211 research outputs found
Metatheoretical critics on current trends in Quantum Mechanics
Is our purpose in this article to review several approaches to modern problems in quantum mechanics from a critical point of view using the approximation of the traditional mathematical thinking. Nevertheless we point out several natural questions that arise in abstract mathematical reasoning
Multiple solutions to a singular Lane-Emden-Fowler equation with convection term
This article concerns the existence of multiple solutions for the problem ââu = K(x)u âÎą + s(Au β + B|âu| Îś ) + f(x) in ⌠u > 0 in ⌠u = 0 on â⌠, where ⌠is a smooth, bounded domain in Rn with n ⼠2, Îą, β, Îś, A, B and s are real positive numbers, and f(x) is a positive real valued and measurable function. We start with the case s = 0 and f = 0 by studying the structure of the range of âu Îąâu. Our method to build Kâs which give at least two solutions is based on positive and negative principal eigenvalues with weight. For s small positive and for values of the parameters in finite intervals, we find multiplicity via estimates on the bifurcation set.Fil: Aranda, Carlos C.. Universidad Nacional de Formosa; ArgentinaFil: Lami Dozo, Enrique Jose. Vrije Unviversiteit Brussel; BĂŠlgica. Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas. Oficina de CoordinaciĂłn Administrativa Saavedra 15. Instituto Argentino de MatemĂĄtica Alberto Calderon; Argentin
LA RAZĂN DE SER DEL GOBIERNO EN COLOMBIA Y LA NECESIDAD DE UNA CLASE POLĂTICA âEDUCADAâ
El Sistema PolĂtico colombiano actualmente consiste en la formulaciĂłn de estrategias de administraciĂłn que permitan potenciar la ârespublicaâ â cosa de todos â para la generaciĂłn de Desarrollo que contribuya a la satisfacciĂłnde intereses nacionales, teniendo como base del sistema o verdadera razĂłn de ser a la persona humana, en el marco de un Estado Social de Derecho, fundamentado lo anterior en la adecuada formaciĂłn y el constante perfeccionamiento de los gobernantes locales, regionales y nacionales
A new methodology for the in vivo estimation of the elastic constants that characterize the patient-specific biomechanical behavior of the human cornea
This work presents a methodology for the in vivo characterization of the complete biomechanical behavior of the human cornea of each patient. Specifically, the elastic constants of a hyperelastic, second-order Ogden model were estimated for 24 corneas corresponding to 12 patients. The finite element method was applied to simulate the deformation of human corneas due to non-contact tonometry, and an iterative search controlled by a genetic heuristic was used to estimate the elastic parameters that most closely approximates the simulated deformation to the real one. The results from a synthetic experiment showed that these parameters can be estimated with an error of about 5%. The results of 24 in vivo corneas showed an overlap of about 90% between simulation and real deformed cornea and a modified Hausdorff distance of 25 mu m, which indicates the great accuracy of the proposed methodology. (C) 2014 Elsevier Ltd. All rights reserved.This project has been partially funded by MECD (reference AP2009-2414) and MINECO (INNPACTO, IPT-2012-0495-300000).Lago, MA.; RupĂŠrez Moreno, MJ.; MartĂnez MartĂnez, F.; Monserrat Aranda, C.; Larra, E.; Gueell, JL.; Peris-Martinez, C. (2015). A new methodology for the in vivo estimation of the elastic constants that characterize the patient-specific biomechanical behavior of the human cornea. Journal of Biomechanics. 48(1):38-43. https://doi.org/10.1016/j.jbiomech.2014.11.009S384348
Clinical Utility of microRNAs in Exhaled Breath Condensate as Biomarkers for Lung Cancer.
