Nonlinear Eigenvalues and Bifurcation Problems for Pucci's Operator

In this paper we extend existing results concerning generalized eigenvalues of Pucci's extremal operators. In the radial case, we also give a complete description of their spectrum, together with an equivalent of Rabinowitz's Global Bifurcation Theorem. This allows us to solve equations involving Pucci's operators

Determinacion de zonas isotermicas y seleccion de estaciones meteorologicas representativas en Aragon como base para la estimacion del impacto del cambio climatico sobre la posible relacion entre mortalidad y temperatura.

Fundamento: En regiones extensas y diversificadas, como Aragón, se cree la necesidad de dividirlas en áreas en función de las variables atmosféricas disponibles, para seleccionar una estación meteorológica representativa. El objeto de este artículo es determinar la existencia de regiones isotérmicas y seleccionar las estaciones representativas con el fin de estudiar la correlación entre variables de temperatura y mortalidad diaria. Métodos: Se seleccionaron datos diarios de temperatura máxima y mínima para el periodo comprendido entre enero de 1987 y diciembre de 2006. Para determinar las zonas isotérmicas se realizó un análisis de conglomerados jerárquicos y un análisis factorial discriminante, así como un tratamiento previo de datos de relleno de lagunas y detección de heterogeneidades en las series climáticas. Se analizaron datos de 93 estaciones (44 en Huesca, 15 en Teruel y 34 en Zaragoza). Resultados: De los resultados del análisis para la regionalización de Aragón extrajimos que un solo factor explica la varianza de cada serie. En temperaturas máximas ese único factor explicó el 93,43% de la varianza y la estación que representó un mayor factor de correlación fue Huesca-Monflorite (correlación=0,984). Para temperaturas mínimas un único factor explicó el 90,88% de la varianza, siendo la estación con mayor factor de correlación Pallaruelo de Monegros (correlación=0,976). Conclusiones: Se consideró que Aragón es una única región isotérmica con una única estación representativa de la variabilidad de las temperaturas, Zaragoza-Aeropuerto, con una correlación en temperaturas máximas de 0,980 y en mínimas de 0,974. Background: In extensive and diversified regions, such as Aragon, it is believed the need to divide them into areas in terms of the available atmospheric variables with a view to select a representative weather station. The objective of this study was to determine the existence of isothermal regions and select representative stations for Aragon in order to carry out further study on the correlation between variables of temperature and daily mortality. Methods: Daily data on maximum and minimum temperature for the period between January 1987 and December 2006 was selected. In order to determine the isothermal areas a cluster analysis and a discriminate factor analysis were carried out along with a data pretreatment of filled gaps and detection of inhomogeneities in the climatic series. We analyzed data from 93 stations (44 in Huesca, 15 in Teruel and 34 in Zaragoza). Results: The results of the analysis for the regionalization of Aragon lead us to conclude that a unique factor explains the variance of each series; at high temperatures one factor explains 93.43% of the variance and the station with the highest correlation factor is Monflorite-Huesca (correlation = 0.984). At low temperatures one factor explains 90.88% of the variance, with Monegros-Pallaruelo being the station that presents the greatest correlation factor (correlation = 0.976). Conclusions: It was felt that Aragon was a unique isothermal region with one unique representative station of the temperature variability, Zaragoza-Airport with a correlation of 0.980 in maximum temperatures and 0.974 minimum

A supercritical elliptic problem in a cylindrical shell

We consider the problem $$-\Delta u=|u|^{p-2}u in \Omega, u=0 on \partial\Omega,$$ where $\Omega:=\{(y,z)\in\mathbb{R}^{m+1}\times\mathbb{R}^{N-m-1}: 0<a<|y|<b<\infty\}$, $0\leq m\leq N-1$ and $N\geq2$. Let $2_{N,m}^{\ast}:=2(N-m)/(N-m-2)$ if $m<N-2$ and $2_{N,m}^{\ast}:=\infty$ if $m=N-2$ or $N-1$. We show that $2_{N,m}^{\ast}$ is the true critical exponent for this problem, and that there exist nontrivial solutions if $2<p<2_{N,m}^{\ast}$ but there are no such solutions if $p\geq2_{N,m}^{\ast}$

Association of retinal neurodegeneration with the progression of cognitive decline in Parkinson’s disease

