Prototypes for automating product system model assembly

The International Journal of Life Cycle Assessment - The flexibility of life cycle inventory (LCI) background data selection is increasing with the increasing availability of data, but this comes...     

Overview and recommendations for regionalized life cycle impact assessment

The International Journal of Life Cycle Assessment - Regionalized life cycle impact assessment (LCIA) has rapidly developed in the past decade, though its widespread application, robustness, and...     

4-(3,4-dihydro-1H-isoquinolin-2yl)-pyridines and 4-(3,4-dihydro-1H-isoquinolin-2-yl)-quinolines as potent NR1/2B subtype selective NMDA receptor antagonists

A series of 4-(3,4-dihydro-1H-isoquinolin-2yl)-pyridines and analogous quinolines was prepared and evaluated as NR1/2B subtype selective NMDA receptor antagonists. 2-Hydroxyalkylamino substitution combines high affinity with selectivity (vs alpha1 and M1 receptors) and activity in vivo.     

2-(3,4-Dihydro-1H-isoquinolin-2yl)-pyridines as a novel class of NR1/2B subtype selective NMDA receptor antagonists

Recently, we disclosed 4-aminoquinolines as structurally novel NR1/2B subtype selective NMDA receptor antagonists. We would now like to report our findings on structurally related pyridine analogues. The SAR developed in this series resulted in the discovery of high affinity antagonists which are selective (vs alpha1 and M1 receptors) and active in vivo.     

Regulation by neurotransmitter receptors of serotonergic or catecholaminergic neuronal cell differentiation

The murine F9-derived 1C11 clone exhibits a stable epithelial morphology, expresses nestin, an early neuroectodermal marker, and expresses genes involved in neuroectodermal cell fate. Upon appropriate induction, 100% of 1C11 precursor cells develop neurite extensions and acquire neuronal markers (N-CAM, synaptophysin, gammagamma-enolase, and neurofilament) as well as the general functions of either serotonergic (1C11*(/5HT)) (5HT, 5-hydroxytryptamine) or noradrenergic (1C11**(/NE)) (NE, norepinephrine) neurons. The two programs are shown to be mutually exclusive. 1C11 thus behaves as a neuroepithelial cell line with a dual bioaminergic fate. 1C11*(/5HT) cells implement a functional 5-HT transporter and thereby a complete serotonergic phenotype within 4 days, whereas 5-HT(1B/D), 5-HT(2B), and 5-HT(2A) receptors are sequentially induced. The accurate time schedule of catecholaminergic differentiation was defined. Catecholamine synthesis, storage, and catabolism are acquired within 4 days; the noradrenergic phenotype is complete at day 12 and includes a functional norepinephrine transporter and an alpha(1D)-adrenoreceptor (day 8). The time-dependent onset of neurotransmitter-associated functions proper to either program is similar to in vivo observations. Along each pathway, the selective induction of serotonergic or adrenergic receptors is shown to be an essential part of the differentiation program, since they promote an autoregulation of the corresponding phenotype.     

Binding Characteristics of a Potent AMPA Receptor Antagonist [3H]Ro 48-8587 in Rat Brain

Abstract: A new AMPA receptor antagonist, Ro 48-8587, was characterized pharmacologically in vitro. It is highly potent and selective for AMPA receptors as shown by its effects on [³H]AMPA, [³H]kainate, and [³H]MK-801 binding to rat brain membranes and on AMPA- or NMDA-induced depolarization in rat cortical wedges. [³H]Ro 48-8587 bound with a high affinity ( K _D = 3 n M ) to a single population of binding sites with a B _max of 1 pmol/mg of protein in rat whole brain membranes. [³H]Ro 48-8587 binding to rat whole brain membranes was inhibited by several compounds with the following rank order of potency: Ro 48-8587 > 6-nitro-7-sulphamoylbenzo[ f ]quinoxaline-2,3-dione (NBQX) > YM 90K > 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) > quisqualate > AMPA > glutamate > kainate > NMDA. The distribution and abundance of specific binding sites (∼95% of total) in sections of rat CNS, revealed by quantitative receptor radioautography and image analysis, indicated a very discrete localization. Highest binding values were observed in cortical layers (binding in layers 1 and 2 > binding in layers 3–6), hippocampal formation, striatum, dorsal septum, reticular thalamic nucleus, cerebellar molecular layer, and spinal cord dorsal horn. At 1 n M , the values for specific binding were highest in the cortical layers 1 and 2 and lowest in the brainstem (∼2.6 and 0.4 pmol/mg of protein, respectively). Ro 48-8587 is a potent and selective AMPA receptor antagonist with improved binding characteristics (higher affinity, selectivity, and specific binding) compared with those previously reported.     

