bluuebunny/crossref_metadata_2025 huggingface dataset:
1α,25‐Dihydroxyvitamin D3 down‐regulates expression of prostate specific membrane antigen in prostate cancer cells
Authors: Serda Rita E. , Bisoffi Marco , Thompson Todd A. , Ji Ming , Omdahl John L. , Sillerud Laurel O.
Published: February 2008

BACKGROUND

Prostate specific membrane antigen (PSMA) expression correlates with prostate cancer grade and is increased in hormone‐refractory prostate cancer. The increased expression of PSMA following androgen deprivation therapy may be a consequence of the down‐regulation of PSMA expression by androgen. Moreover, 1α,25‐dihydroxyvitamin D3 (1,25‐VD) has been shown to suppress prostate cancer progression as well as cell motility and invasion. Since PSMA is positively correlated with both of these characteristics, we hypothesized that 1,25‐VD would regulate PSMA expression.

METHODS

LNCaP prostate cancer cells were treated with 1,25‐VD, followed by analysis of cell surface PSMA expression. The PSMA enhancer, located within the third intron of the PSMA gene, was cloned into a reporter vector and regulation by 1,25‐VD was investigated. The role of the androgen receptor (AR) in 1,25‐VD mediated suppression of PSMA expression was examined using Casodex and AR specific siRNA.

RESULTS

Surface expression of PSMA was significantly decreased in a dose‐dependent manner by 10 nM 1,25‐VD or greater. Regulation by 1,25‐VD occurred at the level of the PSMA enhancer. Over‐expression of the vitamin D receptor (VDR) also decreased expression of PSMA. Additionally, suppression of AR translation using siRNA technology blocked the suppressive effect of 1,25‐VD on PSMA expression, however inhibition of PSMA expression by 1,25‐VD occurred in the absence of androgens.

CONCLUSIONS

Suppression of PSMA by 1,25‐VD occurs at the level of the PSMA enhancer and is elevated by over‐expression of the VDR. This regulation involves the AR, but is not dependent on the presence of androgens. Prostate 68: 773–783, 2008. © 2008 Wiley‐Liss, Inc.
An iterative knowledge‐based scoring function for protein–protein recognition
Authors: Huang Sheng‐You , Zou Xiaoqin
Published: February 2008

Using an efficient iterative method, we have developed a distance‐dependent knowledge‐based scoring function to predict protein–protein interactions. The function, referred to as ITScore‐PP, was derived using the crystal structures of a training set of 851 protein–protein dimeric complexes containing true biological interfaces. The key idea of the iterative method for deriving ITScore‐PP is to improve the interatomic pair potentials by iteration, until the pair potentials can distinguish true binding modes from decoy modes for the protein–protein complexes in the training set. The iterative method circumvents the challenging reference state problem in deriving knowledge‐based potentials. The derived scoring function was used to evaluate the ligand orientations generated by ZDOCK 2.1 and the native ligand structures on a diverse set of 91 protein–protein complexes. For theboundtest cases, ITScore‐PP yielded a success rate of 98.9% if the top 10 ranked orientations were considered. For the more realisticunboundtest cases, the corresponding success rate was 40.7%. Furthermore, for faster orientational sampling purpose, several residue‐level knowledge‐based scoring functions were also derived following the similar iterative procedure. Among them, the scoring function that uses the side‐chain center of mass (SCM) to represent a residue, referred to as ITScore‐PP(SCM), showed the best performance and yielded success rates of 71.4% and 30.8% for the bound and unbound cases, respectively, when the top 10 orientations were considered. ITScore‐PP was further tested using two other published protein–protein docking decoy sets, the ZDOCK decoy set and the RosettaDock decoy set. In addition to binding mode prediction, the binding scores predicted by ITScore‐PP also correlated well with the experimentally determined binding affinities, yielding a correlation coefficient ofR= 0.71 on a test set of 74 protein–protein complexes with known affinities. ITScore‐PP is computationally efficient. The average run time for ITScore‐PP was about 0.03 second per orientation (including optimization) on a personal computer with 3.2 GHz Pentium IV CPU and 3.0 GB RAM. The computational speed of ITScore‐PP(SCM) is about an order of magnitude faster than that of ITScore‐PP. ITScore‐PP and/or ITScore‐PP(SCM) can be combined with efficient protein docking software to study protein–protein recognition. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Biological roles of specific peptides in enzymes
Authors: Meroz Yasmine , Horn David
Published: February 2008

