Solution SERS of an insoluble synthetic organic pigment-quinacridone quinone-employing calixarenes as dispersive cavitands

3 páginas, 5 figuras.A possibility of getting SERS spectra of insoluble aromatic compounds in colloidal silver solutions is described. The method tested for the organic pigment quinacridone quinone consists of dispersing it in calix[n]arenes. The potentials of such cavitands, both as dispersing and as silver functionalization agents, is reported as a function of the substitution in their lower rim and their cavity size.This work has been financially supported by the Ministerio de Ciencia e Innovacio´n of Spain (Projects FIS2007-63065 and CONSOLIDER CSD2007-0058/TCP) and the Comunidad de Madrid (MICROSERES II Project S2009/TIC1476).Peer reviewe

Probabilistic analysis of random nonlinear oscillators subject to small perturbations via probability density functions: Theory and computing

[EN] We study a class of single-degree-of-freedom oscillators whose restoring function is affected by small nonlinearities and excited by stationary Gaussian stochastic processes. We obtain, via the stochastic perturbation technique, approximations of the main statistics of the steady state, which is a random variable, including the first moments, and the correlation and power spectral functions. Additionally, we combine this key information with the principle of maximum entropy to construct approximations of the probability density function of the steady state. We include two numerical examples where the advantages and limitations of the stochastic perturbation method are discussed with regard to certain general properties that must be preservedThis work has been supported by the Spanish Ministerio de Economia, Industria y Competitividad (MINECO), the Agencia Estatal de Investigacion (AEI), and Fondo Europeo de Desarrollo Regional (FEDER UE) Grant PID2020-115270GB-I00. The authors express their deepest thanks and respect to the reviewers for their valuable commentsCortés, J.; López-Navarro, E.; Romero, J.; Roselló, M. (2021). Probabilistic analysis of random nonlinear oscillators subject to small perturbations via probability density functions: Theory and computing. European Physical Journal Plus. 136(7):1-23. https://doi.org/10.1140/epjp/s13360-021-01672-wS1231367W.L. Oberkampf, S.M. De Land, B.M. Rutherford, K.V. Diegert, K.F. Alvin, Error and uncertainty in modeling and simulation. Reliab. Eng. Syst. Saf. 75, 333–357 (2002)T. Soong, Random Differential Equations in Science and Engineering, vol. 103 (Academic Press, New York, 1973)Kloeden, P., Platen, E.: Numerical Solution of Stochastic Differential Equations, Ser. Stochastic Modelling and Applied Probability, vol. 23. Springer, Berlin Heidelberg (1992)J.L. Bogdanoff, J.E. Goldberg, M. Bernard, Response of a simple structure to a random earthquake-type disturbance. Bull. Seismol. Soc. Am. 51, 293–310 (1961)L. Su, G. Ahmadi, Earthquake response of linear continuous structures by the method of evolutionary spectra. Eng. Struct. 10, 47–56 (1988)X. Jin, Y. Tian, Y. Wang, Z. Huang, Explicit expression of stationary response probability density for nonlinear stochastic systems. Acta Mech. 232, 2101–2114 (2021)D. Lobo, T. Ritto, D. Castello, E. Cataldo, Dynamics of a Duffing oscillator with the stiffness modeled as a stochastic process. Int. J. Non-Linear Mech. 116, 273–280 (2019)Y. Lin, G. Cai, Probabilistic Structural Dynamics: Advanced Theory and Applications (McGraw-Hill, Cambridge, 1995)C. To, Nonlinear Random Vibration: Analytical Techniques and Applications (Swets & Zeitlinger, New York, 2000)M. Kaminski, The Stochastic Perturbation Method for Computational Mechanics (Wiley, New York, 2013)J.J. Stoker, Nonlinear Vibrations (Wiley (Interscience), New York, 1950)N. McLachlan, Laplace Transforms and Their Applications to Differential Equations, vol. 103 (Dover Publ. INc., New York, 2014)R.F. Steidel, An Introduction to Mechanical Vibrations (Wiley, New York, 1989)G. Casella, R. Berger, Statistical Inference (Cengage Learning, New Delhi, 2007)H.V. Storch, F.W. Zwiers, Statistical Analysis in Climate Research (Cambridge University Press, Cambridge, 2001)J.V. Michalowicz, J.M. Nichols, F. Bucholtz, Handbook of Differential Entropy (CRC Press, Boca Raton, 2018)H. Banks, H. Shuhua, W. Clayton Thompson, Modelling and Inverse Problems in the Presence of Uncertainty (Ser. Monographs and Research Notes in Mathematics. CRC Press, Boca Raton, 2001)Garg, V.K., Wang, Y.-C.: 1 - signal types, properties, and processes. In: Chen, W.-K. (ed.) The Electrical Engineering Handboo

