Naar een gereedschapskist voor transitiemonitoring: Een verkenning van de bruikbaarheid van methoden, modellen en concepten uit de strategisch management-, diffusie- en sociale netwerkliteratuur

This report explores the applicability of a number of methods, models, and concepts from the literature on strategic management, diffusion, and social networks with respect to the monitoring of transition processes. First, transition theory is analysed to identify aspects that should be monitored. Subsequently, the possible contribution of the various methods, models, and concepts to monitor these aspects is determined. In dit rapport wordt voor een aantal methoden, modellen en concepten uit de strategisch management-, diffusie- en sociale netwerkliteratuur verkend wat de toepassingsmogelijkheden zijn in het kader van transitiemonitoring. Daartoe wordt eerst uit de transitietheorie afgeleid welke aspecten in kaart moeten worden gebracht. Vervolgens wordt voor de verschillende methoden, modellen en concepten nagegaan aan welke toepassingen een bijdrage kan worden geleverd.Institutional and Behavioral Economics,

Relevamiento e interpretación de los recursos ambientales y patrimoniales compartidos en el corredor del Río Uruguay

Este trabajo de investigación capitaliza la experiencia desarrollada durante los años 2010/2011 en el “Plan de Recuperación del Patrimonio hispánico-guaraní en el Corredor del Río Uruguay”; y avanza hacia la profundización de los aspectos vinculados al medio ambiente, la cultura y el turismo desde un enfoque territorial transnacional. Si bien existen estudios particularizados sobre diferentes aspectos que caracterizan áreas, localidades o sectores urbanos del corredor, no se han realizado aún estudios desde una visión integradora. La propuesta para caracterizarlos, a partir de la presente investigación, tanto como un Paisaje Cultural a poner en valor, como un Itinerario cultural compartido con eje en el río Uruguay, constituye un nuevo enfoque para la integración de conocimientos aportados por las diferentes disciplinas concurrentes, a fin de complementar y ampliar con los aportes de los actores locales. El equilibrio entre objetivos sociales, económicos y ambientales del desarrollo sustentable es el argumento central del modelo conceptual que sustenta esta investigación. Se ha caracterizado el territorio del Corredor del bajo Río Uruguay a partir las marcas territoriales evidenciadas, fundamentalmente, en los enclaves patrimoniales relacionados con la producción rural e industrial. El corredor fluvial es un exponente del desarrollo de industrias agroalimentarias,similares en ambas márgenes, que han integrado un mismo sistema político desde las épocas virreinales, con un mismo esquema de explotación de sus recursos y con desarrollos complementarios. El río Uruguay ha sido el motor generador y sustento de las actividades productivas. Como resultado de esta investigación, que involucra el relevamiento de los sistemas de nodos patrimoniales de las localidades en ambas orillas (RA-ROU) del Corredor del bajo Río Uruguay (por ejemplo: Colón-Paysandú/ Concordia-Salto/ Yeruá- Purificación), donde los rasgos ambientales y culturales compartidos podrán interrelacionarse desde la gestión integral del patrimonio, la educación y el turismo, se ha concluido que los enclaves relacionados con la actividad agrícola yganadera, en particular con la industria cárnica presente en exsaladeros, caleras y frigoríficos así como los enclaves agrícolas constituidos históricamente por las colonias de inmigrantes, se reproducen espejadamente en ambas márgenes del río.This research capitalises the investigation carried out during the years 2010/2011, in the “Recovery Plan for Hispanic-Guarani Heritage Corridor of the Uruguay River” fostering all aspects related to the environment, culture and tourism from a transnational territorial approach. Although there are studies on different aspects characterizing areas, locations or urban areas of the corridor in particular, there are no studies from an integrated viewpoint. The proposal of its characterisation, through this research, both as a Cultural landscape to be valued, and as a shared cultural itinerary with axis in the Uruguay River, is a new approach for integrating knowledge provided by the concurrent different disciplines, to complement and expand the contributions of local actors. The balance between social, economic and environmental objectives of sustainable development is thecentral argument of the conceptual model underlying this research.The Corridor of the Uruguay River area has been characterized through territorial marks mainly evidenced on heritage sites related to rural and industrial production, since the river corridor is an example of the development of similar food industries on both sides, which have integrated the same political system from colonial times, with the same pattern of exploitation of its resources and complementary developments, being the Uruguay river the generator engine and support of most production activities. As a result of this research, which involves the survey of the heritage node systems of the localities on both banks (RA-ROU) of the Corridor of the low Uruguay River, for example: Colón-Paysandú / Concordia- Salto / Yeruá- Purification, where the shared environmental and cultural features may interact, from the integrated management of heritage, education and tourism, it has been concluded that the enclaves related to agriculture and livestock, in particular to the meat industry, present in ex salteries, lime kilns and slaughterhouses as well as agricultural enclaves historically constituted by immigrant colonies have reproduce themselves in similar ways on both river banks