It has recently been shown (Kunik et al., PLOS Comput Biol 2007;3(8):e167) that the occurrence of specific peptides (SPs) on sequences of enzymes allows for accurate EC classification of enzymes. We inquire whether these SPs play important roles in bringing about the enzymatic function. This is assessed by cross‐checking the occurrence of SPs on enzymes with Swiss‐Prot annotations and PDB spatial structures of enzymes. Analyzing the coverage of functional annotations of enzymes, we demonstrate that SPs contain major fractions of all annotated features. This result is statistically highly significant and associates over 10% of all SPs with important biological markers. Concentrating on DNA binding regions, relevant to LexA repressor enzymes, we find interesting coverage patterns. Moreover, for the same data, we demonstrate that SPs allow for subclassification of the relevant bacteria into phylogenetic classes. An analysis of mutagen annotations on SPs appearing on all enzymes leads to the conclusion that mutations on SPs tend to damage the enzymatic function much more than expected from a background model, hence SPs are of high importance to enzymatic functions. SPs that lie in 3D pockets that are shared by active and binding sites, are shown to be significantly enriched by glycine, leading to the hypothesis that they are responsible for conformational plasticity. Finally we show that SPs can partially resolve outstanding difficult problems of convergent evolution by representing correctly enzyme functions in spite of remote homologies in sequence and in structure. Proteins 2008. © 2008 Wiley‐Liss, Inc.
On the relationship between the protein structure and protein dynamics
Authors: Lu Chih‐Hao , Huang Shao‐Wei , Lai Yan‐Long , Lin Chih‐Peng , Shih Chien‐Hua , Huang Cuen‐Chao , Hsu Wei‐Lun , Hwang Jenn‐Kang
Published: February 2008

Recently, we have developed a method (Shih et al., Proteins: Structure, Function, and Bioinformatics 2007;68: 34–38) to compute correlation of fluctuations of proteins. This method, referred to as the protein fixed‐point (PFP) model, is based on the positional vectors of atoms issuing from the fixed point, which is the point of the least fluctuations in proteins. One corollary from this model is that atoms lying on the same shell centered at the fixed point will have the same thermal fluctuations. In practice, this model provides a convenient way to compute the average dynamical properties of proteins directly from the geometrical shapes of proteins without the need of any mechanical models, and hence no trajectory integration or sophisticated matrix operations are needed. As a result, it is more efficient than molecular dynamics simulation or normal mode analysis. Though in the previous study the PFP model has been successfully applied to a number of proteins of various folds, it is not clear to what extent this model will be applied. In this article, we have carried out the comprehensive analysis of the PFP model for a dataset comprising 972 high‐resolution X‐ray structures with pairwise sequence identity ≤25%. We found that in most cases the PFP model works well. However, in case of proteins comprising multiple domains, each domain should be treated separately as an independent dynamical module with its own fixed point; and in case of the protein complex comprising a number of subunits, if functioning as a biological unit, the whole complex should be considered as one single dynamical module with one fixed point. Under such considerations, the resultant correlation coefficient between the computed and the X‐ray structural B‐factors for the data set is 0.59 and 75% (727/972) of proteins with a correlation coefficient ≥0.5. Our result shows that the fixed‐point model is indeed quite general and will be a useful tool for high throughput analysis of dynamical properties of proteins. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Insights into the interactions between HIV‐1 integrase and human LEDGF/p75 by molecular dynamics simulation and free energy calculation
Authors: Zhao Yaxue , Li Weihua , Zeng Juan , Liu Guixia , Tang Yun
Published: February 2008

Human cellular protein LEDGF/p75 (lens epithelium‐derived growth factor) is an important binding partner of human immunodeficiency virus type 1 (HIV‐1) integrase (IN). Without LEDGF/p75, HIV‐1 can not complete its life cycle. To study the detailed interactions between LEDGF/p75 and HIV‐1 IN, and then obtain the hotspots at the binding interface, 13 ns molecular dynamics simulations were carried out here. One‐hundred snapshots extracted from the last 4 ns trajectories were used for calculation of binding free energy and decomposition of the energy by residue. First, the structural changes and their dynamic interactions were investigated focused on the production stage. And then, the free energy was discussed. On the basis of the above results, it could be suggested that residues Gln168, Glu170, and Thr174 in chain A of IN, Thr125, and Trp131 in chain B of IN as well as Ile365, Asp366, Phe406, and Val408 in LEDGF/p75 were responsible for their binding. These results might be helpful for discovery and design of small molecules to interrupt the interaction between HIV‐1 IN and LEDGF/p75. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Relationship between energy distribution and fold stability: Insights from molecular dynamics simulations of native and mutant proteins
Authors: Morra Giulia , Colombo Giorgio
Published: February 2008

