Search

Im Projekt MAGGIE wurden für das genossenschaftliche historische Stadtquartier „Margaretenau“ in Regensburg Musterlösungen für energieoptimiertes Wohnen mit innovativen Wandaufbauten aus solaraktiven Baukonstruktionen und einer vorhersagebasierten Versorgungstechnologie erforscht. Dazu wurde ein bestehendes Wohngebäude als Demonstrations- und Versuchsobjekt mit einem neuartigen, besonders effizienten Hybridsystem aus Wärmepumpentechnologie und Kraft- Wärme-Kopplung ausgestattet und untersucht, ergänzt durch eine dynamische Wärmelogistik zur Verringerung von Verteilungsverlusten. Das System wurde durch ein neu entwickeltes, allgemein einsetzbares Planungs-, Optimierungs- und Steuerungstool ausgelegt und im Betrieb geregelt. Die in Echtzeit laufende Nachoptimierung des Systems während des Betriebs greift dabei auf reale Monitoringdaten zu. Die Einbindung von Nutzerbedarfsprofilen, Strombörse und Wetterdaten in die Steuerung gestattet einen dynamischen und perspektivischen Anlagenbetrieb zur Maximierung der Solar- und Umweltwärme-Anteile der Energieversorgung und leistet damit einen wirksamen Beitrag zu einem emissionsarmen, klimafreundlichen Gebäudebetrieb. Für die denkmalgerechte Modernisierung der historischen Fassaden wurde ein solaraktives und solaradaptives Außenputzsystem entwickelt und in der Realität getestet. Am Bestandsgebäude kam anstelle eines Wärmedämmverbundsystems ein innovativer Dämmputz mit Mikrohohlglaskugeln zum Einsatz. Die Skalierbarkeit erlaubt eine abschnittsweise Modernisierung des gesamten Ensembles über mehrere Jahre. Durch die hohe Energieeffizienz wird die Warmmiete für die Bewohner der genossenschaftlichen Siedlung durch die Modernisierungsmaßnahmen nicht erhöht, so dass auch nach der Modernisierung ein bezahlbares Wohnen sichergestellt wird.

Funder: Cambridge Arthritis Research Endeavour (CARE), Funder: Leeds NIHR Biomedical Research Centre, Funder: Manchester NIHR Biomedical Research Centre, Funder: National Institute for Health Research; Id: http://dx.doi.org/10.13039/501100000272, Funder: NIHR Manchester BRC; Id: http://dx.doi.org/10.13039/100014653, OBJECTIVES: Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models. METHODS: Genome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)-based heritability estimate (h2 SNP ) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation. RESULTS: We identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10-9 ), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10-45 ) and Wnt signaling (adjusted P = 9.5 × 10-58 ). The heritability of PsA in this cohort was found to be moderate (h2 SNP = 0.63), which was similar to the heritability of PsC (h2 SNP = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data. CONCLUSION: Key biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care.

Cryptorchidism occurs frequently in children with cystic fibrosis. Among boys with cryptorchidism and abrogated mini-puberty, the development of the epididymis and the vas deferens is frequently impaired. This finding suggests that a common cause underlies the abnormal development of Ad spermatogonia and the epididymis. The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette transporter protein that acts as a chloride channel. The CFTR gene has been associated with spermatogenesis and male fertility. In boys with cryptorchidism, prepubertal hypogonadotropic hypogonadism induces suboptimal expression of the ankyrin-like protein gene, ASZ1, the P-element induced wimpy testis-like gene, PIWIL, and CFTR. The abrogated expression of these gene leads to transposon reactivation, and ultimately, infertility. Curative gonadotropin-releasing hormone agonist (GnRHa) treatment stimulates the expression of CFTR and PIWIL3, which play important roles in the development of Ad spermatogonia and fertility. Furthermore, GnRHa stimulates the expression of the epididymal androgen-sensitive genes, CRISP1, WFDC8, SPINK13, and PAX2, which thereby promotes epididymal development. This review focuses on molecular evidence that favors a role for CFTR in cryptorchidism-induced infertility. Based on information available in the literature, we interpreted our RNA-Seq expression data obtained from samples before and after randomized GnRHa treatment in boys with bilateral cryptorchidism. We propose that, in boys with cryptorchidism, CFTR expression is controlled by luteinizing hormone and testosterone. Moreover, CFTR regulates the activities of genes that are important for fertility and Wolffian duct differentiation.RéSUMé: La cryptorchidie survient fréquemment chez les enfants atteints de mucoviscidose et une altération du développement de l’épididyme et du canal déférent a été observée chez les garçons cryptorchides avec une mini-puberté abrogée. Cela suggère que le développement anormal des spermatogonies Ad et de l’épididyme ont une cause commune. CFTR est. une protéine de transport de cassette de liaison à l’ATP qui agit comme un canal chlorure. Plus précisément, le CFTR a été associé à la spermatogenèse et à la fertilité masculine. Chez les garçons cryptorchides, l’hypogonadisme hypogonadotrope prépubère induit une expression sous-optimale d’ASZ1, de quatre gènes PIWIL et de CFTR, entraînant la réactivation des transposons et l’infertilité. Le traitement curatif à la GnRHa stimule l’expression des gènes CFTR et PIWIL3 qui sont importants pour le développement des spermatogonies Ad et la fertilité subséquente. En outre. Le traitement à la GnRHa stimule les gènes épididymaires sensibles aux androgènes CRISP1, WFDC8, SPINK13, PAX2 favorisant le développement de l’épididyme. Cette revue se concentre sur les preuves moléculaires en faveur du rôle du CFTR dans l’infertilité causée par la cryptorchidie. Nous avons interprété les données d’expression de RNAseq obtenues avec des échantillons avant et après un traitement randomisé à la GnRHa chez des garçons cryptorchides bilatéraux dans le contexte des informations disponibles dans la littérature. Nous proposons que chez les garçons cryptorchides, le CFTR est. contrôlé par l’hormone lutéinisante (LH) et la testostérone et influence les activités des gènes qui sont importants pour la fertilité et la différenciation du canal de Wolff.