Ibrutinib modifies the function of monocyte/macrophage population in chronic lymphocytic leukemia

In lymphoid organs, nurse-like cells (NLCs) show properties of tumor-associated macrophages, playing a crucial role in chronic lymphocytic leukemia (CLL) cell survival. Ibrutinib, a potent inhibitor of Bruton's tyrosine kinase (BTK), is able to counteract pro-survival signals in CLL cells. Since the effects on CLL cells have been studied in the last years, less is known about the influence of ibrutinib on NLCs properties. We sought to determine how ibrutinib modifies NLCs functions focusing on the balance between immunosuppressive and inflammatory features. Our data show that ibrutinib targets BTK expressed by NLCs modifying their phenotype and function. Treatment with ibrutinib reduces the phagocytic ability and increases the immunosuppressive profile of NLCs exacerbating the expression of M2 markers. Accordingly, ibrutinib hampers LPS-mediated signaling, decreasing STAT1 phosphorylation, while allows IL-4-mediated STAT6 phosphorylation. In addition, NLCs treated with ibrutinib are able to protect CLL cells from drug-induced apoptosis partially through the secretion of IL-10. Results from patient samples obtained prior and after 1 month of treatment with ibrutinib show an accentuation of CD206, CD11b and Tie2 in the monocytic population in the peripheral blood. Our study provides new insights into the immunomodulatory action of ibrutinib on monocyte/macrophage population in CLL

Presencia del patrimonio cultural colonial hispánico-guaraní en el corredor del río Uruguay Estudio de caso: Franja costera entre Concepción del Uruguay y Concordia, provincia de Entre Ríos

Este proyecto plantea la investigación, evaluación, valoración, conservación y difusión del patrimonioarqueológico e histórico y su entorno como caso testigo de una tendencia mundial cada vez más afianzada: el estudio del patrimonio cultural y natural como una integridad.La hipótesis plantea que a lo largo del río Uruguay se encuentran una serie de construcciones realizadas en piedra y/o ladrillo en relación con antiguos caminos reales de carretas y de postas sobre una franja de cinco leguas paralela al río Uruguay en sus dos orillas.Se tomó, de manera arbitraria, la región comprendida entre Concordia y Concepción del Uruguay, en particular las localidades de San José, Ubajay y Pto. Yeruá, en la Provincia de Entre Ríos como muestra dentro de un universo mucho más amplio.Esta hipótesis inicial de proyecto de investigación ha sido ampliamente corroborada en los fondos documentales así como en los trabajos de campo realizados. Se ha concluido que al fortalecerseYapeyú como pueblo y centro económico de las misiones jesuíticas durante el período hispánico–guaraní en la costa del río Uruguay, los misioneros comienzan a descender hacia el sur bordeando el Uruguay medio, a lo largo de las dos costas, y a través de los ríos, estableciendo una red de postas, caleras, puestos, puertos y otros establecimientos productivos que comienzan a reportarse en los documentos de archivo a partir de 1747.La construcción de una analítica crítica de fuentes, documentos y cartografía, así como los estudios arqueológicos y arquitectónicos, realizados durante los trabajos de campo han permitido reconstruir conceptualmente la lógica territorial de ocupación del espacio del sistema jesuítico guaraní, entendiendo que cada sitio o conjunto de sitios signados en mapas, se relacionan con pasos del río habituales, redes de caminos, y construcciones como almacenes y otras para apoyar la navegación y el transporte de cargas.Estos hallazgos, en su primera etapa, revelarían que la provincia de Entre Ríos estaría integrada a un corredor cultural que la vincula históricamente con otros sitios de la región, en particular con el antiguo pueblo misionero de Yapeyú, Corrientes

Liquid Crystal-Templated Porous Microparticles via Photopolymerization of Temperature-Induced Droplets in a Binary Liquid Mixture

Porous polymeric microspheres are an emerging class of materials, offering stimuli-responsive cargo uptake and release. Herein, we describe a new approach to fabricate porous microspheres based on temperature-induced droplet formation and light-induced polymerization. Microparticles were prepared by exploiting the partial miscibility of a thermotropic liquid crystal (LC) mixture composed of 4-cyano-4'-pentylbiphenyl (5CB, unreactive mesogens) with 2-methyl-1,4-phenylene bis4-[3-(acryloyloxy)propoxy] benzoate (RM257, reactive mesogens) in methanol (MeOH). Isotropic 5CB/RM257-rich droplets were generated by cooling below the binodal curve (20 °C), and the isotropic-to-nematic transition occurred after cooling below 0 °C. The resulting 5CB/RM257-rich droplets with radial configuration were subsequently polymerized under UV light, resulting in nematic microparticles. Upon heating the mixture, the 5CB mesogens underwent a nematic-isotropic transition and eventually became homogeneous with MeOH, while the polymerized RM257 preserved its radial configuration. Repeated cycles of cooling and heating resulted in swelling and shrinking of the porous microparticles. The use of a reversible materials templating approach to obtain porous microparticles provides new insights into binary liquid manipulation and potential for microparticle production

