Lipopolysaccharide-specific acyloxyacyl hydrolase

" An acyloxyacyl hydrolase from the human promyelocyte cell line HL-60 has been found to specifically hydrolyze fatty acids from their ester linkages to hydroxy groups of 3-hydroxyfatty acids, the latter being being bound in turn to lipopolysaccharide glycosaminyl residues. The hydrolyzed fatty acids may include dodecanoic acid, tetradecanoic acid and hexadecanoic acid. This enzyme showed a molecular weight by gel exclusion chromatography between about 50,000 Daltons and about 70,000 Daltons, and a molecular weight by polyacrylamide gel electrophoresis with sodium dodecylsulphate, using reduced molecular weight standards, of approximately 54,000 to 60,000 Daltons. Altered bacterial lipopolysaccharide substantially without fatty acids bound in ester linkage to hydroxy groups of 3-hydroxyfatty acids covalently linked to a glucosaminyl moiety of lipopolysaccharide lipid A are produced. Since the structure of the lipid A moiety is highly conserved, acyloxyacyl hydrolase may act on lipopolysaccharide of many different pathogenic bacteria (for example Salmonella, Escherichia, Hemophilus, and Neisseria). Such altered bacterial lipopolysaccharide, having toxicity reduced more than immunostimulatory activity, may be therapeutically useful: (1) as vaccines to prevent Gram-negative bacterial diseases by inducing antibodies to lipopolysaccharide O-polysaccharide or R-core antigens, (2) as antidotes to treat or prevent Gram-negative bacterial sepsis (""septic shock""), or (3) as adjuvants to enhance formation of antibodies to other antigens. the acyloxyacyl hydrolase itself may be prophylactically or therapeutically useful to detoxify endogenous lipopolysaccharide in patients with Gram-negative bacterial diseases. The enzyme may also be used to remove toxic lipopolysaccharide from therapeutic injectants. "Board of Regents, University of Texas Syste

Mutuality talk in a family-owned multinational: anthropological categories & critical analyses of corporate ethicizing

This article draws on work carried out as part of a collaboration between an elite business school and a family-owned multinational corporation, concerned with promoting ‘mutuality in business’ as a new frontier of responsible capitalism. While the business school partners treated mutuality as a new principle central to an emergent ethical capitalism, the corporation claimed mutuality as a long-established value unique to their company. Both interpretations foreground a central problem in recent writing on the anthropology of business/corporations: the tension between the claim that economic life is always embedded within a moral calculus, and the shift towards increasingly ethical behaviour among many corporations. Further, recent work in the anthropology of business rejects normative evaluations of corporate ethicizing. When corporations lay claim to ethical renewal, but maintain a commitment to competition and growth, then anthropologists must balance a sympathetic engagement with corporate ethicizing, and critical engagement with growth-based strategie

Reforming the international monetary system in the 1970s and 2000s: would an SDR substitution account have worked?

Advocates of a more pluralistic international monetary and financial system seek to reduce reliance on a single national currency and to bring international liquidity under collective control. One recently revived proposal would transform US dollar official reserves into claims denominated in the IMF's key currency basket, Special Drawing Rights (SDRs). Drawing on new archival evidence and simulations, this article highlights issues that derailed earlier agreement on such an account and shortcomings of design and ambition revealed by subsequent developments. One design issue was account losses if US dollar yields failed to exceed SDR yields enough to offset dollar depreciation. In fact, uncovered interest parity did not hold and could well have left the account persistently insolvent. Another shortcoming was ambition: the proposed account proved simply too small to achieve the desired lowering of the dollar's share of foreign exchange reserves. Any new proposal needs to address these shortcomings

Reforming the International Monetary System in the 1970s and 2000s: Would an SDR Substitution Account Have Worked