Modulation of serotonergic receptor signaling and cross-talk by prion protein

The inducible serotonergic 1C115-HT cell line expresses a defined set of serotonergic receptors of the 5-HT2B, 5-HT1B/D, and 5-HT2A subtypes, which sustain a regulation of serotonergic associated functions through G-protein-dependent signaling. 1C115-HT cells have been instrumental to assign a signaling function to the cellular prion protein PrPC. Here, we establish that antibody-mediated ligation of PrPC concomitant to agonist stimulation of 5-HT receptors modulates the couplings of all three serotonergic receptors present on 1C115-HT cells. Specific impacts of PrP antibodies were monitored depending on the receptor and pathway considered. PrPC ligation selectively cancels the 5-HT2A-PLC response, decreases the 5-HT1B/D negative coupling to adenylate cyclase, and potentiates the 5-HT2B-PLA2 coupling. As a result, PrPC ligation disturbs the functional interactions occurring between the signaling pathways of the three receptor subtypes. In 1C115-HT cells, antagonizing cross-talks arising from 5-HT2B and 5-HT2A receptors control the 5-HT1B/D function. PrPC ligation reinforces the negative regulation exerted by 5-HT2B on 5-HT1B/D receptors. On the other hand it abrogates the blocking action of 5-HT2A on the regulatory loop linking 5-HT1B/D receptors. We propose that the ligation of PrPC affects the potency or dynamics of G-protein activation by agonist-bound serotonergic receptors. Finally, the PrPC-dependent modulation of 5-HT receptor couplings is restricted to 1C115-HT cells expressing a complete serotonergic phenotype. It critically involves a PrPC-caveolin platform implemented on the neurites of 1C115-HT cells during differentiation. Our findings define PrPC as a modulator of 5-HT receptor coupling to G-proteins and thereby as a protagonist contributing to the homeostasis of serotonergic neurons. They provide a foundation for uncovering the impact of prion infection on serotonergic functions.     

When the Background Matters: Using Scenarios from Integrated Assessment Models in Prospective Life Cycle Assessment

Prospective life cycle assessment (LCA) needs to deal with the large epistemological uncertainty about the future to support more robust future environmental impact assessments of technologies. This study proposes a novel approach that systematically changes the background processes in a prospective LCA based on scenarios of an integrated assessment model (IAM), the IMAGE model. Consistent worldwide scenarios from IMAGE are evaluated in the life cycle inventory using ecoinvent v3.3. To test the approach, only the electricity sector was changed in a prospective LCA of an internal combustion engine vehicle (ICEV) and an electric vehicle (EV) using six baseline and mitigation climate scenarios until 2050. This case study shows that changes in the electricity background can be very important for the environmental impacts of EV. Also, the approach demonstrates that the relative environmental performance of EV and ICEV over time is more complex and multifaceted than previously assumed. Uncertainty due to future developments manifests in different impacts depending on the product (EV or ICEV), the impact category, and the scenario and year considered. More robust prospective LCAs can be achieved, particularly for emerging technologies, by expanding this approach to other economic sectors beyond electricity background changes and mobility applications as well as by including uncertainty and changes in foreground parameters. A more systematic and structured composition of future inventory databases driven by IAM scenarios helps to acknowledge epistemological uncertainty and to increase the temporal consistency of foreground and background systems in LCAs of emerging technologies.     