Neuroinflammation-Related Proteins NOD2 and Spp1 Are Abnormally Upregulated in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown etiology and poorly understood pathophysiology. There is no specific biomarker either for diagnosis or prognosis. The aim of our study was to investigate differentially expressed proteins in the CSF and serum from patients with ALS to determine their role in the disease process and evaluate their utility as diagnostic or prognostic biomarkers. We performed mass spectrometry in the CSF from 3 patients with ALS and 3 healthy controls (HCs). The results were compared with motor cortex dysregulated transcripts obtained from 11patients with sporadic ALS and 8 HCs. Candidate proteins were tested using ELISA in the serum of 123 patients with ALS, 30 patients with Alzheimer disease (AD), 28 patients with frontotemporal dementia (FTD), and 102 HCs. Patients with ALS, AD, and FTD were prospectively recruited from January 2003 to December 2020. A group of age-matched HCs was randomly selected from the Sant Pau Initiative on Neurodegeneration cohort of the Sant Pau Memory Unit. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and osteopontin (Spp1) were differentially expressed in the CSF and the motor cortex transcriptome of patients with ALS compared with that in HCs (p < 0.05). NOD2 and Spp1 levels were significantly higher in sera from patients with ALS than in HCs (p < 0.001). Receiver operating characteristic analysis showed an area under the curve of 0.63 for NOD2 and 0.81 for Spp1. NOD2 levels were significantly lower in patients with AD and FTD than in patients with ALS (p < 0.0001), but we found no significant differences in Spp1 levels between patients with ALS, AD (p = 0.51), and FTD (p = 0.42). We found a negative correlation between Spp1 levels and ALS functional rating scale (r = −0.24, p = 0.009). Our discovery-based approach identified NOD2 as a novel biomarker in ALS and adds evidence to the contribution of Spp1 in the disease process. Both proteins are involved in innate immunity and autophagy and are increased in the serum from patients with ALS. Our data support a relevant role of neuroinflammation in the pathophysiology of the disease and may identify targets for disease-modifying treatments in ALS. Further longitudinal studies should investigate the diagnostic and prognostic value of NOD2 and Spp1 in clinical practice

The Impact Of Rituximab Infusion Protocol On The Long-term Outcome In Anti-musk Myasthenia Gravis

Objective: To evaluate whether the clinical benefit and relapse rates in anti-muscle-specific kinase (MuSK) myasthenia gravis (MG) differ depending on the protocol of rituximab followed. Methods: This retrospective multicentre study in patients with MuSK MG compared three rituximab protocols in terms of clinical status, relapse, changes in treatment, and adverse side effects. The primary effectiveness endpoint was clinical relapse requiring a further infusion of rituximab. Survival curves were estimated using Kaplan-Meier methods and survival analyses were undertaken using Cox proportional-hazards models. Results: Twenty-five patients were included: 11 treated with protocol 4 + 2 (375 mg/m(2)/4 weeks, then monthly for 2 months), five treated with protocol 1 + 1 (two 1 g doses 2 weeks apart), and nine treated with protocol 4 (375 mg/m(2)/4 weeks). Mean follow-up was 5.0 years (SD 3.3). Relapse occurred in 18.2%, 80%, and 33.3%, and mean time to relapse was 3.5 (SD 1.5), 1.1 (SD 0.4), and 2.5 (SD 1.4) years, respectively. Based on Kaplan-Meier estimates, patients treated with protocol 4 + 2 had fewer and later relapses than patients treated with the other two protocols (log-rank test P = 0.0001). Patients treated with protocol 1 + 1 had a higher risk of relapse than patients treated with protocol 4 + 2 (HR 112.8, 95% CI, 5.7-2250.4, P = 0.002). Patients treated with protocol 4 showed a trend to a higher risk of relapse than those treated with protocol 4 + 2 (HR 9.2, 95% CI 0.9-91.8, P = 0.059). InterpretationThis study provides class IV evidence that the 4 + 2 rituximab protocol has a lower clinical relapse rate and produces a more durable response than the 1 + 1 and 4 protocols in patients with MuSK MG