This study represents a novel proof of concept of the clinical utility of miRNAs from exhaled breath condensate (EBC) as biomarkers of lung cancer (LC). Genome-wide miRNA profiling and machine learning analysis were performed on EBC from 21 healthy volunteers and 21 LC patients. The levels of 12 miRNAs were significantly altered in EBC from LC patients where a specific signature of miR-4507, miR-6777-5p and miR-451a distinguished these patients with high accuracy. Besides, a distinctive miRNA profile between LC adenocarcinoma and squamous cell carcinoma was observed, where a combined panel of miR-4529-3p, miR-8075 and miR-7704 enabling discrimination between them. EBC levels of miR-6777-5p, 6780a-5p and miR-877-5p predicted clinical outcome at 500 days. Two additional miRNA signatures were also associated with other clinical features such as stage and invasion status. Dysregulated EBC miRNAs showed potential target genes related to LC pathogenesis, including CDKN2B, PTEN, TP53, BCL2, KRAS and EGFR. We conclude that EBC miRNAs might allow the identification, stratification and monitorization of LC, which could lead to the development of precision medicine in this and other respiratory diseases
Phase II study of high-sensitivity genotyping of KRAS, NRAS, BRAF and PIK3CA to ultra-select metastatic colorectal cancer patients for panitumumab plus FOLFIRI: the ULTRA trial
Background: Several studies show the importance of accurately quantifying not only KRAS and other low-abundant mutations because benefits of anti-EGFR therapies may depend on certain sensitivity thresholds. We assessed whether ultra-selection of patients using a high-sensitive digital PCR (dPCR) to determine KRAS, NRAS, BRAF and PIK3CA status can improve clinical outcomes of panitumumab plus FOLFIRI. Patients and methods: This was a single-arm phase II trial that analysed 38 KRAS, NRAS, BRAF and PIK3CA hotspots in tumour tissues of irinotecan-resistant metastatic colorectal cancer patients who received panitumumab plus FOLFIRI until disease progression or early withdrawal. Mutation profiles were identified by nanofluidic dPCR and correlated with clinical outcomes (ORR, overall response rate; PFS, progression-free survival; OS, overall survival) using cut-offs from 0% to 5%. A quantitative PCR (qPCR) analysis was also performed. Results: Seventy-two evaluable patients were enrolled. RAS (KRAS/NRAS) mutations were detected in 23 (32%) patients and RAS/BRAF mutations in 25 (35%) by dPCR, while they were detected in 7 (10%) and 11 (15%) patients, respectively, by qPCR. PIK3CA mutations were not considered in the analyses as they were only detected in 2 (3%) patients by dPCR and in 1 (1%) patient by qPCR. The use of different dPCR cut-offs for RAS (KRAS/NRAS) and RAS/BRAF analyses translated into differential clinical outcomes. The highest ORR, PFS and OS in wild-type patients with their lowest values in patients with mutations were achieved with a 5% cut-off. We observed similar outcomes in RAS/BRAF wild-type and mutant patients defined by qPCR. Conclusions: High-sensitive dPCR accurately identified patients with KRAS, NRAS, BRAF and PIK3CA mutations. The optimal RAS/BRAF mutational cut-off for outcome prediction is 5%, which explains that the predictive performance of qPCR was not improved by dPCR. The biological and clinical implications of low-frequent mutated alleles warrant further investigations
Enzyme replacement therapy with galsulfase in 34 children younger than five years of age with MPS VI
Background: Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic and multisystem lysosomal storage disease with a wide disease spectrum. Clinical and biochemical improvements have been reported for MPS VI patients on enzyme replacement therapy (ERT) with rhASB (recombinant human arylsulfatase B; galsulfase, Naglazyme (R), BioMarin Pharmaceutical Inc.), making early diagnosis and intervention imperative for optimal patient outcomes. Few studies have included children younger than five years of age. This report describes 34 MPS VI patients that started treatment with galsulfase before five years of age.Methods: Data from patients who initiated treatment at <5 years of age were collected from patients' medical records. Baseline and follow-up assessments of common symptoms that led to diagnosis and that were used to evaluate disease progression and treatment efficacy were evaluated.Results: A significant negative correlation was seen with treatment with ERT and urinary GAG levels. of those with baseline and follow-up growth data, 47% remained on their pre-treatment growth curve or moved to a higher percentile after treatment. of the 9 patients with baseline and follow-up sleep studies, 5 remained unaffected and 1 patient initially with mild sleep apnea showed improvement. Data regarding cardiac, ophthalmic, central nervous system, hearing, surgical interventions and development are also reported. No patient discontinued treatment due to an adverse event and all that were treatment-emergent resolved.Conclusions: the prescribed dosage of 1 mg/kg IV weekly with galsulfase ERT is shown to be safe and effective in slowing and/or improving certain aspects of the disease, although patients should be closely monitored for complications associated with the natural history of the disease, especially cardiac valve involvement and spinal cord compression. A long-term follow-up investigation of this group