In view of the growth of clinical risk prediction models using genetic data, there is an increasing need for studies that use appropriate methods to select the optimum number of features from a large number of genetic variants with a high degree of redundancy between features due to linkage disequilibrium (LD). Filter feature selection methods based on information theoretic criteria, are well suited to this challenge and will identify a subset of the original variables that should result in more accurate prediction. However, data collected from cohort studies are often high-dimensional genetic data with potential confounders presenting challenges to feature selection and risk prediction machine learning models. Patients with psoriasis are at high risk of developing a chronic arthritis known as psoriatic arthritis (PsA). The prevalence of PsA in this patient group can be up to 30% and the identification of high risk patients represents an important clinical research which would allow early intervention and a reduction of disability. This also provides us with an ideal scenario for the development of clinical risk prediction models and an opportunity to explore the application of information theoretic criteria methods. In this study, we developed the feature selection and psoriatic arthritis (PsA) risk prediction models that were applied to a cross-sectional genetic dataset of 1462 PsA cases and 1132 cutaneous-only psoriasis (PsC) cases using 2-digit HLA alleles imputed using the SNP2HLA algorithm. We also developed stratification method to mitigate the impact of potential confounder features and illustrate that confounding features impact the feature selection. The mitigated dataset was used in training of seven supervised algorithms. 80% of data was randomly used for training of seven supervised machine learning methods using stratified nested cross validation and 20% was selected randomly as a holdout set for internal validation. The risk prediction models were then further validated in UK Biobank dataset containing data on 1187 participants and a set of features overlapping with the training dataset.Performance of these methods has been evaluated using the area under the curve (AUC), accuracy, precision, recall, F1 score and decision curve analysis(net benefit). The best model is selected based on three criteria: the ‘lowest number of feature subset’ with the ‘maximal average AUC over the nested cross validation’ and good generalisability to the UK Biobank dataset. In the original dataset, with over 100 different bootstraps and seven feature selection (FS) methods, HLA_C_*06 was selected as the most informative genetic variant. When the dataset is mitigated the single most important genetic features based on rank was identified as HLA_B_*27 by the seven different feature selection methods, consistent with previous analyses of this data using regression based methods. However, the predictive accuracy of these single features in post mitigation was found to be moderate (AUC= 0.54 (internal cross validation), AUC=0.53 (internal hold out set), AUC=0.55(external data set)). Sequentially adding additional HLA features based on rank improved the performance of the Random Forest classification model where 20 2-digit features selected by Interaction Capping (ICAP) demonstrated (AUC= 0.61 (internal cross validation), AUC=0.57 (internal hold out set), AUC=0.58 (external dataset)). The stratification method for mitigation of confounding features and filter information theoretic feature selection can be applied to a high dimensional dataset with the potential confounders.

Digitalization has become a megatrend that any strategy needs to take in to account and deal with in great detail. In particular, managers must address the question of how digitalization can be used to seize opportunities and mini-mize risks. This is a guide for the integration of digitalization in strategic management. It is structured along a classic strategy process consisting of three phases: analysis, formulation , and implementation. For each phase, proven strategic management tools are presented and examined from the angle of digitalization. In this context, the concept of business eco systems is gaining in importance, especially in analysing an industry. As digitalization advances, it is becoming increasingly apparent that fixed industry boundaries are breaking down. In a business eco system, both cross-industry and cross-company data and information flows are used in providing customer-oriented products and services. In the context of increasing digitalization, it is important to remember that the purchasing process can often be influenced quickly and easily by several people at various points. Business eco systems also influence the mission and vision of an organization. Informulating their future performance mandate, companies increasingly interact with other organizations. The extent to which they focus on this interaction influences the strategic direction of their new market structures. In addition, «product leadership» and «efficiency optimization» through digitalization have proven themselves to be useful impact directions. Both a strong individualization of services and customer-oriented pricing structures are becoming more important as strategic elements because digitized processes are making them comparatively cost-effective and easier to implement. And, of course, data enhancement as a new service is dominating the interplay of strategy elements. In deploying a strategy, one thing remains constant, even in the age of digitalization: The successful implementation of a strategy requires the attention of all employees, starting with top management. Through acting as rolemodels and engaging in transparent communication, leaders can make a significant contribution to ensuring that strategies are effective and thus contribute to the sustain able success of an organization. The objective and the key results are instruments that are directly applicable for this purpose.

