New cis-configured aziridine-2-carboxylates as aspartic acid protease inhibitors

A series of 52 cis‐configured 1‐alkyl‐3‐phenylaziridine‐2‐carboxylates were synthesized as new pseudo‐irreversible inhibitors of Candida albicans secreted aspartic acid protease 1 (SAP1), SAP2, SAP3, and SAP8. Some of the compounds, which were obtained as diastereomers with S,S‐ and R,R‐configured aziridine rings by Cromwell synthesis of racemic (2R,3S+2S,3R)‐dibromophenylpropionic acid ester with amines, followed by ester hydrolysis and coupling to hydrophobic amino acid esters, were separated by preparative HPLC. The absolute configuration of the aziridine ring was assigned by a combination of experimental circular dichroism (CD) investigations and quantum chemical CD calculations. In agreement with previous docking studies, the diastereomers all exhibit similar activity. The compounds were found to be more active against the related mammalian enzyme cathepsin D, presumably due to productive interactions of the N‐alkyl substituent with the highly lipophilic S2 pocket. The most active inhibitors ( 5 , 9 , 10 , 21 , and 28 ), characterized by benzyl, cyclohexylmethyl, tert‐butyl, or 1,4‐dimethylpentyl moieties at the aziridine nitrogen atom, exhibit k_2nd values between 500 and 900×10³ M ^?1 min^?1 and K_i values near or below 1 μM for cathepsin D.     

Immunohistochemical localization of androgen receptors in the urogenital tracts of human embryos

The aim of this study was to investigate androgen receptor (AR) expression in the developing human urogenital tract. The distribution of AR was examined in paraffin-embedded tissue sections of the lower urogenital tract using 55 human embryos of 8-12 weeks of gestation. Immunohistochemistry was performed for AR detection and gender was determined by polymerized chain reaction. There were no differences in the distribution of AR in male and female embryos at any stage of gestation. AR was present only in the mesenchymal tissues of the urogenital sinus at 8 weeks whilst the epithelium was negative, but after 9 weeks the epithelium also showed progressively more positive staining. In the phallus, AR staining was prominent. There was far less staining in the epithelium of the urethral groove from 8 to 10 weeks, whilst the mesenchyme of the urethral folds showed positive staining. At 11 and 12 weeks, both the urethral groove and folds showed uniform staining. The genital tubercle, genital swelling and bulbourethral gland precusors were also positively stained, although paramesonephric ducts were negative. Staining was observed in the mesonephric duct from 9 weeks. There was an absence of staining in the rectum at all stages of gestation. The expression of AR in an epithelium may be dependent upon the mesenchyme. Mesenchymal-epithelial interactions played an important role in development, as has been described in experimental animals. AR expression could play a part in the growth of the genital organs.     

Seismic retrofitting of severely damaged RC connections made with recycled concrete using CFRP sheets

An experimental and numerical program is carried out in this research to investigate the influence of CFRP sheets on the cyclic behavior of unconfined connections made with recycled concrete. Cement is partially replaced by silica fume, iron filling and pulverised fuel ash using two different percentages: 15% and 20%. Each specimen is partially loaded at the first stage and then specimens are repaired using CFRP sheets. The repaired specimens are then laterally loaded until failure. In addition, a finite element model is built in ABAQUS and verified using the experimental results. The experimental results have shown that the repaired specimens have regained almost double the capacity of the un-repaired specimens and hence the adopted repair configuration is recommended for retrofitting seismically vulnerable RC connections. Increasing cement replacement percentage by silica fume, fuel ash or iron filling from 15% to 20% has reduced joint carrying capacity and weakened the joint. It is recommended using 15% pulverised fuel ash or silica fume as cement partial replacement to enhance the strength and ultimate drift of beam-column joints under cyclic loading. Iron filling concrete is also recommended but the enhancement is relatively less than that found with pulverised fuel ash concrete and silica fume concrete.     

An implementation of optimized framework for action classification using multilayers neural network on selected fused features

Pattern Analysis and Applications - In video sequences, human action recognition is a challenging problem due to motion variation, in frame person difference, and setting of video recording in the...     

