The pneumococcal response to oxidative stress includes a role for Rgg

Streptococcus pneumoniae resides in the oxygen-rich environment of the upper respiratory tract, and therefore the ability to survive in the presence of oxygen is an important aspect of its in vivo survival. To investigate how S. pneumoniae adapts to oxygen, we determined the global gene expression profile of the micro-organism in aerobiosis and anaerobiosis. It was found that exposure to aerobiosis elevated the expression of 54 genes, while the expression of 15 genes was downregulated. Notably there were significant changes in putative genome plasticity and hypothetical genes. In addition, increased expression of rgg, a putative transcriptional regulator, was detected. To test the role of Rgg in the pneumococcal oxidative stress response, an isogenic mutant was constructed. It was found that the mutant was sensitive to oxygen and paraquat, but not to H2O2. In addition, the absence of Rgg strongly reduced the biofilm-forming ability of an unencapsulated pneumococcus. Virulence studies showed that the median survival time of mice infected intranasally with the rgg mutant was significantly longer than that of the wild-type-infected group, and the animals infected with the mutant developed septicaemia later than those infected intranasally with the wild-type

On relativization of the Sommerfeld-Gamow-Sakharov factor

The Sommerfeld-Gamow-Sakharov factor is considered for the general case of arbitrary masses and energies. It is shown that the scalar triangular one-loop diagram gives the Coulomb singularity in radiative corrections at the threshold. The singular part of the correction is factorized at the complete Born cross section regardless of its partial wave decomposition. Different approaches to generalize the factor are discussed.Comment: 9 pages, 4 figures; references and discussion are extende

The Astrophysics of Ultrahigh Energy Cosmic Rays

The origin of the highest energy cosmic rays is still unknown. The discovery of their sources will reveal the workings of the most energetic astrophysical accelerators in the universe. Current observations show a spectrum consistent with an origin in extragalactic astrophysical sources. Candidate sources range from the birth of compact objects to explosions related to gamma-ray bursts or to events in active galaxies. We discuss the main effects of propagation from cosmologically distant sources including interactions with cosmic background radiation and magnetic fields. We examine possible acceleration mechanisms leading to a survey of candidate sources and their signatures. New questions arise from an observed hint of sky anisotropies and an unexpected evolution of composition indicators. Future observations may reach the necessary sensitivity to achieve charged particle astronomy and to observe ultrahigh energy photons and neutrinos, which will further illuminate the workings of the universe at these extreme energies. In addition to fostering a new understanding of high-energy astrophysical phenomena, the study of ultrahigh energy cosmic rays can constrain the structure of the Galactic and extragalactic magnetic fields as well as probe particle interactions at energies orders of magnitude higher than achieved in terrestrial accelerators.Comment: Draft of solicited review article; 44 pages and 12 figures; Final version to appear in Annual Review of Astronomy and Astrophysics vol. 49 (2011

Schwarzschild black hole levitating in the hyperextreme Kerr field

The equilibrium configurations between a Schwarzschild black hole and a hyperextreme Kerr object are shown to be described by a three-parameter subfamily of the extended double-Kerr solution. For this subfamily, its Ernst potential and corresponding metric functions, we provide a physical representation which employs as arbitrary parameters the individual Komar masses and relative coordinate distance between the sources. The calculation of horizon's local angular velocity induced in the Schwarzschild black hole by the Kerr constituent yields a simple expression inversely proportional to the square of the distance parameter.Comment: 6 pages, 1 figure; improved versio