The paper at hand takes the widely used Lotka-Volterra model from biology and transfers it to the supply chain context. The model is used to analyse whether supply chain partners can benefit from symbiotic mutualism. Results show that in certain situations, both mutualism partners disappear from the marketplace, while in other situations, one of the partners survives while the other dies. The model furthermore shows that symbiotic mutualism exists in which both supply chain partners can benefit from the collaboration and a stable coexistence can be reached.

Coopetition, die Kooperation von Wettbewerbern, gewinnt an Bedeutung und gilt als strategische Form der Unternehmensentwicklung. Der Beitrag entwickelt eine Taxonomie für Coopetition, auf deren Grundlage Strategieentscheidungen getroffen werden können. Anhand von Beispielen aus der Logistikbranche werden Handlungsempfehlungen und ein Referenzmodell für die Praxis abgeleitet.

The paper at hand takes the widely used Lotka-Volterra model from biology and transfers it to the supply chain context. The model is used to analyse whether supply chain partners can benefit from symbiotic mutualism. Results show that in certain situations, both mutualism partners disappear from the marketplace, while in other situations, one of the partners survives while the other dies. The model furthermore shows that symbiotic mutualism exists in which both supply chain partners can benefit from the collaboration and a stable coexistence can be reached.

Developmental cell fate specification is a unidirectional process that can be reverted in response to injury or experimental reprogramming. Whether differentiation and de-differentiation trajectories intersect mechanistically is unclear. Here, we performed comparative screening in lineage-related mouse naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), and identified the constitutively expressed zinc finger transcription factor (TF) Zfp281 as a bidirectional regulator of cell state interconversion. We showed that subtle chromatin binding changes in differentiated cells translate into activation of the histone H3 lysine 9 (H3K9) methyltransferase Ehmt1 and stabilization of the zinc finger TF Zic2 at enhancers and promoters. Genetic gain-of-function and loss-of-function experiments confirmed a critical role of Ehmt1 and Zic2 downstream of Zfp281 both in driving exit from the ESC state and in restricting reprogramming of EpiSCs. Our study reveals that cell type-invariant chromatin association of Zfp281 provides an interaction platform for remodeling the cis-regulatory network underlying cellular plasticity.

The prognosis of patients with blast crisis (BC) chronic myeloid leukemia (CML) is still dismal. Allogeneic stem cell transplantation (alloSCT) represents the only curative treatment option, but data on transplant outcomes are scarce. We therefore conducted a retrospective, registry based study of adult patients allografted for BC CML focusing on patients with active disease at transplant and pre-transplant prognostic factors. A total of 170 patients allografted for BC CML after tyrosine kinase inhibitor pre-treatment between 2004 and 2016 were analyzed. Prior to transplant, 95 patients were in remission, whereas 75 patients had active BC. In multivariable analysis of the entire cohort, active BC at transplant was the strongest factor associated with decreased overall survival (OS, HR 1.87, P=0.010) and shorter leukemia-free survival (LFS, HR 1.69, P=0.017). For patients with BC in remission at transplant, advanced age (?45 years), lower performance status (?80%), longer interval from diagnosis BC to transplant (>12 months), myeloablative conditioning, and unrelated donor (UD) transplant were risk factors for inferior survival. In patients with active BC, only UD transplant was significantly associated with prolonged LFS and trended towards improved OS. In summary, survival of patients allografted for BC CML was strongly dependent on the pre-transplant remission status. In patients with remission of BC, conventional prognostic factors remained the major determinants of outcome, whereas in those with active BC at transplant, UD transplantation was associated with prolonged LFS in our study.

