Uncertainty analysis in the 1996 performance assessment for the Waste Isolation Pilot Plant

The appropriate treatment of uncertainty is now widely recognized as an essential component of performance assessments (PAs) for complex systems. When viewed at a high-level, the uncertainty in such analyses can typically be partitioned into two types: (1) stochastic uncertainty, which arises because the system can behave in many different ways and is thus a property of the system itself, and (2) subjective uncertainty, which arises from a lack of knowledge about quantities that are believed to have (or, at least, are assumed to have) fixed values and is thus a property of the analysts carrying out the study. The 1996 PA for the Waste Isolation Pilot Plant (WIPP) carried out at Sandia National Laboratories (SNL) will be used to illustrate the treatment of these two types of uncertainty in a real analysis. In particular, this PA supported a compliance certification application (CCA) by the US Department of Energy (DOE) to the US Environmental Protection Agency (EPA) for the certification of the WIPP for the geologic disposal of transuranic waste. Insights on the conceptual and computational structure of PAs for complex systems gained from these and other analyses are being incorporated into a new software system under development at SNL to facilitate the performance of analyses that maintain a separation between stochastic and subjective uncertainty

Evaluation of severe accident risks, Peach Bottom, Unit 2: Main report

In support of the Nuclear Regulatory Commission's (NRC's) assessment of the risk from severe accidents at commercial nuclear power plants in the US reported NUREG-1150, the Severe Accident Risk Reduction Program (SARRP) has completed a revised calculation of the risk to the general public from severe accidents at the Peach Bottom Atomic Power Station, Unit 2. This power plant, located in southeastern Pennsylvania, is operated by the Philadelphia Electric Company. The emphasis in this risk analysis was not on determining a so-called'' point estimate of risk. Rather, it was to determine the distribution of risk, and to discover the uncertainties that account for the breadth of this distribution. Off-site risk initiated by events both internal and external to the power station were assessed. 39 refs., 174 figs., 133 tabs

Human Mas-related G protein-coupled receptors-X1 induce chemokine receptor 2 expression in rat dorsal root ganglia neurons and release of chemokine ligand 2 from the human LAD-2 mast cell line

Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct and induction of the early growth response protein-1 via extracellular signal-regulated kinases-1/2 known to play a significant role in the development of inflammatory pain. Furthermore, we observed MRGPR-X1-induced up-regulation of the chemokine receptor 2 (CCR2) via NFAT, which is considered as a key event in the onset of neuropathic pain and, so far, has not yet been described for any endogenous neuropeptide. Up-regulation of CCR2 is often associated with increased release of its endogenous agonist chemokine ligand 2 (CCL2). We also found MRGPR-X1-promoted release of CCL2 in a human connective tissue mast cell line endogenously expressing MRGPR-X1. Thus, we provide first evidence to suggest that MRGPR-X1 induce expression of chronic pain markers in DRG neurons and propose a so far unidentified signaling circuit that enhances chemokine signaling by acting on two distinct yet functionally co-operating cell types. Given the important role of chemokine signaling in pain chronification, we propose that interruption of this signaling circuit might be a promising new strategy to alleviate chemokine-promoted pain

Data incongruence and the problem of avian louse phylogeny

Recent studies based on different types of data (i.e. morphological and molecular) have supported conflicting phylogenies for the genera of avian feather lice (Ischnocera: Phthiraptera). We analyse new and published data from morphology and from mitochondrial (12S rRNA and COI) and nuclear (EF1-) genes to explore the sources of this incongruence and explain these conflicts. Character convergence, multiple substitutions at high divergences, and ancient radiation over a short period of time have contributed to the problem of resolving louse phylogeny with the data currently available. We show that apparent incongruence between the molecular datasets is largely attributable to rate variation and nonstationarity of base composition. In contrast, highly significant character incongruence leads to topological incongruence between the molecular and morphological data. We consider ways in which biases in the sequence data could be misleading, using several maximum likelihood models and LogDet corrections. The hierarchical structure of the data is explored using likelihood mapping and SplitsTree methods. Ultimately, we concede there is strong discordance between the molecular and morphological data and apply the conditional combination approach in this case. We conclude that higher level phylogenetic relationships within avian Ischnocera remain extremely problematic. However, consensus between datasets is beginning to converge on a stable phylogeny for avian lice, at and below the familial rank