Effects of plasma treatment and metal-ion chelation on lightfastness of dyed polyester/cotton fabric

Polyester/cotton blend fabric was dyed with Chemistron dye—a mixture of reactive/disperse dyes. Dyed fabrics were subjected to radiofrequency (RF) plasma treatment of different duration and were subsequently treated with metal salts. The effect of surface modification by plasma and dye–metal complex on colorfastness to light is discussed. Evaluation of the improvement in lightfastness was made using the CIE system of color measurement with a standard illuminant D65 and 10° standard observer. The color parameters and color deviations were obtained by Data flash–100 color measurement spectrophotometer with chroma QC 3.0 color quality control software. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 292–299, 2001     

A Maillard reaction product enhances eNOS activity in human endothelial cells

Nitric oxide (NO) produced by the endothelial nitric oxide synthase (eNOS) is an important signaling molecule in the cardiovascular system. Although dietary factors can modulate eNOS activity, putative effects of processed food are barely investigated. We aimed to examine whether the model Maillard reaction product 3‐hydroxy‐2‐methyl‐1‐propyl‐4(1H)‐pyridone (HMPP), formed from maltol or starch and propylamine, affects the eNOS system. Incubation of EA.hy926 endothelial cells with 30–300 μM HMPP for 18 h enhanced endothelial NO release measured with the fluorescent probe diaminofluorescein‐2 and eNOS activity determined by the [14C]L‐arginine‐[14C]L‐citrulline conversion assay. HMPP increased NO production also in two different types of primary human endothelial cells. Protein levels of eNOS and inducible NO synthase remained unaltered by HMPP. HMPP inhibited eNOS activity within the first 2–4 h, whereas it potently increased eNOS activity after 12–24 h. Levels of eNOS phosphorylation, expression of heat‐shock protein 90, caveolin‐1 and various antioxidant enzymes were not affected. Intracellular reactive oxygen species remained unchanged by HMPP. This is the first study to demonstrate positive effects of a Maillard reaction product on eNOS activity and endothelial NO production, which is considered favourable for cardiovascular protection.     

Comparison of crashes during public holidays and regular weekends

Traffic collisions and fatalities during the holiday festive periods are apparently on the rise in Alberta, Canada, despite the enhanced enforcement and publicity campaigns conducted during these periods. Using data from 2004 to 2008, this research identifies the factors that delineate between crashes that occur during public holidays and those occurring during normal weekends. We find that fatal and injury crashes are over-represented during holidays. Amongst the three risky behaviors targeted in the holiday blitzes (driver intoxication, unsafe speeding and restraint use), non-use of restraint is more prevalent whereas driver intoxication and unsafe speeding are less prevalent during holidays. The mixed results obtained suggest that it may be time to consider a more balanced approach to the enhanced enforcement and publicity campaigns.     

Determination of neo- and D-chiro-inositol hexakisphosphate in soils by solution 31P NMR spectroscopy

The inositol phosphates are an abundant but poorly understood group of organic phosphorus compounds found widely in the environment. Four stereoisomers of inositol hexakisphosphate (IP(6)) occur, although for three of these (scyllo, neo, and D-chiro) the origins, dynamics, and biological function remain unknown, due in large part to analytical limitations in their measurement in environmental samples. We synthesized authentic neo- and D-chiro-IP(6) and used them to identify signals from these compounds in three soils from the Falkland Islands. Both compounds resisted hypobromite oxidation and gave quantifiable (31)P NMR signals at δ = 6.67 ppm (equatorial phosphate groups of the 4-equatorial/2-axial conformer of neo-IP(6)) and δ = 6.48 ppm (equatorial phosphate groups of the 2-equatorial/4-axial conformer of D-chiro-IP(6)) in soil extracts. Inositol hexakisphosphate accounted for 46-54% of the soil organic phosphorus, of which the four stereoisomers constituted, on average, 55.9% (myo), 32.8% (scyllo), 6.1% (neo), and 5.2% (D-chiro). Reappraisal of the literature based on the new signal assignments revealed that neo- and D-chiro-IP(6) occur widely in both terrestrial and aquatic ecosystems. These results confirm that the inositol phosphates can constitute a considerable fraction of the organic phosphorus in soils and reveal the prevalence of neo- and D-chiro-IP(6) in the environment. The hypobromite oxidation and solution (31)P NMR spectroscopy procedure allows the simultaneous quantification of all four IP(6) stereoisomers in environmental samples and provides a platform for research into the origins and ecological significance of these enigmatic compounds.     

A Biochemical Interpretation of Terpene Chemotypes in <Emphasis Type=Italic>Melaleuca alternifolia</Emphasis>

The variation of foliar monoterpenes in the Australian Tea Tree (Melaleuca alternifolia) has been of significant interest both to the essential oil industry as well as to ecologists. The majority of studies on leaf chemistry have been aimed directly towards obtaining oil of higher quality or quantity. In the current study, we aimed to understand how molecular mechanisms contribute to the chemical variability of this species, based on chemical analysis of the leaf oils from a biochemical perspective. Correlations between monoterpenes across the species as well as within chemotypes show strong, persistent patterns, which enable us to establish groups based on possible common biosynthetic origins. We found that three distinct enzymes corresponding to these groups: a sabinene-hydrate synthase, a 1,8-cineole synthase, and a terpinolene synthase may be sufficient to explain all six chemotypes in M. alternifolia.