Modelling the valuesphere and the ecosphere: Integrating the decision makers' perspectives into LCA

Methods for Life Cycle Impact Assessment have to cope with two critical aspects, the uncertainty in values and the (unknown) system behaviour. LCA methodology should cope explicitly with these subjective elements. A structured aggregation procedure is proposed that differentiates between the technosphere and the ecosphere and embeds them in the valuesphere. LCA thus becomes a decision support system that models and combines these three spheres. We introduce three structurally identical types of LCA, each based on one coherent but different set of values. These sets of values can be derived from the Cultural Theory and are labeled as ‘egalitarian', ‘individualistic', and ‘hierarchic'. Within Life Cycle Impact Assessment, a damage oriented assessment model is complemented with both a newly developed precautionary indicator designed to address unknown damage and an indicator for the manageability of environmental damages. The indicators for unknown damage and for manageability complete the set of indicators judged to be relevant by decision makers. The weights given to these indicators are also value-dependent. The framework proposed here answers the criticisms that present LCA methodology does not strictly enough separate subjective from objective elements and that it fails to accurately model environmental impact

Simulation and evaluation of freeze-thaw cryoablation scenarios for the treatment of cardiac arrhythmias

BACKGROUND: Cardiac cryoablation is a minimally invasive procedure to treat cardiac arrhythmias by cooling cardiac tissues responsible for the cardiac arrhythmia to freezing temperatures. Although cardiac cryoablation offers a gentler treatment than radiofrequency ablation, longer interventions and higher recurrence rates reduce the clinical acceptance of this technique. Computer models of ablation scenarios allow for a closer examination of temperature distributions in the myocardium and evaluation of specific effects of applied freeze-thaw protocols in a controlled environment. METHODS: In this work multiple intervention scenarios with two freeze-thaw cycles were simulated with varying durations and starting times of the interim thawing phase using a finite element model verified by in-vivo measurements and data from literature. To evaluate the effects of different protocols, transmural temperature distributions and iceball dimensions were compared over time. Cryoadhesion durations of the applicator were estimated in the interim thawing phase with varying thawing phase starting times. In addition, the increase of cooling rates was compared between the freezing phases, and the thawing rates of interim thawing phases were analyzed over transmural depth. RESULTS: It could be shown that the increase of cooling rate, the regions undergoing additional phase changes and depths of selected temperatures depend on the chosen ablation protocol. Only small differences of the estimated cryoadhesion duration were found for ablation scenarios with interim thawing phase start after 90 s freezing. CONCLUSIONS: By the presented model a quantification of effects responsible for cell death is possible, allowing for the analysis and optimization of cryoablation scenarios which contribute to a higher clinical acceptance of cardiac cryoablation

Predicting the disease severity in male individuals with ornithine transcarbamylase deficiency

Objective: Ornithine transcarbamylase deficiency (OTC-D) is an X-linked metabolic disease and the most common urea cycle disorder. Due to high phenotypic heterogeneity, ranging from lethal neonatal hyperammonemic events to moderate symptoms and even asymptomatic individuals, the prediction of the disease course at an early disease stage is very important to individually adjust therapies such as medical treatment or liver transplantation. In this translational study, we developed a severity-adjusted classification system based on in vitro residual enzymatic OTC activity. Methods: Applying a cell-based expression system, residual enzymatic OTC activities of 71 pathogenic OTC variants were spectrophotometrically determined and subsequently correlated with clinical and biochemical outcome parameters of 119 male individuals with OTC-D (mOTC-D) as reported in the UCDC and E-IMD registries. Results: Integration of multiple data sources enabled the establishment of a robust disease prediction model for mOTC-D. Residual enzymatic OTC activity not only correlates with age at first symptoms, initial peak plasma ammonium concentration and frequency of metabolic decompensations but also predicts mortality. The critical threshold of 4.3% residual enzymatic activity distinguishes a severe from an attenuated phenotype. Interpretation: Residual enzymatic OTC activity reliably predicts the disease severity in mOTC-D and could thus serve as a tool for severity-adjusted evaluation of therapeutic strategies and counselling patients and parents

Structure of human cyclin-dependent kinase inhibitor p19INK4d: comparison to known ankyrin-repeat-containing structures and implications for the dysfunction of tumor suppressor p16INK4a

