对组合钢梁-预制空心板中栓钉连接件的性能分析

在钢-混凝土组合梁中,剪切连接件的机械作用使得纵向剪力转移到钢翼缘/混凝土板的接合处。这种转移能力取决于剪切连接件的强度和混凝土板抵抗由剪力高度集中所导致的纵向开裂的能力。大多数对组合结构的分析都集中在传统的钢筋混凝土和金属面板结构,而对预制空心板中栓钉的剪切能力研究很少。本文对带栓钉的预制空心板组合梁结构提出标准的推力试验方法。一共进行7组测试性试验,试验结果显示新方法符合钢筋混凝土楼板规范要求。在确定这个新的标准方法后,对栓钉进行了72个足尺推力试验,确定了该类型连接件的性能,通过分析试验结果,还指出了各类参数对连接件强度和延性的作用。本文还提出了这种剪力连接件的设计公式。     

A dual isotope approach to identify denitrification in groundwater at a river-bank infiltration site

The identification of denitrification in the Torgau sand and gravel aquifer, Germany, was carried out by a dual isotope method of measuring both the delta 15N and delta 18O in NO3-. Samples were prepared by an anion exchange resin method (Silva et al., J. Hydrol. 228 (2000) 22) with a modification to the AgNO3-drying process from a freeze-drying to an oven-drying method. The occurrence of denitrification in the aquifer was confirmed by comparing the reduction of dissolved oxygen, dissolved organic carbon and NO3- concentrations with the dual isotope signatures. High nitrate concentrations were associated with low delta 15N and delta 18O values, and vice versa. The denitrification accords with a Rayleigh equation with calculated enrichment factors of epsilon = -13.62@1000 for delta 15N and epsilon = -9.80@1000 for delta 18O. The slope of the straight-line relationship between the delta 15N and delta 18O data demonstrated that the enrichment of the heavy nitrogen isotope was higher by a factor of 1.3 compared with the heavy oxygen isotope. It is concluded that the identification of this factor is a useful means for confirming denitrification in future groundwater studies.     

In situ gasification and CO2 separation using chemical looping with a Cu-based oxygen carrier: Performance with bituminous coals

This paper is concerned with the chemical looping combustion of coal in a technique whereby the fuel is gasified in situ using CO₂ in the presence of a batch of supported copper oxide (the “oxygen carrier”) in a single reactor. As the metal oxide becomes depleted, the feed of fuel is discontinued, the inventory of fuel is reduced by further gasification and then the contents are re-oxidised by the admission of air to the reactor, to begin the cycle again. A catalyst support, impregnated with a saturated solution of copper and aluminium nitrates, acted as a durable oxygen carrier over numerous cycles of reduction and oxidation, using air as the oxidant. Two bituminous coals (Taldinskaya, Russia, and Illinois No. 5, USA) were investigated and compared with a lignite (Hambach, Germany). The lignite was highly reactive and was gasified completely by 15 mol% CO₂ in N₂ at 1203 K and 1 bar, so that there was no build up of char in the bed. The bituminous coals produced chars much less reactive than the lignite char, so that there was a steady accumulation of char in the bed with number of cycles, with the degree of accumulation being dependent on the reactivity of the char. Since the kinetics of gasification by CO₂ of the chars from either bituminous coal were slow, their rates were controlled by intrinsic chemical kinetics and were not affected by the ability of the oxygen carrier to alter the rates of external mass transfer when gasification is rapid. However, it is likely that rates of gasification in the presence of the carrier are still larger than in its absence, owing to the overall lower [CO] present in the bulk of the fluidised bed during chemical looping. At the temperature used, the carrier was cycling between Cu and Cu₂O, since CuO is only stable if the partial pressure of O₂ exceeds 0.03 bar at 1203 K. The CuO decomposes to Cu₂O and O₂ relatively rapidly at these temperatures, once the oxygen concentration is effectively zero. It was impossible to ascertain in our experiments whether the oxygen so generated, after the switching of the air for nitrogen before the start of the succeeding cycle of gasification, made any substantial difference to the reactivity of the char present in the bed. The rate of oxidation of the carrier was found to be much more rapid than the rate of oxidation of the inventory of char. This allows a preferential oxidation of the carrier and most likely accounts for why progressively less CO and CO₂ is produced during successive cycles with short periods of oxidation: the increasingly reduced carrier reacts more rapidly than the char. There was no obvious impact from the sulphur contained in the fuels, but longer-term testing is needed. No agglomeration between the carrier particles and the ash was observed, despite the high temperatures during oxidation.     