Most proteins must fold to a well‐defined structure with a minimal stability to perform their function. Here we use a simple, molecular dynamics‐based, energy decomposition approach to map the principal energetic interactions in a set of proteins representative of different folds. This work involves the all‐atom simulation and analysis of the native structures and mutants of five different proteins representative of an all‐alpha (yACPB, Protein A), all‐beta (SH3), and a mixed α/β fold (Proteins G and L). Given a certain structure, a native sequence and a set of mutants, we show that our model discriminates the ability of a mutation to yield a more or less stable protein, in agreement with experimental data, catching the principal energetic determinants of protein stabilization. Our approach identifies the interaction determinants responsible to define a fold and shows that mutations can either modulate the strength of pair‐wise coupling between residues important for folding, or modify the profile of the principal interactions. Furthermore, we address the question of how to evaluate the fitness of a sequence to a given structure by comparing the information contained in the energy map, which recapitulates the chemistry of the sequence, to that contained in the contact map, which recapitulates the fold topology. The results show that the better fit between the energetic properties of the sequence and the fold topology corresponds to a higher stabilization of the protein. We discuss the relevance of these observations to the analysis of protein designability and to the rational evolution of new sequences. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Crystal structure of Natratoxin, a novel snake secreted phospholipaseA2 neurotoxin from Naja atra venom inhibiting A‐type K+ currents
Authors: Hu Pu , Sun Lei , Zhu Zhi‐Qiang , Hou Xiao‐Wei , Wang Shu , Yu Shan‐Shan , Wang Hui‐Li , Zhang Ping , Wang Ming , Niu Li‐Wen , Teng Mai‐Kun , Ruan Di‐Yun
Published: February 2008

Snake secreted phospholipasesA2 (sPLA2s) are widely used as pharmacological tools to investigate their role in diverse pathophysiological processes. Some members of snake venom sPLA2s have been found to block voltage‐activated K+ channels (Kv channels). However, most studies involved in their effects on ion channels were indirectly performed on motor nerve terminals while few studies were directly done on native neurons. Here, a novel snake sPLA2 peptide neurotoxin, Natratoxin, composed of 119 amino acid residues and purified from Naja atra venom was reported. It was characterized using whole‐cell patch‐clamp in acutely dissociated rat dorsal root ganglion (DRG) neurons. It was found to effectively inhibit A‐type K+ currents and cause alterations of channel gating characters, such as the shifts of steady‐state activation and inactivation curves to hyperpolarization direction and changes of V1/2 and slope factor. Therefore, Natratoxin was suggested to be a gating modifier of Kv channel. In addition, this inhibitory effect was found to be independent of its enzymatic activity. These results suggested that the toxin enacted its inhibitory effect by binding to Kv channel. To further elucidate the structural basis for this electrophysiological phenomenon, we determined the crystal structure of Natratoxin at 2.2 Å resolution by molecular replacement method and refined to an R‐factor of 0.190. The observed overall fold has a different structural organization from other K+ channel inhibitors in animal toxins. Compared with other Kv channel inhibitors, a similar putative functional surface in its C‐terminal was revealed to contribute to protein–protein interaction in such a blocking effect. Our results demonstrated that the spatial distribution of key amino acid residues matters most in the recognition of this toxin towards its channel target rather than its type of fold. Proteins 2008. © 2008 Wiley‐Liss, Inc.
US grower perceptions and experiences with glyphosate‐resistant weeds
Authors: Foresman Chuck , Glasgow Les
Published: February 2008

BACKGROUND: A survey of 400 growers of maize, soybeans and cotton was made in the United States to determine perceptions, experiences and management practices with glyphosate‐resistant weeds. The survey included growers in the north (corn belt) and south (cotton belt) of the USA in spring 2006.

RESULTS: Interestingly, 24 and 39% of northern and southern growers, respectively, assumed they had glyphosate weed resistance on their farm. Of the 200 southern growers interviewed, 67% had planted continuous glyphosate‐resistant (GR) crops for a period of 3–5 years. According to the survey respondents, the key method for managing glyphosate‐resistant weeds was to rotate to other herbicides.

CONCLUSION: Growers do value GR crop technology but are adopting measures to manage resistance only as needed. Copyright © 2008 Society of Chemical Industry
Field resistance to QoI fungicides in Podosphaera fusca is not supported by typical mutations in the mitochondrial cytochrome b gene
Authors: Fernández‐Ortuño Dolores , Torés Juan A , de Vicente Antonio , Pérez‐García Alejandro
Published: February 2008

BACKGROUND: A single nucleotide polymorphism in the mitochondrial cytochrome b gene confers resistance to strobilurin (QoI) fungicides in phytopathogenic fungi. Recent studies have revealed worrying levels of resistance to strobilurins in Podosphaera fusca (Fr.) U Braun & N Shishkoff comb. nov. [ = Sphaerothecafusca (Fr.) S Blumer], the main causal agent of cucurbit powdery mildew in Spain. In the present study the underlying resistance mechanism to QoI fungicides in the Spanish populations of P. fusca was investigated.

RESULTS: Analysis of the Qo domains of cytochrome b in a collection of isolates revealed that none of the typical mutations conferring resistance to QoI, including the G143A and F129L substitutions, was present in the QoI‐resistant isolates. Moreover, although different amino acid polymorphisms were observed in the two regions spanning the Qo site, none of them consistently distinguished QoI‐resistant from QoI‐sensitive strains. Exposure to salicylhydroxamic acid (SHAM), a specific inhibitor of alternative oxidase, in the presence of trifloxystrobin did not have any effect on QoI resistance, ruling out alternative respiration as the mechanism of resistance. Sensitivity tests to a battery of respiration inhibitors revealed high levels of cross‐resistance to all Qo‐inhibitors tested but not to Qi‐inhibitors, these features resembling those of a target‐site‐based resistance.

