Different perceptions of adaptation to climate change: a mental model approach applied to the evidence from expert interviews

We argue that differences in the perception and governance of adaptation to climate change and extreme weather events are related to sets of beliefs and concepts through which people understand the environment and which are used to solve the problems they face (mental models). Using data gathered in 31 in-depth interviews with adaptation experts in Europe, we identify five basic stakeholder groups whose divergent aims and logic can be related to different mental models they use: advocacy groups, administration, politicians, researchers, and media and the public. Each of these groups uses specific interpretations of climate change and specifies how to deal with climate change impacts. We suggest that a deeper understanding and follow-up of the identified mental models might be useful for the design of any stakeholder involvement in future climate impact research processes. It might also foster consensus building about adequate adaptation measures against climate threats in a society

Human-computer interaction to human-computer-context interaction : towards a conceptual framework for conducting user studies for shifting interfaces

Computer interfaces have been diversifying: from mobile and wearable technologies to the human body as an interface. Moreover, new sensing possibilities have allowed input to interfaces to go beyond the traditional mouse- and keyboard. This has resulted in a shift from manifest to latent interactions, where interactions between the human and the computer are becoming less visible. Currently, there is no framework available that fully captures the complexity of the multidimensional, multimodal, often latent interactions with these constantly shifting interfaces. In this manuscript, the Hu-man-Computer-Context Interaction (HCCI) framework is proposed. This framework defines 5 relevant interaction levels to be considered during user research in all stages of the new product development process in order to optimize user experience. More specifically, the interaction context is defined in terms of user-object, user-user, user-content, user-platform and user-context interactions. The HCCI framework serves as a concrete tool to use in a new product development process by HCI researchers, design-ers, and developers and aims to be technology independent and future-proof. This framework is a preliminary suggestion to be matched against other innovation devel-opment projects and needs to be further validated

Chemokine Transfer by Liver Sinusoidal Endothelial Cells Contributes to the Recruitment of CD4+ T Cells into the Murine Liver

Leukocyte adhesion and transmigration are central features governing immune surveillance and inflammatory reactions in body tissues. Within the liver sinusoids, chemokines initiate the first crucial step of T-cell migration into the hepatic tissue. We studied molecular mechanisms involved in endothelial chemokine supply during hepatic immune surveillance and liver inflammation and their impact on the recruitment of CD4+ T cells into the liver. In the murine model of Concanavalin A-induced T cell-mediated hepatitis, we showed that hepatic expression of the inflammatory CXC chemokine ligands (CXCL)9 and CXCL10 strongly increased whereas homeostatic CXCL12 significantly decreased. Consistently, CD4+ T cells expressing the CXC chemokine receptor (CXCR)3 accumulated within the inflamed liver tissue. In histology, CXCL9 was associated with liver sinusoidal endothelial cells (LSEC) which represent the first contact site for T-cell immigration into the liver. LSEC actively transferred basolaterally internalized CXCL12, CXCL9 and CXCL10 via clathrin- coated vesicles to CD4+ T cells leading to enhanced transmigration of CXCR4+ total CD4+ T cells and CXCR3+ effector/memory CD4+ T cells, respectively in vitro. LSEC-expressed CXCR4 mediated CXCL12 transport and blockage of endothelial CXCR4 inhibited CXCL12-dependent CD4+ T-cell transmigration. In contrast, CXCR3 was not involved in the endothelial transport of its ligands CXCL9 and CXCL10. The clathrin-specific inhibitor chlorpromazine blocked endothelial chemokine internalization and CD4+ T-cell transmigration in vitro as well as migration of CD4+ T cells into the inflamed liver in vivo. Moreover, hepatic accumulation of CXCR3+ CD4+ T cells during T cell-mediated hepatitis was strongly reduced after administration of chlorpromazine. These data demonstrate that LSEC actively provide perivascularly expressed homeostatic and inflammatory chemokines by CXCR4- and clathrin-dependent intracellular transport mechanisms thereby contributing to the hepatic recruitment of CD4+ T-cell populations during immune surveillance and liver inflammation

Therapeutic implications of improved molecular diagnostics for rare CNS-embryonal tumor entities: results of an international, retrospective study

BACKGROUND: Only few data are available on treatment-associated behavior of distinct rare CNS-embryonal tumor entities previously treated as "CNS-primitive neuroectodermal tumors" (CNS-PNET). Respective data on specific entities, including CNS neuroblastoma, FOXR2 activated (CNS NB-FOXR2), and embryonal tumor with multi-layered rosettes (ETMR) are needed for development of differentiated treatment strategies. METHODS: Within this retrospective, international study, tumor samples of clinically well-annotated patients with the original diagnosis of CNS-PNET were analyzed using DNA methylation arrays (n=307). Additional cases (n=66) with DNA methylation pattern of CNS NB-FOXR2 were included irrespective of initial histological diagnosis. Pooled clinical data (n=292) were descriptively analyzed. RESULTS: DNA methylation profiling of "CNS-PNET" classified 58(19%) cases as ETMR, 57(19%) as HGG, 36(12%) as CNS NB-FOXR2, and 89(29%) cases were classified into 18 other entities. Sixty-seven (22%) cases did not show DNA methylation patterns similar to established CNS tumor reference classes. Best treatment results were achieved for CNS NB-FOXR2 patients (5-year PFS: 63%±7%, OS: 85%±5%, n=63), with 35/42 progression-free survivors after upfront craniospinal irradiation (CSI) and chemotherapy. The worst outcome was seen for ETMR and HGG patients with 5-year PFS of 18%±6% and 22%±7%, and 5-year OS of 24%±6% and 25%±7%, respectively. CONCLUSION: The historically reported poor outcome of CNS-PNET patients becomes highly variable when tumors are molecularly classified based on DNA methylation profiling. Patients with CNS NB-FOXR2 responded well to current treatments and a standard-risk-CSI based regimen may be prospectively evaluated. The poor outcome of ETMR across applied treatment strategies substantiates the necessity for evaluation of novel treatments

Global optimization of bounded factorable functions with discontinuities

A deterministic global optimization method is developed for a class of discontinuous functions. McCormick’s method to obtain relaxations of nonconvex functions is extended to discontinuous factorable functions by representing a discontinuity with a step function. The properties of the relaxations are analyzed in detail; in particular, convergence of the relaxations to the function is established given some assumptions on the bounds derived from interval arithmetic. The obtained convex relaxations are used in a branch-and-bound scheme to formulate lower bounding problems. Furthermore, convergence of the branch-and-bound algorithm for discontinuous functions is analyzed and assumptions are derived to guarantee convergence. A key advantage of the proposed method over reformulating the discontinuous problem as a MINLP or MPEC is avoiding the increase in problem size that slows global optimization. Several numerical examples for the global optimization of functions with discontinuities are presented, including ones taken from process design and equipment sizing as well as discrete-time hybrid systems.Statoil AS

The cluster problem revisited

In continuous branch-and-bound algorithms, a very large number of boxes near global minima may be visited prior to termination. This so-called cluster problem (J Glob Optim 5(3):253–265, 1994) is revisited and a new analysis is presented. Previous results are confirmed, which state that at least second-order convergence of the relaxations is required to overcome the exponential dependence on the termination tolerance. Additionally, it is found that there exists a threshold on the convergence order pre-factor which can eliminate the cluster problem completely for second-order relaxations. This result indicates that, even among relaxations with second-order convergence, behavior in branch-and-bound algorithms may be fundamentally different depending on the pre-factor. A conservative estimate of the pre-factor is given for α BB relaxations