This paper analyzes the discussion of a substitution account in the 1970s and how the account might have performed had it been agreed in 1980. The substitution account would have allowed central banks to diversify away from the dollar into the IMF’s Special Drawing Right (SDR), comprised of US dollar, Deutschmark, French franc (later euro), Japanese yen and British pound, through transactions conducted off the market. The account’s dollar assets could fall short of the value of its SDR liabilities, and hedging would have defeated the purpose of preventing dollar sales. In the event, negotiators were unable to agree on how to distribute the open-ended cost of covering any shortfall if the dollar’s depreciation were to exceed the value of any cumulative interest rate premium on the dollar. As it turned out, the substitution account would have encountered solvency problems had the US dollar return been based on US treasury bill yields, even if a substantial fraction of the IMF’s gold had been devoted to meet the shortfall at recent high prices for gold. However, had the US dollar return been based on US treasury bond yields, the substitution account would have been solvent even without any gold backing

A signature invariant for knotted Klein graphs

We define some signature invariants for a class of knotted trivalent graphs using branched covers. We relate them to classical signatures of knots and links. Finally, we explain how to compute these invariants through the example of Kinoshita's knotted theta graph.Comment: 23 pages, many figures. Comments welcome ! Historical inaccuracy fixe

The buried Balmer-edge signatures from quasars

In our previous paper, we have reported the detection of a Balmer edge absorption feature in the polarized flux of one quasar (Ton 202). We have now found similar Balmer edge features in the polarized flux of four more quasars (4C09.72, 3C95, B2 1208+32, 3C323.1), and possibly a few more, out of 14 newly observed with the VLT and Keck telescopes. In addition, we also re-observed Ton 202, but we did not detect such a dramatic feature, apparently due to polarization variability (the two observations are one-year apart). The polarization measurements of some quasars are affected by an interstellar polarization in our Galaxy, but the measurements have been corrected for this effect reasonably well. Since the broad emission lines are essentially unpolarized and the polarization is confined only to the continuum in the five quasars including Ton 202 in both epochs, the polarized flux is considered to originate interior to the broad emission line region. The Balmer edge feature seen in the polarized flux is most simply interpreted as an intrinsic spectral feature of the quasar UV/optical continuum, or the ``Big Blue Bump'' emission. In this case, the edge feature seen in absorption indeed indicates the thermal and optically-thick nature of the continuum emitted. However, we also discuss other possible interpretations.Comment: Accepted for publication in MNRAS; 31 pages, 38 figures with reduced resolutions; the paper with a full resolution is at http://www.roe.ac.uk/~mk/papers/04Ba_vk.ps.g

Optimisation of growth conditions for ovine airway epithelial cell differentiation at an air-liquid interface

Respiratory tract infections are of significant concern in the agriculture industry. There is a requirement for the development of well-characterised in vitro epithelial cell culture models in order to dissect the diverse molecular interactions occurring at the host-pathogen interface in airway epithelia. We have analysed key factors that influence growth and differentiation of ovine tracheal epithelial cells in an air-liquid interface (ALI) culture system. Cellular differentiation was assessed at 21 days post-ALI, a time-point which we have previously shown to be sufficient for differentiation in standard growth conditions. We identified a dose-dependent response to epidermal growth factor (EGF) in terms of both epithelial thickening and ciliation levels. Maximal ciliation levels were observed with 25 ng ml-1 EGF. We identified a strict requirement for retinoic acid (RA) in epithelial differentiation as RA exclusion resulted in the formation of a stratified squamous epithelium, devoid of cilia. The pore-density of the growth substrate also had an influence on differentiation as high pore-density inserts yielded higher levels of ciliation and more uniform cell layers than low pore-density inserts. Differentiation was also improved by culturing the cells in an atmosphere of sub-ambient oxygen concentration. We compared two submerged growth media and observed differences in the rate of proliferation/expansion, barrier formation and also in terminal differentiation. Taken together, these results indicate important differences between the response of ovine tracheal epithelial cells and other previously described airway epithelial models, to a variety of environmental conditions. These data also indicate that the phenotype of ovine tracheal epithelial cells can be tailored in vitro by precise modulation of growth conditions, thereby yielding a customisable, potential infection model