Retinal thickness may serve as a biomarker in Parkinson’s disease (PD). In this prospective longitudinal study, we aimed to determine if PD patients present accelerated thinning rate in the parafoveal ganglion cell-inner plexiform layer (pfGCIPL) and peripapillary retinal nerve fiber layer (pRNFL) compared to controls. Additionally, we evaluated the relationship between retinal neurodegeneration and clinical progression in PD. A cohort of 156 PD patients and 72 controls underwent retinal optical coherence tomography, visual, and cognitive assessments between February 2015 and December 2021 in two Spanish tertiary hospitals. The pfGCIPL thinning rate was twice as high in PD (β [SE] = −0.58 [0.06]) than in controls (β [SE] = −0.29 [0.06], p < 0.001). In PD, the progression pattern of pfGCIPL atrophy depended on baseline thickness, with slower thinning rates observed in PD patients with pfGCIPL below 89.8 µm. This result was validated with an external dataset from Moorfields Eye Hospital NHS Foundation Trust (AlzEye study). Slow pfGCIPL progressors, characterized by older at baseline, longer disease duration, and worse cognitive and disease stage scores, showed a threefold increase in the rate of cognitive decline (β [SE] = −0.45 [0.19] points/year, p = 0.021) compared to faster progressors. Furthermore, temporal sector pRNFL thinning was accelerated in PD (β time x group [SE] = −0.67 [0.26] μm/year, p = 0.009), demonstrating a close association with cognitive score changes (β [SE] = 0.11 [0.05], p = 0.052). This study suggests that a slower pattern of pfGCIPL tissue loss in PD is linked to more rapid cognitive decline, whereas changes in temporal pRNFL could track cognitive deterioration

First detection of acceleration and deceleration in protostellar Jets? Time variability in the Chamaeleontis II outflows

Context. Kinematical and time variability studies of protostellar jets are fundamental for understanding the dynamics and the physics of these objects. Such studies remain very sporadic, since they require long baselines before they can be accomplished. Alms. We present for the first time a multi-epoch (20 years baseline) kinematical investigation of HH 52, 53, and 54 at optical and near-IR wavelengths, along with medium (optical) and high resolution (NIR) spectroscopic analyses, probing the kinematical and physical time variability conditions of the gas along the flows. Methods. By means of multi-epoch and multi-wavelength narrow-band images, we derived proper motions (PMs), tangential velocities, velocity and flux variability of the knots. Radial velocities and physical parameters of the gas were derived from spectroscopy. Finally, spatial velocities and inclination of the flows were obtained by combining both imaging and spectroscopy. Results. The PM analysis reveals three distinct, partially overlapping outflows. Spatial velocities of the knots vary from 50 km s -1 to 120 km s-1. The inclinations of the three flows are 58 ± 3°, 84 ± 2°, and 67 ± 3° (HH 52, HH 53, and HH 54 flows, respectively). In 20 years, about 60% of the observed knots show some degree of flux variability. Our set of observations apparently indicates acceleration and deceleration in a variety of knots along the jets. For about 20% of the knots, mostly coincident with working surfaces or interacting knots along the flows, a relevant variability in both flux and velocity is observed. We argue that both variabilities are related and that all or part of the kinetic energy lost by the interacting knots is successively radiated. The physical parameters derived from the diagnostics are quite homogeneous along and among the three outflows. The analysis indicates the presence of very light (NH � 103 cm-3), ionised (Te,. � 0.2-0.6), and hot (Te � 14000-26000 K) flows, impacting a denser medium. Several knots are deflected, especially in the HH 52 flow. At least for a couple of them (HH 54 G and GO), the deflection originates from the collision of the two. For the more massive parts of the flow, the deflection is likely the result of the flow collision with a dense cloud or with clumps. Finally, we discuss the possible driving sources of the flows. ©ESO 2009

Detection of dengue virus serotype 2 in aedes aegypti in Quintana Roo, Mexico, 2011

Abstract. In October 2011, the State Health Department announced that several laboratory-confirmed cases of dengue had occurred among residents in two neighborhoods of Benito Juarez, Quintana Roo State, Mexico. To identify the dengue virus serotype(s) temporally and spatially associated with the cases, entomologic-based virus surveillance was initiated in October 2011 in both neighborhoods. Adult mosquitoes were collected from 88 houses by CDCbackpack aspirator, and all female Aedes aegypti L. (n = 419) were individually homogenized and assayed in pools of as many as 10 by reverse transcriptionpolymerase chain reaction (RT-PCR) using dengue virus-specific primers. Five (12%) of 41 pools were positive for dengue virus RNA. The individual mosquitoes that comprised the pools were analyzed separately by RT-PCR using dengue virus serotype-specific primers. Six mosquitoes were positive for dengue virus serotype-2 (DENV-2) RNA, three of which were collected in the same house. The mean number of female Ae. aegypti collected in each house was 4.76 ± 6.19. The overall dengue virus-infection rate in female Ae. aegypti was 1.4%. Interestingly, most (60%) of mosquito females were collected only from 15 (17%) houses. In summary, we provide evidence of recent DENV-2 transmission in Quintana Roo State

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses.