Molecular Phylogenetic Evaluation of Classification and Scenarios of Character Evolution in Calcareous Sponges (Porifera, Class Calcarea)

Calcareous sponges (Phylum Porifera, Class Calcarea) are known to be taxonomically difficult. Previous molecular studies have revealed many discrepancies between classically recognized taxa and the observed relationships at the order, family and genus levels; these inconsistencies question underlying hypotheses regarding the evolution of certain morphological characters. Therefore, we extended the available taxa and character set by sequencing the complete small subunit (SSU) rDNA and the almost complete large subunit (LSU) rDNA of additional key species and complemented this dataset by substantially increasing the length of available LSU sequences. Phylogenetic analyses provided new hypotheses about the relationships of Calcarea and about the evolution of certain morphological characters. We tested our phylogeny against competing phylogenetic hypotheses presented by previous classification systems. Our data reject the current order-level classification by again finding non-monophyletic Leucosolenida, Clathrinida and Murrayonida. In the subclass Calcinea, we recovered a clade that includes all species with a cortex, which is largely consistent with the previously proposed order Leucettida. Other orders that had been rejected in the current system were not found, but could not be rejected in our tests either. We found several additional families and genera polyphyletic: the families Leucascidae and Leucaltidae and the genus Leucetta in Calcinea, and in Calcaronea the family Amphoriscidae and the genus Ute. Our phylogeny also provided support for the vaguely suspected close relationship of several members of Grantiidae with giantortical diactines to members of Heteropiidae. Similarly, our analyses revealed several unexpected affinities, such as a sister group relationship between Leucettusa (Leucaltidae) and Leucettidae and between Leucascandra (Jenkinidae) and Sycon carteri (Sycettidae). According to our results, the taxonomy of Calcarea is in desperate need of a thorough revision, which cannot be achieved by considering morphology alone or relying on a taxon sampling based on the current classification below the subclass level

Potential pitfalls of modelling ribosomal RNA data in phylogenetic tree reconstruction: Evidence from case studies in the Metazoa

<p>Abstract</p> <p>Background</p> <p>Failure to account for covariation patterns in helical regions of ribosomal RNA (rRNA) genes has the potential to misdirect the estimation of the phylogenetic signal of the data. Furthermore, the extremes of length variation among taxa, combined with regional substitution rate variation can mislead the alignment of rRNA sequences and thus distort subsequent tree reconstructions. However, recent developments in phylogenetic methodology now allow a comprehensive integration of secondary structures in alignment and tree reconstruction analyses based on rRNA sequences, which has been shown to correct some of these problems. Here, we explore the potentials of RNA substitution models and the interactions of specific model setups with the inherent pattern of covariation in rRNA stems and substitution rate variation among loop regions.</p> <p>Results</p> <p>We found an explicit impact of RNA substitution models on tree reconstruction analyses. The application of specific RNA models in tree reconstructions is hampered by interaction between the appropriate modelling of covarying sites in stem regions, and excessive homoplasy in some loop regions. RNA models often failed to recover reasonable trees when single-stranded regions are excessively homoplastic, because these regions contribute a greater proportion of the data when covarying sites are essentially downweighted. In this context, the RNA6A model outperformed all other models, including the more parametrized RNA7 and RNA16 models.</p> <p>Conclusions</p> <p>Our results depict a trade-off between increased accuracy in estimation of interdependencies in helical regions with the risk of magnifying positions lacking phylogenetic signal. We can therefore conclude that caution is warranted when applying rRNA covariation models, and suggest that loop regions be independently screened for phylogenetic signal, and eliminated when they are indistinguishable from random noise. In addition to covariation and homoplasy, other factors, like non-stationarity of substitution rates and base compositional heterogeneity, can disrupt the signal of ribosomal RNA data. All these factors dictate sophisticated estimation of evolutionary pattern in rRNA data, just as other molecular data require similarly complicated (but different) corrections.</p

Magnetic resonance imaging of anterior cruciate ligament rupture

BACKGROUND: Magnetic resonance (MR) imaging is a useful diagnostic tool for the assessment of knee joint injury. Anterior cruciate ligament repair is a commonly performed orthopaedic procedure. This paper examines the concordance between MR imaging and arthroscopic findings. METHODS: Between February, 1996 and February, 1998, 48 patients who underwent magnetic resonance (MR) imaging of the knee were reported to have complete tears of the anterior cruciate ligament (ACL). Of the 48 patients, 36 were male, and 12 female. The average age was 27 years (range: 15 to 45). Operative reconstruction using a patellar bone-tendon-bone autograft was arranged for each patient, and an arthroscopic examination was performed to confirm the diagnosis immediately prior to reconstructive surgery. RESULTS: In 16 of the 48 patients, reconstructive surgery was cancelled when incomplete lesions were noted during arthroscopy, making reconstructive surgery unnecessary. The remaining 32 patients were found to have complete tears of the ACL, and therefore underwent reconstructive surgery. Using arthroscopy as an independent, reliable reference standard for ACL tear diagnosis, the reliability of MR imaging was evaluated. The true positive rate for complete ACL tear diagnosis with MR imaging was 67%, making the possibility of a false-positive report of "complete ACL tear" inevitable with MR imaging. CONCLUSIONS: Since conservative treatment is sufficient for incomplete ACL tears, the decision to undertake ACL reconstruction should not be based on MR findings alone

Interaction between Purkinje Cells and Inhibitory Interneurons May Create Adjustable Output Waveforms to Generate Timed Cerebellar Output

We develop a new model that explains how the cerebellum may generate the timing in classical delay eyeblink conditioning. Recent studies show that both Purkinje cells (PCs) and inhibitory interneurons (INs) have parallel signal processing streams with two time scales: an AMPA receptor-mediated fast process and a metabotropic glutamate receptor (mGluR)-mediated slow process. Moreover, one consistent finding is an increased excitability of PC dendrites (in Larsell's lobule HVI) in animals when they acquire the classical delay eyeblink conditioning naturally, in contrast to in vitro studies, where learning involves long-term depression (LTD). Our model proposes that the delayed response comes from the slow dynamics of mGluR-mediated IP3 activation, and the ensuing calcium concentration change, and not from LTP/LTD. The conditioned stimulus (tone), arriving on the parallel fibers, triggers this slow activation in INs and PC spines. These excitatory (from PC spines) and inhibitory (from INs) signals then interact at the PC dendrites to generate variable waveforms of PC activation. When the unconditioned stimulus (puff), arriving on the climbing fibers, is coupled frequently with this slow activation the waveform is amplified (due to an increased excitability) and leads to a timed pause in the PC population. The disinhibition of deep cerebellar nuclei by this timed pause causes the delayed conditioned response. This suggested PC-IN interaction emphasizes a richer role of the INs in learning and also conforms to the recent evidence that mGluR in the cerebellar cortex may participate in slow motor execution. We show that the suggested mechanism can endow the cerebellar cortex with the versatility to learn almost any temporal pattern, in addition to those that arise in classical conditioning

Electroanalysis may be used in the Vanillin Biotechnological Production

This study shows that electroanalysis may be used in vanillin biotechnological production. As a matter of fact, vanillin and some molecules implicated in the process like eugenol, ferulic acid, and vanillic acid may be oxidized on electrodes made of different materials (gold, platinum, glassy carbon). By a judicious choice of the electrochemical method and the experimental conditions the current intensity is directly proportional to the molecule concentrations in a range suitable for the biotechnological process. So, it is possible to imagine some analytical strategies to control some steps in the vanillin biotechnological production: by sampling in the batch reactor during the process, it is possible to determine out of line the concentration of vanillin, eugenol, ferulic acid, and vanillic acid with a gold rotating disk electrode, and low concentration of vanillin with addition of hydrazine at an amalgamated electrode. Two other possibilities consist in the introduction of electrodes directly in the batch during the process; the first one with a gold rotating disk electrode using linear sweep voltammetry and the second one requires three gold rotating disk electrodes held at different potentials for chronoamperometry. The last proposal is the use of ultramicroelectrodes in the case when stirring is not possible