Global symplectic coordinates on gradient Kaehler-Ricci solitons

A classical result of D. McDuff asserts that a simply-connected complete Kaehler manifold $(M,g,\omega)$ with non positive sectional curvature admits global symplectic coordinates through a symplectomorphism $\Psi: M\rightarrow R^{2n}$ (where $n$ is the complex dimension of $M$), satisfying the following property (proved by E. Ciriza): the image $\Psi (T)$ of any complex totally geodesic submanifold $T\subset M$ through the point $p$ such that $\Psi(p)=0$, is a complex linear subspace of $C^n \simeq R^{2n}$. The aim of this paper is to exhibit, for all positive integers $n$, examples of $n$-dimensional complete Kaehler manifolds with non-negative sectional curvature globally symplectomorphic to $R^{2n}$ through a symplectomorphism satisfying Ciriza's property.Comment: 8 page

Single-Cell Analysis of Murine Long-Term Hematopoietic Stem Cells Reveals Distinct Patterns of Gene Expression during Fetal Migration

<div><h3>Background</h3><p>Long-term hematopoietic stem cells (LT-HSCs) migrate from the fetal liver (FL) to the fetal bone marrow (FBM) during development. Various adhesion and chemotactic receptor genes have been implicated in the migration of adult LT-HSCs. However, their role in the migration of fetal LT-HSCs is not clearly understood due, in part, to the rare number of these cells in fetal tissues, which preclude classical gene expression analysis. The aim of this study is to characterize the expression of migration related genes in fetal LT-HSC across different anatomical locations during development.</p> <h3>Methodology/Principal Findings</h3><p>We isolated fetal LT-HSC from different developmental stages, as well as different anatomical locations, and performed single-cell multiplex RT-qPCR and flow cytometry analysis of eight molecules involved in adult LT-HSC migration. Our results show that the gene expression of the chemokine receptor <em>Cxcr4</em> in LT-HSC varies across developmental microenvironments and times, while the cadherin <em>Cdh2</em> (<em>Ncad</em>) and the calcium receptor <em>Casr</em> show higher gene expression and variability only in FBM at 17.5 days post coitum (dpc). The cadherin <em>Cdh5</em> (<em>Vecad</em>) maintains high expression variability only during fetal development, while the integrin subunit <em>Itga5 (α5)</em> increases its variability after 14.5 dpc. The integrin subunits <em>Itga4</em> (<em>α4</em>) and <em>Itgal</em> (<em>Lfa1</em>), as well as the selectin ligand <em>Selplg (Psgl1)</em>, did not show differences in their expression in single LT-HSCs irrespective of the developmental times or anatomical microenvironments studied.</p> <h3>Conclusions/Significance</h3><p>Our data demonstrate that the expression pattern of phenotypically identical, single LT-HSCs fluctuates as a function of developmental stage and anatomical microenvironment. This is the first exhaustive gene expression comparison of migration-related molecules in fetal tissues across developmental times, enhancing the understanding of LT-HSC migration fate decisions during development.</p> </div

Bifurcation of critical points for continuous families of C^2 functionals of Fredholm type

Given a continuous family of C^2 functionals of Fredholm type, we show that the non-vanishing of the spectral flow for the family of Hessians along a known (trivial) branch of critical points not only entails bifurcation of nontrivial critical points but also allows to estimate the number of bifurcation points along the branch. We use this result for several parameter bifurcation, estimating the number of connected components of the complement of the set of bifurcation points and apply our results to bifurcation of periodic orbits of Hamiltonian systems. By means of a comparison principle for the spectral flow, we obtain lower bounds for the number of bifurcation points of periodic orbits on a given interval in terms of the coefficients of the linearization

Intrapericardial delivery of apa-microcapsules as promising stem cell therapy carriers in an experimental acute myocardial infarction model

The administration of cardiosphere-derived cells (CDCs) after acute myocardial infarction (AMI) is very promising. CDC encapsulation in alginate-poly-L-lysine-alginate (APA) could increase cell survival and adherence. The intrapericardial (IP) approach potentially achieves high concentrations of the therapeutic agent in the infarcted area. We aimed to evaluate IP therapy using a saline vehicle as a control (CON), a dose of 30 × 106 CDCs (CDCs) or APA microcapsules containing 30 × 106 CDCs (APA-CDCs) at 72 h in a porcine AMI model. Magnetic resonance imaging (MRI) was used to determine the left ventricular ejection fraction (LVEF), infarct size (IS), and indexed end diastolic and systolic volumes (EDVi; ESVi) pre-and 10 weeks post-injection. Programmed electrical stimulation (PES) was performed to test arrhythmia inducibility before euthanasia. Histopathological analysis was carried out afterwards. The IP infusion was successful in all animals. At 10 weeks, MRI revealed significantly higher LVEF in the APA-CDC group compared with CON. No significant differences were observed among groups in IS, EDVi, ESVi, PES and histopathological analyses. In conclusion, the IP injection of CDCs (microencapsulated or not) was feasible and safe 72 h post-AMI in the porcine model. Moreover, CDCs APA encapsulation could have a beneficial effect on cardiac function, reflected by a higher LVEF at 10 weeks. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

¿Por qué la representatividad de la muestra no siempre es importante?

