Effects of deep inspiration breath hold on prone photon or proton irradiation of breast and regional lymph nodes

We report on a comparative dosimetrical study between deep inspiration breath hold (DIBH) and shallow breathing (SB) in prone crawl position for photon and proton radiotherapy of whole breast (WB) and locoregional lymph node regions, including the internal mammary chain (LN_MI). We investigate the dosimetrical effects of DIBH in prone crawl position on organs-at-risk for both photon and proton plans. For each modality, we further estimate the effects of lung and heart doses on the mortality risks of different risk profiles of patients. Thirty-one patients with invasive carcinoma of the left breast and pathologically confirmed positive lymph node status were included in this study. DIBH significantly decreased dose to heart for photon and proton radiotherapy. DIBH also decreased lung doses for photons, while increased lung doses were observed using protons because the retracting heart is displaced by low-density lung tissue. For other organs-at-risk, DIBH resulted in significant dose reductions using photons while minor differences in dose deposition between DIBH and SB were observed using protons. In patients with high risks for cardiac and lung cancer mortality, average thirty-year mortality rates from radiotherapy-related cardiac injury and lung cancer were estimated at 3.12% (photon DIBH), 4.03% (photon SB), 1.80% (proton DIBH) and 1.66% (proton SB). The radiationrelated mortality risk could not outweigh the similar to 8% disease-specific survival benefit of WB + LN_MI radiotherapy in any of the assessed treatments

The twilight of the Liberal Social Contract? On the Reception of Rawlsian Political Liberalism

This chapter discusses the Rawlsian project of public reason, or public justification-based 'political' liberalism, and its reception. After a brief philosophical rather than philological reconstruction of the project, the chapter revolves around a distinction between idealist and realist responses to it. Focusing on political liberalism’s critical reception illuminates an overarching question: was Rawls’s revival of a contractualist approach to liberal legitimacy a fruitful move for liberalism and/or the social contract tradition? The last section contains a largely negative answer to that question. Nonetheless the chapter's conclusion shows that the research programme of political liberalism provided and continues to provide illuminating insights into the limitations of liberal contractualism, especially under conditions of persistent and radical diversity. The programme is, however, less receptive to challenges to do with the relative decline of the power of modern states

Constitutivism

A brief explanation and overview of constitutivism

Equilibrium analysis in multi-echelon supply chain with multi-dimensional utilities of inertial players

In a supply chain, the importance of information elicitation from the supply chain players is vital to design supply chain network. The rationality and self-centredness of these players causes the information asymmetry in the supply chain and thus situation of conflict and non-participation of the players in the network design process. In such situations, it is required to analyse the supply chain players’ behaviour in order to explore potential for coordination through incentives. In this paper, a novel approach of social utility analysis is proposed to elicit the information for supply chain coordination among the supply chain players in a dyadic relationship – supplier and buyer. In principal, we consider a monopsony situation where buyer is a dominant player. With the objective of maximizing the social utility, efforts have been made to value behavioural issues in supply chain. On the other hand, the reluctance of player due to the information asymmetry is measured in the form of inertia – an offset to the supply chain profit. The suppliers’ behaviour is analysed with three distinct level of risk for two types of the product in procurement process. The useful insight from this paper is in supplier selection process where the reluctance of supplier offsets supply chain profit. The paper provides recommendations to supply chain managers for efficient decision-making ability in supplier selection process

Bunyaviridae RNA Polymerases (L-Protein) Have an N-Terminal, Influenza-Like Endonuclease Domain, Essential for Viral Cap-Dependent Transcription

