Flavour-coherent propagators and Feynman rules: Covariant cQPA formulation

We present a simplified and generalized derivation of the flavour-coherent propagators and Feynman rules for the fermionic kinetic theory based on coherent quasiparticle approximation (cQPA). The new formulation immediately reveals the composite nature of the cQPA Wightman function as a product of two spectral functions and an effective two-point interaction vertex, which contains all quantum statistical and coherence information. We extend our previous work to the case of nonzero dispersive self-energy, which leads to a broader range of applications. By this scheme, we derive flavoured kinetic equations for local 2-point functions $S^{}_\mathbf{k}(t,t)$, which are reminiscent of the equations of motion for the density matrix. We emphasize that in our approach all the interaction terms are derived from first principles of nonequilibrium quantum field theory.Comment: 20 pages, 3 figures. Minor modifications, version published in JHE

The origin of life: chemical evolution of a metabolic system in a mineral honeycomb?

For the RNA-world hypothesis to be ecologically feasible, selection mechanisms acting on replicator communities need to be invoked and the corresponding scenarios of molecular evolution specified. Complementing our previous models of chemical evolution on mineral surfaces, in which selection was the consequence of the limited mobility of macromolecules attached to the surface, here we offer an alternative realization of prebiotic group-level selection: the physical encapsulation of local replicator communities into the pores of the mineral substrate. Based on cellular automaton simulations we argue that the effect of group selection in a mineral honeycomb could have been efficient enough to keep prebiotic ribozymes of different specificities and replication rates coexistent, and their metabolic cooperation protected from extensive molecular parasitism. We suggest that mutants of the mild parasites persistent in the metabolic system can acquire useful functions such as replicase activity or the production of membrane components, thus opening the way for the evolution of the first autonomous protocells on Earth

Antibody-based protection against HIV infection by vectored immunoprophylaxis

Despite tremendous efforts, development of an effective vaccine against human immunodeficiency virus (HIV) has proved an elusive goal. Recently, however, numerous antibodies have been identified that are capable of neutralizing most circulating HIV strains. These antibodies all exhibit an unusually high level of somatic mutation, presumably owing to extensive affinity maturation over the course of continuous exposure to an evolving antigen. Although substantial effort has focused on the design of immunogens capable of eliciting antibodies de novo that would target similar epitopes, it remains uncertain whether a conventional vaccine will be able to elicit analogues of the existing broadly neutralizing antibodies. As an alternative to immunization, vector-mediated gene transfer could be used to engineer secretion of the existing broadly neutralizing antibodies into the circulation. Here we describe a practical implementation of this approach, which we call vectored immunoprophylaxis (VIP), which in mice induces lifelong expression of these monoclonal antibodies at high concentrations from a single intramuscular injection. This is achieved using a specialized adeno-associated virus vector optimized for the production of full-length antibody from muscle tissue. We show that humanized mice receiving VIP appear to be fully protected from HIV infection, even when challenged intravenously with very high doses of replication-competent virus. Our results suggest that successful translation of this approach to humans may produce effective prophylaxis against HIV

Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission

The vast majority of new HIV infections result from relatively inefficient transmission of the virus across mucosal surfaces during sexual intercourse. A consequence of this inefficiency is that small numbers of transmitted founder viruses initiate most heterosexual infections. This natural bottleneck to transmission has stimulated efforts to develop interventions that are aimed at blocking this step of the infection process. Despite the promise of this strategy, clinical trials of preexposure prophylaxis have had limited degrees of success in humans, in part because of lack of adherence to the recommended preexposure treatment regimens. In contrast, a number of existing vaccines elicit systemic immunity that protects against mucosal infections, such as the vaccines for influenza and human papilloma virus. We recently demonstrated the ability of vectored immunoprophylaxis (VIP) to prevent intravenous transmission of HIV in humanized mice using broadly neutralizing antibodies. Here we demonstrate that VIP is capable of protecting humanized mice from intravenous as well as vaginal challenge with diverse HIV strains despite repeated exposures. Moreover, animals receiving VIP that expresses a modified VRC07 antibody were completely resistant to repetitive intravaginal challenge by a heterosexually transmitted founder HIV strain, suggesting that VIP may be effective in preventing vaginal transmission of HIV between humans