AbstractBackground: The four members of the INK4 gene family (p16INK4a, p15INK4b, p18INK4c and p19INK4d) inhibit the closely related cyclin-dependent kinases CDK4 and CDK6 as part of the regulation of the G1→S transition in the cell-division cycle. Loss of INK4 gene product function, particularly that of p16INK4a, is found in 10–60% of human tumors, suggesting that broadly applicable anticancer therapies might be based on restoration of p16INK4a CDK inhibitory function. Although much less frequent, defects of p19INK4d have also been associated with human cancer (osteosarcomas). The protein structures of some INK4 family members, determined by nuclear magnetic resonance (NMR) spectroscopy and X-ray techniques, have begun to clarify the functional role of p16INK4a and the dysfunction introduced by the mutations associated with human tumors.Results: The crystal structure of human p19INK4d has been determined at 1.8 å resolution using multiple isomorphous replacement methods. The fold of p19INK4d produces an oblong molecule comprising five approximately 32-residue ankyrin-like repeats. The architecture of the protein demonstrates the high structural similarity within the INK4 family. Comparisons to other ankyrin-repeat-containing proteins (GABPβ, 53BP2 and myotrophin) show similar structures with comparable hydrogen-bonding patterns and hydrophobic interactions. Such comparisons highlight the splayed β-loop geometry that is specific to INK4 inhibitors. This geometry is the result of a modified ankyrin structure in the second repeat.Conclusions: Among the INK4 inhibitors, the highest amino acid sequence conservation is found in the helical stacks; this conservation creates a conserved β-loop geometry specific to INK4 inhibitors. Therefore, in addition to models which predict that the conserved helix α6 is responsible for CDK inhibition, a binding mode whereby the loops of INK4 proteins bind to the CDKs should also be considered. A similar loop-based interaction is seen in the complex formed between the ankyrin-repeat-containing protein GABPβ and_GABPα. This mode of binding would be consistent with the observation that p16INK4a is sensitive to deleterious mutations found throughout this tumor suppressor protein; these mutations probably destabilize the three-dimensional structure

Seasonality, drivers, and isotopic composition of soil CO2 fluxes from tropical forests of the Congo Basin

Soil respiration is an important carbon flux and key process determining the net ecosystem production of terrestrial ecosystems. To address the lack of quantification and understanding of seasonality in soil respiration of tropical forests in the Congo Basin, soil CO2 fluxes and potential controlling factors were measured annually in two dominant forest types (lowland and montane) of the Congo Basin over 2 years at varying temporal resolution. Soil CO2 fluxes from the Congo Basin resulted in 3.45 +/- 1.14 and 3.13 +/- 1.22 mu mol CO2 m(-2) s(-1) for lowland and montane forests, respectively. Soil CO2 fluxes in montane forest soils showed a clear seasonality with decreasing flux rates during the dry season. Montane forest soil CO2 fluxes were positively correlated with soil moisture, while CO2 fluxes in the lowland forest were not. Smaller differences of delta C-1(3) values of leaf litter, soil organic carbon (SOC), and soil CO2 indicated that SOC in lowland forests is more decomposed than in montane forests, suggesting that respiration is controlled by C availability rather than environmental factors. In general, C in montane forests was more enriched in C-13 throughout the whole cascade of carbon intake via photosynthesis, litterfall, SOC, and soil CO2 compared to lowland forests, pointing to a more open system. Even though soil CO2 fluxes are similarly high in lowland and montane forests of the Congo Basin, the drivers of them seem to be different, i.e., soil moisture for montane forest and C availability for lowland forest

26Al kinematics: superbubbles following the spiral arms? : Constraints from the statistics of star clusters and HI supershells

High energy resolution spectroscopy of the 1.8 MeV radioactive decay line of 26Al with the SPI instrument on board the INTEGRAL satellite has recently revealed that diffuse 26Al has large velocities in comparison to other components of the interstellar medium in the Milky Way. 26Al shows Galactic rotation in the same sense as the stars and other gas tracers, but reaches excess velocities up to 300 km s−1Peer reviewe

Erratum: SC83288 is a clinical development candidate for the treatment of severe malaria

No abstract available

Properties of Accretion Flows Around Coalescing Supermassive Black Holes

What are the properties of accretion flows in the vicinity of coalescing supermassive black holes (SBHs)? The answer to this question has direct implications for the feasibility of coincident detections of electromagnetic (EM) and gravitational wave (GW) signals from coalescences. Such detections are considered to be the next observational grand challenge that will enable testing general relativity in the strong, nonlinear regime and improve our understanding of evolution and growth of these massive compact objects. In this paper we review the properties of the environment of coalescing binaries in the context of the circumbinary disk and hot, radiatively inefficient accretion flow models and use them to mark the extent of the parameter space spanned by this problem. We report the results from an ongoing, general relativistic, hydrodynamical study of the inspiral and merger of black holes, motivated by the latter scenario. We find that correlated EM+GW oscillations can arise during the inspiral phase followed by the gradual rise and subsequent drop-off in the light curve at the time of coalescence. While there are indications that the latter EM signature is a more robust one, a detection of either signal coincidentally with GWs would be a convincing evidence for an impending SBH binary coalescence. The observability of an EM counterpart in the hot accretion flow scenario depends on the details of a model. In the case of the most massive binaries observable by the Laser Interferometer Space Antenna, upper limits on luminosity imply that they may be identified by EM searches out to z~0.1-1. However, given the radiatively inefficient nature of the gas flow, we speculate that a majority of massive binaries may appear as low luminosity AGN in the local universe.Comment: Revised version accepted to Class. Quantum Grav. for proceedings of 8th LISA Symposium. 15 pages, 3 figures, includes changes suggested in referee report