Uncertainty analysis in LCA using precalculated aggregated datasets

Purpose

Some LCA software tools use precalculated aggregated datasets because they make LCA calculations much quicker. However, these datasets pose problems for uncertainty analysis. Even when aggregated dataset parameters are expressed as probability distributions, each dataset is sampled independently. This paper explores why independent sampling is incorrect and proposes two techniques to account for dependence in uncertainty analysis. The first is based on an analytical approach, while the other uses precalculated results sampled dependently.

Methods

The algorithm for generating arrays of dependently presampled aggregated inventories and their LCA scores is described. These arrays are used to calculate the correlation across all pairs of aggregated datasets in two ecoinvent LCI databases (2.2, 3.3 cutoff). The arrays are also used in the dependently presampled approach. The uncertainty of LCA results is calculated under different assumptions and using four different techniques and compared for two case studies: a simple water bottle LCA and an LCA of burger recipes.

Results and discussion

The meta-analysis of two LCI databases shows that there is no single correct approximation of correlation between aggregated datasets. The case studies show that the uncertainty of single-product LCA using aggregated datasets is usually underestimated when the correlation across datasets is ignored and that the magnitude of the underestimation is dependent on the system being analysed and the LCIA method chosen. Comparative LCA results show that independent sampling of aggregated datasets drastically overestimates the uncertainty of comparative metrics. The approach based on dependently presampled results yields results functionally identical to those obtained by Monte Carlo analysis using unit process datasets with a negligible computation time.

Conclusions

Independent sampling should not be used for comparative LCA. Moreover, the use of a one-size-fits-all correction factor to correct the calculated variability under independent sampling, as proposed elsewhere, is generally inadequate. The proposed approximate analytical approach is useful to estimate the importance of the covariance of aggregated datasets but not for comparative LCA. The approach based on dependently presampled results provides quick and correct results and has been implemented in EcodEX, a streamlined LCA software used by Nestlé. Dependently presampled results can be used for streamlined LCA software tools. Both presampling and analytical solutions require a preliminary one-time calculation of dependent samples for all aggregated datasets, which could be centrally done by database providers. The dependent presampling approach can be applied to other aspects of the LCA calculation chain.

     

The application of the pedigree approach to the distributions foreseen in ecoinvent v3

Purpose

Data used in life cycle inventories are uncertain (Ciroth et al. Int J Life Cycle Assess 9(4):216–226, 2004). The ecoinvent LCI database considers uncertainty on exchange values. The default approach applied to quantify uncertainty in ecoinvent is a semi-quantitative approach based on the use of a pedigree matrix; it considers two types of uncertainties: the basic uncertainty (the epistemic error) and the additional uncertainty (the uncertainty due to using imperfect data). This approach as implemented in ecoinvent v2 has several weaknesses or limitations, one being that uncertainty is always considered as following a lognormal distribution. The aim of this paper is to show how ecoinvent v3 will apply this approach to all types of distributions allowed by the ecoSpold v2 data format.

Methods

A new methodology was developed to apply the semi-quantitative approach to distributions other than the lognormal. This methodology and the consequent formulas were based on (1) how the basic and the additional uncertainties are combined for the lognormal distribution and on (2) the links between the lognormal and the normal distributions. These two points are summarized in four principles. In order to test the robustness of the proposed approach, the resulting parameters for all probability density functions (PDFs) are tested with those obtained through a Monte Carlo simulation. This comparison will validate the proposed approach.

Results and discussion

In order to combine the basic and the additional uncertainties for the considered distributions, the coefficient of variation (CV) is used as a relative measure of dispersion. Formulas to express the definition parameters for each distribution modeling a flow with its total uncertainty are given. The obtained results are illustrated with default values; they agree with the results obtained through the Monte Carlo simulation. Some limitations of the proposed approach are cited.

Conclusions

Providing formulas to apply the semi-quantitative pedigree approach to distributions other than the lognormal will allow the life cycle assessment (LCA) practitioner to select the appropriate distribution to model a datum with its total uncertainty. These data variability definition technique can be applied on all flow exchanges and also on parameters which play an important role in ecoinvent v3.