Midlands Cadences: Narrative Voices in the Work of Alan Sillitoe

This paper will examine excerpts from a range of Alan Sillitoe’s prose fiction, most notably Saturday Night and Sunday Morning (1958) and short stories from the collection The Loneliness of the Long-Distance Runner (1958), via a comparative exploration of the texts’ representations of Midlands English demotic. Both texts enact Bakhtin’s notion of novelistic dialogism and find much expressive capital in the tension between discourses: between the oral and the written. Indeed, it could be argued that much of Sillitoe’s work functions as a direct challenge to dominant notions of the literary. The narrative discourse attempts to trace a link between the quotidian experience of the Midlands English working classes represented and the demotic language which they speak. His technique also explores the link between language and sensibility; i.e. verbal articulacy need not be a limit to expression of a character’s distinctive identity. In contrast to the more radical techniques of novelists like James Kelman and Irvine Welsh, all instances of phonetically-rendered demotic remain imprisoned by what Joyce called ‘perverted commas’ – as direct speech. However, the diegetic narrative discourse itself is redolent of registers rooted in 1950s English working class life. The texts also contain different methods of representing their protagonists’ consciousness through their own idiolect. In Saturday Night and Sunday Morning, this is evidenced by the use of the second person ‘you’. It functions simultaneously as a representation of Seaton’s consciousness in the oral register which he might choose to articulate it, and as a dialogic ‘sideways glance’ at the reader and assumed shared experience. The second is more redolent of internal monologue, using the first-person form (as seen in the homodiegetic narration of the second novel); crucially, though, it remains in Standard English, if explicitly orientated towards oral register. Sillitoe’s is a novelistic discourse which refuses to normalise itself to accord with the conventions of classic realism, and as such prefigures the ambitions of many contemporary writers who incline their narrative voices towards the oral – asserting the right of a character’s dialect/idiolect to be the principal register of the narrative. The paper will demonstrate this thesis through the ideas of Bakhtin, and through an analytical taxonomy derived from literary stylistics. It aims to propose a model which can be used to analyse and explore any fiction which has been labelled as ‘working class’, and asserts that such an approach leads to a more principled characterisation of working class fiction (based on its use of language) than current literary-critical discussions based simply on cultural/social context and biography

Integrative analysis of large scale expression profiles reveals core transcriptional response and coordination between multiple cellular processes in a cyanobacterium

<p>Abstract</p> <p>Background</p> <p>Cyanobacteria are the only known prokaryotes capable of oxygenic photosynthesis. They play significant roles in global biogeochemical cycles and carbon sequestration, and have recently been recognized as potential vehicles for production of renewable biofuels. <it>Synechocystis </it>sp. PCC 6803 has been extensively used as a model organism for cyanobacterial studies. DNA microarray studies in <it>Synechocystis </it>have shown varying degrees of transcriptome reprogramming under altered environmental conditions. However, it is not clear from published work how transcriptome reprogramming affects pre-existing networks of fine-tuned cellular processes.</p> <p>Results</p> <p>We have integrated 163 transcriptome data sets generated in response to numerous environmental and genetic perturbations in <it>Synechocystis</it>. Our analyses show that a large number of genes, defined as the core transcriptional response (CTR), are commonly regulated under most perturbations. The CTR contains nearly 12% of <it>Synechocystis </it>genes found on its chromosome. The majority of genes in the CTR are involved in photosynthesis, translation, energy metabolism and stress protection. Our results indicate that a large number of differentially regulated genes identified in most reported studies in <it>Synechocystis </it>under different perturbations are associated with the general stress response. We also find that a majority of genes in the CTR are coregulated with 25 regulatory genes. Some of these regulatory genes have been implicated in cellular responses to oxidative stress, suggesting that reactive oxygen species are involved in the regulation of the CTR. A Bayesian network, based on the regulation of various KEGG pathways determined from the expression patterns of their associated genes, has revealed new insights into the coordination between different cellular processes.</p> <p>Conclusion</p> <p>We provide here the first integrative analysis of transcriptome data sets generated in a cyanobacterium. This compilation of data sets is a valuable resource to researchers for all cyanobacterial gene expression related queries. Importantly, our analysis provides a global description of transcriptional reprogramming under different perturbations and a basic framework to understand the strategies of cellular adaptations in <it>Synechocystis</it>.</p

Optical pump rectification emission: route to terahertz free-standing surface potential diagnostics

We introduce a method for diagnosing the electric surface potential of a semiconductor based on THz surface generation. In our scheme, that we name Optical Pump Rectification Emission, a THz field is generated directly on the surface via surface optical rectification of an ultrashort pulse after which the DC surface potential is screened with a second optical pump pulse. As the THz generation directly relates to the surface potential arising from the surface states, we can then observe the temporal dynamics of the static surface field induced by the screening effect of the photo-carriers. Such an approach is potentially insensitive to bulk carrier dynamics and does not require special illumination geometries

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P &lt; 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T&gt;C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P &lt; .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies