Analytical uncertainty propagation in life cycle inventory and impact assessment: application to an automobile front panel

Background, aim, and scope

Uncertainty information is essential for the proper use of life cycle assessment (LCA) and environmental assessments in decision making. So far, parameter uncertainty propagation has mainly been studied using Monte Carlo techniques that are relatively computationally heavy to conduct, especially for the comparison of multiple scenarios, often limiting its use to research or to inventory only. Furthermore, Monte Carlo simulations do not automatically assess the sensitivity and contribution to overall uncertainty of individual parameters. The present paper aims to develop and apply to both inventory and impact assessment an explicit and transparent analytical approach to uncertainty. This approach applies Taylor series expansions to the uncertainty propagation of lognormally distributed parameters.

Materials and methods

We first apply the Taylor series expansion method to analyze the uncertainty propagation of a single scenario, in which case the squared geometric standard deviation of the final output is determined as a function of the model sensitivity to each input parameter and the squared geometric standard deviation of each parameter. We then extend this approach to the comparison of two or more LCA scenarios. Since in LCA it is crucial to account for both common inventory processes and common impact assessment characterization factors among the different scenarios, we further develop the approach to address this dependency. We provide a method to easily determine a range and a best estimate of (a) the squared geometric standard deviation on the ratio of the two scenario scores, “A/B”, and (b) the degree of confidence in the prediction that the impact of scenario A is lower than B (i.e., the probability that A/B<1). The approach is tested on an automobile case study and resulting probability distributions of climate change impacts are compared to classical Monte Carlo distributions.

Results

The probability distributions obtained with the Taylor series expansion lead to results similar to the classical Monte Carlo distributions, while being substantially simpler; the Taylor series method tends to underestimate the 2.5% confidence limit by 1-11% and the 97.5% limit by less than 5%. The analytical Taylor series expansion easily provides the explicit contributions of each parameter to the overall uncertainty. For the steel front end panel, the factor contributing most to the climate change score uncertainty is the gasoline consumption (>75%). For the aluminum panel, the electricity and aluminum primary production, as well as the light oil consumption, are the dominant contributors to the uncertainty. The developed approach for scenario comparisons, differentiating between common and independent parameters, leads to results similar to those of a Monte Carlo analysis; for all tested cases, we obtained a good concordance between the Monte Carlo and the Taylor series expansion methods regarding the probability that one scenario is better than the other.

Discussion

The Taylor series expansion method addresses the crucial need of accounting for dependencies in LCA, both for common LCI processes and common LCIA characterization factors. The developed approach in Eq. 8, which differentiates between common and independent parameters, estimates the degree of confidence in the prediction that scenario A is better than B, yielding results similar to those found with Monte Carlo simulations.

Conclusions

The probability distributions obtained with the Taylor series expansion are virtually equivalent to those from a classical Monte Carlo simulation, while being significantly easier to obtain. An automobile case study on an aluminum front end panel demonstrated the feasibility of this method and illustrated its simultaneous and consistent application to both inventory and impact assessment. The explicit and innovative analytical approach, based on Taylor series expansions of lognormal distributions, provides the contribution to the uncertainty from each parameter and strongly reduces calculation time.     

Emergence and Pathogenicity of Highly Virulent Cryptococcus gattii Genotypes in the Northwest United States

Cryptococcus gattii causes life-threatening disease in otherwise healthy hosts and to a lesser extent in immunocompromised hosts. The highest incidence for this disease is on Vancouver Island, Canada, where an outbreak is expanding into neighboring regions including mainland British Columbia and the United States. This outbreak is caused predominantly by C. gattii molecular type VGII, specifically VGIIa/major. In addition, a novel genotype, VGIIc, has emerged in Oregon and is now a major source of illness in the region. Through molecular epidemiology and population analysis of MLST and VNTR markers, we show that the VGIIc group is clonal and hypothesize it arose recently. The VGIIa/IIc outbreak lineages are sexually fertile and studies support ongoing recombination in the global VGII population. This illustrates two hallmarks of emerging outbreaks: high clonality and the emergence of novel genotypes via recombination. In macrophage and murine infections, the novel VGIIc genotype and VGIIa/major isolates from the United States are highly virulent compared to similar non-outbreak VGIIa/major-related isolates. Combined MLST-VNTR analysis distinguishes clonal expansion of the VGIIa/major outbreak genotype from related but distinguishable less-virulent genotypes isolated from other geographic regions. Our evidence documents emerging hypervirulent genotypes in the United States that may expand further and provides insight into the possible molecular and geographic origins of the outbreak.     

Stalk phase formation: effects of dehydration and saddle splay modulus

One of the earliest lipid intermediates forming in the course of membrane fusion is the lipid stalk. Although many aspects of the stalk hypothesis were elaborated theoretically and confirmed by experiments it remained unresolved whether stalk formation is always an energy consuming process or if there are conditions where the stalks are energetically favorable and form spontaneously resulting in an equilibrium stalk phase. Motivated by a recent breakthrough experiments we analyze the physical factors determining the spontaneous stalk formation. We show that this process can be driven by interplay between two factors: the elastic energy of lipid monolayers including a contribution of the saddle splay deformation and the energy of hydration repulsion acting between apposing membranes. We analyze the dependence of stalk formation on the saddle splay (Gaussian) modulus of the lipid monolayers and estimate the values of this modulus based on the experimentally established phase boundary between the lamellar and the stalk phases. We suggest that fusion proteins can induce stalk formation just by bringing the membranes into close contact, and accumulating, at least locally, a sufficiently large energy of the hydration repulsion.     

