Uncertainty and precaution in European environmental risk assessment of chemicals

It is recognised that there is a need for a proper treatment and transparency of uncertainty in risk assessment and management, especially in view of the upcoming proposed new chemical policy REACH, which delegates the responsibility for conducting risk assessments to industry. The current EU risk assessment for new and existing substances is largely deterministic and prudential measures are implicitly embedded in calculation schemes and rules. In this paper, a more probabilistic approach to risk assessment is advocated. The advantage is twofold: 1) inherent variability and other uncertainty pertaining to exposure and effects are transparently taken into account, while at the same time 2) issues of caution are explicitly transferred to the risk management phase. The result of a probabilistic risk assessment as suggested is improved transparency with quantitative and qualitative uncertainty estimates. Such uncertainty information can be used to discuss precautionary measures in the context of risk management.</jats:p

A Peptide Core Motif for Binding to Heterotrimeric G Protein α Subunits

Recently, in vitro selection using mRNA display was used to identify a novel peptide sequence that binds with high affinity to G{alpha}i1. The peptide was minimized to a 9-residue sequence (R6A-1) that retains high affinity and specificity for the GDP-bound state of G{alpha}i1 and acts as a guanine nucleotide dissociation inhibitor (GDI). Here we demonstrate that the R6A-1 peptide interacts with G{alpha} subunits representing all four G protein classes, acting as a core motif for G{alpha} interaction. This contrasts with the consensus G protein regulatory(GPR) sequence, a 28-mer peptide GDI derived from the GoLoco (G{alpha}i/0-Loco interaction)/GPR motif that shares no homology with R6A-1 and binds only to G{alpha}i1-3 in this assay. Binding of R6A-1 is generally specific to the GDP-bound state of the G{alpha} subunits and excludes association with G{beta}{gamma}. R6A-G{alpha}i1 complexes are resistant to trypsin digestion and exhibit distinct stability in the presence of Mg2+, suggesting that the R6A and GPR peptides exert their activities using different mechanisms. Studies using G{alpha}i1/G{alpha}s chimeras identify two regions of G{alpha}i1 (residues 1–35 and 57–88) as determinants for strong R6A-Gi{alpha}1 interaction. Residues flanking the R6A-1 peptide confer unique binding properties, indicating that the core motif could be used as a starting point for the development of peptides exhibiting novel activities and/or specificity for particular G protein subclasses or nucleotide-bound states

Simultaneous Kummer congruences and E∞\mathbb{E}_\infty-orientations of KO and tmf

Building on results of M. Ando, M.J. Hopkins and C. Rezk, we show the existence of uncountably many $\mathbb{E}_\infty$-String orientations of real K-theory KO and of topological modular forms tmf, generalizing the $\hat{A}$- (resp. the Witten) genus. Furthermore, the obstruction to lifting an $\mathbb{E}_\infty$-String orientations from KO to tmf is identified with a classical Iwasawa-theoretic condition. The common key to all these results is a precise understanding of the classical Kummer congruences, imposed for all primes simultaneously. This result is of independent arithmetic interest.Comment: final versio

The evolution of an allosteric site in phosphorylase

AbstractBackground: Glycogen phosphorylases consist of a conserved catalytic core onto which different regulatory sites are added. By comparing the structures of isozymes, we hope to understand the structural principles of allosteric regulation in this family of enzymes. Here, we focus on the differences in the glucose 6-phosphate (Glc-6-P) binding sites of two isozymes.Results We have refined the structure of Glc-6-P inhibited yeast phosphorylase b to 2.6 å and compared it with known structures of muscle phosphorylase. Glc-6-P binds in a novel way, interacting with a distinct set of secondary elements. Structural links connecting the Glc-6-P binding sites and catalytic sites are conserved, although the specific contacts are not.Conclusion Our comparison reveals that the Glc-6-P binding site was modified over the course of evolution from yeast to vertebrates to become a bi-functional switch. The additional ability of muscle phosphorylase to be activated by AMP required the recruitment of structural elements into the binding site and sequence changes to create a binding subsite for adenine, whilst maintaining links to the catalytic site

Values Following a Major Terrorist Incident: Finnish Adolescent and Student Values Before and After September 11, 2001

The horrific terrorist attacks on the United States on September 11, 2001, left an indelible mark on perceptions of security and threat across the world. This paper uses Schwartz’s (1992) value circumplex model to examine value change across matched high school and university student samples in Finland, questioned before and after the World Trade Center (WTC) and associated attacks. In Study 1 (N5419), security values of adolescents were higher the day following the WTC attacks than before, but fell back toward pre-attack levels in the subsequent two samples. In contrast, levels of stimulation were lower following the terrorist incidents. In Study 2 (N5222), security levels of students were also higher following the WTC attacks, but again were closer to pre-attack levels in a subsequent cohort

Validation of the nickel biotic ligand model for locally relevant species in Australian freshwaters

Australian freshwaters have relatively low water hardness and different calcium (Ca) to magnesium (Mg) ratios compared with those in Europe. The hardness values of a substantial proportion of Australian freshwaters fall below the application boundary of the existing European nickel biotic ligand models (Ni BLMs) of 2 mg Ca/L. Toxicity testing was undertaken using Hydra viridissima to assess the predictive ability of the existing Ni BLM for this species in extremely soft waters. This testing revealed an increased competitive effect of Ca and Mg with Ni for binding to the biotic ligand in soft water