CONCLUSIONS: The results indicate that the mechanism responsible for QoI resistance in P. fusca is not linked to typical mutations in cytochrome b gene and that the absence of the G143A substitution cannot be explained by an intron following codon 143. These are important observations, especially in relation to the possible molecular diagnosis of resistance. Copyright © 2008 Society of Chemical Industry
Atomistic study of magnetism effect on structural stability in Fe3Al and Fe3AlX (X = H, B, C, N, O) alloys
Authors: Kellou A. , Grosdidier T. , Raulot J. M. , Aourag H.
Published: February 2008

Atomistic modeling based on the density‐functional theory (DFT) within the generalized‐gradient approximation (GGA) is used to study the magnetic properties Fe3Al and Fe3AlX (X = H, B, C, N, O) compounds. The phase stability and the structural parameters are calculated for the selected iron‐aluminide alloys. The magnetic effects in Fe3AlX are shown and the predicted properties agree very well with the available experimental data. In the case of Fe3Al alloy, the DO3 structure is found to be more favorable than the L12 one. To the authors' knowledge, this is the first time that spin‐polarized GGA calculations have given the correct ground state of the Fe3Al alloys. In addition, the hypothetical phase of Fe3AlX′ (X′ = H, B, N, and O) structure is compared to the experimentally observed Fe3AlC structure. The unusual effect on magnetic properties of the C addition is shown. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Negative compressibility, negative Poisson's ratio, and stability
Authors: Lakes Rod , Wojciechowski K. W.
Published: February 2008

The role of negative compressibility is considered in detail. Experimental observations of negative bulk modulus in pre‐strained foam are presented and interpreted. A constrained microscopic model which exhibits negative compressibility is proposed. Some other negative and counterintuitive properties of matter, like negative Poisson's ratio, negative thermal expansion, negative specific heat, and negative pressure are also discussed. A simple thermodynamic model with negative thermal expansion is presented. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Isotopomeric characterization of N2O produced, consumed, and emitted by automobiles
Authors: Toyoda Sakae , Yamamoto Sei‐ichiro , Arai Shinji , Nara Hideki , Yoshida Naohiro , Kashiwakura Kiriko , Akiyama Ken‐ichi
Published: February 2008

Fossil fuel combustion is the second largest anthropogenic source of nitrous oxide (N2O) after agriculture. The estimated global N2O flux from combustion sources, as well as from other sources, still has a large uncertainty. Herein, we characterize automobile sources using N2O isotopomer ratios (nitrogen and oxygen isotope ratios and intramolecular site preference of 15N, SP) to assess their contributions to total global sources and to deconvolute complex production/consumption processes during combustion and subsequent catalytic treatments of exhaust. Car exhaust gases were sampled under running and idling state, and N2O isotopomer ratios were measured by mass spectrometry. The N2O directly emitted from an engine of a vehicle running at constant velocity had almost constant isotopomer ratios (δ15Nbulk = −28.7 ± 1.2‰, δ18O = 28.6 ± 3.3‰, and SP = 4.2 ± 0.8‰) irrespective of the velocity. After passing through catalytic converters, the isotopomer ratios showed an increase which varied with the temperature and the aging of the catalysts. The increase suggests that both production and consumption of N2O occur on the catalyst and that their rates can be comparable. It was noticed that in the idling state, the N2O emitted from a brand new car has higher isotopomer ratios than that from used cars, which indicate that technical improvements in catalytic converters can reduce the N2O from mobile combustion sources. On average, the isotopomeric signatures of N2O finally emitted from automobiles are not sensitive to running/idling states or to aging of the catalysts. Characteristic average isotopomer ratios of N2O from automobile sources are estimated at −4.9 ± 8.2‰, 43.5 ± 13.9‰, and 12.2 ± 9.1‰ for δ15Nbulk, δ18O, and SP, respectively. Copyright © 2008 John Wiley & Sons, Ltd.
Liquid chromatography/mass spectrometric studies on atorvastatin and its stress degradation products
Authors: Shah Ravi P. , Kumar Vijay , Singh Saranjit
Published: February 2008