1alpha,25(OH)2D3 causes a rapid increase in phosphatidylinositol-specific PLC-beta activity via phospholipase A2-dependent production of lysophospholipid

1alpha,25(OH)(2)D(3) activates protein kinase C (PKC) in rat growth plate chondrocytes via mechanisms involving phosphatidylinositol-specific phospholipase C (PI-PLC) and phospholipase A(2) (PLA(2)). The purpose of this study was to determine if 1alpha,25(OH)(2)D(3) activates PI-PLC directly or through a PLA(2)-dependent mechanism. We determined which PLC isoforms are present in the growth plate chondrocytes, and determined which isoform(s) of PLC is(are) regulated by 1alpha,25(OH)(2)D(3). Inhibitors and activators of PLA(2) were used to assess the inter-relationship between these two phospholipid-signaling pathways. PI-PLC activity in lysates of prehypertrophic and upper hypertrophic zone (growth zone) cells that were incubated with 1alpha,25(OH)(2)D(3), was increased within 30s with peak activity at 1-3 min. PI-PLC activity in resting zone cells was unaffected by 1alpha,25(OH)(2)D(3). 1beta,25(OH)(2)D(3), 24R,25(OH)(2)D(3), actinomycin D and cycloheximide had no effect on PLC in lysates of growth zone cells. Thus, 1alpha,25(OH)(2)D(3) regulation of PI-PLC enzyme activity is stereospecific, cell maturation-dependent, and nongenomic. PLA(2)-activation (mastoparan or melittin) increased PI-PLC activity to the same extent as 1alpha,25(OH)(2)D(3); PLA(2)-inhibition (quinacrine, oleyloxyethylphosphorylcholine (OEPC), or AACOCF(3)) reduced the effect of 1alpha,25(OH)(2)D(3). Neither arachidonic acid (AA) nor its metabolites affected PI-PLC. In contrast, lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) activated PI-PLC (LPE>LPC). 1alpha,25(OH)(2)D(3) stimulated PI-PLC and PKC activities via Gq; GDPbetaS inhibited activity, but pertussis toxin did not. RT-PCR showed that the cells express PLC-beta1a, PLC-beta1b, PLC-beta3 and PLC-gamma1 mRNA. Antibodies to PLC-beta1 and PLC-beta3 blocked the 1alpha,25(OH)(2)D(3) effect; antibodies to PLC-delta and PLC-gamma did not. Thus, 1alpha,25(OH)(2)D(3) regulates PLC-beta through PLA(2)-dependent production of lysophospholipid.     

A single transmembrane site in the KCNE-encoded proteins controls the specificity of KvLQT1 channel gating

KCNEs are a family of genes encoding small integral membrane proteins whose role in governing voltage-gated potassium channel gating is emerging. Whether each member of this homologous family interacts with channel proteins in the same manner is unknown; however, it is clear that the functional effect of each KCNE on channel gating is different. The specificity of KCNE1 (minK) and KCNE3 control of activation of the potassium channel KvLQT1 maps to a triplet of amino acids within the KCNE transmembrane domain by chimera analysis. We now define the structural determinants of functional specificity within this triplet. The central amino acid of the triplet (Thr-58 of minK and Val-72 of KCNE3) is essential for the specific control of voltage-dependent channel activation characteristics of both minK and KCNE3. Using site-directed mutations that substitute minK and KCNE3 residues, we determined that a hydroxylated central amino acid is necessary for the slow sigmoidal activation produced by minK. The precise spacing of the hydroxyl group was required for minK-like activation. An aliphatic amino acid substituted at position 58 of minK is capable of reproducing KCNE3-like kinetics and voltage-independent constitutive current activation. The bulk of the central residue is another critical parameter, indicating precise positioning of this portion of the KCNE proteins within the channel complex. An intermediate phenotype produced by several smaller aliphatic-substituted mutants yields conditional voltage independence that is distinct from the voltage-dependent gating process, suggesting that KCNE3 traps the channel in a stable open state. From these results, we propose a model of KCNE-potassium channel interaction where the functional consequence depends on the precise contact at a single amino acid.     

14-3-3 amplifies and prolongs adrenergic stimulation of HERG K+ channel activity

Acute stress provokes lethal cardiac arrhythmias in the hereditary long QT syndrome. Here we provide a novel molecular mechanism linking beta-adrenergic signaling and altered human ether-a-go-go related gene (HERG) channel activity. Stress stimulates beta-adrenergic receptors, leading to cAMP elevations that can regulate HERG K+ channels both directly and via phosphorylation by cAMP-dependent protein kinase (PKA). We show that HERG associates with 14-3-3epsilon to potentiate cAMP/PKA effects upon HERG. The binding of 14-3-3 occurs simultaneously at the N- and C-termini of the HERG channel. 14-3-3 accelerates and enhances HERG activation, an effect that requires PKA phosphorylation of HERG and dimerization of 14-3-3. The interaction also stabilizes the lifetime of the PKA-phosphorylated state of the channel by shielding the phosphates from cellular phosphatases. The net result is a prolongation of the effect of adrenergic stimulation upon HERG activity. Thus, 14-3-3 interactions with HERG may provide a unique mechanism for plasticity in the control of membrane excitability and cardiac rhythm.