fatigue response. Results At HT, FT, and ET, reductions in maximal voluntary force (MVC; −11, −20 and −27%, respectively, P ≤ 0.01), potentiated twitch force (−15, −23 and −23%, respectively, P < 0.05), voluntary activation (FT, −15 and ET, −18%, P ≤ 0.01), and voluntary activation measured with TMS (−11, −15 and −17%, respectively, P ≤ 0.01) were evident. The fatigue response was robust across both trials; the change in MVC at each time point demonstrated a good level of reliability (CV range 6–11%; ICC2,1 0.83–0.94), whilst the responses identified with motor nerve stimulation showed a moderate level of reliability (CV range 5–18%; ICC2,1 0.63–0.89) and the data obtained with motor cortex stimulation showed an excellent level of reliability (CV range 3–6%; ICC2,1 0.90–0.98). Conclusion Simulated soccer exercise induces a significant level of fatigue, which is consistent on repeat tests, and involves both central and peripheral mechanisms

GeoGebra Applets for Fostering Conceptual Understanding in Algebra

This paper discusses two GeoGebra applets, Radical and Parabola, that are designed to strengthen the conceptual understanding of specific topics in algebra. The design and pedagogical basis of the applets are presented. The integration of the applets in teaching Grade 9 mathematics in a partner high school in the Philippines is then discussed. Finally, we report feedback gathered from students and teachers during this integration. Their feedback indicates the potential of these applets for improving students’ learning of algebra