Chronic lung allograft dysfunction (CLAD) remains the major obstacle to long‐term survival following lung transplantation (LuTx). Morphologically CLAD is defined by obliterative remodelling of the small airways (bronchiolitis obliterans, BO) as well as a more recently described collagenous obliteration of alveoli with elastosis summarised as alveolar fibroelastosis (AFE). Both patterns are not restricted to pulmonary allografts, but have also been reported following haematopoietic stem cell transplantation (HSCT) and radio chemotherapy (RC). In this study we performed compartment‐specific morphological and molecular analysis of BO and AFE lesions in human CLAD (n = 22), HSCT (n = 29) and RC (n = 6) lung explants, utilising conventional histopathology, laser‐microdissection, PCR techniques and immunohistochemistry to assess fibrosis‐associated gene and protein expression. Three key results emerged from our analysis of fibrosis‐associated genes: (i) generally speaking, “BO is BO”. Despite the varying clinical backgrounds, the molecular characteristics of BO lesions were found to be alike in all groups. (ii) “AFE is AFE”. In all groups of patients suffering from restrictive changes to lung physiology due to AFE there were largely – but not absolutely ‐ identical gene expression patterns. iii) BO concomitant to AFE after LuTx is characterised by an AFE‐like molecular microenvironment, representing the only exception to (i). Additionally, we describe an evolutionary model for the AFE pattern: a non‐specific fibrin‐rich reaction to injury pattern triggers a misguided resolution attempt and eventual progression towards manifest AFE. Our data point towards an absence of classical fibrinolytic enzymes and an alternative fibrin degrading mechanism via macrophages, resulting in fibrous remodelling and restrictive functional changes. These data may serve as diagnostic adjuncts and help to predict the clinical course of respiratory dysfunction in LuTx and HSCT patients. Moreover, analysis of the mechanism of fibrinolysis and fibrogenesis may unveil potential therapeutic targets to alter the course of the eventually fatal lung remodelling.

This paper relates the notion of insight in problem solving to the current debate concerning epistemological and ontological emergence. The psychological school that stresses the relevance of insight for solving certain types of problems has been Gestalt theory. In classical Gestaltist writings, however, there is not much information about the question of whether or not insights are wholes with emergent properties. It is only in the more recent literature that this question is formulated. The present paper provides examples of insight problems (section I). Then it shows how insight was characterized in Gestalt theoretical writings, in particular by K. Duncker (II), and how this relates to the philosophical debate on emergence (III). After presenting two stances in research on problem solving that resemble the positions arguing for epistemological and ontological emergence (IV), I conclude with suggesting an alternative by complementing the basic part-whole framework with bidirectional processes found in perceptual reversals of ambiguous figures (V). In so doing I suggest to understand insight as ‘intersight,’ which is not an emergent whole, but a hinge or switch that mediates between two or more part-whole structures (here: problem and solution)., Philosophy Kitchen - Rivista di filosofia contemporanea, N. 11 (2019): Parti, insiemi, sistemi. Il concetto di emergenza in filosofia

The notion of ontography is characterizable as open-source, both due to its collaborative development, its heterogeneous backgrounds and its broad applicability. In my paper, I concretize these open-source aspects of ontography firstly by redefining it with reference to E. Winkler’s dialogue Die Erkundung der Linie and secondly by applying it to the Gestalttheoretical topics of figure-ground reversals and bidirectional part-whole relations.

Megatrends wie Digitalisierung, Globalisierung und Mobilität bieten vielerlei Chancen, bergen aber auch etliche Gefahren. Die Rahmenbedingungen, unter denen Organisationen funktionsfähig bleiben müssen, werden zunehmend komplexer. Diese Ausgangslage lässt sich mit dem VUCA-Modell beschreiben. V steht für Volatilität, U für Unsicherheit, C für Komplexität und A für Ambiguität, also Mehrdeutigkeit. Daher die häufige Aussage: «Wir leben heute in einer VUCA-Welt.»