A comprehensive mass fragmentation pathway of atorvastatin, which has not been reported so far, was established by subjecting the drug to multi‐stage mass spectrometric (MSn) studies. It was used along with liquid chromatography/mass spectrometric (LC/MS) and liquid chromatography/time‐of‐flight mass spectrometric (LC/TOFMS) analyses to identify the drug degradation products formed under stress conditions of hydrolysis, oxidation and photolysis. Other than lactone, which is a reported hydrolysis product, six unknown hydrolytic products could be identified, viz., dehydrated drug, dehydrated drug lactone, and diastereomers of the drug, drug lactone, dehydrated drug, and dehydrated drug lactone. Among the two products separated under oxidative conditions, one was lactone, again formed as a result of drug hydrolysis in an acidic environment of peroxide solution. The other was similar to a reported oxidative product. Under photolytic conditions in solution, one new product could be identified, while most of the others matched with those known from the literature. Hence overall a more complete degradation pathway of the drug was established than known at present, by using a stress testing approach and employing LC/MS techniques. Copyright © 2008 John Wiley & Sons, Ltd.
The stable hydrogen and oxygen isotope variation of water stored in polyethylene terephthalate (PET) bottles
Authors: Spangenberg Jorge E. , Vennemann Torsten W.
Published: February 2008

A set of bottled waters from a single natural spring distributed worldwide in polyethylene terephthalate (PET) bottles has been used to examine the effects of storage in plastic polymer material on the isotopic composition (δ18O and δ2H values) of the water. All samples analyzed were subjected to the same packaging procedure but experienced different conditions of temperature and humidity during storage. Water sorption and the diffusive transfer of water and water vapor through the wall of the PET bottle may cause isotopic exchange between water within the bottle and water vapor in air near the PET‐water interface. Changes of about +4‰ for δ2H and +0.7‰ for δ18O have been measured for water after 253 days of storage within the PET bottle. The results of this study clearly indicate the need to use glass bottles for storing water samples for isotopic studies. It is imperative to transfer PET‐bottled natural waters to glass bottles for their use as calibration material or potential international working standards. Copyright © 2008 John Wiley & Sons, Ltd.
Unusual observations during steroid analysis
Authors: Kwok Wai Him , Leung David K. K. , Leung Gary N. W. , Tang Francis P. W. , Wan Terence S. M. , Wong Colton H. F. , Wong Jenny K. Y.
Published: February 2008

In September 2005, our laboratory detected the presence of 4‐androstene‐3,17‐dione and androsterone in a standard steroid screen of a post‐race gelding urine sample received from an overseas authority. All other urine samples from the same batch tested negative. Subsequent gas chromatography/mass spectrometry (GC/MS) confirmatory analyses, however, repeatedly failed to detect any amount of 4‐androstene‐3,17‐dione and androsterone in the suspicious sample. On the other hand, identical results were obtained when the initial GC/MS screening method was repeated on the suspicious sample as well as on the other samples of the same batch, showing the presence of 4‐androstene‐3,17‐dione and androsterone only in the suspicious sample. These unusual and contradictory findings between the screening and confirmatory procedures were investigated, leading to the unequivocal conclusion that the 4‐androstene‐3,17‐dione and androsterone observed during screening were artefacts from the internal standards, [16,16,17‐d3]‐testosterone and [16,16,17‐d3]‐5α‐androstane‐3α,17β‐diol. The two deuterated internal standards were thought to have undergone first an enzymatic oxidation of the 17β‐hydroxyl group to a 17‐keto function by the enzyme 17β‐hydroxysteroid dehydrogenase; complete deuterium‐hydrogen exchange at C16 during the methanolysis deconjugation step would then produce the two artefacts. The findings from this study highlight the potential problem of using internal standards in qualitative confirmatory analyses, which may lead to undesirable false positive results. Copyright © 2008 John Wiley & Sons, Ltd.
Robust stabilization for uncertain discrete singular systems with state delay
Authors: Wu Zhengguang , Su Hongye , Chu Jian
Published: February 2008

The robust stabilization problem for uncertain discrete singular time‐delay systems is addressed in this paper. In terms of strict linear matrix inequality and a finite sum inequality, a delay‐dependent criterion for the nominal systems to be admissible is obtained. Based on the criterion, a state feedback controller, which guarantees that, for all admissible uncertainties, the resulting closed‐loop system is regular, causal and stable, is constructed. An explicit expression for the desired controller is also given. The obtained results include both delay‐independent and delay‐dependent cases. Some numerical examples are introduced to show the effectiveness of the given results. Copyright © 2008 John Wiley & Sons, Ltd.
Biometric‐based user authentication in mobile ad hoc networks
Authors: Richard Yu F. , Tang Helen , Leung Victor C. M. , Liu Jie , Lung Chung‐Horng
Published: February 2008

As the front line of defense, user authentication is crucial for integrity and confidentiality. Mobile ad hoc networks (MANETs) impose a number of non‐trivial challenges to user authentication such as lack of central coordination and limited resources. In high security MANETs, continuous authentication is desirable so that a system can be monitored for the duration of the session to reduce the vulnerability. Biometrics provides some possible solutions to the authentication problem in MANETs, since it has direct connection with user identity. In this paper, we introduce some biometric technologies and their applications in the authentication problem. Multimodal biometrics can be used to exploit the benefits of one biometric while mitigating the inaccuracies of another. We propose an optimal multimodal biometric‐based continuous authentication scheme in MANETs. Some numerical results show the effectiveness of the proposed scheme. Copyright © 2007 John Wiley & Sons, Ltd.
Pore structure of activated carbon prepared from hazelnut bagasse by chemical activation
Authors: Demiral Hakan , Demiral İlknur , Tümsek Fatma , Karabacakoğlu Belgin
Published: February 2008

