25 research outputs found
Ambiguities in decision-oriented Life Cycle Inventories The Role of mental models
If the complexity of real, socio-economic systems is acknowledged, life cycle inventory analysis (LCI) in life cycle assessment (LCA) cannot be considered as unambiguous, objective, and as an exclusively data and science based attribution of material and energy flows to a product. The paper thus suggests a set of criteria for LCI derived from different scientific disciplines, practice of product design and modelling characteristics of LCI and LCA. A product system with its respective LCI supporting the process of effective and efficient decision-making should ideally be: a) complete, operational, decomposable, non-redundant, minimal, and comparable; b) efficient, i.e., as simple, manageable, transparent, cheap, quick, but still as âadequate' as possible under a functionalistic perspective which takes given economic constraints, material and market characteristics, and the goal and scope of the study into account; c) actor-based when reflecting the decision-makers' action space, risk-level, values, and knowledge (i.e. mental model) in view of the management rules of sustainable development; d) as site- and case-specific as possible, i.e. uses as much site-specific information as possible. This rationale stresses the significance of considering both (i) material and energy flows within the technosphere with regard to the sustainable management rules; (ii) environmental consequences of the environmental interventions on ecosphere. Further, the marginal cost of collecting and computing more and better information about environmental impacts must not exceed the marginal benefits of information for the natural environment. The ratio of environmental benefits to the economic cost of the tool must be efficient compared to other investment options. As a conclusion, in comparative LCAs, the application of equal allocation procedures does not lead to LCA-results on which products made from different materials can be compared in an adequate way. Each product and material must be modelled according to its specific material and market characteristics as well as to its particular management rules for their sustainable use. A generic LCA-methodology including preferences on methodological options is not definabl
Constructing consistent multiscale scenarios by transdisciplinary processes : the case of mountain regions facing global change
Alpine regions in Europe, in particular, face demanding local challenges, e.g., the decline in the agriculture and timber industries, and are also prone to global changes, such as in climate, with potentially severe impacts on tourism. We focus on the Visp region in the Upper Valais, Switzerland, and ask how the process of stakeholder involvement in research practice can contribute to a better understanding of the specific challenges and future development of mountainous regions under global change. Based on a coupled human-environment system (HES) perspective, we carried out a formative scenario analysis to develop a set of scenarios for the future directions of the Visp region. In addition, we linked these regional scenarios to context scenarios developed at the global and Swiss levels via an external consistency analysis. This method allows the coupling of both the scenario building process and the scenarios as such. We used a functional-dynamic approach to theory-practice cooperation, i.e., the involvement of key stakeholders from, for example, tourism, forestry, and administration, differed in type and intensity during the steps of the research process. In our study, we experienced strong problem awareness among the stakeholders concerning the impacts of global change and local challenges. The guiding research question was commonly defined and problem ownership was more or less balanced. We arrived at six multiscale scenarios that open up future trajectories for the Visp region, and present generic strategies to cope with global and local challenges. The results show that local identity, spatial planning, community budget, and demographic development are important steering elements in the regionâs future development. We suggest that method-guided transdisciplinary processes result in a richer picture and a more systemic understanding, which enable a discussion of critical and surprising issues
Formation of cristae and crista junctions in mitochondria depends on antagonism between Fcj1 and Su e/g
Crista junctions (CJs) are important for mitochondrial organization and function, but the molecular basis of their formation and architecture is obscure. We have identified and characterized a mitochondrial membrane protein in yeast, Fcj1 (formation of CJ protein 1), which is specifically enriched in CJs. Cells lacking Fcj1 lack CJs, exhibit concentric stacks of inner membrane in the mitochondrial matrix, and show increased levels of F1FOâATP synthase (F1FO) supercomplexes. Overexpression of Fcj1 leads to increased CJ formation, branching of cristae, enlargement of CJ diameter, and reduced levels of F1FO supercomplexes. Impairment of F1FO oligomer formation by deletion of its subunits e/g (Su e/g) causes CJ diameter enlargement and reduction of cristae tip numbers and promotes cristae branching. Fcj1 and Su e/g genetically interact. We propose a model in which the antagonism between Fcj1 and Su e/g locally modulates the F1FO oligomeric state, thereby controlling membrane curvature of cristae to generate CJs and cristae tips
Methodik
Die vegetationskundliche und strukturelle Zuordnung der Lebensraumtypen erfolgt nach der vorrangig von Braun-Blanquet entwickelten Vegetationsklassifizierung, einer hierarchischen Gliederung der Vegetationstypen (Syntaxonomie), die die Ebenen der Assoziation, des Verbandes, der Ordnung und der Klasse umfasst. Hierbei ist die Assoziation die grundlegende Einheit, in der die Pflanzengesellschaften zusammengefasst werden, die sich durch gleiche charakteristische Arten(gruppen)kombinationen auszeichnen. Der Verband vereinigt Àhnliche Assoziationen. Das sind bereits umfassendere, jedoch standörtlich noch recht einheitliche Vegetationseinheiten. In Ordnungen werden Àhnliche VerbÀnde zusammengefasst. Die Klasse vereinigt Àhnliche Ordnungen