E‐64c‐Hydrazide: A Lead Structure for the Development of Irreversible Cathepsin C Inhibitors

Cathepsin C is a papain‐like cysteine protease with dipeptidyl aminopeptidase activity that is thought to activate various granule‐associated serine proteases. Its exopeptidase activity is structurally explained by the so‐called exclusion domain, which blocks the active‐site cleft beyond the S2 site and, with its Asp 1 residue, provides an anchoring point for the N terminus of peptide and protein substrates. Here, the hydrazide of (2S,3S)‐trans‐epoxysuccinyl‐L ‐leucylamido‐3‐methylbutane (E‐64c) (k₂/K_i=140±5 M ^?1 s^?1) is demonstrated to be a lead structure for the development of irreversible cathepsin C inhibitors. The distal amino group of the hydrazide moiety addresses the acidic Asp 1 residue at the entrance of the S2 pocket by hydrogen bonding while also occupying the flat hydrophobic S1′–S2′ area with its leucine‐isoamylamide moiety. Furthermore, structure–activity relationship studies revealed that functionalization of this distal amino group with alkyl residues can be used to occupy the conserved hydrophobic S2 pocket. In particular, the n‐butyl derivative was identified as the most potent inhibitor of the series (k₂/K_i=56 000±1700 M ^?1 s^?1).     

Studies of the pore-forming domain of a voltage-gated potassium channel protein

Recent mutagenesis studies nave identified a stretch of aminoacid residues which form the ion-selective pore of the voltage-gatedpotassium channel. It has been suggested that this sequenceof amino acids forms a ß-barrel structure making upthe structure of the ion-selective pore [Hartman,H.A., Kirsch,G.E.,DreweJ.A., Taglialatela.M., Joho.R.H. and Brown,A.M. (1991)Science, 251, 942–944; YeUen.G., Jurman,M.E., Abramson,T.and MacKinnon,R. (1991) Science, 251, 939–942; Yool,AJ.and Schwarz.T.L. (1991) Nature, 349, 700–704]. We havesynthesized a polypeptide corresponding to this amino add sequence(residues 431–449 of the ShA potassium channel from Drosophila).A tetrameric version of this sequence was also synthesized byUnking together four of these peptldes onto a branching lysinecore. Fourier transform infrared (FT-LR) and circular dichroism(CD) spectroscopy have been used to investigate the structureof these peptides after their reconstitution into lyso phos-phatidylcholinemicelles and lipid bilayers composed of dimyristoyl phosphatidyfcholineand dimyristoyl phosphatidyl-glycerol. The spectroscopic studiesshow that these peptides are predominantly a-helical in theselipid environments. When Incorporated into planar lipid bilayersboth peptides induce ion channel activity. Molecular modellingstudies based upon the propensity of these peptides to forman -helical secondary structure in a hydrophobfc environmentare described. These results are discussed in the light of recentmutagenesis and binding studies of the Drosophila Shaker potassiumion channel protein     

Computer‐Guided Design,Synthesis, and Biological Evaluation of Quinoxalinebisarylureas as FLT3 Inhibitors

Activating mutations of FMS‐like tyrosine kinase 3 (FLT3) are present in ～30 % of patients with acute myeloid leukemia (AML) and are associated with poor prognosis. Point mutations in the tyrosine kinase domain (TKD) are observed as primary mutations or are acquired as secondary mutations in FLT3 with internal tandem duplications (ITDs) after treatment with tyrosine kinase inhibitors (TKIs). Although dozens of potent inhibitors against FLT3 ITD have been reported, activating TKD point mutations, especially at residues F691 and D835, remain the leading cause for therapy resistance, highlighting the consistent need for new potent inhibitors. Herein we report the identification and characterization of novel quinoxaline‐based FLT3 inhibitors. We used the pharmacophore features of diverse known inhibitors as a starting point for a new optimization algorithm for type II TKIs, starting from an in silico library pharmacophore search and induced‐fit docking in the known FLT3 structure. This led to the design of a set of diverse quinoxalinebisarylureas, which were profiled in an FLT3 kinase activity assay. The most promising compounds were further evaluated in a zebrafish embryo phenotype assay.     

Cardiac and vascular structure and function are related to lipid peroxidation and metabolism

The present study investigated possible relationships between left ventricular mass, intima-media thickness of the carotid artery (IMT), total arterial compliance, and lipid status in a population sample of 58 apparently healthy subjects aged 20 to 69. By stepwise multiple regression analysis, including age, blood pressure, and smoking, left ventricular mass index, measured by M-mode echocardiography, increased by 13.0 g/m² for each 1 standard deviation (SD=0.11 μM, r=0.60, P<0.01) increase in plasma malondialdehyde and 9.50 g/m² per SD increase in plasma 8-iso-prostaglandin F_2α in women only (SD=8.88 ng/L, r=0.44, P=0.01). Each 1-SD (SD=0.27 g/L) increase in apolipoprotein B was associated with a 63 μm increase in IMT (r=0.47, P=0.01) and a 0.27 mL/min/m²/mm Hg (r=−0.60, P<0.01) decrease in stroke index/pulse pressure ratio, reflecting total arterial compliance in women. In men, each 1-SD increase in the proportion of stearic acid (18∶0) in serum cholesterol esters (SD=0.12 percent units) reduced the transmitral E/A ratio, measured by Doppler echocardiography, reflecting left ventricular diastolic function, by 0.10 units (r=−0.29, P<0.05). Thus, important cardiovascular characteristics, such as left ventricular mass, left ventricular diastolic function, carotid IMT, and total arterial compliance, were independently predicted by indices of lipid metabolism and peroxidation in apparently healthy subjects.     

Multivariate Genetic Structure of Externalizing Behavior and Structural Brain Development in a Longitudinal Adolescent Twin Sample

Externalizing behavior in its more extreme form is often considered a problem to the individual, their families, teachers, and society as a whole. Several brain structures have been linked to externalizing behavior and such associations may arise if the (co)development of externalizing behavior and brain structures share the same genetic and/or environmental factor(s). We assessed externalizing behavior with the Child Behavior Checklist and Youth Self Report, and the brain volumes and white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]) with magnetic resonance imaging in the BrainSCALE cohort, which consisted of twins and their older siblings from 112 families measured longitudinally at ages 10, 13, and 18 years for the twins. Genetic covariance modeling based on the classical twin design, extended to also include siblings of twins, showed that genes influence externalizing behavior and changes therein (h² up to 88%). More pronounced externalizing behavior was associated with higher FA (observed correlation r_ph up to +0.20) and lower MD (r_ph up to −0.20), with sizeable genetic correlations (FA r_a up to +0.42; MD r_a up to −0.33). The cortical gray matter (CGM; r_ph up to −0.20) and cerebral white matter (CWM; r_ph up to +0.20) volume were phenotypically but not genetically associated with externalizing behavior. These results suggest a potential mediating role for global brain structures in the display of externalizing behavior during adolescence that are both partially explained by the influence of the same genetic factor.     

Characterization of nonionic and cationic amine-functional polymers by aqueous SEC-MALLS

Molecular weight, root-mean-square radius, and conformational information obtained from aqueous size exclusion chromatography (SEC) and multiangle laser light-scattering (MALLS) detection are examined for amine-functional polymers. These include homopolymers and copolymers of poly(ethenylformamide) and cationic poly(vinylamine). Light-scattering studies for poly(ethenylformamide) employing 15 angles of detection are used to calculate molecular weights as high as 700,000 daltons with a root-mean-square radius of nearly 50 nm. Calculated conformational coefficients indicate a random-coil configuration at low molecular weights and a more compacted conformation at high molecular weights. Molecular weights and root-mean-square radius values for cationic poly(vinylamine) are determined using a three-angle MALLS detector. Root-mean-square radius is strongly dependent on the ionic strength of the mobile phase. Cationic poly(vinylamine) exhibits a rod-like conformation at both low and high ionic strength. Explanations are proposed for this behavior. © 1996 John Wiley & Sons, Inc.