In this study, hazelnut extracted‐bagasse which is a waste from oil factory was used for the production of activated carbon by chemical activation using ZnCl2 and KOH as activating agents. Hazelnut bagasse has been impregnated with aqueous solutions of ZnCl2 and KOH in the ratio of 1–3 g agent per g precursor. The carbonization treatment was performed at 500, 600 and 700 °C for 2 h under nitrogen flow. The surface area, pore volumes, pore size distribution and average pore diameter of the activated carbons were characterized by N2 adsorption at 77 K using the BET, t‐plot and DFT methods. The highest surface areas of activated carbons are 1642 and 1489 m2/g and total pore volumes are 0.964 and 0.9329 cm3 g−1 for KOH and ZnCl2, respectively. The surface chemical characteristics of activated carbon were determined in terms of surface functional groups. These groups were analyzed by Fourier transform infrared (FTIR) spectroscopic method and Boehm's titration method. Surface morphology was investigated by SEM. According to the results, activated carbons prepared from hazelnut bagasse by chemical activation have high surface area and porosity. Copyright © 2008 John Wiley & Sons, Ltd.
Microstructure of the passive layer formed on AA2024‐T3 aluminum alloy surface implanted with nitrogen
Authors: Abreu C. M. , Cristóbal M. J. , Freitas P. , Nóvoa X. R. , Pena G. , Pérez M. C. , Serra C.
Published: February 2008

This work is focused on a detailed analysis of passive layer formed on AA2024‐T3 aluminum alloy, in unmodified and nitrogen‐implanted conditions. This study is the first step in analyzing the possible beneficial effect of nitrogen implantation in the simultaneous improvement of the tribological properties and pitting resistance. The implanted surface has been characterized by XPS and atomic force microscopy (AFM), and SEM/EDX has been used for microstructural characterization. XPS depth profile of the implanted surface shows the formation of AlN through the implanted layer. AFM studies have confirmed the increase of the surface roughness of AA2024‐T3 due to N+ implantation. Another interesting result of the present work is the detection by EDX analysis, of implanted alloy of a specific concentration of the implanted nitrogen in AlCuFeMnSi particles with regards to the other microstructural constituents. Copyright © 2008 John Wiley & Sons, Ltd.
Interfacial chemistry of epoxy adhesives on hydrated cement paste
Authors: Djouani Fatma , Connan Carole , Chehimi Mohamed M. , Benzarti Karim
Published: February 2008

Epoxy resins [diglycidylether of bisphenol A, (DGEBA)] are the main adhesives used in civil engineering for the repair of damaged concrete structures (bridges, walls) or for assembly applications. Their interfacial molecular interactions with cement‐type substrates are thus of prime importance and require surface‐ and interface‐sensitive characterisation tools. In this context, we report an XPS, FTIR and differential scanning calorimeter (DSC) study of the interfacial chemistry of stoichiometric and nonstoichiometric epoxy mixtures [i.e. DGEBA resin and diethylenetriamine hardener (DETA)] coated on the surface of hardened‐cement pastes. XPS highlights the cross‐linking of the epoxy resin by the hardener and allows the detection of subtle mineral‐DETA hydrogen bonding. These specific interactions are confirmed by examination of the OH‐stretching frequency shifts in the FTIR spectra and concern essentially portlandite, one of the constitutive hydrates of cement paste. Additionally, it was found that interactions between the cross‐linked epoxy resin and the underlying‐mineral substrate induce an increase in the glass transition temperature (Tg) of the polymer adhesive from 48 to 66 °C. Copyright © 2008 John Wiley & Sons, Ltd.
Nonparametric sequential evaluation of diagnostic biomarkers
Authors: Liu Aiyi , Wu Chengqing , Schisterman Enrique F.
Published: February 2008

We consider evaluation and comparison of the diagnostic accuracy of biomarkers with continuous test outcomes, possibly correlated due to repeated measurements. We develop nonparametric group sequential testing procedures to evaluate and compare the area of biomarkers under their receiver operating characteristic curves, with either independent or paired test outcomes. These procedures rely on the construction of a two‐dimensional statistic of Whitehead (Statist. Med. 1999; 18:2271–2286) so that design methods based on Brownian motion can be applied. Copyright © 2008 John Wiley & Sons, Ltd.
Discovery of New Hexagonal Supramolecular Nanostructures Formed by Squalenoylation of an Anticancer Nucleoside Analogue
Authors: Couvreur Patrick , Reddy L. Harivardhan , Mangenot Stéphanie , Poupaert Jacques H. , Desmaële Didier , Lepêtre‐Mouelhi Sinda , Pili Barbara , Bourgaux Claudie , Amenitsch H. , Ollivon Michel
Published: February 2008

