78 research outputs found
Deep-brain stimulation for Parkinson's disease
No full textComment on
N Engl J Med. 2010 Jun 3;362(22):2077-91 author reply 988.Ye
Identification of Room Boundaries for Sound Field Estimation
No full textEchoes generated by the sound reflected off the walls of a room carry information about the geometry of the enclosure. Capitalization of this acoustic property could lead to improvements in current state-of-the-art methods for sound field estimation, where prior information can be used to improve the conditioning of the problem. In this thesis, robust and computational efficient methods are developed for identifying first order reflections to estimate the room geometry using small microphone arrays. Furthermore, as the estimation of such reflections becomes even more challenging in actual audio reproduction systems, this work aims to develop methods capable to deal with complications that might arise due to the employed drivers. This is done by considering the estimation problem in two different scenarios. Firstly, the first order reflections estimation problem is posed as a sorting problem. For this case, a set of echoes, received at different microphones, must be grouped accordingly to the wall which originated them. This problem is solved by using a greedy subspace-based algorithm. The proposed approach provides similar performance compared with the state-of-the-art method at a reduced computational cost. For the second scenario, instead of echoes, only raw microphones measurements are available. This instance of the problem is posed under an estimation theory framework, and solved by sequential minimization of a non-linear cost function based on the propagation of waves. Experimental results, evaluated in simulated shoe-box shaped rooms, demonstrate the performance and applicability of the proposed methods for room geometry estimation.Electrical Engineering, Mathematics and Computer ScienceCircuits and System
Arylchlorocarbenes in the synthesis of heterocycles containing two nitrogen atoms
No full textSubstituted pyrazoles and pyrrolo[1,2-c]pyrimidines were prepared from the reaction of arylchlorocarbenes with 1,2-diazabuta-1,3-dienes and 4-vinylpyrimidines, respectively.PT: J; CR: ATTANASI A, 1998, J ORG CHEM, V63, P9880 ATTANASI OA, 1977, SYNLETT, P1128 ATTANASI OA, 1999, TETRAHEDRON LETT, V40, P3891 BONINI BF, 1981, J CHEM SOC P1, P2322 BONNEAU R, 1999, J PHOTOCH PHOTOBIO A, V126, P31 GRAHAM WH, 1965, J AM CHEM SOC, V87, P4396 KUEHNE ME, 1964, J ORG CHEM, V29, P1582 LIU MTH, 1994, INT J CHEM KINET, V26, P1179 MAIBORODA DA, 1997, J ORG CHEM, V62, P7100 MINGUEZ JM, 1996, J ORG CHEM, V61, P4655 MOYANO EL, 1998, J ORG CHEM, V63, P8188 OVERBERGER CG, 1954, J AM CHEM SOC, V76, P1879 PERKAMPUS HH, 1972, TETRAHEDRON, V28, P2099 ROMASHIN YN, 1999, CHEM COMMUN 0307, P447 ROMASHIN YN, 1999, TETRAHEDRON LETT, V40, P7163 WONG JL, 1965, J ORG CHEM, V30, P2398; NR: 16; TC: 6; J9: CHEM COMMUN; PG: 2; GA: 324XFSource type: Electronic(1
PACTO PRIVADO FEUDAL Y ESTRUCTURA PUBLICA EN LA ORGANIZACION DEL PODER POLITICO EN LA ALTA EDAD MEDIA
No full textThe author upholds the idea of the feudalisation of the kingdom of León being before its time, particularly if we compare it with the feudalisation of the county of Barcelona. But this feudal reality does not prevent us from recognising at the same time the continuation and development of another reality: the concept of royal power which the Visigothic legislation had inherited from Rome. This concept survived in a latent state through the 10th century and began to be revived at the beginning of the 11th century with the decreta of 1017 issued by Alfonso V.El autor sostiene la precocidad de la feudalización del reino de León, sobre todo si la comparamos con la del condado de Barcelona. Pero esta realidad feudal no impide reconocer al mismo tiempo la pervivencia y desarrollo de otra realidad: la concepción del poder real que la legislación visigoda había heredado de Roma; concepción que sobrevive en estado de latencia en el siglo X, e inicia su reactivación a comienzos del siglo XI con los decreta de 1017 dados por Alfonso V
Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity.