The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer

TCR repertoire; Breast cancer; Clade mutationsRepertori TCR; Càncer de mama; Mutacions cladeRepertorio TCR; Cáncer de mama; Mutaciones cladoThe detailed molecular characterization of lethal cancers is a prerequisite to understanding resistance to therapy and escape from cancer immunoediting. We performed extensive multi-platform profiling of multi-regional metastases in autopsies from 10 patients with therapy-resistant breast cancer. The integrated genomic and immune landscapes show that metastases propagate and evolve as communities of clones, reveal their predicted neo-antigen landscapes, and show that they can accumulate HLA loss of heterozygosity (LOH). The data further identify variable tumor microenvironments and reveal, through analyses of T cell receptor repertoires, that adaptive immune responses appear to co-evolve with the metastatic genomes. These findings reveal in fine detail the landscapes of lethal metastatic breast cancer

Estudio de las variables que inciden en el rendimiento académico de los estudiantes en la asignatura CENE

Con este estudio se pretende profundizar en los posibles factores que pueden influir en el rendimiento académico de los estudiantes que están cursando las asignaturas Construcción de Elementos No Estructurales I y II, en función de las calificaciones obtenidas en otras asignaturas del grado en Arquitectura Técnica impartido en la Universidad de Alicante. La población objeto de estudio corresponde a los estudiantes que han superado los tres primeros cursos del grado en Arquitectura Técnica, entre los cursos académicos 2010-11, 2011-12 y 2012-13. Se ha realizado un estudio descriptivo, inferencial y de correlación entre los resultados de las asignaturas y un posterior análisis de conglomerados que permite agrupar a los estudiantes en distintos conglomerados o clases (taxonomía). Esta clasificación ha permitido identificar en qué asignaturas destaca cada grupo de estudiantes y en cuáles tienen mayores dificultades, atendiendo a los rendimientos obtenidos en CENE I y CENE II. El conocer estos perfiles puede ayudar en la toma de decisiones para la orientación académica de los estudiantes, ayudando a identificar futuras debilidades en función de las características del alumnado

Antibodies against the flotillin-1/2 complex in patients with multiple sclerosis

Lleixa and Caballero-avila et al. report that antibodies targeting the flotillin-1/2 complex are present in a subgroup of patients with multiple sclerosis. Further studies are needed to understand the clinical and pathological relevance of anti-flotillin-1/2 autoantibodies in multiple sclerosis. Multiple sclerosis is a tissue-specific autoimmune disease of the central nervous system in which the antigen(s) remains elusive. Antibodies targeting the flotillin-1/2 complex have been described in 1-2% of the patients in a recent study. Other candidate antigens as anoctamin-2 or neurofascin-155 have been previously described in multiple sclerosis patients, although their clinical relevance remains uncertain. Our study aims to analyse the frequency and clinical relevance of antibodies against neurofascin-155, anoctamin-2 and flotillin-1/2 complex in multiple sclerosis. Serum (n = 252) and CSF (n = 50) samples from 282 multiple sclerosis patients were included in the study. The control group was composed of 260 serum samples (71 healthy donors and 189 with other neuroinflammatory disorders). Anti-flotillin-1/2, anti-anoctamin-2 and anti-neurofascin-155 antibodies were tested by cell-based assays using transfected cells. We identified six multiple sclerosis patients with antibodies against the flotillin-1/2 complex (2.1%) and one multiple sclerosis patient with antibodies against anoctamin-2 (0.35%). All multiple sclerosis patients were negative for anti-neurofascin-155 antibodies. Three of the anti-flotillin-1/2 positive patients showed anti-flotillin-1/2 positivity in other serum samples extracted at different moments of their disease. Immunoglobulin G subclasses of anti-flotillin-1/2 antibodies were predominantly one and three. We confirm that antibodies targeting the flotillin-1/2 complex are present in a subgroup of patients with multiple sclerosis. Further studies are needed to understand the clinical and pathological relevance of anti-flotillin-1/2 autoantibodies in multiple sclerosis

