143 research outputs found
Ablation of an orthodromic reentrant tachycardia via a concealed accessory pathway targeted in the non-coronary sinus
Modelling vehicles acceleration during overtaking manoeuvres
[EN] Abstract: Overtaking manoeuvre is a key issue for two-lane rural roads. These roads should provide sufficient overtaking sight distance (OSD) at certain locations to allow faster vehicles to pass slower ones. However, overtaking requires occupying the opposing lane, which represents a serious safety concern. Severity of overtaking related crashes is very
high, compared with other manoeuvres. The development of advanced driver assistance systems (ADAS) for overtaking is being a complex task. Only few systems have been developed, but are not still in use. This research incorporated accurate data of real manoeuvres to improve the knowledge of the phenomenon. The trajectory of the overtaking vehicles on the left lane was observed. An instrumented vehicle measured the overtaking time and distance, the abreast position, and the initial and final speed of 180 drivers that passed it during a field experiment. Six different kinematic models (such as uniform acceleration or linear variation of acceleration) were calibrated. Generally, drivers started to accelerate before changing to the opposing lane. These models may be applied to ADAS, to estimate OSD and to improve microsimulation models.Part of this research was included in the project 'Desarrollo de modelos de distancias de visibilidad de adelantamiento', with reference code TRA2010-21736 and subsidised by the Spanish Ministery of Economy and Competitivity. The authors also thank Prof Dr Sayed, from University of British Columbia, for his valuable review.Llorca Garcia, C.; Moreno, AT.; García García, A. (2016). Modelling vehicles acceleration during overtaking manoeuvres. IET Intelligent Transport Systems. 10(3):206-215. https://doi.org/10.1049/iet-its.2015.0035S206215103Gray, R., & Regan, D. M. (2005). Perceptual Processes Used by Drivers During Overtaking in a Driving Simulator. Human Factors: The Journal of the Human Factors and Ergonomics Society, 47(2), 394-417. doi:10.1518/0018720054679443Basilio, N., Morice, A. H. P., Marti, G., & Montagne, G. (2015). High- and Low-Order Overtaking-Ability Affordances. Human Factors: The Journal of the Human Factors and Ergonomics Society, 57(5), 879-894. doi:10.1177/0018720815583581Morice, A. H. P., Diaz, G. J., Fajen, B. R., Basilio, N., & Montagne, G. (2015). An Affordance-Based Approach to Visually Guided Overtaking. Ecological Psychology, 27(1), 1-25. doi:10.1080/10407413.2015.991641Farah, H., Bekhor, S., & Polus, A. (2009). Risk evaluation by modeling of passing behavior on two-lane rural highways. Accident Analysis & Prevention, 41(4), 887-894. doi:10.1016/j.aap.2009.05.006Hassan, Y., Easa, S. M., & El Halim, A. O. A. (1996). Passing sight distance on two-lane highways: Review and revision. Transportation Research Part A: Policy and Practice, 30(6), 453-467. doi:10.1016/0965-8564(95)00032-1Wang, Y., & Cartmell, M. P. (1998). New Model for Passing Sight Distance on Two-Lane Highways. Journal of Transportation Engineering, 124(6), 536-545. doi:10.1061/(asce)0733-947x(1998)124:6(536)Sparks, G. A., Neudorf, R. D., Robinson, J. B. L., & Good, D. (1993). Effect of Vehicle Length on Passing Operations. Journal of Transportation Engineering, 119(2), 272-283. doi:10.1061/(asce)0733-947x(1993)119:2(272)Hanley, P. F., & Forkenbrock, D. J. (2005). Safety of passing longer combination vehicles on two-lane highways. Transportation Research Part A: Policy and Practice, 39(1), 1-15. doi:10.1016/j.tra.2004.09.001Khoury, J. E., & Hobeika, A. G. (2012). Integrated Stochastic Approach for Risk and Service Estimation: Passing Sight Distance Application. Journal of Transportation Engineering, 138(5), 571-579. doi:10.1061/(asce)te.1943-5436.0000366Jenkins, J. M., & Rilett, L. R. (2004). Application of Distributed Traffic Simulation for Passing Behavior Study. Transportation Research Record: Journal of the Transportation Research Board, 1899(1), 11-18. doi:10.3141/1899-02Rakha, H., Ahn, K., & Trani, A. (2004). Development of VT-Micro model for estimating hot stabilized light duty vehicle and truck emissions. Transportation Research Part D: Transport and Environment, 9(1), 49-74. doi:10.1016/s1361-9209(03)00054-3Polus, A., Livneh, M., & Frischer, B. (2000). Evaluation of the Passing Process on Two-Lane Rural Highways. Transportation Research Record: Journal of the Transportation Research Board, 1701(1), 53-60. doi:10.3141/1701-07Harwood, D. W., Gilmore, D. K., & Richard, K. R. (2010). Criteria