Structural investigation of the HIV-1 envelope glycoprotein gp160 cleavage site, 2: relevance of an N-terminal helix

Proteolytic activation of the HIV-1 envelope glycoprotein gp160 is selectively performed by the proprotein convertase furin at the C-terminus of the sequence R508-E-K-R511 (site 1), in spite of the presence of another consensus sequence, Lys500-Ala-Lys-Arg503 (site 2). On the basis of the solution structural analysis of the synthetic peptide p498, spanning the gp160 sequence Pro498-Gly516, we previously suggested a possible role of an N-terminal helix in regulating the exposure and accessibility of the gp160 physiological cleavage site, enclosed in a loop. Here we report on the activity and conformation of the 23-residue peptide h-REKR, designed to exhibit a large N-terminal helix, followed by the gp160 native sequence, Arg508-Gly516. h-REKR is digested by furin with high efficiency, comparable to the full native p498. Circular dichroism analyses, in mixtures from pure water to 98 % trifluoroethanol, outline a significant content of helical structure in the peptide conformation. The molecular model obtained from NMR data collected in trifluoroethanol/water, by means of DYANA and AMBER simulations, indeed has helical structure on a large N-terminal segment. Such a long helix does not seem to affect the loop conformation of the C-terminal site 1-containing sequence, which exhibits the same proton chemical shifts already observed for the full native p498.     

Defining Distinction,or Four Good Reasons for Success: The Extraordinary Career of Renzo Piano

For 30 years, Renzo Piano has been producing distinguished buildings and delighting the world with his innovation and sensitivity. Here, Livio Sacchi attempts to tease out some of the reasons behind Piano's sustained success. Having gained an almost unparalleled international profile during the last couple of decades, a period that has been notoriously difficult for Italian architects, Piano's career has an almost mythic quality. It boasts one of the most unlikely competition wins of all time that ceded one of the most prestigious sites in the world, the Centre Pompidou in Paris, to two completely unknown architects in their late 20s. Copyright © 2007 John Wiley & Sons, Ltd.     

四川盆地西南边缘地区天然气保存条件研究

四川盆地西南边缘地区具有深层震旦系、二叠系产淡水,浅层下三叠统产天然气的特殊性.在充分利用地层流体性质、地层压力等资料综合分析边缘地区各构造保存条件的基础上,认为研究区保存条件主要影响因素为盖层、断层、储集层岩性、露头地表水渗入.震旦系和下二叠统为厚层块状灰岩,在构造作用下容易产生裂隙带,为露头区地表水渗入提供通道.嘉陵江组透镜状储集层的分布特点决定了嘉陵江组受地表水的影响较小.建议盆地西南边缘地区勘探以三叠系嘉陵江组气藏为主.      

Comparison of basic features and origins of oolitic shoal reservoirs between carbonate platform interior and platform margin locations in the Lower Triassic Feixianguan Formation of the Sichuan Basin, southwest China

The oolitic shoal reservoirs of the Lower Triassic Feixianguan Formation carbonates in the Sichuan Basin of southwest China are an important target for gas exploration in the basin.Their occurrence,like other cases worldwide,can be divided into two locations in general,i.e.,platform interior and platform margin locations.Their differences of reservoir features and origins,however,have not been investigated comprehensively due to different exploration degrees.This issue is addressed in this paper,to provide basic data and information for the basin’s hydrocarbon exploration and for the study of carbonate platform sedimentology and reservoir geology worldwide.We compared the features of these two types of reservoirs in detail,including the depositional and diagenetic features,pore types and petrophysical features.Based on the comparison,the origin of the reservoirs was further discussed.It is shown that the reservoirs in platform interior and platform margin locations differ significantly.The interior carbonates were deposited in moderate to high energy settings and the dominant lithologic type was limestone,which was weakly compacted and intensely cemented and has undergone meteoric dissolution.Pore types include intragranular dissolution and moldic pores,with low porosities(<6%) and low permeabilities(<0.1 mD).By contrast,the platform margin carbonates were deposited in relatively high energy settings and mainly consisted of dolostones with some limestones.The rocks were strongly compacted but incompletely cemented.As a result,some primary intergranular pores were preserved.Both meteoric solution and burial solution have taken place.There are various types of pore spaces including intergranular and intercrystalline solution pores and residual intergranular pores.This type of reservoir generally has better petrophysical properties(>9% porosity and >0.1 mD permeability) and pore-throat structures than the interior reservoirs.These differences were influenced by both primary depositional features and secondary diagenesis.For the interior carbonate reservoirs,early meteoric dissolution,weak compaction and strong cementation are important controlling factors.By contrast,the factors controlling the formation of the margin carbonate reservoirs mainly include dolomitization,preservation of primary pores and burial dissolution.     

The Potential of Coherent Radar to Support the Monitoring of the Health State of Buildings

The investigation here described is aimed at evaluating the actual capability of a Real Aperture Radar (RAR) interferometer to detect the natural vibration of urban buildings solely solicited by wind or environmental noise. The paper shortly reviews some of the most relevant non-contacting measurement techniques that can be employed for ambient vibration testing. Then it introduces the proposed RAR measurement technique. Some experimental results taken from a wide set of observations, carried out through a microwave sensor presently available on the market, are discussed. The main factors affecting the measurability of the vibration amplitude and frequency are singled out. The technique is proved to perform high sensitivity displacement measurements, down to a few microns.     

