Performance Bounds for Finite Moving Average Change Detection: Application to Global Navigation Satellite Systems

Due to the widespread deployment of Global Navigation Satellite Systems (GNSSs) for critical road or urban applications, one of the major challenges to be solved is the provision of integrity to terrestrial environments, so that GNSS may be safety used in these applications. To do so, the integrity of the received GNSS signal must be analyzed in order to detect some local effect disturbing the received signal. This is desirable because the presence of some local effect may cause large position errors, and hence compromise the signal integrity. Moreover, the detection of such disturbing effects must be done before some pre-established delay. This kind of detection lies within the field of transient change detection. In this work, a finite moving average stopping time is proposed in order to approach the signal integrity problem with a transient change detection framework. The statistical performance of this stopping time is investigated and compared, in the context of multipath detection, to other different methods available in the literature. Numerical results are presented in order to assess their performance.Comment: 12 pages, 2 figures, transaction paper, IEEE Transaction on Signal Processing, 201

An Updated Focus on Quadruplex Structures as Potential Therapeutic Targets in Cancer

Non-canonical, four-stranded nucleic acids secondary structures are present within regulatory regions in the human genome and transcriptome. To date, these quadruplex structures include both DNA and RNA G-quadruplexes, formed in guanine-rich sequences, and i-Motifs, found in cytosine-rich sequences, as their counterparts. Quadruplexes have been extensively associated with cancer, playing an important role in telomere maintenance and control of genetic expression of several oncogenes and tumor suppressors. Therefore, quadruplex structures are considered attractive molecular targets for cancer therapeutics with novel mechanisms of action. In this review, we provide a general overview about recent research on the implications of quadruplex structures in cancer, firstly gathering together DNA G-quadruplexes, RNA G-quadruplexes as well as DNA i-Motifs.3TR, IMI2 H2020-JTI538 IMI2-2018Instituto de Salud Carlos III AC18/00008Government of Spain FPU16/0582

Poligalacturonasa FaPG1 y CRISPR/Cas9: Editando la firmeza del fruto de fresa

El uso de la técnica CRISPR/Cas9 para la edición de genomas vegetales ha sido ampliamente estudiado y referido en los últimos años. En trabajos recientes, se ha empleado esta técnica para mejorar la vida postcosecha y características organolépticas de frutos modelo como el tomate; sin embargo, los trabajos de edición génica en otros frutos como la fresa son muy escasos. Los cambios en las características y/o composición de las paredes celulares durante la maduración son el principal factor que contribuye a la pérdida de la firmeza del fruto. Estos cambios están promovidos por la inducción de genes que codifican enzimas modificadoras de los polímeros de la pared celular. En el caso de la fresa, trabajos anteriores demostraron que el silenciamiento de genes de poligalacturonasa alarga la vida postcosecha del fruto. En este trabajo se ha evaluado el efecto de la edición del gen de poligalacturonasa FaPG1 mediante el sistema CRISPR/Cas9 en fresa, con el fin último de desarrollar plantas editadas no transgénicas con una vida postcosecha más larga. Para ello, se diseñaron cebadores para amplificar el RNA guía específico para este gen utilizando la aplicación http://crispr.hzau.edu.cn/CRISPR2/ y el genoma de F. vesca v4.0 como referencia. Se transformaron discos de hoja del cv. Chandler mediante A. tumefaciens portando el vector binario pDe-CAS9 que contiene la secuencia codificante de Cas9 y el gen bar para selección en fosfinotricina. Se obtuvieron un total de 40 líneas transgénicas independientes. En el 50% de las plantas analizadas, se comprobó la edición del gen diana mediante el ensayo de la endonucleasa T7. Los productos de amplificación para la zona editada están siendo secuenciados mediante la plataforma Illumina para determinar los patrones de edición que han tenido lugar. Estas líneas serán aclimatadas para su posterior cultivo y evaluación fenotípica en invernadero.AGL2017-86531-C2-1-R; Fondos FEDER; Universidad de Málaga, Campus de Excelencia Internacional Andalucía Tec

Adaptation of targeted nanocarriers to changing requirements in antimalarial drug delivery

The adaptation of existing antimalarial nanocarriers to new Plasmodium stages, drugs, targeting molecules, or encapsulating structures is a strategy that can provide new nanotechnology-based, cost-efficient therapies against malaria. We have explored the modification of different liposome prototypes that had been developed in our group for the targeted delivery of antimalarial drugs to Plasmodium-infected red blood cells (pRBCs). These new models include: (i) immunoliposome-mediated release of new lipid-based antimalarials; (ii) liposomes targeted to pRBCs with covalently linked heparin to reduce anticoagulation risks; (iii) adaptation of heparin to pRBC targeting of chitosan nanoparticles; (iv) use of heparin for the targeting of Plasmodium stages in the mosquito vector; and (v) use of the non-anticoagulant glycosaminoglycan chondroitin 4-sulfate as a heparin surrogate for pRBC targeting. The results presented indicate that the tuning of existing nanovessels to new malaria-related targets is a valid low-cost alternative to the de novo development of targeted nanosystems

