1,973 research outputs found

    Eternity and time in the theology of Karl Barth: an essay in dogmatic and philosophical theology

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    What has Karl Barth (considered by some to be the greatest theologian of the twentieth century) to say about the problem of time and thus eternity? Has what he wrote much significance and how does it relate to both the history of theology and philosophy as well as the modern era?The Enlightenment conditioned the thought of the nineteenth century particularly as regards the possible foundations of systematic theological thought. The dialectic of antitheses (that is of eternity and time, finite and infinite) was subsumed in the complex agnosticism of Kant's transcendental idealism; resolved into overall monistic synthesis by Hegel; broken apart in Trendelenburg's critique; and, finally, reasserted in existential paradox by Kierkegaard. Barth in his early work extended Kierkegaard's precarious Christological Paradox to destruction in a logical reductio thus making a new theological starting-point an imperative need.Barth posited this new beginning in the Word of God, the threefold occurrence of which is grounded upon God and thus the doctrine of God. The historicity of God's own being in his trinitarian life constitutes the 'possibility' of the 'reality' of revelation and as such contains within itself an understanding of time. It is this which is explicated in the main body of the thesis.God's being in the Trinity is being in act and the temporal correlate of this fundamental reality is the doctrine of eternity. Given the exclusive source of the iv knowledge of God in revelation, the 'full contemporaneity* of the divine act assumes crucial significance because the basis of the time of revelation is to be given in revelation itself. The doctrine of *God's time* (eternity) posits the active triumph of God's dynamic freedom in his unseparated past, present and future over the division and loss of 'before' and 'after* in time. The theological impulse of Barth's thought is expressed in the integration of God's being and his perfections.The central doctrine of 'God's time' is exploited throughout the Church Dogmatics in the doctrines of God, election, incarnation, Christology, creation and of 'Man in his Time*. The latter passage, usually seen as Barth's definitive statement on time is in fact merely the overt consummation of a theological theory of time which has been used extensively. Barth's doctrine is a creative developĀ¬ ment of many strands to be found in the Christian tradition. It contains, however, certain flaws and ambiguities which reflect upon the whole theological structure of the Church Dogmatics. Most serious of these is the linguistic dialectic apparent in the negation of man's time and yet the creative derivation of 'God's time' from a selective analysis of common-sense concepts of time. This is the logical Achilles' heel of the finest theological theory of time in the history of the western tradition

    150,000-year palaeoclimate record from northern Ethiopia supports early, multiple dispersals of modern humans from Africa

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    Climatic change is widely acknowledged to have played a role in the dispersal of modern humans out of Africa, but the timing is contentious. Dispersal is often linked to climatic change at ~60,000 years ago, despite increasing evidence for earlier presence of modern humans in Asia. Here we report a deep seismic and near-continuous core record of the last 150,000 years from Lake Tana in the Ethiopian highlands, close to the earliest modern human fossil sites and to postulated dispersal routes. The record shows varied climate at the end of the penultimate glacial, followed by an abrupt change to relatively stable moist climate during the last interglacial. These conditions would have favored population growth and range expansion, supporting models of early, multiple dispersals of modern humans from AfricapublishersversionPeer reviewe

    Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

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    Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45ā€ˆ263 whole blood donors (22ā€ˆ466 men, 22ā€ˆ797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45ā€ˆ042 (99Ā·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1Ā·69 units (95% CI 1Ā·59ā€“1Ā·80; approximately 795 mL) in the 8-week group and by 0Ā·79 units (0Ā·69ā€“0Ā·88; approximately 370 mL) in the 10-week group (p<0Ā·0001 for both). In women, compared with the 16-week group, it increased by 0Ā·84 units (95% CI 0Ā·76ā€“0Ā·91; approximately 395 mL) in the 12-week group and by 0Ā·46 units (0Ā·39ā€“0Ā·53; approximately 215 mL) in the 14-week group (p<0Ā·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0Ā·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

    Ī±1-FANGs: Protein Ligands Selective for the Ī±-Bungarotoxin Site of the Ī±1-Nicotinic Acetylcholine Receptor

