Human Smart Landscape: An Adaptive and Synergistic Approach for the “National Park of Cilento, Vallo di Diano and Alburni”

AbstractThe concept of human smart landscape introduces a perspective of research where the landscape identifies a complex system of relationships among the various smart dimensions (smart economy, smart mobility, smart environment, smart people, smart living, smart governance) and different interpretative approaches, overcoming the consideration of territory as a physical–geometrical reality at the service of economic aspects. The paper, starting from the evolution of the landscape's concept, focuses on the management of its complexity in the transformation processes included in the dynamic context of the landscape's cultural values and in the development strategies designed to support and strengthen these values. A multidimensional methodological framework, oriented to the evaluation and valorisation of landscape complex values, has been structured and tested in the National Park of Cilento, Vallo di Diano and Alburni (Italy)

ntegrated Spatial Assessment: a Multidimensional Approach for Sustainable Planning

EnThe paper presents the different steps of a multidimensional methodological approach for supporting the construction of planning choices, starting from the concept of “integrated assessment”. The integration among Problem Structuring Methods, Public Participation, GIS, Multicriteria and Multigroups Decision Support Systems and Geographic Information Systems identifies a decision-making process explored for the transformation strategies definition in the spatial planning field according to sustainable and complex values

Gutachten zum Investitionsverhalten der Strom- und Gasnetzbetreiber im Rahmen des Evaluierungsberichts nach § 33 Abs. 1 ARegV. Endbericht: Projekt im Auftrag der Bundesnetzagentur

[Einleitung] Seit Anfang 2009 unterliegt die leitungsgebundene Energieversorgung in Deutschland der Anreizregulierung, durch die ein effizienter Betrieb von Strom- und Gasnetzen sichergestellt werden soll. Unklar ist allerdings, inwieweit die Anreizregulierung auch die richtigen Rahmenbedingungen für Investitionen in Ersatz und Ausbau der Netze setzt. Vor diesem Hintergrund wird in dem vorliegenden Bericht das Investitionsverhalten der Netzbetreiber untersucht. Zentrale Fragestellungen dieser Untersuchung sind: - Lassen sich relevante Einflussfaktoren auf das Investitionsverhalten der Netzbetreiber identifizieren? - Welche Rolle spielt dabei die Unterscheidung nach Art des Netzbetreibers (Verteilnetzbetreiber versus Übertragungs- und Fernleitungsnetzbetreiber, beziehungsweise Strom versus Gas)? - Hat die Einführung der Anreizregulierung ab 2009 einen nachweisbaren Einfluss auf das Investitionsverhalten? Davon unabhängig ist die Frage, ob die Netzbetreiber vor und nach Einführung der Anreizregulierung in ausreichendem Umfang investieren. Dies ist nicht Gegenstand der vorliegenden Untersuchung. Die Untersuchung basiert auf Daten und Informationen zum Investitionsverhalten der Unternehmen, die für eine repräsentative Stichprobe der Netzbetreiber in Deutschland erhoben wurden

Generation of Recombinant Chinese Hamster Ovary Cell Lines by Microinjection

Microinjection is a gene transfer technique enabling partial control of plasmid delivery into the nucleus or cytoplasm of cultured animal cells. Here this method was used to establish various recombinant mammalian cell lines. The injection volume was estimated by fluorescence quantification of injected fluorescein isothyocynate (FITC)-dextran. The DNA concentration and injection pressure were then optimized for microinjection into the nucleus or cytoplasm using a reporter plasmid encoding the green fluorescent protein (GFP). Nuclear microinjection was more sensitive to changes in these two parameters than was cytoplasmic microinjection. Under optimal conditions, 80-90% of the cells were GFP-positive 1day after microinjection into the nucleus or the cytoplasm. Recombinant cell lines were recovered following microinjection or calcium phosphate transfection and analyzed for the level and stability of recombinant protein production. In general, the efficiency of recovery of recombinant cell lines and the stability of reporter protein expression over time were higher following microinjection as compared to CaPi transfection. The results demonstrate the feasibility of using microinjection as a method to generate recombinant cell line

