The Sense of the Scripture: Re-Examined in Light of PhilosophIcal Hermeneutics and Recent Literary Approaches

In the context of romanticism in which scientific exegesis emerged in the nineteenth century, the psychological interpretation proposed by Schleiermacher and the positivistic postulates that characterized the theory of understanding set forth by Dilthey have influenced the concept of the literal sense of the Bible, conceived as the sense intended by the author. But hermeneutics has undergone a decisive shift under the influence of the phenomenology of knowledge. The intrinsic and cyclic relationship between the object known and the knowing subject, explored by Heidegger, has been taken up and developed by Bultmann (preunderstanding), Gadamer (appurtenance/fusion of horizons), and Ricoeur (distanciation, cycle of explication-comprehension). The recent literary methods propose certain procedures of the analysis of texts in order to advance the understanding of the sense of the text. The quest centers on the intention of the work rather than the intention of the author and on the role of the subject-reader, which leads to the recognition of multiple readings and the tradition of the effects of the sense. The reflection on the biblical sense requires us, however, to bear in mind some specific characteristics of biblical texts, notably the historical reality at their source and the recovery of the notion of the spiritual sense

The Effects of Oxidation on the Refractive Index of Uranium Thin Films in the Extreme Ultraviolet

We measured the transmittance and reflectance of two samples in the extreme ultraviolet (XUV) at the Advanced Light Source at Lawrence Berkeley National Laboratory. The samples were prepared with approximately 20 nm of UOx with one reactively sputtered onto a diode, and one allowed to oxidize naturally on an identical diode. Fitting the reflectance data to the Parratt model yielded a more precise thickness of the UOx film. This thickness combined with a simple analysis of the transmission measurements provides estimates for the imaginary part of the index of refraction for UOx at approximately every tenth of a nanometer from about 3 nm to 30 nm with emphasis in the 12- to 13-nm range. Using these values, a first approximation for the real part of the refractive index has also been calculated. These values provide researchers with information for modeling, design, and fabrication of optical systems in the extreme ultraviolet

Foldable structures and the natural design of pollen grains

Upon release from the anther, pollen grains of angiosperm flowers are exposed to a dry environment and dehydrate. To survive this process, pollen grains possess a variety of physiological and structural adaptations. Perhaps the most striking of these adaptations is the ability of the pollen wall to fold onto itself to prevent further desiccation. Roger P. Wodehouse coined the term harmomegathy for this folding process in recognition of the critical role it plays in the survival of the pollen grain. There is still, however, no quantitative theory that explains how the structure of the pollen wall contributes to harmomegathy. Here we demonstrate that simple geometrical and mechanical principles explain how wall structure guides pollen grains toward distinct folding pathways. We found that the presence of axially elongated apertures of high compliance is critical for achieving a predictable and reversible folding pattern. Moreover, the intricate sculpturing of the wall assists pollen closure by preventing mirror buckling of the surface. These results constitute quantitative structure-function relationships for pollen harmomegathy and provide a framework to elucidate the functional significance of the very diverse pollen morphologies observed in angiosperms.Physic

Biochemical and Structural Characterization of Selective Allosteric Inhibitors of the Plasmodium falciparum Drug Target, Prolyl-tRNA-synthetase

Plasmodium falciparum (<i>Pf</i>) prolyl-tRNA synthetase (ProRS) is one of the few chemical-genetically validated drug targets for malaria, yet highly selective inhibitors have not been described. In this paper, approximately 40,000 compounds were screened to identify compounds that selectively inhibit <i>Pf</i>ProRS enzyme activity versus Homo sapiens (<i>Hs</i>) ProRS. X-ray crystallography structures were solved for apo, as well as substrate- and inhibitor-bound forms of <i>Pf</i>ProRS. We identified two new inhibitors of <i>Pf</i>ProRS that bind outside the active site. These two allosteric inhibitors showed >100 times specificity for <i>Pf</i>ProRS compared to <i>Hs</i>ProRS, demonstrating this class of compounds could overcome the toxicity related to <i>Hs</i>ProRS inhibition by halofuginone and its analogues. Initial medicinal chemistry was performed on one of the two compounds, guided by the cocrystallography of the compound with <i>Pf</i>ProRS, and the results can instruct future medicinal chemistry work to optimize these promising new leads for drug development against malaria

Identifying the determinants of premature mortality in Russia: overcoming a methodological challenge

<p>Abstract</p> <p>Background</p> <p>It is thought that excessive alcohol consumption is related to the high mortality among working age men in Russia. Moreover it has been suggested that alcohol is a key proximate driver of the very sharp fluctuations in mortality seen in this group since the mid-1980s. Designing an individual-level study suitable to address the potential acute effects of alcohol consumption on mortality in Russia has posed a challenge to epidemiologists, especially because of the need to identify factors that could underlie the rapid changes up and down in mortality rates that have been such a distinctive feature of the Russian mortality crisis. In order to address this study question which focuses on exposures acting shortly before sudden death, a cohort would be unfeasibly large and would suffer from recruitment bias.</p> <p>Methods</p> <p>Although the situation in Russia is unusual, with a very high death rate characterised by many sudden and apparently unexpected deaths in young men, the methodological problem is common to research on any cause of death where many deaths are sudden.</p> <p>Results</p> <p>We describe the development of an innovative approach that has overcome some of these challenges: a case-control study employing proxy informants and external data sources to collect information about proximate determinants of mortality.</p> <p>Conclusion</p> <p>This offers a set of principles that can be adopted by epidemiologists studying sudden and unexpected deaths in other settings.</p

COL4A1 Mutations Cause Ocular Dysgenesis, Neuronal Localization Defects, and Myopathy in Mice and Walker-Warburg Syndrome in Humans

Muscle-eye-brain disease (MEB) and Walker Warburg Syndrome (WWS) belong to a spectrum of autosomal recessive diseases characterized by ocular dysgenesis, neuronal migration defects, and congenital muscular dystrophy. Until now, the pathophysiology of MEB/WWS has been attributed to alteration in dystroglycan post-translational modification. Here, we provide evidence that mutations in a gene coding for a major basement membrane protein, collagen IV alpha 1 (COL4A1), are a novel cause of MEB/WWS. Using a combination of histological, molecular, and biochemical approaches, we show that heterozygous Col4a1 mutant mice have ocular dysgenesis, neuronal localization defects, and myopathy characteristic of MEB/WWS. Importantly, we identified putative heterozygous mutations in COL4A1 in two MEB/WWS patients. Both mutations occur within conserved amino acids of the triple-helix-forming domain of the protein, and at least one mutation interferes with secretion of the mutant proteins, resulting instead in intracellular accumulation. Expression and posttranslational modification of dystroglycan is unaltered in Col4a1 mutant mice indicating that COL4A1 mutations represent a distinct pathogenic mechanism underlying MEB/WWS. These findings implicate a novel gene and a novel mechanism in the etiology of MEB/WWS and expand the clinical spectrum of COL4A1-associated disorders