for Passing Sight Distance for Roadway Design and Marking. Transportation Research Record: Journal of the Transportation Research Board, 2195(1), 36-46. doi:10.3141/2195-05Hegeman, G., Tapani, A., & Hoogendoorn, S. (2009). Overtaking assistant assessment using traffic simulation. Transportation Research Part C: Emerging Technologies, 17(6), 617-630. doi:10.1016/j.trc.2009.04.010Milanés, V., Llorca, D. F., Villagrá, J., Pérez, J., Fernández, C., Parra, I., … Sotelo, M. A. (2012). Intelligent automatic overtaking system using vision for vehicle detection. Expert Systems with Applications, 39(3), 3362-3373. doi:10.1016/j.eswa.2011.09.024Isermann, R., Mannale, R., & Schmitt, K. (2012). Collision-avoidance systems PRORETA: Situation analysis and intervention control. Control Engineering Practice, 20(11), 1236-1246. doi:10.1016/j.conengprac.2012.06.003Petrov, P., & Nashashibi, F. (2014). Modeling and Nonlinear Adaptive Control for Autonomous Vehicle Overtaking. IEEE Transactions on Intelligent Transportation Systems, 15(4), 1643-1656. doi:10.1109/tits.2014.2303995Llorca, C., & García, A. (2011). Evaluation of Passing Process on Two-Lane Rural Highways in Spain with New Methodology Based on Video Data. Transportation Research Record: Journal of the Transportation Research Board, 2262(1), 42-51. doi:10.3141/2262-05Llorca, C., Moreno, A. T., García, A., & Pérez-Zuriaga, A. M. (2013). Daytime and Nighttime Passing Maneuvers on a Two-Lane Rural Road in Spain. Transportation Research Record: Journal of the Transportation Research Board, 2358(1), 3-11. doi:10.3141/2358-01Llorca, C., Moreno, A. T., Pérez-Zuriaga, A. M., & García, A. (2013). Influence of age, gender and delay on overtaking dynamics. IET Intelligent Transport Systems, 7(2), 174-181. doi:10.1049/iet-its.2012.0147Khoury, J. E., & Hobeika, A. (2007). Incorporating Uncertainty into the Estimation of the Passing Sight Distance Requirements. Computer-Aided Civil and Infrastructure Engineering, 22(5), 347-357. doi:10.1111/j.1467-8667.2007.00491.xRakha, H., Snare, M., & Dion, F. (2004). Vehicle Dynamics Model for Estimating Maximum Light-Duty Vehicle Acceleration Levels. Transportation Research Record: Journal of the Transportation Research Board, 1883(1), 40-49. doi:10.3141/1883-05Fitzpatrick, K., Chrysler, S. T., & Brewer, M. (2012). Deceleration Lengths for Exit Terminals. Journal of Transportation Engineering, 138(6), 768-775. doi:10.1061/(asce)te.1943-5436.000038
A mechanism for the extension and unfolding of parallel telomeric G-quadruplexes by human telomerase at single-molecule resolution
30 pags., 10 figs., 1 tab.Telomeric G-quadruplexes (G4) were long believed to form a protective structure at telomeres, preventing their extension by the ribonucleoprotein telomerase. Contrary to this belief, we have previously demonstrated that parallel-stranded conformations of telomeric G4 can be extended by human and ciliate telomerase. However, a mechanistic understanding of the interaction of telomerase with structured DNA remained elusive. Here, we use single-molecule fluorescence resonance energy transfer (smFRET) microscopy and bulk-phase enzymology to propose a mechanism for the resolution and extension of parallel G4 by telomerase. Binding is initiated by the RNA template of telomerase interacting with the G-quadruplex; nucleotide addition then proceeds to the end of the RNA template. It is only through the large conformational change of translocation following synthesis that the G-quadruplex structure is completely unfolded to a linear product. Surprisingly, parallel G4 stabilization with either small molecule ligands or by chemical modification does not always inhibit G4 unfolding and extension by telomerase. These data reveal that telomerase is a parallel G-quadruplex resolvase.Cancer Council NSW RG 11-07 Tracy M Bryan, Cancer Institute NSW Aaron Lavel Moye, Australian Research Council FL140100027 Antoine M van Oijen, Ernest and Piroska Major Foundation Scott B Cohen, Natural Sciences and Engineering Research Council of Canada, Masad J Damha Centre of Excellence for Innovation in Chemistry PERCH-CIC Siritron Samosorn
Research Unit of Natural Products and Organic Synthesis for Drug Discovery NPOS 405/2560 Siritron Samosorn
Cancer Council NSW RG 16-10 Tracy M Brya
Design Criteria for Minimum Passing Zone Lengths: Operational Efficiency and Safety Considerations
Passing zones are provided to improve operational efficiency of two-lane highways where
passes can be performed safely. Minimum passing zone lengths of 120 m were established in
MUTCD and Green Book, although some studies indicate a potential need to increase them.
