946 resultados para Filmer, Robert, Sir, d. 1653.


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Mode of access: Internet.

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Mode of access: Internet.

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First published under title: Ante-Nicene Christian library, Edinburgh, 1867-97.

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Vol. [7], "Life": 2nd ed., 1846. Vol. 5 in two parts, bound in two volumes.

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The cores and dredges described in this report were taken during the Robert Conrad Cruise 8 from November 1963 until August 1964 by the Lamont Geological Observatory, Columbia University from the R/V Robert Conrad. A total of 140 cores and dredges were recovered and are available at Lamont-Doherty Earth Observatory for sampling and study.

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Few reported inhibitors of secretory phospholipase A(2) enzymes inhibit the IIa human isoform (hnpsPLA(2)-IIa) noncovalently at submicromolar concentrations. Herein, the simple chiral precursor D-tyrosine was derivastised to give a series of potent new inhibitors of hnpsPLA(2)-IIa. A 2.2-Angstrom crystal structure shows an inhibitor bound in the active site of the enzyme, chelated to a Ca2+ ion through carboxylate and amide oxygen atoms, H bonded through an amide NH group to His48, with multiple hydrophobic contacts and a T-shaped aromatic-group-His6 interaction. Antiinflammatory activity is also demonstrated for two compounds administered orally to rats.

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Relatively few cyclic peptides have reached the pharmaceutical marketplace during the past decade, most produced through fermentation rather than made synthetically. Generally, this class of compounds is synthesized for research purposes on milligram scales by solid-phase methods, but if the potential of macrocyclic peptidomimetics is to be realized, low-cost larger scale solution-phase syntheses need to be devised and optimized to provide sufficient quantities for preclinical, clinical, and commercial uses. Here, we describe a cheap, medium-scale, solution-phase synthesis of the first reported highly potent, selective, and orally active antagonist of the human C5a receptor. This compound, Ac-Phe[Orn-Pro-D-Cha-Trp-Arg], known as 3D53, is a macrocyclic peptidomimetic of the human plasma protein C5a and displays excellent antiinflammatory activity in numerous animal models of human disease. In a convergent approach, two tripeptide fragments Ac-Phe-Orn-(Boc)-Pro-OH and H-D-Cha-Trp(For)-Arg-OEt were first prepared by high-yielding solution-phase couplings using a mixed anhydride method before coupling them to give a linear hexapeptide which, after deprotection, was obtained in 38% overall yield from the commercially available amino acids. Cyclization in solution using BOP reagent gave the antagonist in 33% yield (13% overall) after HPLC purification. Significant features of the synthesis were that the Arg side chain was left unprotected throughout, the component Boe-D-Cha-OH was obtained very efficiently via hydrogenation Of D-Phe with PtO2 in TFA/water, the tripeptides were coupled at the Pro-Cha junction to minimize racemization via the oxazolone pathway, and the entire synthesis was carried out without purification of any intermediates. The target cyclic product was purified (>97%) by reversed-phase HPLC. This convergent synthesis with minimal use of protecting groups allowed batches of 50100 g to be prepared efficiently in high yield using standard laboratory equipment. This type of procedure should be useful for making even larger quantities of this and other macrocyclic peptidomimetic drugs.

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Developmental vitamin D deficiency (DVD) has been shown to alter the orderly pattern of brain development. Even though the period of vitamin D deficiency is restricted to gestation this is sufficient to induce behavioural abnormalities in the adult offspring consistent with those seen in many animal models of schizophrenia. Given that some of these behavioural alterations could also be an indirect result of either impaired maternal hypothalamic pituitary axis (HPA) function (which in turn could influence maternal care) or the result of a permanent alteration in HPA function in the adult offspring we have examined HPA status in both maternal animals and adult offspring. In this study we have established that HPA function is normal in the maternally vitamin D deficient rat. We replicate the behavioural phenotype of hyperlocomotion whilst establishing that HPA function is also unchanged in the adult mate offspring. We conclude that the behavioural alterations induced by DVD deficiency are due to some adverse event in brain development rather than via an alteration in stress response. (c) 2006 Elsevier Ltd. All rights reserved.

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Tavaly ünnepelte a közgaz¡sz-társadalom Milton Friedman Nobel-­jas közgaz¡sz születésének századik évfordulóját. A jubileumi megemlékezésnek különös aktualitást ad, hogy a 2008 óta tartó pénzügyi világválság hátterében ismét fellobbant a 20. századi közgazdaságtan két meghatározó irányzata - a Friedman nevével fémjelzett monetarizmus és a Keynes és követÅ‘i által követett keynesizmus - közötti vita. E szerteágazó vitasorozat egyik "gyöngyszeme" két nemzetközileg ismert és elismert közgaz¡sz, Tim Congdon és Robert (Lord) Skidelsky, összecsapása a Standpoint hasábjain 2009-ben. A szerzÅ‘ megmutatja, hogy a vita valójában nem a pénz fontosságáról vagy a mennyiségi pénzelmélet igazságáról folyt, hanem egyrészt egy sokkal elvontabb fogalomról: a bizonytalanság közgazdasági szerepérÅ‘l, másrészt gyakorlati, gazdaságpolitikai kér©sekrÅ‘l: a monetáris és a fiskális politika lehetséges hatékonyságáról. A máig is tartó vitában "az inga többször kilengett", hol a keynesiánusok, hol a monetaristák javára, de még semmi nem ‘lt el. ____ Last year economists marked the centenary of the birth of genius among them, Milton Friedman. The commemoration was especially topical because the world financial crisis that erupted in 2008 has brought sharply into focus again the old division in 20th-century economics between monetarism and Keynesianism. One highlight in this series of disputes was the 2009 clash between two internationally known and appreciated economists Tim Congdon and Robert (Lord) Skidelsky in the columns of Standpoint. The central element in the discussion is the role of money: what kind of economic policy to pursue, monetary or fiscal, to pull troubled economies out of crisis. The question closely resembles a decisive dilemma for Keynes in the 1930s. Though Keynes turned against some basic propositions of neoclassical economics, he never challenged the importance of money to the functioning of the economy, or the validity of the quantity theory of money. The author argues here that the issue is not about the formal category of money or demand for it, but about the far deeper economic concept of the role of uncertainty in economics. Another aspect concerns the relative efficiency of various kinds of economic policy, i. e. the strengths and weaknesses of monetary and fiscal policies.

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Approaches to quantify the organic carbon accumulation on a global scale generally do not consider the small-scale variability of sedimentary and oceanographic boundary conditions along continental margins. In this study, we present a new approach to regionalize the total organic carbon (TOC) content in surface sediments (<5 cm sediment depth). It is based on a compilation of more than 5500 single measurements from various sources. Global TOC distribution was determined by the application of a combined qualitative and quantitative-geostatistical method. Overall, 33 benthic TOC-based provinces were defined and used to process the global distribution pattern of the TOC content in surface sediments in a 1°x1° grid resolution. Regional dependencies of data points within each single province are expressed by modeled semi-variograms. Measured and estimated TOC values show good correlation, emphasizing the reasonable applicability of the method. The accumulation of organic carbon in marine surface sediments is a key parameter in the control of mineralization processes and the material exchange between the sediment and the ocean water. Our approach will help to improve global budgets of nutrient and carbon cycles.

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The cores described in this report were taken during the R/V Robert Conrad Cruise 06 from May until June 1963 by the Lamont Geological Observatory, Columbia University. A total of 5 cores were recovered and are available at Lamont-Doherty Earth Observatory for sampling and study.