Innovative root-end filling materials based on calcium-silicates and calcium-phosphates

This in vitro study evaluated the apical sealing ability, bioactivity and biocompatibility of an experimental calcium silicate-based and two light-curing calcium silicate/calcium-phosphate cements as potential root end filling materials. A calcium silicate Portland-based (Control PC), an experimental calcium silicate (Exp. PC) and two light-curing cements (LC-CaP; LC-Si/CaP) were assessed for their alkalinising activity (pH) and biocompatibility. Single-rooted human canines were endodontically treated, filled with gutta-percha and finally submitted to apicoectomy. Root end fillings were performed using all tested cements, and their apical sealing ability was evaluated up to 4 weeks of immersion in simulated body fluid (SBF). The mineral precipitation at the apical region and the cement adaptation to root dentine were also evaluated through non-destructive optical microscopy both at 24?h and after prolonged water storage (four week). LC-CaP and LC-Si/CaP had neutral pH, the greatest sealing ability (24?h) and excellent cytocompatibility. The Exp. PC cement presented sealing ability after two and four weeks, as well as biocompatibility after four and seven days, similar to LC-CaP and LC-Si/CaP. The control PC cement showed the lowest sealing ability and the greatest cytotoxicity. Mineral precipitation was observed in all groups, while some differences were seen in terms of cement adaptation along the root canal dentine walls. The experimental light-curable cements as well as the experimental PC might be suitable root end filling materials with appropriate (in vitro) sealing ability, biocompatibility and aptitude to induce mineral precipitation.     

Mechanisms and products of surface-mediated reductive dehalogenation of carbon tetrachloride by Fe(II) on goethite

Natural attenuation processes of chlorinated solvents in soils and groundwaters are increasingly considered as options to manage contaminated sites. Under anoxic conditions, reactions with ferrous iron sorbed at iron(hyro)xides may dominate the overall transformation of carbon tetrachloride (CCl4) and other chlorinated aliphatic hydrocarbons. We investigated mechanisms and product formation of CCl4 reduction by Fe(II) sorbed to goethite, which may lead to completely dehalogenated products or to chloroform (CHCl3), a toxic product which is fairly persistent under anoxic conditions. A simultaneous transfer of two electrons and cleavage of two C-Cl bonds of CCl4 would completely circumvent chloroform production. To distinguish between initial one- or two-bond cleavage, 13C-isotope fractionation of CCl4 was studied for reactions with Fe(II)/ goethite (isotopic enrichment factor epsilon = -26.5% percent per thousand) and with model systems for one C-Cl bond cleavage and either single-electron transfer (Fe(II) porphyrin, epsilon = -26.1 percent per thousand) or partial two-electron transfer (polysulfide, epsilon = -22.2 percent per thousand). These epsilon values differ significantlyfrom calculations for simultaneous cleavage of two C-Cl bonds (epsilon approximately equal to -50 percent per thousand), indicating that only one C-Cl bond is broken in the critical first step of the reaction. At pH 7, reduction of CCl4 by Fe(II)/ goethite produced approximately 33% CHCl3, 20% carbon monoxide (CO), and up to 40% formate (HCOO-). Addition of 2-propanol-d8 resulted in 33% CDCl3 and only 4% CO, indicating that both products were generated from trichloromethyl radicals (*CCl3), chloroform by reaction with hydrogen radical donors and CO by an alternative pathway likely to involve surface-bound intermediates. Hydrolysis of CO to HCOO-was surface-catalyzed by goethite butwastoo slow to account for the measured formate concentrations. Chloroform yields slightly increased with pH at constant Fe(II) sorption density, suggesting that pH-dependent surface processes direct product branching ratios. Surface-stabilized intermediates may thus facilitate abiotic mineralization of CCl4, whereas the presence of H radical donors, such as natural organic matter, enhances formation of toxic CHCl3.     

Thermodynamic and dynamic fragility in metallic glass-formers

This paper focuses on the study of glasses using models of thermodynamic and transport properties (e.g. heat capacity, viscosity and liquid fragility) for various alloys in comparison with organic and inorganic substances. The work attempts to identify possible correlations and trends in these properties which can relate to indicators of melt fragility for metallic glasses. The ratio of the specific heat integral between selected temperatures gives only a rough indication of the fragility behaviour. More insight is gained by considering the thermodynamic fragility index derived from the potential energy landscape model having either a hyperbolic or Gaussian distribution of energy minima. The Wang–Angell–Richert correlation holds for some metallic glasses. Deviations from it help in identifying hidden transitions in the liquid state.     

Cancer of the anal canal and local control

Patients with advanced human immunodeficiency virus (HIV) infection are susceptible to infections with Mycobacterium avium complex (MAC). Interleukin (IL)-10 may impair immunity to MAC; therefore, the effect of different MAC preparations on IL-10 production was examined in mononuclear cell cultures from HIV-infected patients. IL-10 levels in cultures for 26 patients were higher than those in 20 control cultures. The highest IL-10 levels were found in cultures from patients with the most advanced HIV disease. Monocytes were the major IL-10 producers, while little IL-10 could be attributed to Th2 lymphocytes. Cultures for patients produced reduced levels of tumor necrosis factor-alpha and normal levels of IL-12; the production of these cytokines increased after neutralization of IL-10. Circulating IL-10 was higher in HIV-infected patients than in controls, with the highest levels in the AIDS group. Elevated monocyte/macrophage-derived IL-10 production may contribute to the high susceptibility to MAC infection seen in patients with advanced HIV disease.