Thrombospondin-1 mediates muscle damage in brachio-cervical inflammatory myopathy and systemic sclerosis

To describe the clinical, serologic and histologic features of a cohort of patients with brachio-cervical inflammatory myopathy (BCIM) associated with systemic sclerosis (SSc) and unravel disease-specific pathophysiologic mechanisms occurring in these patients. We reviewed clinical, immunologic, muscle MRI, nailfold videocapillaroscopy, muscle biopsy, and response to treatment data from 8 patients with BCIM-SSc. We compared cytokine profiles between patients with BCIM-SSc and SSc without muscle involvement and controls. We analyzed the effect of the deregulated cytokines in vitro (fibroblasts, endothelial cells, and muscle cells) and in vivo. All patients with BCIM-SSc presented with muscle weakness involving cervical and proximal muscles of the upper limbs plus Raynaud syndrome, telangiectasia and/or sclerodactilia, hypotonia of the esophagus, and interstitial lung disease. Immunosuppressive treatment stopped the progression of the disease. Muscle biopsy showed pathologic changes including the presence of necrotic fibers, fibrosis, and reduced capillary number and size. Cytokines involved in inflammation, angiogenesis, and fibrosis were deregulated. Thrombospondin-1 (TSP-1), which participates in all these 3 processes, was upregulated in patients with BCIM-SSc. In vitro, TSP-1 and serum of patients with BCIM-SSc promoted proliferation and upregulation of collagen, fibronectin, and transforming growth factor beta in fibroblasts. TSP-1 disrupted vascular network, decreased muscle differentiation, and promoted hypotrophic myotubes. In vivo, TSP-1 increased fibrotic tissue and profibrotic macrophage infiltration in the muscle. Patients with SSc may present with a clinically and pathologically distinct myopathy. A prompt and correct diagnosis has important implications for treatment. Finally, TSP-1 may participate in the pathologic changes observed in muscle

Investigación metodológica y coordinación vertical en las asignaturas del área de construcción en el grado de arquitectura técnica

El trabajo desarrollado consiste en la implantación de una metodología docente basada en la necesidad de coordinación de las asignaturas de construcción. La práctica profesional del Arquitecto Técnico obliga a la planificación estructural en función de la tipología de elementos no estructurales que componen la edificación. Por ello, se ha considerado necesaria la coordinación de ambas disciplinas. Para llevarla a cabo, se ha desarrollado esta metodología docente en las asignaturas de Construcción de Elementos Estructurales y Construcción de elementos no Estructurales, que se imparten en el grado en Arquitectura Técnica. En ambas asignaturas, durante los últimos cursos, se ha trabajado con imágenes en dos y tres dimensiones, pero en esta ocasión se pretende que exista una coordinación entre las soluciones constructivas estructurales y no estructurales. Para ello se ha planteado la necesidad de que los estudiantes se enfrenten a la resolución de detalles constructivos, con una perspectiva tridimensional que es considerada necesaria para entender la interacción de los elementos en las obras de edificación. Para llevar a cabo esta nueva experiencia, los estudiantes han solucionado detalles constructivos complejos y han defendido la solución adoptada exponiendo sus trabajos en el aula y en las zonas comunes del edificio EPS IV