Positive Selection of B Cells Expressing Low Densities of Self-reactive BCRs

B cell tolerance or autoimmunity is determined by selective events. Negative selection of self-reactive B cells is well documented and proven. In contrast, positive selection of conventional B cells is yet to be firmly established. Here, we demonstrate that developing self-reactive B cells are not always highly sensitive to the deletion mechanisms imposed by membrane-bound self-antigens. At low amounts, membrane-bound antigens allow survival of B cells bearing a single high affinity self-reactive B cell receptor (BCR). More importantly, we show that forced allelic inclusion modifies B cell fate; low quantities of self-antigen induce the selection and accumulation of increased numbers of self-reactive B cells with decreased expression of antigen-specific BCRs. By directly measuring antigen binding by intact B cells, we show that the low amounts of self-antigen select self-reactive B cells with a lower association constant. A fraction of these B cells is activated and secretes autoantibodies that form circulating immune complexes with self-antigen. These findings demonstrate that conventional B cells can undergo positive selection and that the fate of a self-reactive B cell depends on the quantity of self-antigen, the number of BCRs engaged, and on its overall antigen-binding avidity, rather than on the affinity of individual BCRs

Discovery of a Companion Candidate in the HD169142 Transition Disk and the Possibility of Multiple Planet Formation

We present L' and J-band high-contrast observations of HD169142, obtained with the VLT/NACO AGPM vector vortex coronagraph and the Gemini Planet Imager, respectively. A source located at 0".156+/-0".032 north of the host star (PA=7.4+/-11.3 degrees) appears in the final reduced L' image. At the distance of the star (~145 pc), this angular separation corresponds to a physical separation of 22.7+/-4.7 AU, locating the source within the recently resolved inner cavity of the transition disk. The source has a brightness of L'=12.2+/-0.5 mag, whereas it is not detected in the J band (J>13.8 mag). If its L' brightness arose solely from the photosphere of a companion and given the J-L' color constraints, it would correspond to a 28-32 MJupiter object at the age of the star, according to the COND models. Ongoing accretion activity of the star suggests, however, that gas is left in the inner disk cavity from which the companion could also be accreting. In this case the object could be lower in mass and its luminosity enhanced by the accretion process and by a circumplanetary disk. A lower mass object is more consistent with the observed cavity width. Finally, the observations enable us to place an upper limit on the L'-band flux of a second companion candidate orbiting in the disk annular gap at ~50 AU, as suggested by millimeter observations. If the second companion is also confirmed, HD169142 might be forming a planetary system, with at least two companions opening gaps and possibly interacting with each other.Comment: Accepted to ApJL, see also Biller et al. 201

Diabetes induced by gain-of-function mutations in the Kir6.1 subunit of the KATP channel

Gain-of-function (GOF) mutations in the pore-forming (Kir6.2) and regulatory (SUR1) subunits of K(ATP) channels have been identified as the most common cause of human neonatal diabetes mellitus. The critical effect of these mutations is confirmed in mice expressing Kir6.2-GOF mutations in pancreatic β cells. A second K(ATP) channel pore-forming subunit, Kir6.1, was originally cloned from the pancreas. Although the prominence of this subunit in the vascular system is well documented, a potential role in pancreatic β cells has not been considered. Here, we show that mice expressing Kir6.1-GOF mutations (Kir6.1[G343D] or Kir6.1[G343D,Q53R]) in pancreatic β cells (under rat-insulin-promoter [Rip] control) develop glucose intolerance and diabetes caused by reduced insulin secretion. We also generated transgenic mice in which a bacterial artificial chromosome (BAC) containing Kir6.1[G343D] is incorporated such that the transgene is only expressed in tissues where Kir6.1 is normally present. Strikingly, BAC-Kir6.1[G343D] mice also show impaired glucose tolerance, as well as reduced glucose- and sulfonylurea-dependent insulin secretion. However, the response to K(+) depolarization is intact in Kir6.1-GOF mice compared with control islets. The presence of native Kir6.1 transcripts was demonstrated in both human and wild-type mouse islets using quantitative real-time PCR. Together, these results implicate the incorporation of native Kir6.1 subunits into pancreatic K(ATP) channels and a contributory role for these subunits in the control of insulin secretion

towards a local comprehensive productive development strategy a methodological proposal for the metropolitan city of naples