Common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, displays impaired terminal B-cell differentiation and defective antibody responses. Incomplete genetic penetrance and ample phenotypic expressivity in CVID suggest the participation of additional pathogenic mechanisms. Monozygotic (MZ) twins discordant for CVID are uniquely valuable for studying the contribution of epigenetics to the disease. Here, we generate a single-cell epigenomics and transcriptomics census of naïve-to-memory B cell differentiation in a CVID-discordant MZ twin pair. Our analysis identifies DNA methylation, chromatin accessibility and transcriptional defects in memory B-cells mirroring defective cell-cell communication upon activation. These findings are validated in a cohort of CVID patients and healthy donors. Our findings provide a comprehensive multi-omics map of alterations in naïve-to-memory B-cell transition in CVID and indicate links between the epigenome and immune cell cross-talk. Our resource, publicly available at the Human Cell Atlas, gives insight into future diagnosis and treatments of CVID patients.We thank the CERCA Program/Generalitat de Catalunya and the Josep Carreras Foundation for institutional support. This publication is part of the Human Cell Atlas; www.humancellatlas.org/publications. This study was funded by: Spanish Ministry of Science and Innovation (grant number PID2020-117212RB-I00/AEI/10.13038/501100011033) (E.B.), Instituto de Salud Carlos III (ISCIII), Ref. AC18/00057, associated with i-PAD project (ERARE European Union program) (E.B.), the Jeffrey Modell Foundation (E.B.), Wellcome Sanger core funding (grant no. WT206194) (R.V.-T.), the Chan Zuckerberg Initiative (grant 2020-216799) (R.V.-T. and E.B.), an EMBO short-term fellowship (J.R.U.), Fondo de Investigación Sanitaria Instituto de Salud Carlos III (FIS PI16/01605) (L.P.-M.), the Spanish Ministry of Science, Innovation and Universities (SAF2017-89109-P; AEI/FEDER, UE) (H.H.), Instituto de Salud Carlos III, Ministry of Health (PI16/00759) and European Regional Development Fund-European Social Fund—FEDER-FSE) (C.R-G.), Grupo DISA (OA18/017) (C.R.-G.), the UK Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0426) (G.K.) and Medical Research Council (MR/S000437/1) (G.K.). We are indebted to the donors for participating in this research. We thank Antonio Garcia-Gomez for graphical design support, Sarah Teichmann for her useful feedback, Hamish King for helping with single-cell germinal center dataset availability, Xi Chen for performing scATAC-seq analysis, Kirsty Ambridge and Elena Prigmore for their involvement in single-cell RNA library generation, Martin Prete for creating online visualizations for our cell atlas and Esther Castaño and Beatriz Barroso from CCiTUB Cytometry Unit for their support with single-cell sorting and Dr. Carla Gianelli and Dr. Rebeca Rodríguez Pena for the patient follow-up in the CVID cohort

The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer

The natural history of cancers associated with virus exposure is intriguing, since only a minority of human tissues infected with these viruses inevitably progress to cancer. However, the molecular reasons why the infection is controlled or instead progresses to subsequent stages of tumorigenesis are largely unknown. In this article, we provide the first complete DNA methylomes of double-stranded DNA viruses associated with human cancer that might provide important clues to help us understand the described process. Using bisulfite genomic sequencing of multiple clones, we have obtained the DNA methylation status of every CpG dinucleotide in the genome of the Human Papilloma Viruses 16 and 18 and Human Hepatitis B Virus, and in all the transcription start sites of the Epstein-Barr Virus. These viruses are associated with infectious diseases (such as hepatitis B and infectious mononucleosis) and the development of human tumors (cervical, hepatic, and nasopharyngeal cancers, and lymphoma), and are responsible for 1 million deaths worldwide every year. The DNA methylomes presented provide evidence of the dynamic nature of the epigenome in contrast to the genome. We observed that the DNA methylome of these viruses evolves from an unmethylated to a highly methylated genome in association with the progression of the disease, from asymptomatic healthy carriers, through chronically infected tissues and pre-malignant lesions, to the full-blown invasive tumor. The observed DNA methylation changes have a major functional impact on the biological behavior of the viruses