Normalization references for Europe and North America for application with USEtox? characterization factors

Purpose

In life cycle impact assessment, normalization can be a very effective tool for the life cycle assessment practitioner to interpret results and put them into perspective. The paper presents normalization references for the recently developed USEtox? model, which aims at calculating globally applicable characterization factors. Normalization references for Europe and North America are determined, and guidance for expansions to other geographical regions is provided.

Materials and methods

The base years of the European and North American inventories are 2004 and 2002/2008, respectively. Emission data were extracted from two literature sources referring to each of the considered regions. The inventory for North America was adapted to avoid extrapolation of data from other regions and thus bring consistency with the emission inventory for Europe. In spite of different inventory assumptions, a similar coverage of substances was obtained for both regions with relatively high representation of metals and a number of organic compounds, mainly consisting of non-methane volatile organic compounds and pesticides. The two inventory sets were eventually characterized with the characterization factors (CFs) calculated with the version 1.0 of the USEtox? model and substance database; both interim and recommended CFs were used.

Results and discussion

Normalization references are provided for Europe and North America for the three USEtox? toxic impact categories; ratios between the normalization references for the two regions in all cases lie below a factor of 3. Causes for the observed discrepancies are found to be different inventory assumptions as well as variations in the type and intensity of actual emissions between the two regions. Additional causes are inventories that only cover a limited number of substances, and the characterization model, which can only provide interim factors for certain substances like metal compounds. Based on these causes and on a review of recent studies on normalization references, a list of substances to be prioritized when collecting emission data was built, demonstrating the importance of metals.

Conclusions

In the perspective of further refining the presented normalization references and of calculating new references for other regions, guidance is provided including a list of priority substances that should be considered when building emission inventories for normalization references.     

Building a radial spoke: flagellar radial spoke protein 3 (RSP3) is a dimer

Radial spokes are critical multisubunit structures required for normal ciliary and eukaryotic flagellar motility. Experimental evidence indicates the radial spokes are mechanochemical transducers that transmit signals from the central pair apparatus to the outer doublet microtubules for local control of dynein activity. Recently, progress has been made in identifying individual components of the radial spoke, yet little is known about how the radial spoke is assembled or how it performs in signal transduction. Here we focus on radial spoke protein 3 (RSP3), a highly conserved AKAP located at the base of the radial spoke stalk and required for radial spoke assembly on the doublet microtubules. Biochemical approaches were taken to further explore the functional role of RSP3 within the radial spoke structure and for control of motility. Chemical crosslinking, native gel electrophoresis, and epitope-tagged RSP3 proteins established that RSP3 forms a dimer. Analysis of truncated RSP3 proteins indicates the dimerization domain coincides with the previously characterized axoneme binding domain in the N-terminus. We propose a model in which each radial spoke structure is built on an RSP3 dimer, and indicating that each radial spoke can potentially localize multiple PKAs or AKAP-binding proteins in position to control dynein activity and flagellar motility.     

Accelerated poly(A) loss on alpha-tubulin mRNAs during protein synthesis inhibition in Chlamydomonas

Detachment of flagella in Chlamydomonas reinhardii stimulates a rapid accumulation of tubulin mRNAs. The induced tubulin mRNAs are normally rapidly degraded following flagellar regeneration, but inhibition of protein synthesis with cycloheximide prevents their degradation. alpha-Tubulin poly(A) tail lengths were measured during normal accumulation and degradation, and in cycloheximide-treated cells. To measure alpha-tubulin mRNA poly(A) chain lengths with high resolution, specific 3' fragments of alpha 1- and alpha 2-tubulin mRNAs, generated by RNase H digestion of mRNA-oligonucleotide hybrids, were sized by Northern analysis. Both alpha-tubulin mRNAs have a newly synthesized poly(A) chain of about 110 adenylate residues. The poly(A) tails shorten with time, and show an average length of 40 to 60 adenylate residues by 90 minutes after deflagellation, at which time induced alpha-tubulin mRNA is being rapidly degraded. Poly(A) loss is significantly accelerated in cycloheximide-treated cells, and this loss is not attributible simply to the longer time the stabilized molecules spend in the cytoplasm. A large fraction of alpha-tubulin mRNA accumulates as mRNA with very short poly(A) tails (less than 10 residues) in the presence of cycloheximide, indicating that deadenylated alpha-tubulin mRNAs can be stable in vivo, at least in the absence of protein synthesis. The rate and extent of poly(A) loss in cycloheximide are greater for alpha 2-tubulin mRNA than for alpha 1-tubulin mRNA. This difference cannot be attributed to differential ribosome loading. This finding is interesting in that the two mRNAs are very similar in sequence with the exception of their 3' untranslated regions.     