„A long-standing dilemma in theories of management surrounds the question of whether effective managerial action is better served by „rational analysis” or „creative intuition“ (Sadler-Smith, 2004, S. 155). Im Strategischen Management hat die rational-analytische Perspektive eine lange Tradition (Mintzberg, Ahlstrand & Lampel, 2009, S. 19). Dabei wird vielfach von einer Überlegenheit gegenüber anderen Ansätzen ausgegangen: „One of the most basic assumptions about management is that systematic and careful analysis yields choices which are superior to those coming from intuitive processes“ (Khatri & Ng, 2000, S. 58). In diesem Kontext kann Intuition als Kontrastkonzept zu Rationalität beziehungsweise Analytik verstanden werden. Vermehrt hat Intuition als Untersuchungsgegenstand im Zusammenhang mit Strategieprozessen Beachtung erhalten (Elbanna, Child & Dayan, 2013, S. 149; Hodgkinson et al., 2009, S. 277; Matzler, Uzelac & Bauer, 2014a, S. 252; Sadler-Smith & Burke-Smalley, 2015, S. 10). Damit verbunden ist auch ein Wandel in der normativen Sicht auf Intuition: „Making decisions on the basis of intuition is increasingly viewed as a viable approach in today’s business environment, because few strategic decisions have the advantage of complete, accurate and timely information“ (Elbanna, Child & Dayan, 2013, S. 150). Intuition wurde lange als „Tabuthema“ (Gigerenzer & Gaissmaier, 2015, S. 34) behandelt, mit „Magie“ und „Mystizismus“ verbunden (Matzler, Uzelac & Bauer, 2014a, S. 252) und als „irrational“ und „unzuverlässig“ abgetan (Pretz, 2011, S. 17). Während Intuition über viele Jahre als „Antithese“ zu rationaler Analyse betrachtet wurde (Sadler-Smith & Burke, 2009, S. 239), ist seit einigen Jahren vermehrt ein nüchterner und pragmatischerer Umgang festzustellen. Für Führungspersonen wie CEOs und Verwaltungsräte einerseits, wie auch für die betriebswirtschaftliche Wissenschaft andererseits, ist folgendes Forschungsergebnis von besonderer Relevanz: Unternehmen mit Managern vom Typ „intuitiv-analytisch“ weisen eine deutlich höhere Profitabilität zum Durchschnitt auf als Unternehmen mit Managern vom Typ „analytisch“ respektive vom Typ „intuitiv“ (Matzler, Uzelac & Bauer, 2014b, S. 35). Daraus lässt sich deduktiv die folgende Basisthese ableiten: Strategieprozesse, die sowohl Analytik als auch Intuition berücksichtigen, führen zu besseren Ergebnissen, als solche, die allein auf Analytik oder Intuition basieren. Die bisherige Literatur im Strategischen Management, welche eine ganzheitliche Sicht auf Strategieprozesse zulässt, ist fragmentiert. Es fehlt ein integrierter, auf Forschungsergebnisse abgestützter, theoretischer Bezugsrahmen, welcher sowohl Analytik und Intuition in Strategieprozessen unter Berücksichtigung von Heuristiken und Verzerrungen verknüpft. Die Dissertation hat zum Ziel, für die Wissenschaft einen theoretischen Bezugsrahmen herzuleiten, um bestehende Erkenntnisse in einem Gesamtkonzept zu konsolidieren. Daraus lässt sich gezielt weiterer Forschungsbedarf mit Hypothesen ableiten. Für die Praxis und deren Akteure in Strategieprozessen wie Verwaltungsräte, CEOs, Konzern- und Geschäftsleitungen sowie Unternehmensberatungen kann ein theoretischer Bezugsrahmen hilfreich sein, um ein besseres Verständnis für „gute“ Strategieprozesse zu erhalten. Zudem dient ein Rahmenkonzept der strukturierten Wissensvermittlung in der Aus- und Weiterbildung. Basis für die Herleitung des theoretischen Bezugsrahmens bildet die Literatur. Der empirische Teil der Dissertation ist noch nicht definiert.

Die jüngsten politisch-protektionistischen Entwicklungen sind ein Beispiel für das zuneh­ mend komplexer werdende Marktumfeld. Für das Management von Unternehmen mit internationalen Geschäftsbeziehungen stellt sich Frage: Was sind die Auswirkungen auf die Supply Chain? Im folgenden Beitrag wird ein praktikables Managementtool vorgestellt, das hilft, in vier Schritten tatsächliche Risiken für Märkte und Produktgruppen zu bewerten.

In the past decade, live-cell single molecule imaging studies have provided unique insights on how DNA-binding molecules such as transcription factors explore the nuclear environment to search for and bind to their targets. However, due to technological limitations, single molecule experiments in living specimens have largely been limited to monolayer cell cultures. Lattice light-sheet microscopy overcomes these limitations and has now enabled single molecule imaging within thicker specimens such as embryos. Here we describe a general procedure to perform single molecule imaging in living Drosophila melanogaster embryos using lattice light-sheet microscopy. This protocol allows direct observation of both transcription factor diffusion and binding dynamics. Finally, we illustrate how this Drosophila protocol can be extended to other thick samples using single molecule imaging in live mouse embryos as an example.

Projektleitende von Change-Vorhaben müssen häufig führen, ohne selbst Weisungsbefugnis zu besitzen. Eine solche laterale Führung erfordert ganz besondere Fähigkeiten und Methoden. Das Toolkit stellt eine Methode vor, wie die wichtigsten Promotoren und deren Position im Bezug auf das Veränderungsvorhaben visualisiert werden können.

International audience; European great cities are now facing four major challenges. The first one is about managing drinking water in urban areas (distribution, prices, access and supply). Water management has become the main tool to protect water extraction areas or manage the ground- and surface water in unpolluted areas out of the city. The second challenge concerns the sanitation of waste- and rainwater. The long-term goal implies separation storm water and rainwater more efficiently, without congesting municipal networks during rainy periods and modernizing the processes used to purify industrial and domestic waste water. The third challenge refers to water courses and small urban rivers. Cities now strive to reclaim rivers that were once buried, through reopening them. That goes along with a transformation of riverbanks to large public spaces by pushing back roads and economic activities. The last challenge deals with the urban resilience to flood risks as a new alternative to local flood risk management policies, which are still very much focused on standard and heavy flood protection (dykes, dams, etc.). The first two topics are about the “little water cycle” (water management from the collecting points to the treatment plants before returning to the natural environment). The last two issues relate to the big “natural” cycle of water. The following paper proposes a reflection on strategies by three of the biggest European metropolises in regards to their water management policies and their proceeding -via urban planning projects- to merge the two “water cycles”. The article is based on the result of international projects in which two of the authors have been involved in.

Summary: An electric utility operates the power system on an island, and wishes to implement system upgrades, including the installation of distribution-level solar photovoltaic (PV) arrays and battery energy storage systems (BESS) at various sites around the island. The residential and light commercial loads are dispersed throughout the island, primarily near the coast. Currently five medium-voltage distribution feeders emanate from a single power station, which is located near the coast and accessible from the sea. Two of these feeders are primarily responsible for serving remote customers. Power generation is via four sets of tandem diesel generators. There is no connection to a larger power system from the mainland. Because it is difficult to choose among the many potential upgrade options available, including resource siting and capacity, the DER-CAM+ optimization tool was utilized to provide insight into the characteristics of an optimal solution. The tool is a recent upgrade on DERCAM, itself a product of Lawrence Berkeley National Laboratory's research program. The upgrade includes the ability to model power distribution systems and considers possible investment options, by examining their effect on the cost of energy and on CO2 emissions. In the present study, the addition of PV and BESS at a number of pre-selected sites was considered. The analysis showed that the addition of large PV arrays, with peak power essentially matching the peak load on the system, is economically advantageous. Multiple sites allow larger overall PV deployment than a single site, as a result of distribution system constraints. The analysis also showed that the economics of optimal resource dispatch alone are not sufficient to justify the deployment of battery storage. However, battery storage could be mandatory to satisfy operational needs. Further exploration of the optimization surface revealed that, while not optimal, the cost of operation with battery storage is still lower than for the base case of diesel generation only, and not much different from the optimal case.

This paper presents a novel demand response estimation framework for residential and commercial buildings using a combination of EnergyPlus and two-state models for thermostatically controlled loads. Specifically, EnergyPlus models for commercial and multi-dwelling residential units are applied to construct exhaustive datasets (i.e., with more than 300M data points) that capture the detailed load response and complex thermodynamics of several building types. Subsequently, regression models are fit to each dataset to predict DR potential based on key inputs, including hour of day, set point change and outside air temperature. For single residential units, and residential thermostatically controlled loads (i.e. water heaters and refrigerators) a two-state model from the literature is applied. The proposed framework is then validated for commercial buildings through a comparison with a dataset composed of 11 buildings during 12 demand response events. In addition, the use of the proposed simplified DR estimation framework is presented in terms of two cases (1) peak load shed prediction in an individual building and (2) aggregated DR up/down capacity from a large-scale group of different buildings.

Purpose Retinitis pigmentosa (RP) is a progressive retinal degeneration in which the retina loses nearly all of its photoreceptor cells and undergoes major structural changes. Little is known regarding the role the resident glia, the Müller glia, play in the progression of the disease. In this article, we define gene expression changes in Müller glial cells (MGCs) from two different mouse models of RP, the retinal degeneration 1 (rd1) and rhodopsin knockout (Rhod-ko) models. The RNA repertoire of single MGCs was comprehensively profiled, and a comparison was made between MGCs from wild-type (WT) and mutant retinas. Two time points were chosen for analysis, one at the peak of rod photoreceptor death and one during the period of cone photoreceptor death. Methods Retinas were dissociated, and single MGCs were chosen under a dissecting microscope using a micropipette. Single cell cDNAs were generated and genome-wide profiles were obtained by hybridization to Affymetrix arrays. A comparison was made among all samples to discover the changes in gene expression during the periods of rod and cone photoreceptor death. Results MGCs respond to retinal degeneration by undergoing gliosis, a process marked by the upregulation of glial fibrillary acidic protein (Gfap). Many additional transcripts were found to change. These can be placed into functional clusters, such as retinal remodeling, stress response, and immune-related response. Conclusions A high degree of heterogeneity among the individual cells was observed, possibly due to their different spatial proximities to dying cells and/or inherent heterogeneity among MGCs.

Microgrids are an increasingly common component of the evolving electricity grids with the potential to improve local reliability, reduce costs, and increase penetration rates for distributed renewable generation. The additional complexity of microgrids often leads to increased investment costs, creating a barrier for widespread adoption. These costs may result directly from specific needs for islanding detection, protection systems and power quality assurance that would otherwise be avoided in simpler system configurations. However, microgrids also facilitate additional value streams that may make up for their increased costs and improve the economic viability of microgrid deployment. This paper analyses the literature currently available on research relevant to value streams occurring in microgrids that may contribute to offset the increased investment costs. A review on research related to specific microgrid requirements is also presented.