Recientemente hemos constatado que se ha generalizado la idea errónea de que, a fin de que los resultados de un estudio epidemiológico sean generalizables, la muestra a estudio debe ser representativa de la población general. Se trata, desgraciadamente de un error persistente en investigación biomédica que radica en la tergiversación de las definiciones de la estadística descriptiva y la estadística inferencial1 . Dado que no se puede estudiar la población completa, toda investigación debe apoyarse en muestras, más o menos grandes, de esa población. Decimos que una muestra es representativa cuando su estructura en relación a las variables de interés (proporción de varones y mujeres, de expuestos y no expuestos o de sanos y enfermos..., por ejemplo) es la misma que la de la población de la que procede

Development, characterization and sterilisation of Nanocellulose-alginate-(hyaluronic acid)- bioinks and 3D bioprinted scaffolds for tissue engineering

3D-bioprinting is an emerging technology of high potential in tissue engineering (TE), since it shows effective control over scaffold fabrication and cell distribution. Biopolymers such as alginate (Alg), nanofibrillated cellulose (NC) and hyaluronic acid (HA) offer excellent characteristics for use as bioinks due to their excellent biocompatibility and rheological properties. Cell incorporation into the bioink requires sterilisation assurance, and autoclave, β-radiation and γ-radiation are widely used sterilisation techniques in biomedicine; however, their use in 3D-bioprinting for bioinks sterilisation is still in their early stages. In this study, different sterilisation procedures were applied on NC-Alg and NC-Alg-HA bioinks and their effect on several parameters was evaluated. Results demonstrated that NC-Alg and NC-Alg-HA bioinks suffered relevant rheological and physicochemical modifications after sterilisation; yet, it can be concluded that the short cycle autoclave is the best option to sterilise both NC-Alg based cell-free bioinks, and that the incorporation of HA to the NC-Alg bioink improves its characteristics. Additionally, 3D scaffolds were bioprinted and specifically characterized as well as the D1 mesenchymal stromal cells (D1-MSCs) embedded for cell viability analysis. Notably, the addition of HA demonstrates better scaffold properties, together with higher biocompatibility and cell viability in comparison with the NC-Alg scaffolds. Thus, the use of MSCs containing NC-Alg based scaffolds may become a feasible tissue engineering approach for regenerative medicine.Author thanks the Basque Government for granted fellowship to S. Ruiz-Alonso (PRE_2020_2_0143). This study was financially supported by the Basque Country Government (IT907-16), the Ministerio de Economía, Industria y Competitividad (FEDER funds, project RTC-2016- 5451-1), Fundación Mutua Madrileña (project FMM-AP17196-2019), the Instituto de Salud Carlos III, ERDF funds (DTS19/00145) and by the Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía (project no. PY18-2470 and SOMM17/6109/UGR, FEDER Funds). Authors also wish to thank the intellectual and technical assistance from the ICTS “NANBIOSIS”, more specifically by the Drug Formulation Unit (U10) of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) at the University of Basque Country (UPV/ EHU

El Servicio de Validación de Copernicus EMS como vector de mejora de la cartografía de emergencias basada en Sentinel