MAP7 and MUCL1 are biomarkers of Vitamin D3-induced tolerogenic dendritic cells in multiple sclerosis patients

The administration of autologous tolerogenic dendritic cells (tolDC) has become a promising alternative for the treatment of autoimmune diseases, such as multiple sclerosis (MS). Specifically, the use of vitamin D3 for the generation of tolDC (vitD3-tolDC) constitutes one of the most widely studied approaches, as it has evidenced significant immune regulatory properties, both in vitro and in vivo. In this article, we generated human vitD3-tolDC from monocytes from healthy donors and MS patients, characterized in both cases by a semi-mature phenotype, secretion of IL-10 and inhibition of allogeneic lymphocyte proliferation. Additionally, we studied their transcriptomic profile and selected a number of differentially expressed genes compared to control mature and immature dendritic cells for their analysis. Among them, qPCR results validated CYP24A1, MAP7 and MUCL1 genes as biomarkers of vitD3-tolDC in both healthy donors and MS patients. Furthermore, we constructed a network of protein interactions based on the literature, which manifested that MAP7 and MUCL1 genes are both closely connected between them and involved in immune-related functions. In conclusion, this study evidences that MAP7 and MUCL1 constitute robust and potentially functional biomarkers of the generation of vitD3-tolDC, opening the window for their use as quality controls in clinical trials for MS

A new class of exact solutions of the Schrodinger equation

The aim of this paper is to find the exact solutions of the Schrodinger equation. As is known, the Schrodinger equation can be reduced to the continuum equation. In this paper, using the non-linear Legendre transform the equation of continuity is linearized. Particular solutions of such a linear equation are found in the paper and an inverse Legendre transform is considered for them with subsequent construction of solutions of the Schrodinger equation. Examples of the classical and quantum systems are considered.Comment: 26 pages, 34 figure

Genetic, vascular, and amyloid components of cerebral blood flow in a preclinical population

Aging-related cognitive decline can be accelerated by a combination of genetic factors, cardiovascular and cerebrovascular dysfunction, and amyloid-β burden. Whereas cerebral blood flow (CBF) has been studied as a potential early biomarker of cognitive decline, its normal variability in healthy elderly is less known. In this study, we investigated the contribution of genetic, vascular, and amyloid-β components of CBF in a cognitively unimpaired (CU) population of monozygotic older twins. We included 134 participants who underwent arterial spin labeling (ASL) MRI and [18F]flutemetamol amyloid-PET imaging at baseline and after a four-year follow-up. Generalized estimating equations were used to investigate the associations of amyloid burden and white matter hyperintensities with CBF. We showed that, in CU individuals, CBF: 1) has a genetic component, as within-pair similarities in CBF values were moderate and significant (ICC > 0.40); 2) is negatively associated with cerebrovascular damage; and 3) is positively associated with the interaction between cardiovascular risk scores and early amyloid-β burden, which may reflect a vascular compensatory response of CBF to early amyloid-β accumulation. These findings encourage future studies to account for multiple interactions with CBF in disease trajectory analyses

5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer

The authors would like to acknowledge the support of The University of Cambridge, Cancer Research UK (CRUK SEB-Institute Group Award A ref10182; CRUK Senior fellowship C10112/A11388 to AEKI) and Hutchison Whampoa Limited. The Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre. FF is a ULB Professor funded by grants from the F.N.R.S. and Télévie, the IUAP P7/03 programme, the ARC (AUWB-2010-2015 ULB-No 7), the WB Health program and the Fonds Gaston Ithier. Data access: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jpwzvsowiyuamzs&acc=GSE47592Background : The discovery of cytosine hydroxymethylation (5hmC) as a mechanism that potentially controls DNA methylation changes typical of neoplasia prompted us to investigate its behaviour in colon cancer. 5hmC is globally reduced in proliferating cells such as colon tumours and the gut crypt progenitors, from which tumours can arise. Results : Here, we show that colorectal tumours and cancer cells express Ten-Eleven-Translocation (TET) transcripts at levels similar to normal tissues. Genome-wide analyses show that promoters marked by 5hmC in normal tissue, and those identified as TET2 targets in colorectal cancer cells, are resistant to methylation gain in cancer. In vitro studies of TET2 in cancer cells confirm that these promoters are resistant to methylation gain independently of sustained TET2 expression. We also find that a considerable number of the methylation gain-resistant promoters marked by 5hmC in normal colon overlap with those that are marked with poised bivalent histone modifications in embryonic stem cells. Conclusions : Together our results indicate that promoters that acquire 5hmC upon normal colon differentiation are innately resistant to neoplastic hypermethylation by mechanisms that do not require high levels of 5hmC in tumours. Our study highlights the potential of cytosine modifications as biomarkers of cancerous cell proliferation.Publisher PDFPeer reviewe