No full textIn humans, insulin sensitivity varies according to time of day, with decreased values in the evening and at night. Mechanisms responsible for the diurnal variation in insulin sensitivity are unclear. We investigated whether human adipose tissue (AT) expresses intrinsic circadian rhythms in insulin sensitivity that could contribute to this phenomenon. Subcutaneous and visceral AT biopsies were obtained from extremely obese participants (body mass index, 41.8 ± 6.3 kg/m(2); 46 ± 11 y) during gastric-bypass surgery. To assess the rhythm in insulin signaling, AKT phosphorylation was determined every 4 h over 24 h in vitro in response to different insulin concentrations (0, 1, 10, and 100 nM). Data revealed that subcutaneous AT exhibited robust circadian rhythms in insulin signaling (PThis study was supported by Spanish Government of Economy and Competitiveness (Grant SAF2014–52480-R) and from European Regional Development Fund (ERDF) (to M.G.), Grant SAF2011–22812 (to O.M.-A.), the Seneca Foundation from the Government of Murcia (15123/PI/10; to M.G.), and by U.S. National Institutes of Health Grants R01-DK099512 (National Institute of Diabetes and Digestive and Kidney Diseases) and R01-HL118601 (National Heart, Lung, and Blood Institute) (to F.A.J.L.S.). Author contributions: M. P. Carrasco-Benso conducted the experiments, performed the cultures, analyzed data, and wrote the paper; B. Rivero-Gutierrez performed Western blot experiments; J. Lopez-Minguez performed the cultures; A. Anzola performed Western blot experiments; A. Diez-Noguera analyzed circadian data; J. A. Madrid gave advice for circadian aspects; J. A. Lujan recruited the study participants and performed the biopsies; O. Martínez-Augustin directed the Western blot experiments; and F. A. J. L. Scheer and M. Garaulet designed research, wrote the paper, and have primary responsibility for final content.S
Improving home insurance ratemaking with geographically weighted poisson regression (GWPR) model: Assessing water damage risk
No full textThis study examines the consideration of spatial heterogeneity in the development of Home Insurance rates, specifcally focusing on water damage throughout Spain. This focus arises from the need to establish a methodology that not only improves ratemaking procedures for water damage but also acknowledges the potential impacts of climate change, allowing diferentiation in the efect of variables such as rainfall depending on the location and frequency of water claims. By using the GWPR model, spatial heterogeneity is taken into account and the ratemaking process is enhanced by identifying spatial clusters related to the frequency of water damage claims. Moreover, an empirical development has been carried out employing a database of home insurance data for water coverage in the Spanish territory. The variables selected in this process are not only associated with weather, but also with characteristics of the policies, housing, and socio-economic conditions of the policyholdersGrant: MICIU/AEI/10.13039/501100011033 and by FEDER, UE (PID2022-136547NB-I00). Dr. Roman Minguez-Salido.Grant: MICIU/AEI. FEDER UE (PID2022-136252NB-I00).
Grant: GRIN (2022-GRIN-34336).
Grant: SBPLY (21/180225/000110
Monocyte glycolysis determines CD8+ T cell functionality in human Chagas disease
No full textChagas disease is a life-long pathology resulting from Trypanosoma cruzi infection. It represents one of the most frequent causes of heart failure and sudden death in Latin America. Herein we provide evidence that aerobic glycolytic pathway activation in monocytes drives nitric oxide (NO) production, triggering tyrosine nitration (TN) on CD8 T cells and dysfunction in patients with chronic Chagas disease. Monocytes from patients exhibited higher frequency of hypoxia inducible factor (HIF)-1α and increased expression of its target genes/proteins. Non-classical monocytes are expanded in patients´ peripheral blood and represent an important source of NO. Monocytes entail CD8 T cell surface nitration since both the frequency of non-classical monocytes and that of NO-producing monocytes, positively correlated with the percentage of TN+ lymphocytes. Inhibition of glycolysis in (in vitro) infected peripheral blood mononuclear cells decreased the inflammatory properties of monocytes/macrophages diminishing the frequency of IL-1β- and NO-producing cells. In agreement, glycolysis inhibition reduced the percentage of TN+CD8 T cells improving their functionality. Altogether, these results clearly evidence that glycolysis governs oxidative stress on monocytes and modulates monocyte-T cell interplay in human chronic Chagas disease. Understanding the pathological immune mechanisms that sustains inflammatory environment in human pathology is key to design improved therapies.Fil: Sanmarco, Liliana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Eberhardt, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Bergero, Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Quebrada Palacio, Luz Piedad. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; ArgentinaFil: Martino Adami, Pamela Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Visconti, Laura Marina. Hospital Nuestra Señora de la Misericordia; ArgentinaFil: Minguez, Angel Ramón. Hospital Nuestra Señora de la Misericordia; ArgentinaFil: Hernández-Vasquez, Yolanda. Instituto Nacional de Parasitologia Mario Fatala Chaben; ArgentinaFil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Postan, Miriam. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; ArgentinaFil: Aoki, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin
Contributions from Spatial Models to Non-Life Insurance Pricing: An Empirical Application to Water Damage Risk.