In this study, the dynamically folded conformation of squalene (SQ) is taken advantage of to link this natural compound to the anticancer nucleoside analogue gemcitabine (gem) in order to achieve the spontaneous formation of nanoassemblies (SQgem) in water. Cryogenic transmission electron microscopy examination reveals particles (104 nm) with a hexagonal or multifaceted shape that display an internal structure made of reticular planes, each particle being surrounded by an external shell. X‐ray diffraction evidences the hexagonal molecular packing of SQgem, resulting from the stacking of direct or inverse cylinders. The respective volumes of the gem and SQ molecules as well as molecular modeling of SQgem suggest the stacking of inverse hexagonal phases, in which the central aqueous core, consisting of water and gem molecules, is surrounded by SQ moieties. These SQgem nanoassemblies also exhibit impressively greater anticancer activity than gem against a solid subcutaneously grafted tumor, following intravenous administration. To our knowledge, this is the first demonstration of hexagonal phase organization with a SQ derivative.
Architecture framework human view: The NATO approach
Authors: Handley Holly A. H. , Smillie Robert J.
Published: February 2008

The NATO Research and Technology Organization (RTO) Panel on Human Factors and Medicine (HFM‐155) Human View Workshop was convened to discuss and propose a cross‐national Human View, that is, an architectural view that focuses on the human as part of a system. Progress on the idea of a human view had already been made by several different groups working in different countries. The purpose of the workshop panel was to evaluate these emerging human view concepts, propose a candidate human view construct, and develop an outline of a NATO‐wide Human View Handbook. This paper describes the outcomes of the workshop and presents the content of the draft human view suggested by the panel members. The proposed human view was purposely designed to be independent of any specific architecture framework and adaptable to different implementation processes. © 2008 Wiley Periodicals, Inc. Syst Eng 11
Effects of tobacco compounds on gene expression in fetal lung fibroblasts
Authors: Sohn Sung‐Hwa , Kim Ki‐Nam , Kim In kyoung , Lee Eun‐Il , Ryu Jae‐Jun , Kim Meyoung‐Kon
Published: February 2008

The goal of this study was to determine the effects of tobacco compounds on gene expression in a human fetal lung cell line (WI38). In the present study, we investigated the effects of tobacco compounds (nicotine, benzo(a)pyrene (B(a)P), and 2‐Naphthylamine) on gene expression profiles in human fetal fibroblasts using cDNA microarray and real‐time PCR. WI38 cells were cultured in Eagle's minimum essential medium (MEM) supplemented with 10% fetal bovine serum, 2% 200 mML‐glutamine, and a 2% penicillin and streptomycin solution. Tissue culture flasks (T‐25 cm2) containing confluent lung fibroblasts were incubated at 37°C for 24 h with 5 mL of medium supplemented with 10 μM of a tobacco compound (nicotine, B(a)P, or 2‐Naphthylamine). The gene expression profiles for the W138 cells varied depending on the tobacco compound. The cDNA microarray analysis revealed that apoptosis‐related genes such asDNASE2,MADD,MST1,NME3,RARG,TNFRSF1A,BAD, andDFFBgenes were down‐regulated in tobacco compound‐treated WI38 cells. We also observed significant increases inArntgene expression by real‐time PCR in tobacco compound‐treated WI38 cells. Tobacco compounds can affect apoptosis, immunity, and growth in WI38 cells. A microarray‐based genomic survey is a high‐throughput approach for the evaluation of gene expression in cell lines treated with tobacco compounds. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Comparing the relative toxicity of malathion and malaoxon in blue catfish Ictalurus furcatus
Authors: Aker Winfred G. , Hu Xiaoke , Wang Peng , Hwang Huey‐Min
Published: February 2008

Malathion inhibits the critical body enzyme, acetylcholinesterase (AChE). This capability requires that malathion should first be converted to malaoxon to become an active anticholinesterase agent. Conversion can be caused by oxidation in mammals, insects, plants, and in sunlight. In this study, the effects of malathion and malaoxon on catfish Ictalurus furcatus were evaluated. After 96‐h exposures, the LC50 (concentration that causes 50% mortality) and IC50 (concentration that causes 50% enzyme inhibition) for malaoxon were lower than corresponding values for malathion. The overall mean 96‐h LC50 is 17.0 ppm for malathion and 3.1 ppm for malaoxon. IC50 values for malathion are 8.5 ppm for brain, 10.3 ppm for liver, and 16.6 ppm for muscle. Corresponding values for malaoxon are 2.3, 3.7, and 6.8 ppm, respectively. All the AChE activities in malathion‐ and malaoxon‐exposed catfish brain showed significant inhibition. The oxidation product malaoxon demonstrated higher inhibition on AChE activity than did malathion. Moreover, malaoxon showed significant inhibition on butyrylcholinesterase (BChE) in the liver if the concentrations were increased to more than 1 ppm. Malathion showed no difference between treatment group and control group. Compared with malathion, malaoxon showed higher inhibition on monoamine activity than that of malathion. The results indicated that the oxidative product malaoxon is more toxic than the parent compound malathion. AChE, BChE, and monoamine activities are confirmed as bioindicators of malathion exposure in blue catfish, I. furcatus. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Monitoring of DNA breakage in embryonic stages of the African catfish Clarias gariepinus (Burchell, 1822) after exposure to lead nitrate using alkaline comet assay
Authors: Osman Alaa G. M. , Mekkawy Imam A. , Verreth Johan , Wuertz Sven , Kloas Werner , Kirschbaum Frank
Published: February 2008