However, no changes have been recommended pending further research on the safety of short
passing zones.
The objective of this study is to develop design and marking criteria for minimum
passing zone lengths that consider traffic operational efficiency and safety.
In the first part of this study, a traffic microsimulation was carried out with Aimsun
software. The calibration and validation included the observation of 1,750 passing maneuvers in
Spain. The results indicate that passing zones shorter than 250 m add very little to operational
efficiency. In the second part of the study, a reliability analysis was applied. It quantified the
probability that a passing maneuver was completed beyond the end of the passing zone (noncompliant
passing maneuvers). Afterwards, the number of non-compliant passing maneuvers
was calculated. Traffic flow as well as passing zone length were contributing factors..
Findings from the analysis indicate that the minimum passing zone length should be
increased to a minimum of 275 m, for high traffic volumes, 300 m for medium traffic volumes
and 350 m for low traffic volumes. From this length, the number of non-compliant passing
maneuvers decreases. The marginal increase in the minimum length of passing zones can
potentially improve safety without significantly reducing the operational efficiency. The results
can be directly used by practitioners to establish the minimum passing zone length based on the
range of hourly volumes and the level of risk willing to assume.The authors thank the Spanish Ministry of Science and Innovation, which subsidizes the research project Estudio Experimental de la Funcionalidad y Seguridad de las Carreteras Convencionales (experimental study on road safety and traffic operation on two-lane rural roads).Moreno Chou, AT.; Llorca Garcia, C.; Lenorzer, A.; Casas, J.; García García, A. (2015). Design Criteria for Minimum Passing Zone Lengths: Operational Efficiency and Safety Considerations. Transportation Research Record. 2486:19-27. doi:10.3141/2486-03S1927248
Antibodies Targeted to the Brain with Image-Guided Focused Ultrasound Reduces Amyloid-β Plaque Load in the TgCRND8 Mouse Model of Alzheimer's Disease
Immunotherapy for Alzheimer's disease (AD) relies on antibodies directed against toxic amyloid-beta peptide (Aβ), which circulate in the bloodstream and remove Aβ from the brain [1], [2]. In mouse models of AD, the administration of anti-Aβ antibodies directly into the brain, in comparison to the bloodstream, was shown to be more efficient at reducing Aβ plaque pathology [3], [4]. Therefore, delivering anti-Aβ antibodies to the brain of AD patients may also improve treatment efficiency. Transcranial focused ultrasound (FUS) is known to transiently-enhance the permeability of the blood-brain barrier (BBB) [5], allowing intravenously administered therapeutics to enter the brain [6]–[8]. Our goal was to establish that anti-Aβ antibodies delivered to the brain using magnetic resonance imaging-guided FUS (MRIgFUS) [9] can reduce plaque pathology. To test this, TgCRND8 mice [10] received intravenous injections of MRI and FUS contrast agents, as well as anti-Aβ antibody, BAM-10. MRIgFUS was then applied transcranially. Within minutes, the MRI contrast agent entered the brain, and BAM-10 was later found bound to Aβ plaques in targeted cortical areas. Four days post-treatment, Aβ pathology was significantly reduced in TgCRND8 mice. In conclusion, this is the first report to demonstrate that MRIgFUS delivery of anti-Aβ antibodies provides the combined advantages of using a low dose of antibody and rapidly reducing plaque pathology
Rapid Accumulation of Polymorphonuclear Neutrophils in the Corpus luteum during Prostaglandin F2α-Induced Luteolysis in the Cow
Prostaglandin F2α (PGF2α) induces luteolysis within a few days in cows, and immune cells increase in number in the regressing corpus luteum (CL), implying that luteolysis is an inflammatory-like immune response. We investigated the rapid change in polymorphonuclear neutrophil (PMN) numbers in response to PGF2α administration as the first cells recruited to inflammatory sites, together with mRNA of interleukin-8 (IL-8: neutrophil chemoattractant) and P-selectin (leukocyte adhesion molecule) in the bovine CL. CLs were collected by ovariectomy at various times after PGF2α injection. The number of PMNs was increased at 5 min after PGF2α administration, whereas IL-8 and P-selectin mRNA increased at 30 min and 2 h, respectively. PGF2α directly stimulated P-selectin protein expression at 5–30 min in luteal endothelial cells (LECs). Moreover, PGF2α enhanced PMN adhesion to LECs, and this enhancement by PGF2α was inhibited by anti-P-selectin antibody, suggesting that P-selectin expression by PGF2α is crucial in PMN migration. In conclusion, PGF2α rapidly induces the accumulation of PMNs into the bovine CL at 5 min and enhances PMN adhesion via P-selectin expression in LECs. It is suggested that luteolytic cascade by PGF2α may involve an acute inflammatory-like response due to rapidly infiltrated PMNs