Distributed energy resources gain an increased importance in commercial and industrial building design. Combined heat and power (CHP) units are considered as one of the key technologies for cost and emission reduction in buildings. In order to make optimal decisionson investment and operation for these technologies, detailed system models are needed. These models are often formulated as linear programming problems to keep computational costs and complexity in a reasonable range. However, CHP systems involve variations of the efficiency for large nameplate capacity ranges and in case of part load operation, which can be even of non-linear nature. Since considering these characteristics would turn the models into non23 linear problems, in most cases only constant efficiencies are assumed. This paper proposes possible solutions to address this issue. For a mixed integer linear programming problem two approaches are formulated using binary and Special-Ordered-Set (SOS) variables. Both suggestions have been implemented into the optimization model DER-CAM to simulate investment decisions of CHP micro-turbines and CHP fuel cells with variable efficiencies. The approaches have further been applied successfully in a case study with four different commercial buildings. Comparison of the results between the standard version and the new approaches indicate that total annual system costs remain almost unchanged. System performance is subject to change and storage technologies become more important. Part load operation has mainly been found important for fuel cell units. The micro-turbine is found almost exclusively in full load, thus rendering the application of the new approaches for this technology unnecessary for the considered unit sizes and building types. The approach using binary variables was the most promising method to model variable efficiencies in terms of computational costs and results. It should especially be considered for specific fuel cell technologies. Further investigation on the impacts of this approach on the prediction of fuel cell and micro-turbine performance is suggested.

Studies of mammalian tissue culture cells indicate that the conserved and distinct NDR isoforms, NDR1 and NDR2, play essential cell biological roles. However, mice lacking either Ndr1 or Ndr2 alone develop normally. Here, we studied the physiological consequences of inactivating both NDR1 and NDR2 in mice, showing that the lack of both Ndr1/Ndr2 (called Ndr1/2-double null mutants) causes embryonic lethality. In support of compensatory roles for NDR1 and NDR2, total protein and activating phosphorylation levels of the remaining NDR isoform were elevated in mice lacking either Ndr1 or Ndr2. Mice retaining one single wild-type Ndr allele were viable and fertile. Ndr1/2-double null embryos displayed multiple phenotypes causing a developmental delay from embryonic day E8.5 onwards. While NDR kinases are not required for notochord formation, the somites of Ndr1/2-double null embryos were smaller, irregularly shaped and unevenly spaced along the anterior-posterior axis. Genes implicated in somitogenesis were down-regulated and the normally symmetric expression of Lunatic fringe, a component of the Notch pathway, showed a left-right bias in the last forming somite in 50% of all Ndr1/2-double null embryos. In addition, Ndr1/2-double null embryos developed a heart defect that manifests itself as pericardial edemas, obstructed heart tubes and arrest of cardiac looping. The resulting cardiac insufficiency is the likely cause of the lethality of Ndr1/2-double null embryos around E10. Taken together, we show that NDR kinases compensate for each other in vivo in mouse embryos, explaining why mice deficient for either Ndr1 or Ndr2 are viable. Ndr1/2-double null embryos show defects in somitogenesis and cardiac looping, which reveals their essential functions and shows that the NDR kinases are critically required during the early phase of organogenesis.

Immunoglobulin-derived light chain amyloidosis can occasionally be associated with localized disease. We present a patient with localized lymph node light chain amyloidosis without an underlying monoclonal protein or lymphoproliferative disorder and review the literature of lymph node amyloidosis discussing work-up and risk factors for systemic progression.

Some philosophers enrich their ontological theories with graphical elements. Others declare 'ontography' as coequal or superior to ontology to justify and disclose methodical ways with which being can be modelled or experienced. This article will provide a survey of the idea of ontography. Out of historical instances, a definition will be developed and its applicability be demonstrated by means of an identification of H. Rombach's Strukturontologie as being 'ontographical' according to parts of the definition. The conclusion of this article will suggest further developments for ontography., I castelli di Yale online, volume III, numero 2, 2015

According to Jerne's network hypothesis, the binding site of an anti-idiotypic antibody also represents the internal image of an epitope present on a foreign, or even a self antigen. In recent years, antigen mimicry has been defined at the molecular level for some xeno-antigens. However, until now there has been no demonstration of structural mimicry between a human anti-idiotypic antibody and a self structure. To address this question, we used human IgE as the self structure and a well-defined anti-human IgE mAb (BSW17). We describe the isolation of two anti- idiotypic antibodies specific for the anti-IgE antibody BSW17 from a non-immune human Fab phage display library. Interestingly, these two anti-idiotypic antibodies mimic the same molecular surface region as a previously described IgE peptide mimotope isolated by panning on BSW17, but they cover a much larger epitope on the IgE molecule. Accordingly, immunisation of rabbits with the two anti-idiotypic antibodies induced high-affinity antibodies with the same characteristics as BSW17. Thus, our data demonstrate that it is possible to isolate anti-idiotypic antibodies derived from the human genome without the need for hyperimmunization, and confirm Jerne's hypothesis that both foreign antigens and self structures can be mimicked by our own immunoglobulins.