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    Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that play a central role in neuronal and neuromuscular signal transduction. Here, we have developed FANG ligands, fibronectin antibody-mimetic nicotinic acetylcholine receptor-generated ligands, using mRNA display. We generated a 1 trillion-member primary e10FnIII library to target a stabilized Ī±1 nicotinic subunit (Ī±211). This library yielded 270000 independent potential protein binding ligands. The lead sequence, Ī±1-FANG1, represented 25% of all library sequences, showed the highest-affinity binding, and competed with Ī±-bungarotoxin (Ī±-Btx). To improve this clone, a new library based on Ī±1-FANG1 was subjected to heat, protease, binding, off-rate selective pressures, and point mutations. This resulted in Ī±1-FANG2 and Ī±1-FANG3. These proteins bind Ī±211 with KDvalues of 3.5 nM and 670 pM, respectively, compete with Ī±-Btx, and show improved subunit specificity. Ī±1-FANG3 is thermostable (T_m = 62 Ā°C) with a 6 kcal/mol improvement in folding free energy compared with that of the parent Ī±1-FANG1. Ī±1-FANG3 competes directly with the Ī±-Btx binding site of intact neuromuscular heteropentamers [(Ī±1)_2Ī²1Ī³Ī“] in mammalian culture-derived cellular membranes and in Xenopus laevis oocytes expressing these nAChRs. This work demonstrates that mRNA display against a monomeric ecto-domain of a pentamer has the capability to select ligands that bind that subunit in both a monomeric and a pentameric context. Overall, our work provides a route to creating a new family of stable, well-behaved proteins that specifically target this important receptor family

    Ī±1-FANGs: Protein Ligands Selective for the Ī±-Bungarotoxin Site of the Ī±1-Nicotinic Acetylcholine Receptor

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    Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that play a central role in neuronal and neuromuscular signal transduction. Here, we have developed FANG ligands, fibronectin antibody-mimetic nicotinic acetylcholine receptor-generated ligands, using mRNA display. We generated a 1 trillion-member primary e10FnIII library to target a stabilized Ī±1 nicotinic subunit (Ī±211). This library yielded 270000 independent potential protein binding ligands. The lead sequence, Ī±1-FANG1, represented 25% of all library sequences, showed the highest-affinity binding, and competed with Ī±-bungarotoxin (Ī±-Btx). To improve this clone, a new library based on Ī±1-FANG1 was subjected to heat, protease, binding, off-rate selective pressures, and point mutations. This resulted in Ī±1-FANG2 and Ī±1-FANG3. These proteins bind Ī±211 with KDvalues of 3.5 nM and 670 pM, respectively, compete with Ī±-Btx, and show improved subunit specificity. Ī±1-FANG3 is thermostable (T_m = 62 Ā°C) with a 6 kcal/mol improvement in folding free energy compared with that of the parent Ī±1-FANG1. Ī±1-FANG3 competes directly with the Ī±-Btx binding site of intact neuromuscular heteropentamers [(Ī±1)_2Ī²1Ī³Ī“] in mammalian culture-derived cellular membranes and in Xenopus laevis oocytes expressing these nAChRs. This work demonstrates that mRNA display against a monomeric ecto-domain of a pentamer has the capability to select ligands that bind that subunit in both a monomeric and a pentameric context. Overall, our work provides a route to creating a new family of stable, well-behaved proteins that specifically target this important receptor family

    Fluid venting in the eastern Aleutian subduction zone

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    Fluid venting has been observed along 800 km of the Alaska convergent margin. The fluid venting sites are located near the deformation front, are controlled by subsurface structures, and exhibit the characteristics of cold seeps seen in other convergent margins. The more important characteristics include (1) methane plumes in the lower water column with maxima above the seafloor which are traceable to the initial deformation ridges; (2) prolific colonies of vent biota aligned and distributed in patches controlled by fault scarps, overā€steepened folds or outcrops of bedding planes; (3) calcium carbonate and barite precipitates at the surface and subsurface of vents; and (4) carbon isotope evidence from tissue and skeletal hard parts of biota, as well as from carbonate precipitates, that vents expel either methaneā€ or sulfideā€dominated fluids. A biogeochemical approach toward estimating fluid flow rates from individual vents based on oxygen flux measurements and vent fluid analysis indicates a mean value of 5.5Ā±0.7 L māˆ’2 dāˆ’1 for tectonicsā€induced water flow [Wallmann et al., 1997b]. A geophysical estimate of dewatering from the same area [von Huene et al., 1997] based on sediment porosity reduction shows a fluid loss of 0.02 L māˆ’2 dāˆ’1 for a 5.5 km wide converged segment near the deformation front. Our videoā€guided surveys have documented vent biota across a minimum of 0.1% of the area of the convergent segment off Kodiak Island; hence an average rate of 0.006 L māˆ’2 dāˆ’1 is estimated from the biogeochemical approach. The two estimates for tectonicsā€induced water flow from the accretionary prism are in surprisingly good agreement
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