Bunyaviruses are a large family of segmented RNA viruses which, like influenza virus, use a cap-snatching mechanism for transcription whereby short capped primers derived by endonucleolytic cleavage of host mRNAs are used by the viral RNA-dependent RNA polymerase (L-protein) to transcribe viral mRNAs. It was recently shown that the cap-snatching endonuclease of influenza virus resides in a discrete N-terminal domain of the PA polymerase subunit. Here we structurally and functionally characterize a similar endonuclease in La Crosse orthobunyavirus (LACV) L-protein. We expressed N-terminal fragments of the LACV L-protein and found that residues 1-180 have metal binding and divalent cation dependent nuclease activity analogous to that of influenza virus endonuclease. The 2.2 Å resolution X-ray crystal structure of the domain confirms that LACV and influenza endonucleases have similar overall folds and identical two metal binding active sites. The in vitro activity of the LACV endonuclease could be abolished by point mutations in the active site or by binding 2,4-dioxo-4-phenylbutanoic acid (DPBA), a known influenza virus endonuclease inhibitor. A crystal structure with bound DPBA shows the inhibitor chelating two active site manganese ions. The essential role of this endonuclease in cap-dependent transcription was demonstrated by the loss of transcriptional activity in a RNP reconstitution system in cells upon making the same point mutations in the context of the full-length LACV L-protein. Using structure based sequence alignments we show that a similar endonuclease almost certainly exists at the N-terminus of L-proteins or PA polymerase subunits of essentially all known negative strand and cap-snatching segmented RNA viruses including arenaviruses (2 segments), bunyaviruses (3 segments), tenuiviruses (4–6 segments), and orthomyxoviruses (6–8 segments). This correspondence, together with the well-known mapping of the conserved polymerase motifs to the central regions of the L-protein and influenza PB1 subunit, suggests that L-proteins might be architecturally, and functionally equivalent to a concatemer of the three orthomyxovirus polymerase subunits in the order PA-PB1-PB2. Furthermore, our structure of a known influenza endonuclease inhibitor bound to LACV endonuclease suggests that compounds targeting a potentially broad spectrum of segmented RNA viruses, several of which are serious or emerging human, animal and plant pathogens, could be developed using structure-based optimisation

Organic-rich sediments in brine-filled Shaban- and Kebrit Deeps, Northern Red Sea

The element compositions Si, Ca and Al of up to 2 1.1 ka old sediments in about 10 in long cores from the southern basin of the Shaban and Kebrit deeps in the northern Red Sea allowed a classification of major sediment types in carbonate sands and -muds and siliceous oozes. A FeOOH-enriched sediment horizon and a few samples with high Zn values in the Kebrit core indicate a hydrothermal origin probably near the brine-sea water interface with subsequent transport of hydrothermal compounds into the deep sediments. High organic carbon contents up to 8.4% are positively correlated with the Ba concentrations, which suggests that high bioproductivity, and rapid deposition (C-14 dating suggests a sedimentation rate near 70 cm/ka) led to the formation of sapropelic sediments between 11.8 and 13.6 ka (Younger Dryas). Organic petrological observations showed that the sediment organic material largely consists of <20 gm-sized roundish fecal pellets (intimate mixtures of organic matter and inorganic constituents) and bituminite. Terrestrial organic matter (pollens of land plants, fusinite etc.) is very rare in the sediment cores from both deeps. Organic-geochemical investigations of kerogens and organic extracts show that a significant (hydrothermal) hydrocarbon production did not occur in near-surface sediments of the Shaban and Kebrit deeps. Rock Eval pyrolysis of kerogens characterised the organic matter to be of type II quality. The delta C-13 values of the kerogens from the most prominent sapropel in the Shaban deep indicate an enrichment of(C-12-rich) nutrients in the water column during postglacial sapropel formation in the Younger Dryas. The n-alkane spectra are dominated by short chain lengths between n-C-15 and n-C-25 Prevailing n-C-15 to n-C-25 alkanes in low mature sediments are indicative of algal and microbial source. Pristane/phytane ratios are generally low (< I to similar to 1) which suggests that anoxic conditions prevailed within the anaerobic brine-filled deeps for the whole time covered by the sediments. This again indicates that sapropel formation was caused by high bioproductivity in the northern Red Sea rather than episodic stagnation with better preservation of the organic matter. Long-chain alkenones and sterols are the dominating compounds of the lipid fraction. Cholesterol contents in the sediment cores reflect phases of eukaryotes production in the water column, whereas the positive correlations of dinosterol with TOC and the amounts of total extract suggests that the major organic carbon source in the northern Red Sea during postglacial high-productivity stages were dinoflagellates. Another important carbon source, however, is indicated by the occurrence of 22,29,30-trisnorhopan-21 -one (TNH). Although the formation of TNH from its precursors is not fully understood, this compound probably results from microbial. degradation of intact bacteriohopanepolyols (BHP), which can be used as indicators for bacterial abundances and phyla. TNH is most likely produced at the brine-sea water interface where sedimenting organic matter accumulates and, if the redoxcline corresponds to the density gradient, the organic matter is subjected to efficient aerobic bacterial degradation processes. However, during high bioproductivity stage (Younger Dryas) the redoxcline was probably higher in the water column and thus, a significant TNH production at the brine-sea water interface did not occur at times of sapropel formation in the northern Red Sea deeps. (C) 2007 Elsevier B.V All rights reserved

Genome-Wide Association Analysis of Oxidative Stress Resistance in Drosophila melanogaster

Background: Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress. Methods and Findings: We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genomewide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs) associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67–79 % and 56–66 % of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis. Conclusions: We identified novel candidate genes associated with variation in resistance to oxidative stress that hav