Hippocampal CA3 Transcriptome Signature Correlates with Initial Precipitating Injury in Refractory Mesial Temporal Lobe Epilepsy
Background: Prolonged febrile seizures constitute an initial precipitating injury (IPI) commonly associated with refractory mesial temporal lobe epilepsy (RMTLE). in order to investigate IPI influence on the transcriptional phenotype underlying RMTLE we comparatively analyzed the transcriptomic signatures of CA3 explants surgically obtained from RMTLE patients with (FS) or without (NFS) febrile seizure history. Texture analyses on MRI images of dentate gyrus were conducted in a subset of surgically removed sclerotic hippocampi for identifying IPI-associated histo-radiological alterations.Methodology/Principal Findings: DNA microarray analysis revealed that CA3 global gene expression differed significantly between FS and NFS subgroups. An integrative functional genomics methodology was used for characterizing the relations between GO biological processes themes and constructing transcriptional interaction networks defining the FS and NFS transcriptomic signatures and its major gene-gene links (hubs). Co-expression network analysis showed that: i) CA3 transcriptomic profiles differ according to the IPI; ii) FS distinctive hubs are mostly linked to glutamatergic signalization while NFS hubs predominantly involve GABAergic pathways and neurotransmission modulation. Both networks have relevant hubs related to nervous system development, what is consistent with cell genesis activity in the hippocampus of RMTLE patients. Moreover, two candidate genes for therapeutic targeting came out from this analysis: SSTR1, a relevant common hub in febrile and afebrile transcriptomes, and CHRM3, due to its putative role in epilepsy susceptibility development. MRI texture analysis allowed an overall accuracy of 90% for pixels correctly classified as belonging to FS or NFS groups. Histological examination revealed that granule cell loss was significantly higher in FS hippocampi.Conclusions/Significance: CA3 transcriptional signatures and dentate gyrus morphology fairly correlate with IPI in RMTLE, indicating that FS-RMTLE represents a distinct phenotype. These findings may shed light on the molecular mechanisms underlying refractory epilepsy phenotypes and contribute to the discovery of novel specific drug targets for therapeutic interventions
Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease
Background
1Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes.
Methodology
We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.
Principal Findings
We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD.
Significance
Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches
Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19 A Living Systematic Review of Multiple Streams of Evidence
Background:
Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19).
Purpose:
To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. (PROSPERO registration: CRD42020178187)
Data Sources:
21 standard, World Health Organization–specific and COVID-19–specific databases, without language restrictions, until 1 May 2020.
Study Selection:
Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included.
Data Extraction:
Independent and duplicate screening, data abstraction, and risk of bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews).
Data Synthesis:
123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs.
Limitation:
Direct studies in COVID-19 are limited and poorly reported.
Conclusion:
Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers
Derecho ex cathedra. 1847-1936 Diccionario de catedráticos españoles
Edición revisada 2020.Publicación de las entradas biográficas del Diccionario de catedráticos españoles de Derecho, accesible en http://www.uc3m.es/diccionariodecatedraticos. Al dar forma de libro al material hemos prescindido de algunos elementos informativos, que se mantienen en la página electrónica indicada. Se recogen ahora solamente a los ingresados en el cuerpo con anterioridad a la guerra civil.Publication of the biographical entries of the Diccionario de catedráticos españoles de Derecho, accessible at http://www.uc3m.es/diccionariodecatedraticos. By giving those material book form, we have dispensed with some informative elements, however kept on the web page. Only professors apointed prior to the Civil War are now included.Esta publicación forma parte del proyecto “La memoria del jurista español: génesis y
desarrollo de las disciplinas jurídicas” (ref. DER2014-55035-C2-1-P/DER2014-55035-C2-2-P), financiado por el Ministerio de Economía, Industria y Competitividad (España)
- …