No full textThis paper explores the application of spatial models to non-life insurance data focused on the multi-risk home insurance branch. In the pricing modelling and rating process, spatial information should be considered by actuaries and insurance managers because frequencies and claim sizes may vary by region and the premium should be different considering this rating variable. In addition, it is relevant to examine the spatial dependence due to the fact that the frequency of claims in neighbouring regions is often expected to be more closely related than those in regions far from each other. In this paper, a comparison between spatial models, such as spatial autoregressive models (SAR), the spatial error model (SEM), and the spatial Durbin model (SDM), and a non-spatial model has been developed. The data used for this analysis are for a home insurance portfolio located in Spain, from which we have selected peril of water coverage.904 K
MicroRNA-based classification of hepatocellular carcinoma and oncogenic role of miR-517a
No full textBackground & Aims
Hepatocellular carcinoma (HCC) is a heterogeneous tumor that develops via activation of multiple pathways and molecular alterations. It has been a challenge to identify molecular classes of HCC and design treatment strategies for each specific subtype. MicroRNAs (miRNAs) are involved in HCC pathogenesis, and their expression profiles have been used to classify cancers. We analyzed miRNA expression in human HCC samples to identify molecular subclasses and oncogenic miRNAs.
Methods
We performed miRNA profiling of 89 HCC samples using a ligation-mediated amplification method. Subclasses were identified by unsupervised clustering analysis. We identified molecular features specific for each subclass using expression pattern (Affymetrix U133 2.0; Affymetrix, Santa Clara, CA), DNA change (Affymetrix STY Mapping Array), mutation (CTNNB1), and immunohistochemical (phosphor[p]–protein kinase B, p–insulin growth factor–IR, p-S6, p–epidermal growth factor receptor, β-catenin) analyses. The roles of selected miRNAs were investigated in cell lines and in an orthotopic model of HCC.
Results
We identified 3 main clusters of HCCs: the wingless-type MMTV integration site (32 of 89; 36%), interferon-related (29 of 89; 33%), and proliferation (28 of 89; 31%) subclasses. A subset of patients with tumors in the proliferation subclass (8 of 89; 9%) overexpressed a family of poorly characterized miRNAs from chr19q13.42. Expression of miR-517a and miR-520c (from ch19q13.42) increased proliferation, migration, and invasion of HCC cells in vitro. MiR-517a promoted tumorigenesis and metastatic dissemination in vivo.
Conclusions
We propose miRNA-based classification of 3 subclasses of HCC. Among the proliferation class, miR-517a is an oncogenic miRNA that promotes tumor progression. There is rationale for developing therapies that target miR-517a for patients with HCC
Evaluation of the Performance of the IDvet IFN-Gamma Test for Diagnosis of Bovine Tuberculosis in Spain
No full textAuthor Contributions:
MdC, AB, PP, and JA conceived and performed the statistical analyses. MdC, and JA drafted the manuscript. JN, EP, AG, JS, RD, and OM participated in the generation, collection and curation of the data, and collaborated in interpretation of the results. AP, LdJ, and JA designed the study and coordinated the work. All authors revised critically the manuscript. All authors read and approved the final manuscript.In Spain, the national bovine tuberculosis (bTB) eradication program is based on yearly skin testing of every ≥6 weeks old animal using the single or comparative tuberculin test and parallel use of the interferon-gamma (IFN-γ) assay as an ancillary diagnostic test in infected herds. There are several versions of the latter. Recently, a new commercial IDvet IFN-γ assay has been authorized for use in the program, but there is limited scientific evidence about its performance in different epidemiological settings. Therefore, two studies to evaluate the performance of the IDvet assay were conducted. In study 1, a concordance analysis between the new IDvet and the Bovigam IFN-γ assay in use in Spain for over 10 years was conducted. In study 2, results from the IDvet assay when applied in tandem with a single intradermal tuberculin (SIT) test were used to evaluate the concordance between both tests and to estimate their sensitivity (Se) and specificity (Sp) using a Bayesian latent-class model. Field data from cattle herds located in Madrid and Castilla y Leon (Spain) were collected. For study 1, herd selection was based on a high expected prevalence of reactors to the IFN-γ assay, while herds were selected at random to estimate Se and Sp of the new IDvet assay in study 2. Agreement between the results obtained with both kits for IFN-γ assay was poor (Kappa = 0.20), and a receiver operating characteristic (ROC) analysis indicated a low Se of the new IDvet relative to the Bovigam in a heavily bTB infected population. The Bayesian latent-class analysis estimated the Se of the IDvet assay to be 36.7% [95% probability posterior interval (PPI) 14.7-78.8%] with estimated Sp close to 100% when the cut-off recommended by the manufacturer (35) was applied. At the alternative cut-off values of 16 and 4, the estimated Se of the IDvet assay increased to 49.0% (PPI: 24.8-94.1%) and 56.0% (PPI: 30.8-96.3%), respectively, while maintaining a high specificity. The results suggest that the new IDvet assay may have lower sensitivity than the Bovigam for diagnosis of bTB in cattle herds in Spain, and that adjusting its cut-off might be considered.Comunidad de MadridMinisterio de Economía, Comercio y Empresa ( España)Depto. de Sanidad AnimalCentro de Vigilancia Sanitaria Veterinaria (VISAVET)TRUEpu
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