[EN] The Copernicus Emergency Management Service (CEMS) is coordinated by the European Commission and “provides all actors involved in the management of natural disasters, man-made emergency situations, and humanitarian crises with timely and accurate geo-spatial information derived from satellite remote sensing and complemented by available in situ or open data sources”. It includes two components, Early Warning and Monitoring and Mapping. The latter provides on demand geo-spatial information derived from satellite imagery during all phases of the disaster management cycle. It includes 3 systems, Rapid Mapping (RM), Risk and Recovery Mapping (RRM), and a Validation Service. RM provides geospatial information immediately after a disaster to assess its impact; RRM in the prevention, preparation and reconstruction phases; and the Validation Service is in charge of validating and verifying the products generated by both, and of collecting and analyzing users’ feedback. The wide spectrum of activities framed in the Validation Service has allowed it to become a vector to improve the Mapping component through the testing of new methodologies, data input type, or approach for the creation of emergency cartography in the frame of the CEMS. The present paper introduces the main investigation lines based on Sentinel-1 and 2 for flood and fire monitoring that could be implemented in the CEMS services taking into consideration the characteristics of the Mapping component in terms of products to create and time constraints. The applicability of Sentinel-1 for flood monitoring based on the backscattering, the MultiTemporal Coherence (MTC), and dual polarization; and for burnt area delineation based on MTC was studied, while Sentinel-2 was used for burnt area delineation based on vegetation indices. Results indicate that proposed methodologies might be appropriate for the creation of crisis information products in large areas, due to the relative easy and fast implementation compared to classic photo interpretation, although further applicability analyses should be carried out.[ES] El Servicio de Gestión de Emergencias de Copernicus (CEMS), está coordinado por la Comisión Europea y “provee de información geoespacial precisa y oportuna derivada de la teledetección satelital y completada por fuentes de datos disponibles in situ o abiertas a todos los actores involucrados en la gestión de emergencias, bien sean derivadas de desastres naturales o producidos por el hombre, o de crisis humanitarias”. El servicio tiene dos componentes, uno de alerta temprana y monitoreo y otro de creación de mapas. El servicio de mapeo se encarga de proveer, bajo demanda, a los diferentes agentes de emergencias de información geoespacial derivada de imágenes de satélite en todas las fases de la gestión de emergencias, consta de 3 sistemas, Rapid Mapping (RM), Risk and Recovery Mapping (RRM), y Validation. RM aporta información inmediatamente después de un desastre para evaluar su impacto; RRM en las fases de prevención, preparación y reconstrucción; y la Validación se encarga de validar y verificar los productos generados por ambos, y de recoger y analizar los comentarios de los usuarios. El amplio espectro de actividades enmarcadas en él le ha permitido ser vector de mejora de los servicios de mapeo de emergencias mediante el testeo de nuevas metodologías, tipos de datos, o enfoques para la creación de cartografías de emergencias en el marco de CEMS. El presente artículo describe las principales líneas de investigación en el uso de datos Sentinel-1 y 2 para la monitorización de inundaciones e incendios, que se podrían implementar en el futuro en el marco de CEMS. La aplicabilidad de Sentinel-1 para el monitoreo de inundaciones basado en la retrodispersión, la coherencia multitemporal (MTC) y la polarización dual; y se estudió la delimitación del área quemada basada en MTC. Sentinel-2 se usó para delimitar áreas quemadas en base a índices de vegetación. Los resultados indican que las metodologías propuestas podrían ser apropiadas para la creación de productos de información de crisis en grandes áreas, debido a la implementación relativamente fácil y rápida en comparación con la fotointerpretación clásica, aunque deberían realizarse más análisis para su aplicación en el marco de CEMS.The authors gratefully acknowledge the contribution of Massimiliano Rossi and Antigoni Maistrali for the preparation of the materials analysed in this work.Donezar-Hoyos, U.; Albizua-Huarte, L.; Amezketa-Lizarraga, E.; Barinagarrementeria-Arrese, I.; Ciriza, R.; De Blas-Corral, T.; Larrañaga-Urien, A.... (2020). The Copernicus EMS Validation service as a vector for improving the emergency mapping based on Sentinel data. Revista de Teledetección. 0(56):23-34. https://doi.org/10.4995/raet.2020.13770OJS233405

Optical tweezers in a dusty universe: Modeling optical forces for space tweezers applications

Optical tweezers are powerful tools based on focused laser beams. They are able to trap, manipulate, and investigate a wide range of microscopic and nanoscopic particles in different media, such as liquids, air, and vacuum. Key applications of this contactless technique have been developed in many fields. Despite this progress, optical trapping applications to planetary exploration are still to be developed. Here we describe how optical tweezers can be used to trap and characterize extraterrestrial particulate matter. In particular, we exploit light scattering theory in the T-matrix formalism to calculate radiation pressure and optical trapping properties of a variety of complex particles of astrophysical interest. Our results open perspectives in the investigation of extraterrestrial particles on our planet, in controlled laboratory experiments, aiming for space tweezers applications: optical tweezers used to trap and characterize dust particles in space or on planetary bodies surface

EoE CONNECT, the European Registry of Clinical, Environmental, and Genetic Determinants in Eosinophilic Esophagitis:rationale, design, and study protocol of a large-scale epidemiological study in Europe

BACKGROUND: The growing prevalence of eosinophilic esophagitis (EoE) represents a considerable burden to patients and health care systems. Optimizing cost-effective management and identifying mechanisms for disease onset and progression are required. However, the paucity of large patient cohorts and heterogeneity of practice hinder the defining of optimal management of EoE. METHODS: EoE CONNECT is an ongoing, prospective registry study initiated in 2016 and currently managed by EUREOS, the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract. Patients are managed and treated by their responsible specialists independently. Data recorded using a web-based system include demographic and clinical variables; patient allergies; environmental, intrapartum, and early life exposures; and family background. Symptoms are structurally assessed at every visit; endoscopic features and histological findings are recorded for each examination. Prospective treatment data are registered sequentially, with new sequences created each time a different treatment (active principle, formulation, or dose) is administered to a patient. EoE CONNECT database is actively monitored to ensure the highest data accuracy and the highest scientific and ethical standards. RESULTS: EoE CONNECT is currently being conducted at 39 centers in Europe and enrolls patients of all ages with EoE. In its aim to increase knowledge, to date EoE CONNECT has provided evidence on the effectiveness of first- and second-line therapies for EoE in clinical practice, the ability of proton pump inhibitors to induce disease remission, and factors associated with improved response. Drug effects to reverse fibrous remodeling and endoscopic features of fibrosis in EoE have also been assessed. CONCLUSION: This prospective registry study will provide important information on the epidemiological and clinical aspects of EoE and evidence as to the real-world and long-term effectiveness and safety of therapy. These data will potentially be a vital benchmark for planning future EoE health care services in Europe