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Measurement of the behavior of liquid MEA and DEA at temperatures from (293.15 to 423.15) K and pressures up to 90 MPa
Densities in the homogeneous liquid phase of (mono-)ethanolamine (MEA) and diethanolamine (DEA) were investigated using a commercially available high-pressure vibrating-tube densimeter (VTD). Due to the melting point of the experimental materials, the setup of the VTD had to be modified by an insulated housing of the entire piping including the pressure pump. The insulated housing could be heated up by a temperature-controlled heating fan. The liquid samples with a purity of (0.9994 or 0.9950) mole fraction, respectively, were decanted within an inert protective argon atmosphere and further degassed by several freezeâpumpâthaw cycles. Density measurements were carried out at temperatures between (293, respectively, 313 and 423) K and at pressures between (5 and 90) MPa. The resulting 140, respectively, 120 data points, explicitly extend the published database for MEA and DEA, with regards to pressure. A comparison with the currently used equations of state for MEA and DEA revealed a maximum relative deviation of â 0.18 % for MEA and â 0.41 % for DEA, each at the highest investigated temperature and pressure. Considering the measurement uncertainties in temperature, pressure, and oscillation period, as well as uncertainties resulting from the calibration and from the impurities of the sample, the combined expanded relative uncertainty (â=â2) in density varied from (0.1027 to 0.1038) % and from (0.1104 to 0.1130) %, respectively. The VTD was previously calibrated by comprehensive measurements of water and helium and had been further validated by measurements with pure propane
Speeds of sound in methanol at temperatures from 233.33 to 353.21 K at pressures up to 20 MPa
We report experimental speeds of sound in methanol. Measurements were conducted at temperatures from 233 to 353 K with pressures up to 20 MPa using the double-path length pulse-echo technique. The relative expanded combined uncertainty (â=â2) in measurement was estimated to vary from 0.012 to 0.014%, considering contributions from temperature, pressure, path length calibration, pulse timing, and purity of the sample. Experimental speeds of sound gained in the scope of this work were compared with the equation of state by de Reuck and Craven, as well as with further data from literature
Constructing Consistent Multiscale Scenarios by Transdisciplinary Processes: the Case of Mountain Regions Facing Global Change
Alpine regions in Europe, in particular, face demanding local challenges, e.g., the decline in the agriculture and timber industries, and are also prone to global changes, such as in climate, with potentially severe impacts on tourism. We focus on the Visp region in the Upper Valais, Switzerland, and ask how the process of stakeholder involvement in research practice can contribute to a better understanding of the specific challenges and future development of mountainous regions under global change. Based on a coupled human-environment system (HES) perspective, we carried out a formative scenario analysis to develop a set of scenarios for the future directions of the Visp region. In addition, we linked these regional scenarios to context scenarios developed at the global and Swiss levels via an external consistency analysis. This method allows the coupling of both the scenario building process and the scenarios as such. We used a functional-dynamic approach to theory-practice cooperation, i.e., the involvement of key stakeholders from, for example, tourism, forestry, and administration, differed in type and intensity during the steps of the research process. In our study, we experienced strong problem awareness among the stakeholders concerning the impacts of global change and local challenges. The guiding research question was commonly defined and problem ownership was more or less balanced. We arrived at six multiscale scenarios that open up future trajectories for the Visp region, and present generic strategies to cope with global and local challenges. The results show that local identity, spatial planning, community budget, and demographic development are important steering elements in the region's future development. We suggest that method-guided transdisciplinary processes result in a richer picture and a more systemic understanding, which enable a discussion of critical and surprising issues
The real type and ideal type of transdisciplinary processes: part Iâtheoretical foundations
Transdisciplinarity integrates or relates different epistemics from science and practice (Mode 2 transdisciplinarity) or from branches of disciplines if interdisciplinary integration is impossible (Mode 1 transdisciplinarity). The paper explains, based on an analysis of the historical development of the Mode 2 transdisciplinarity concept, how transdisciplinary processes link interdisciplinary applied research and multi-stakeholder discourses by facilitating methods. We elaborate on what type of problems may be managed using what knowledge, how this might be accomplished, what types of objectives are desired, and by what organizational means. Thus the paper presents ontology, epistemology, methodology, functionality, and organization of an ideal type of transdisciplinary process. Socially robust orientations are the expected outcomes of this process. These orientations provide science-based, state-of-the-art, socially accepted options of solutions which acknowledge uncertainties and the incompleteness of different forms of epistemics (i.e., of knowing or thought), in particular within the sustainable transitioning of complex real-world problems