Protease-activated receptor 1 knockout reduces experimentally induced liver fibrosis

Thrombin inhibition protects against liver fibrosis. However, it is not known whether the thrombin profibrogenic effect is due to effects on blood coagulation or to signaling via protease-activated receptors (PARs). We took advantage of the lack of blood coagulation defects in PAR-1-knockout mice. Acute carbon tetrachloride (CCl(4)) toxicity was similar in wild-type (WT), PAR-1(-/-), and PAR-1(+/-) mice as judged by aminotransferase levels, area of liver necrosis, and liver peroxidation measured by Fourier-transformed infrared spectroscopy. Fifteen mice/group received CCl(4) or its solvent for 6 wk (300 microl/kg, 3 times a week). Fibrosis area was increased 10-fold by CCl(4) treatment in WT mice. PAR-1 deficiency protected against fibrosis, with 36% and 56% decrease in PAR-1(+/-) and PAR-1(-/-) mice, respectively (P < 0.001). Similar results were obtained for area of activated fibrogenic cells (64% and 79% decrease in PAR-1(+/-) and PAR-1(-/-) mice, respectively, P < 0.001). These findings were corroborated by measurements of type I collagen, matrix metalloproteinase-2, and PDGF-beta receptor mRNA levels. There was also a significant decrease in T lymphocyte infiltration in PAR-1-deficient mice. Altogether, these results suggest that thrombin profibrogenic effects are independent of effects on blood coagulation and are instead due to direct effects on fibrogenic cells and possibly on T lymphocytes.     

Activities of daily living and cardiovascular complications following elective, noncardiac surgery

BACKGROUND: Algorithms for preoperative cardiac evaluation prior to noncardiac surgery use indices of the metabolic equivalent of activities of daily living (METs). We evaluated METs as a predictor of cardiac complications following elective, noncardiac surgery. METHODS: A study was performed in an outpatient university preadmission center METs were estimated prospectively for 5,939 inpatients admitted for elective, noncardiac surgery who underwent a preanesthetic assessment within two months prior to surgery. Cardiac outcomes were retrieved retrospectively from relational databases. Outcomes included death, myocardial infarction, acute congestive failure, arrhythmias, cardiac arrest, acute ischemia, acute renalfailure, stroke, respiratory failure, severe hypertension, peripheral vascular occlusion, and pericardial effusion. Adverse outcomes were correlated with age, gender, surgical procedure, activities, and the American Society of Anesthesiologist's Physical Status (ASA-PS) using receiver operator characteristic curve analysis. RESULTS: 94 of 5,939 (1.6 percent) patients had cardiac complications; 16 died, six from their cardiac complication. 38.3 percent of complications occurred following vascular surgery. Using a multinomial logistic regression analysis, both age and physical status were highly significant predictors (p < 0.001) but METs was not (p = 0. 793). Receiver operator characteristic (ROC) curves were usedfor predictive value of variables. Area of the curves for age versus cardiac complications and death were 0.814 and 0.782; for physical status, 0.744 and 0.803; for METs, 0.664 and 0.524. CONCLUSIONS: METs are not a reliable index for the prediction of adverse cardiac events following elective, noncardiac surgery. Age and physical status are more predictive. Adverse cardiac outcomes are most frequent following vascular surgery.