Exploring Sustainable Supply Chain Management: A Social Network Perspective

Purpose The implementation of sustainable supply chain management (SCM) calls for an acknowledgement of uncertainty inherent in complex environment. Confucianist society forms social networks in Confucianist society, called guanxi networks, influence economic behaviours and business practices in the workplace. The purpose of this study is to explore how these social networks influence the implementation of sustainable SCM. In doing so, this study aims to critically investigate the constructs of guanxi networks, their impact on flow of supply chain capital and how this leverages the implementation of sustainable SCM. Design/methodology/approach Two systematic literature reviews are conducted to understand the constructs of social networks in Confucianist culture and their impacts on the flow of supply chain capitals. The reviews also analyse evidence related to the economic, social and environmental practices to reveal the current state of the literature and research gaps. Propositions and a framework are developed to support future research in this area. Findings The constructs of ganqing, renqing, xinren and mianzi in guanxi networks have expanded the contexts of social networks in Western literature. Guanxi networks increase the flow of supply chain capital and generate trust between players, thus enhancing capabilities to implement sustainable SCM. Guanxi networks also create the mechanism of network governance with which to increase sustainable SCM implementation under the institutional logics of sustainability. Research limitations/implications The conceptual framework and justification are based on the reviews of current studies in the field. Future empirical study is encouraged to test the propositions, both in Confucianist culture and other countries with culture of social networks. Originality/value Social networks are socially constructed concepts. The constructs of guanxi networks revealed in this study have developed the knowledge of Western-based social network theory. Besides, arguments from a social network perspective provide an alternative answer to explain increased behavioural commitment and companies’ investment in sustainable SCM. This study helps practitioners understand the logic of this social norm and to use it to maximise their operation outputs, including sustainable SCM implementation

Retinal gene therapy with a large MYO7A cDNA using adeno-associated virus.

Usher 1 patients are born profoundly deaf and then develop retinal degeneration. Thus they are readily identified before the onset of retinal degeneration, making gene therapy a viable strategy to prevent their blindness. Here, we have investigated the use of adeno-associated viruses (AAVs) for the delivery of the Usher 1B gene, MYO7A, to retinal cells in cell culture and in Myo7a-null mice. MYO7A cDNA, under control of a smCBA promoter, was packaged in single AAV2 and AAV5 vectors and as two overlapping halves in dual AAV2 vectors. The 7.9-kb smCBA-MYO7A exceeds the capacity of an AAV vector; packaging of such oversized constructs into single AAV vectors may involve fragmentation of the gene. Nevertheless, the AAV2 and AAV5 single vector preparations successfully transduced photoreceptor and retinal pigment epithelium cells, resulting in functional, full-length MYO7A protein and correction of mutant phenotypes, suggesting successful homologous recombination of gene fragments. With discrete, conventional-sized dual AAV2 vectors, full-length MYO7A was detected, but the level of protein expression was variable, and only a minority of cells showed phenotype correction. Our results show that MYO7A therapy with AAV2 or AAV5 single vectors is efficacious; however, the dual AAV2 approach proved to be less effective

Higher Equations of Motion in Boundary Liouville Field Theory

In addition to the ordinary bulk higher equations of motion in the boundary version of the Liouville conformal field theory, an infinite set of relations containing the boundary operators is found. These equations are in one-to-one correspondence with the singular representations of the Virasoro algebra. We comment on the possible applications in the context of minimal boundary Liouville gravity.Comment: 18 page

Metabolite biomarker discovery for metabolic diseases by flux analysis

Metabolites can serve as biomarkers and their identification has significant importance in the study of biochemical reaction and signalling networks. Incorporating metabolic and gene expression data to reveal biochemical networks is a considerable challenge, which attracts a lot of attention in recent research. In this paper, we propose a promising approach to identify metabolic biomarkers through integrating available biomedical data and disease-specific gene expression data. A Linear Programming (LP) based method is then utilized to determine flux variability intervals, therefore enabling the analysis of significant metabolic reactions. A statistical approach is also presented to uncover these metabolites. The identified metabolites are then verified by comparing with the results in the existing literature. The proposed approach here can also be applied to the discovery of potential novel biomarkers. © 2012 IEEE.published_or_final_versio

Mol-CycleGAN - a generative model for molecular optimization

Designing a molecule with desired properties is one of the biggest challenges in drug development, as it requires optimization of chemical compound structures with respect to many complex properties. To augment the compound design process we introduce Mol-CycleGAN - a CycleGAN-based model that generates optimized compounds with high structural similarity to the original ones. Namely, given a molecule our model generates a structurally similar one with an optimized value of the considered property. We evaluate the performance of the model on selected optimization objectives related to structural properties (presence of halogen groups, number of aromatic rings) and to a physicochemical property (penalized logP). In the task of optimization of penalized logP of drug-like molecules our model significantly outperforms previous results