of children will provide further information on the benefits of early treatment as well as disease progression and treatment efficacy and safety in this young patient population. (C) 2013 Elsevier Inc. All rights reserved.BioMarin Pharmaceutical Inc.ShireGenzymeBioMarinFiocruz MS, Inst Nacl Saude Mulher Crianca & Adolescente Fern, Ctr Genet Med, BR-22250020 Rio de Janeiro, RJ, BrazilUniv Fed Bahia, Serv Genet Med, Salvador, BA, BrazilHosp Albert Sabin, Fortaleza, Ceara, BrazilUniv Fed Mato Grosso do Sul, Fac Med, Campo Grande, MS USAUniv SĂŁo Paulo, Inst Crianca, SĂŁo Paulo, BrazilHosp Barao de Lucena, Recife, PE, BrazilUniv Fed Parana, Hosp Clin, BR-80060000 Curitiba, Parana, BrazilCtr Reabilitacao Infantil, Natal, RN, BrazilHosp Univ Maranhao, Sao Luis, MA, BrazilUniversidade Federal de SĂŁo Paulo, Ctr Referencia Erros Inatos Metab, SĂŁo Paulo, SP, BrazilHosp SĂŁo Paulo, Enzyme Replacement Therapy Serv, Hosp & Maternidade Celso Pierro, SĂŁo Paulo, BrazilUniv Fed Rio Grande do Norte, HOSPED, Hosp Pediat Prof Heriberto Ferreira Bezerra, Natal, RN, BrazilUniv Fortaleza, Fortaleza, Ceara, BrazilUniv Fed Rio Grande do Norte, BR-59072970 Natal, RN, BrazilUniv Fed Triangulo Mineiro, Uberaba, MG, BrazilHosp Clin Acre, Rio Branco, AC, BrazilUniv Fed Espirito Santo, HUCAM, Vitoria, ES, BrazilUniversidade Federal de SĂŁo Paulo, Ctr Referencia Erros Inatos Metab, SĂŁo Paulo, SP, BrazilHosp SĂŁo Paulo, Enzyme Replacement Therapy Serv, Hosp & Maternidade Celso Pierro, SĂŁo Paulo, BrazilWeb of Scienc
Amber and the Cretaceous Resinous Interval
Amber is fossilized resin that preserves biological remains in exceptional detail, study of which has revolutionized understanding of past terrestrial organisms and habitats from the Early Cretaceous to the present day. Cretaceous amber outcrops are more abundant in the Northern Hemisphere and during an interval of about 54 million years, from the Barremian to the Campanian. The extensive resin production that generated this remarkable amber record may be attributed to the biology of coniferous resin producers, the growth of resiniferous forests in proximity to transitional sedimentary environments, and the dynamics of climate during the Cretaceous. Here we discuss the set of interrelated abiotic and biotic factors potentially involved in resin production during that time. We name this period of mass resin production by conifers during the late Mesozoic, fundamental as an archive of terrestrial life, the `Cretaceous Resinous Interval (CREI).This work was supported by the Spanish Ministerio de Ciencia, InnovaciĂłn y Universidades [research agreement CRE CGL2017-84419 AEI/FEDER, UE] and by the ConsejerĂa de Industria, Turismo, InnovaciĂłn, Transporte y Comercio of the Gobierno de Cantabria through the public enterprise EL SOPLAO S.L. [research agreement #20963 with University of Barcelona and research contract Ref. VAPC 20225428 to CN-IGME CSIC, both 2022â2025]; the Conselho Nacional de Pesquisa (Brazil) [research grand PQ 304529/19â2]; National Geographic Global Exploration Fund Northern Europa [research agreement GEFNE 127-14]; Deutsche Forschungsgemeinschaft (DFG) [research agreement SO 894/6-1]; VolkswagenStiftung [research agreement 90946]; the Secretary of Universities and Research (Government of Catalonia) and by the Horizon 2020 program of research and innovation of the European Union under the Marie-Curie [research contract no. 801370, Beatriu de PinĂłs]; the Secretary of Universities and Research (Government of Catalonia) and the European Social Fund [research contract 2021FI_B2 00003]; this work is a contribution to the grant RYC2021-032907-I, funded by the MCIN/AEI/10.13039/501100011033 and by the European Union ÂŤNextGenerationEUÂť/PRTR; and the National Agency for Research and Development (ANID) Scholarship Program [BECAS CHILE 2020-Folio 72210321].Abstract
Keywords
1. Introduction
2. Definition of the Cretaceous Resinous Interval
3. Conditional factors on resin production and preservation
3.1. Abiotic factors
3.1.1. Atmospheric gas composition, temperature, and wildfires
3.1.2. Volcanism and changes in sea level
3.1.3. Oceanic physicochemical properties and hurricanes
3.1.4. Climatic overview throughout the CREI
3.2. Biotic factors
4. Present limitations and future directions
5. Conclusions
Funding
Author contributions
Declaration of Competing Interest
Acknowledgements
Appendix A. Supplementary data
Data availability
Reference
Toward understanding and exploiting tumor heterogeneity
The extent of tumor heterogeneity is an emerging theme that researchers are only beginning to understand. How genetic and epigenetic heterogeneity affects tumor evolution and clinical progression is unknown. The precise nature of the environmental factors that influence this heterogeneity is also yet to be characterized. Nature Medicine, Nature Biotechnology and the Volkswagen Foundation organized a meeting focused on identifying the obstacles that need to be overcome to advance translational research in and tumor heterogeneity. Once these key questions were established, the attendees devised potential solutions. Their ideas are presented here
Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in âs = 7 TeV pp collisions with the ATLAS detector
A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fbâ1 of protonâproton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
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