Purpose: Identify homogeneous areas for metropolitan cities in order to activate a new governance based on territorial synergistic and symbiotic conditions, thus increasing multidimensional territorial productive processes through spatial planning.Methodology/Approach: The adopted methodology aimed at structuring a Spatial Decision Support System (SDSS) through three main phases: 1) Selection of criteria and indicators; 2) Statistical implementation procedures; 3) Multi-criteria evaluation.Findings: Experimentation of a useful procedure for supporting the elaboration of strategic metropolitan plans oriented to development strategies for achieving a comprehensive territorial productivity. The obtained results can support the selection of territorial opportunities able to integrate complementary local resources and to activate synergies and symbiosis among them, combining tangible and intangible components.Research Limitation/implication: The research is the first step of a more general study that will be improved with the availability of more data, especially with reference to the industrial and economic processes.Originality/Value of paper: Proposal of an approach based on a complete integration between Geographic Information System, Multivariate Analysis and Multi-Criteria Evaluation in order to improve the governance of metropolitan cities

Trypanosoma cruzi Induces Regulatory B Cell Alterations in Patients With Chronic Chagas Disease

The clinical evolution of patients with chronic Chagas disease (CCD) is mainly associated with an excessive inflammation and a defective immunomodulatory profile caused by the interaction between T. cruzi and the host. Regulatory B (Breg) cells exert immune suppression mostly through IL-10 production (B10 cells), but also through IL-10-independent mechanisms. Previously, we demonstrated that CCD patients with cardiomyopathy show changes in the ex vivo Breg cell phenotypic distribution although maintain IL-10 production capacity. Here, we sought to identify potential alterations on Breg cells upon in vitro stimulation. Isolated B cells from CCD patients with or without cardiomyopathy and non-infected (NI) donors were stimulated with T. cruzi lysate or CpG + CD40L, and characterized by flow cytometry based on the expression of CD24, CD27, CD38, and the regulatory molecules IL-10 and PD-L1. IL-10 and IL-17 secretion in the supernatant of B cells was evaluated by ELISA. Data showed that T. cruzi stimulation diminished the expression of CD24 and CD38 on CD27− B cells while reducing the percentage of CD24high inside CD27+ B cells. Furthermore, T. cruzi induced a regulatory B cell phenotype by increasing B10 cells and IL-10 secretion in all the groups. The innate-like B10 cells expansion observed in patients with cardiomyopathy would be associated with CD27− B10 cell subsets, while no predominant phenotype was found in the other groups. Patients with cardiomyopathy also displayed higher IL-17 secretion levels in T. cruzi–activated B cells. CpG + CD40L stimulation revealed that B cells from CCD patients and NI donors had the same ability to differentiate into B10 cells and secrete IL-10 in vitro. Additionally, CCD patients showed an increased frequency of CD24−CD27− B cells and a reduction in the percentage of CD24highCD27+ Breg cells, which appeared to be inversely correlated with the presence of T. cruzi DNA in blood. Finally, CCD patients exhibited a higher frequency of PD-L1+ B cells in T. cruzi–stimulated samples, suggesting that IL-10-independent mechanisms could also be tangled in the control of inflammation. Altogether, our results provide evidence about the potential role of Breg cells in the immune response developed against T. cruzi and its contribution to chronic Chagas cardiomyopathy.Fil: Girard, Magalí Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Ossowski, Micaela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Muñoz Calderon, Arturo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Fernández, Marisa. Instituto Nacional de Parasitología “Dr. Mario Fatala Chabén”; ArgentinaFil: Hernandez Vasquez, Yolanda Maria. Instituto Nacional de Parasitología Dr. Mario Fatala C; ArgentinaFil: Chadi, Raúl. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Ignacio Pirovano; ArgentinaFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin