The Priming Function of In-car Audio Instruction

Studies to date have focused on the priming power of visual road signs, but not the priming potential of audio road scene instruction. Here, the relative priming power of visual, audio and multisensory road scene instructions were assessed. In a lab-based study, participants responded to target road scene turns following visual, audio or multisensory road turn primes which were congruent or incongruent to the primes in direction, or control primes. All types of instruction (visual, audio, multisensory) were successful in priming responses to a road scene. Responses to multisensory-primed targets (both audio and visual) were faster than responses to either audio or visual primes alone. Incongruent audio primes did not affect performance negatively in the manner of incongruent visual or multisensory primes. Results suggest that audio instructions have the potential to prime drivers to respond quickly and safely to their road environment. Peak performance will be observed if audio and visual road instruction primes can be timed to co-occur

Representing ‘Place’: City Climate Commissions and the Institutionalisation of Experimental Governance in Edinburgh

Against the backdrop of increasingly fragmented and poly-centric urban climate governance, this article examines the establishment of city climate ‘commissions’ as an experimental means of addressing the challenge of climate change at the city-scale. In doing so it addresses the question: What constitutes diversity in voices and perspectives when trying to represent the city as a place for climate action? To answer this question, the article presents an analysis of the Edinburgh Climate Commission’s establishment, drawing on participatory ethnographic research carried out by a researcher embedded within the project team. The account of how this new mode of urban governance was both conceptualised and then put into practice offers a new institutional angle to the literature on urban ‘experimentation.’ Through our reflective analysis we argue that aspirations to ensure pre-defined ‘key’ industries (high carbon emitters) are accounted for in commissioner recruitment, and an over-emphasis on capturing discernible ‘impacts’ in the short term (by involving organisations already pro-active in sustainable development) hindered an opportunity to embrace new perspectives on urban futures and harness the innovative potential of cities to engage with the multifaceted nature of the climate challenge. Furthermore, new insight into the relationship between local authorities and other ‘place-based’ agents of change opens up important questions regarding how to balance the attainment of legitimacy within the political status quo, and the prospect of a new radical politics for urban transformation

RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma.

Activating mutations in KRAS occur in 32% of lung adenocarcinomas (LUAD). Despite leading to aggressive disease and resistance to therapy in preclinical studies, the KRAS mutation does not predict patient outcome or response to treatment, presumably due to additional events modulating RAS pathways. To obtain a broader measure of RAS pathway activation, we developed RAS84, a transcriptional signature optimised to capture RAS oncogenic activity in LUAD. We report evidence of RAS pathway oncogenic activation in 84% of LUAD, including 65% KRAS wild-type tumours, falling into four groups characterised by coincident alteration of STK11/LKB1, TP53 or CDKN2A, suggesting that the classifications developed when considering only KRAS mutant tumours have significance in a broader cohort of patients. Critically, high RAS activity patient groups show adverse clinical outcome and reduced response to chemotherapy. Patient stratification using oncogenic RAS transcriptional activity instead of genetic alterations could ultimately assist in clinical decision-making

Castor bean organelle genome sequencing and worldwide genetic diversity analysis

Castor bean is an important oil-producing plant in the Euphorbiaceae family. Its high-quality oil contains up to 90% of the unusual fatty acid ricinoleate, which has many industrial and medical applications. Castor bean seeds also contain ricin, a highly toxic Type 2 ribosome-inactivating protein, which has gained relevance in recent years due to biosafety concerns. In order to gain knowledge on global genetic diversity in castor bean and to ultimately help the development of breeding and forensic tools, we carried out an extensive chloroplast sequence diversity analysis. Taking advantage of the recently published genome sequence of castor bean, we assembled the chloroplast and mitochondrion genomes extracting selected reads from the available whole genome shotgun reads. Using the chloroplast reference genome we used the methylation filtration technique to readily obtain draft genome sequences of 7 geographically and genetically diverse castor bean accessions. These sequence data were used to identify single nucleotide polymorphism markers and phylogenetic analysis resulted in the identification of two major clades that were not apparent in previous population genetic studies using genetic markers derived from nuclear DNA. Two distinct sub-clades could be defined within each major clade and large-scale genotyping of castor bean populations worldwide confirmed previously observed low levels of genetic diversity and showed a broad geographic distribution of each sub-clade

Evaluation of Hungarian Wines for Resveratrol by Overpressured Layer Chromatography

A method, including solid phase extraction sample preparation, overpressured layer chromatographic separation and subsequent densitometric evaluation, was developed for measurement of total resveratrol (cis- and trans-isomers) content of wine. The amount of resveratrol was determined in wine samples from different winemaking regions of Hungary. The total resveratrol was high in Hungarian red wines (3.6–11 mg/L), and much lower in white ones (0.04–1.5 mg/L)

Structural Comparison of Human Mammalian Ste20-Like Kinases

BACKGROUND: The serine/threonine mammalian Ste-20 like kinases (MSTs) are key regulators of apoptosis, cellular proliferation as well as polarization. Deregulation of MSTs has been associated with disease progression in prostate and colorectal cancer. The four human MSTs are regulated differently by C-terminal regions flanking the catalytic domains. PRINCIPAL FINDINGS: We have determined the crystal structure of kinase domain of MST4 in complex with an ATP-mimetic inhibitor. This is the first structure of an inactive conformation of a member of the MST kinase family. Comparison with active structures of MST3 and MST1 revealed a dimeric association of MST4 suggesting an activation loop exchanged mechanism of MST4 auto-activation. Together with a homology model of MST2 we provide a comparative analysis of the kinase domains for all four members of the human MST family. SIGNIFICANCE: The comparative analysis identified new structural features in the MST ATP binding pocket and has also defined the mechanism for autophosphorylation. Both structural features may be further explored for inhibitors design. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1

Statistical Characterization of the Charge State and Residue Dependence of Low-Energy CID Peptide Dissociation Patterns

Data mining was performed on 28 330 unique peptide tandem mass spectra for which sequences were assigned with high confidence. By dividing the spectra into different sets based on structural features and charge states of the corresponding peptides, chemical interactions involved in promoting specific cleavage patterns in gas-phase peptides were characterized. Pairwise fragmentation maps describing cleavages at all Xxx-Zzz residue combinations for b and y ions reveal that the difference in basicity between Arg and Lys results in different dissociation patterns for singly charged Arg-and Lys-ending tryptic peptides. While one dominant protonation form (proton localized) exists for Arg-ending peptides, a heterogeneous population of different protonated forms or more facile interconversion of protonated forms (proton partially mobile) exists for Lys-ending peptides. Cleavage C-terminal to acidic residues dominates spectra from singly charged peptides that have a localized proton and cleavage N-terminal to Pro dominates those that have a mobile or partially mobile proton. When Pro is absent from peptides that have a mobile or partially mobile proton, cleavage at each peptide bond becomes much more prominent. Whether the above patterns can be found in b ions, y ions, or both depends on the location of the proton holder(s) in multiply protonated peptides. Enhanced cleavages C-terminal to branched aliphatic residues (Ile, Val, Leu) are observed in both b and y ions from peptides that have a mobile proton, as well as in y ions from peptides that have a partially mobile proton; enhanced cleavages Nterminal to these residues are observed in b ions from peptides that have a partially mobile proton. Statistical tools have been designed to visualize the fragmentation maps and measure the similarity between them. The pairwise cleavage patterns observed expand our knowledge of peptide gas-phase fragmentation behaviors and may be useful in algorithm development that employs improved models to predict fragment ion intensities. Low-energy collision-induced dissociation (CID) in mass spectrometry has been used extensively in peptide sequencing for protein identification and analysis of protein modifications. 1,2 Computer algorithms are employed to automate the spectral analysis and assign peptide sequences to the fragmentation spectra. 2-4 Numerous peptide fragmentation spectra are obtained everyday, but only a low percentage (e.g., 10-35%) of them are successfully identified by readily available algorithms. [5][6][7][8] One explanation for the high failure rate of current algorithms is the very simple fragmentation model on which they are based, which assumes that cleavage will occur mainly, if not exclusively, at the amide bonds between consecutive amino acid residues to produce ions of identical abundance (or intensity), regardless of the identity or the chemical property of the residues. 4,9 Although intensity patterns of the fragment ions from the same peptide under the same experimental settings are highly reproducible, current readily available algorithms only use the mass-to-charge (m/z) information from a tandem mass (MS/MS) spectrum and ignore the other information availablesthe relative intensity information. While this approach is sufficient to identify many peptides, many others yield fragmentation patterns that significantly deviate from a uniform fragmentation model. 8 A more detailed and chemically meaningful fragmentation model might improve algorithm performance and might include using different models for different candidate sequences. In addition, the gas-phase unimolecula

A major QTL controlling apple skin russeting maps on the linkage group 12 of 'Renetta Grigia di Torriana'

Background: Russeting is a disorder developed by apple fruits that consists of cuticle cracking followed by the replacement of the epidermis by a corky layer that protects the fruit surface from water loss and pathogens. Although influenced by many environmental conditions and orchard management practices, russeting is under genetic control. The difficulty in classifying offspring and consequent variable segregation ratios have led several authors to conclude that more than one genetic determinant could be involved, although some evidence favours a major gene (Ru). Results: In this study we report the mapping of a major genetic russeting determinant on linkage group 12 of apple as inferred from the phenotypic observation in a segregating progeny derived from 'Renetta Grigia di Torriana', the construction of a 20 K Illumina SNP chip based genetic map, and QTL analysis. Recombination analysis in two mapping populations restricted the region of interest to approximately 400 Kb. Of the 58 genes predicted from the Golden Delicious sequence, a putative ABCG family transporter has been identified. Within a small set of russeted cultivars tested with markers of the region, only six showed the same haplotype of 'Renetta Grigia di Torriana'. Conclusions: A major determinant (Ru_RGT) for russeting development putatively involved in cuticle organization is proposed as a candidate for controlling the trait. SNP and SSR markers tightly co-segregating with the Ru_RGT locus may assist the breeder selection. The observed segregations and the analysis of the 'Renetta Grigia di Torriana' haplotypic region in a panel of russeted and non-russeted cultivars may suggest the presence of other determinants for russeting in apple