CARD8 rs2043211 (p.C10X) polymorphism is not associated with disease susceptibility or cardiovascular events in Spanish rheumatoid arthritis patients

Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis, which is the main cause of increased cardiovascular (CV) morbidity and mortality in RA patients. CARD8 is a constituent of inflammasome, which regulates interleukin 1-beta production, and has been associated with a worse disease course in early RA. One thousand six hundred twenty-one patients fulfilling the 1987 ACR classification criteria for RA and 1300 matched controls, were genotyped for the CARD8 rs2043211 (30T > A, p.C10X) single-nucleotide polymorphism (SNP) using predesigned TaqMan SNP genotyping assay. The genotyping success rate in our study was greater than 94%. We assessed CARD8 rs2043211 gene polymorphism results in 1530 Spanish RA patients in whom information on CV disease and CV risk factors was available at the time of the study. Also, a subgroup of patients with no history of CV events (n = 276) was assessed for the potential influence of the rs2043211 variant in the development of subclinical atherosclerosis, by measurement of carotid intima-media thickness (IMT) and presence of carotid plaques. No statistically significant differences in allele or genotype frequencies for the rs2043211 CARD8 gene variant between patients with RA and controls were seen. Similarly, CARD8 rs2043211 (30T > A, p.C10X) SNP did not influence the development of CV events or the risk of CV events throughout the time. Likewise, no significant association between this gene variant and carotid IMT or the presence of plaques was found. In summary, our results do not support a role of the CARD8 rs2043211 gene variant in susceptibility to RA or in the development of CV disease in patients with RA

Lack of Association between ABO, PPAP2B, ADAMST7, PIK3CG, and EDNRA and Carotid Intima-Media Thickness, Carotid Plaques, and Cardiovascular Disease in Patients with Rheumatoid Arthritis

Introduction. Rheumatoid arthritis (RA) is a polygenic disease associated with accelerated atherosclerosis and increased cardiovascular (CV) mortality. Recent studies have identified the ABO rs579459, PPAP2B rs17114036, and ADAMTS7 rs3825807 polymorphisms as genetic variants associated with coronary artery disease and the PIK3CG rs17398575 and EDNRA rs1878406 polymorphisms as the most significant signals related to the presence of carotid plaque in nonrheumatic Caucasian individuals. Accordingly, we evaluated the potential relationship between these 5 polymorphisms and subclinical atherosclerosis (assessed by carotid intima-media thickness (cIMT) and presence/absence of carotid plaques) and CV disease in RA. Material and Methods. 2140 Spanish RA patients were genotyped for the 5 polymorphisms by TaqMan assays. Subclinical atherosclerosis was evaluated in 620 of these patients by carotid ultrasonography technology. Results. No statistically significant differences were found when each polymorphism was assessed according to cIMT values and presence/absence of carotid plaques in RA, after adjusting the results for potential confounders. Moreover, no significant differences were obtained when RA patients were stratified according to the presence/absence of CV disease after adjusting for potential confounders. Conclusion. Our results do not confirm association between ABO rs579459, PPAP2B rs17114036, ADAMTS7 rs3825807, PIK3CG rs17398575, and EDNRA rs1878406 and subclinical atherosclerosis and CV disease in RA.European Union FEDER Funds and “Fondo de Investigación Sanitaria” (Grants PI06/0024, PS09/00748, and PI12/00060) from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Programs RD12/0009/0013 and RD12/0009/0004 (RIER) from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain) and in part by grants from the European IMI BTCure Program.Peer reviewe

Lack of association between ABO, PPAP2B, ADAMST7, PIK3CG, and EDNRA and carotid intima-media thickness, carotid plaques, and cardiovascular disease in patients with rheumatoid arthritis

Introduction. Rheumatoid arthritis (RA) is a polygenic disease associated with accelerated atherosclerosis and increased cardiovascular (CV) mortality. Recent studies have identified the ABO rs579459, PPAP2B rs17114036, and ADAMTS7 rs3825807 polymorphisms as genetic variants associated with coronary artery disease and the PIK3CG rs17398575 and EDNRA rs1878406 polymorphisms as the most significant signals related to the presence of carotid plaque in nonrheumatic Caucasian individuals. Accordingly, we evaluated the potential relationship between these 5 polymorphisms and subclinical atherosclerosis (assessed by carotid intima-media thickness (cIMT) and presence/absence of carotid plaques) and CV disease in RA. Material and Methods. 2140 Spanish RA patients were genotyped for the 5 polymorphisms by TaqMan assays. Subclinical atherosclerosis was evaluated in 620 of these patients by carotid ultrasonography technology. Results. No statistically significant differences were found when each polymorphism was assessed according to cIMT values and presence/absence of carotid plaques in RA, after adjusting the results for potential confounders. Moreover, no significant differences were obtained when RA patients were stratified according to the presence/absence of CV disease after adjusting for potential confounders. Conclusion. Our results do not confirm association between ABO rs579459, PPAP2B rs17114036, ADAMTS7 rs3825807, PIK3CG rs17398575, and EDNRA rs1878406 and subclinical atherosclerosis and CV disease in RA