As renewable energy production increases and the electricity market paradigm changes Demand Response (DR) programs are at the forefront of the effort to reduce peak loads. Another emerging trend is microgrids, which allow for the integration of renewable distributed energy resources (DER) into power systems controlled at the local level. Therefore, the potential of microgrids to participate in DR simultaneously lowering electricity costs and supporting reliable macrogrid operation should be analyzed. Santa Rita “Green” Jail (SRJ), run by the local County government, is a microgrid demonstration project integrating 1MW fuel cell, 1.2MW PV and 2MW 4MWh of electrical storage. The interaction of these DER can save electricity costs and lower demand peaks. As the markets and tariffs for DR are not straightforward an analysis is needed to tap the full potential of the installed infrastructure. As a public sector demonstration project SRJ can encourage broader adaption of DER and electric storage. This report evaluates the potential for DR for SRJ focusing on the value of electric storage under different utility DR programs. Key operating characteristics are determined to ensure viable operation in different use cases. Also, load shed and shift capabilities are evaluated to identify their economic value under DR programs compared to electrical storage. The Distributed Energy Resources Customer Adoption Model (DER-CAM) is able to find the optimal battery operation schedule. DER-CAM was enhanced by DR capabilities and load shed and shift modules to optimize operational behavior based on DER generation, load and DR events. This report demonstrates how much the microgrid can save by participating in DR. It is identified which DR program is most viable and which barriers and success factors must be considered. Finally, the amount of peak load mitigation that can be delivered to the macrogrid by SRJ to help meet national and federal policy targets for DR is presented. Keywords

Connection of electric storage technologies to smartgrids will have substantial implications for building energy systems. Local storage will enable demand response. When connected to buildings, mobile storage devices such as electric vehicles (EVs) are in competition with conventional stationary sources at the building. EVs can change the financial as well as environmental attractiveness of on-site generation (e.g. PV or fuel cells). In order to examine the impact of EVs on building energy costs and CO2 emissions, a distributed-energy-resources adoption problem is formulated as a mixed-integer linear program with minimization of annual building energy costs or CO2 emissions and solved for 2020 technology assumptions. The mixedinteger linear program is applied to a set of 139 different commercial buildings in California and example results as well as the aggregated economic and environmental benefits are reported. Special constraints for the available PV, solar thermal, and EV parking lots at the commercial buildings are considered. The research shows that EV batteries can be used to reduce utility-related energy costs at the smart grid or commercial building due to arbitrage of energy between buildings with different tariffs. However, putting more emphasis on CO2 emissions makes stationary storage more attractive and stationary storage capacities increase while the attractiveness of EVs decreases. The limited availability of EVs at the commercial building decreases the attractiveness of EVs and if PV is chosen by the optimization, then it is mostly used to charge the stationary storage at the commercial building and not the EVs connected to the building.

Connecting electric storage technologies to smartgrids will have substantial implications in building energy systems. Local storage will enable demand response. Mobile storage devices in electric vehicles (EVs) are in direct competition with conventional stationary sources at the building. EVs will change the financial as well as environmental attractiveness of on-site generation (e.g. PV, or fuel cells). In order to examine the impact of EVs on building energy costs and CO2 emissions in 2020, a distributed-energy-resources adoption problem is formulated as a mixed-integer linear program with minimization of annual building energy costs or CO2 emissions. The mixed-integer linear program is applied to a set of 139 different commercial buildings in California and example results as well as the aggregated economic and environmental benefits are reported. The research shows that considering second life of EV batteries might be very beneficial for commercial buildings.

In an effort to create broad access to its optimization software, Lawrence Berkeley National Laboratory (LBNL), in collaboration with the University of California at Davis (UC Davis) and OSISoft, has recently developed a Software as a Service (SaaS) Model for reducing energy costs, cutting peak power demand, and reducing carbon emissions for multipurpose buildings. UC Davis currently collects and stores energy usage data from buildings on its campus. Researchers at LBNL sought to demonstrate that a SaaS application architecture could be built on top of this data system to optimize the scheduling of electricity and heat delivery in the building. The SaaS interface, known as WebOpt, consists of two major parts: a) the investment & planning and b) the operations module, which builds on the investment & planning module. The operational scheduling and load shifting optimization models within the operations module use data from load prediction and electrical grid emissions models to create an optimal operating schedule for the next week, reducing peak electricity consumption while maintaining quality of energy services. LBNL's application also provides facility managers with suggested energy infrastructure investments for achieving their energy cost and emission goals based on historical data collected with OSISoft's system. This paper describes these models as well as the SaaS architecture employed by LBNL researchers to provide asset scheduling services to UC Davis. The peak demand, emissions, and cost implications of the asset operation schedule and investments suggested by this optimization model are analyzed.