Hybrid optimization approach for the design of mechanisms using a new error estimator

A hybrid optimization approach for the design of linkages is presented. The method is applied to the dimensional synthesis of mechanism and combines the merits of both stochastic and deterministic optimization. The stochastic optimization approach is based on a real-valued evolutionary algorithm (EA) and is used for extensive exploration of the design variable space when searching for the best linkage. The deterministic approach uses a local optimization technique to improve the efficiency by reducing the high CPU time that EA techniques require in this kind of applications. To that end, the deterministic approach is implemented in the evolutionary algorithm in two stages. The first stage is the fitness evaluation where the deterministic approach is used to obtain an effective new error estimator. In the second stage the deterministic approach refines the solution provided by the evolutionary part of the algorithm. The new error estimator enables the evaluation of the different individuals in each generation, avoiding the removal of well-adapted linkages that other methods would not detect. The efficiency, robustness, and accuracy of the proposed method are tested for the design of a mechanism in two examples.This paper has been developed in the framework of the Project DPI2010-18316 funded by the Spanish Ministry of Economy and Competitiveness

Optical Temperature Sensor Capabilities of the Green Upconverted Luminescence of Er3+ in La3NbO7 Ceramic Powders

We present a study of the Er3+ upconverted luminescence in erbium doped Lanthanum Niobium Oxide, La3NbO7, ceramic powder, prepared by solid state reaction. This study focuses on the analysis of the feasibility of this system as a temperature sensor. Efficient UC luminescence was observed under the 975 nm excitation showing intense green, red and NIR (850 nm) emission bands. The NIR luminescence centred at about 850 nm and lying on the first biological window is mainly insensitive to the temperature. In contrast, the upconverted green bands, associated with the (2H11/2,4S3/2) !4I15/2 transitions, showed a high sensibility to temperature. Their temperature dependence was studied from RT up to 525 K, paying special attention to the physiological range of temperature (303–318 K). The high thermal sensitivities obtained, in comparison with other Er3+ and Er3+-Yb3+ based optical temperature sensors in such ranges, suggest the potential application of this phosphor in thermal sensing, suitable for both biological systems and other industrial applications requiring higher temperatures.This research has been partially supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (MICINN) through the Spanish projects RTI2018-101020-B-100 and PID2019- 106383GB-C44, by the Madrid Government (Comunidad de Madrid-Spain) under the Multiannual Agreement with UC3Min the line of Excellence of University Professors (EPUC3MXX) and in the context of the V PRICIT (Regional Programme of Research and Technological Innovation) by the Agencia Canaria de Investigación, Innovación y Sociedad de la Información (ACIISI) (ProID2017010078). M.A.H.-R. thanks MINECO for the FPI grant (BES-2014-068666). U.R.R.-M. thanks Gobierno de Canarias and EU-FEDER for grant ProID2020010067

Analysis of Synaptic Proteins in the Cerebrospinal Fluid as a New Tool in the Study of Inborn Errors of Neurotransmission

Abstract In a few rare diseases, specialised studies in cerebrospinal fluid (CSF) are required to identify the underlying metabolic disorder. We aimed to explore the possibility of detecting key synaptic proteins in the CSF, in particular dopaminergic and gabaergic, as new procedures that could be useful for both pathophysiological and diagnostic purposes in investigation of inherited disorders of neurotransmission. Dopamine receptor type 2 (D2R), dopamine transporter (DAT) and vesicular monoamine transporter type 2 (VMAT2) were analysed in CSF samplesfrom 30 healthy controls (11 days to 17 years) by western blot analysis. Because VMAT2 was the only protein with intracellular localisation, and in order to compare results, GABA vesicular transporter, which is another intracellular protein, was also studied. Spearman’s correlation and Student’s t tests were applied to compare optical density signals between different proteins. All these synaptic proteins could be easily detected and quantified in the CSF. DAT, D2R and GABA VT expression decrease with age, particularly in the first months of life, reflecting the expected intense synaptic activity and neuronal circuitry formation. A statistically significant relationship was found between D2R and DAT expression, reinforcing the previous evidence of DAT regulation by D2R. To our knowledge, there are no previous studies on human CSF reporting a reliable analysis of these proteins. These kinds of studies could help elucidate new causes of disturbed dopaminergic and gabaergic transmission as well as understanding different responses to L-dopa in inherited disorders affecting dopamine metabolism. Moreover, this approach to synaptic activity in vivo can be extended to different groups of proteins and diseases

Classificatory Theory in Data-Intensive Science: The Case of Open Biomedical Ontologies

publication-status: Publishedtypes: ArticleThis is the author's version of a paper that was subsequently published in International Studies in the Philosophy of Science. Please cite the published version by following the DOI link.Knowledge-making practices in biology are being strongly affected by the availability of data on an unprecedented scale, the insistence on systemic approaches and growing reliance on bioinformatics and digital infrastructures. What role does theory play within data-intensive science, and what does that tell us about scientific theories in general? To answer these questions, I focus on Open Biomedical Ontologies, digital classification tools that have become crucial to sharing results across research contexts in the biological and biomedical sciences, and argue that they constitute an example of classificatory theory. This form of theorizing emerges from classification practices in conjunction with experimental know-how and expresses the knowledge underpinning the analysis and interpretation of data disseminated online.Economic and Social Research Council (ESRC)The British AcademyLeverhulme Trus

Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

We show in human immunodeficiency virus-positive persons that the coronary artery disease effect of an unfavorable genetic background is comparable to previous studies in the general population, and comparable in size to traditional risk factors and antiretroviral regimens known to increase cardiovascular ris

Molecular Evidence for a Functional Ecdysone Signaling System in Brugia malayi

Filarial parasites such as Brugia malayi and Onchocerca volvulus are the causative agents of the tropical diseases lymphatic filariasis and onchocerciasis, which infect 150 million people, mainly in Africa and Southeast Asia. Filarial nematodes have a complex life cycle that involves transmission and development within both mammalian and insect hosts. The successful completion of the life cycle includes four molts, two of which are triggered upon transmission from one host to the other, human and mosquito, respectively. Elucidation of the molecular mechanisms involved in the molting processes in filarial nematodes may yield a new set of targets for drug intervention. In insects and other arthropods molting transitions are regulated by the steroid hormone ecdysone that interacts with a specialized hormone receptor composed of two different proteins belonging to the family of nuclear receptors. We have cloned from B. malayi two members of the nuclear receptor family that show many sequence and biochemical properties consistent with the ecdysone receptor of insects. This finding represents the first report of a functional ecdysone receptor homolog in nematodes. We have also established a transgenic hormone induction assay in B. malayi that can be used to discover ecdysone responsive genes and potentially lead to screening assays for active compounds for pharmaceutical development

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. METHODS: In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. RESULTS: A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥ 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. CONCLUSIONS: In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD

Educación popular y los esquemas privatizantes en educación

Reunión: Educación Popular y los Esquemas Privatizantes en Educación, 30 jun. 1988, Santiago, C