Increasing lead contamination in Egyptian ecosystems and high lead concentrations in food items have raised concern for human health and stimulated studies on monitoring ecotoxicological impact of lead‐caused genotoxicity. In this work, the alkaline comet assay was modified for monitoring DNA strand breakage in sensitive early life stages of the African catfish Clarias gariepinus. Following exposure to 100, 300, and 500 μg/L lead nitrate, DNA strand breakage was quantified in embryos at 30, 48, 96, 144, and 168 h post‐fertilization (PFS). For quantitative analysis, four commonly used parameters (tail % DNA, %TDNA; head % DNA, %HDNA; tail length, TL; tail moment, TM) were analyzed in 96 nuclei (in triplicates) at each sampling point. The parameter %TDNA revealed highest resolution and lowest variation. A strong correlation between lead concentration, time of exposure, and DNA strand breakage was observed. Here, genotoxicity detected by comet assay preceded the manifested malformations assessed with conventional histology. Qualitative evaluation was carried out using five categories are as follows: undamaged (%TDNA ≤ 10%), low damaged (10% < %TDNA ≤ 25%), median damaged (25 < %TDNA ≤ 50%), highly damaged (50 < %TDNA ≤ 75%), and extremely damaged (%TDNA > 75%) nuclei confirming a dose and time‐dependent shift towards increased frequencies of highly and extremely damaged nuclei. A protective capacity provided by a hardened chorion is a an interesting finding in this study as DNA damage in the prehatching stages 30 h‐PFS and 48 h‐PFS was low in all treatments (qualitative and quantitative analyses). These results clearly show that the comet assay is a sensitive tool for the detection of genotoxicity in vulnerable early life stages of the African catfish and is a method more sensitive than histological parameters for monitoring genotoxic effects. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Prediction of pre‐eclampsia by uterine artery Doppler imaging: relationship to gestational age at delivery and small‐for‐gestational age
Authors: Yu C. K. H. , Khouri O. , Onwudiwe N. , Spiliopoulos Y. , Nicolaides K. H.
Published: February 2008

Objectives

To determine the relationship between pre‐eclampsia, small‐for‐gestational age (SGA) and gestational age at delivery, and the effect of this relationship on the prediction of pre‐eclampsia by uterine artery Doppler imaging.

Methods

This was a multicenter prospective Doppler study of the uterine artery at 22–24 weeks of gestation in unselected women with singleton pregnancies.

Results

In the 30 639 pregnancies examined, the median uterine artery pulsatility index (PI) was 1.0 and the 95th centile was 1.58. In 614 (2%) cases the woman developed pre‐eclampsia and in this group there was an inverse significant association between the gestational age at delivery and prevalence of SGA (r = − 0.99, P < 0.0001), and between the gestational at delivery and mean uterine artery PI (r = − 0.51, P < 0.0001) and prevalence of mean uterine artery PI above the 95th centile (r = − 0.99, P < 0.0001). The mean uterine artery PI was above the 95th centile in 77.2% of women who developed pre‐eclampsia requiring delivery before 34 weeks, in 35.9% of those delivering at 34–37 weeks and in 21.9% of those delivering after 37 weeks. The respective percentages were 82.3%, 46.9% and 28.8% for those with pre‐eclampsia and SGA, and 43.8%, 21.2% and 8.4% for those with SGA but without pre‐eclampsia.

Conclusions

Pre‐eclampsia requiring early delivery is more likely to be associated with SGA than less severe pre‐eclampsia in women who deliver at term. Doppler ultrasound assessment of the uterine arteries is more effective in identifying pre‐eclampsia requiring preterm than term delivery. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.
A method for measuring the reflectance of cloth samples in detergency tests
Authors: Thompson W. E.
Published: February 2008

The scanning of a number of swatches on a turntable rotating at 78 r.p.m. or faster, with a Hunter reflectometer yields the average reflectance of the set. The use of a glass plate to cover the cloth samples does not affect the reflectance measurement. Much time and work can be saved by application of the scanning technique to detergency tests employing multiple swatches of cloth.
Consumer Motivations for Pursuing Genetic Testing and their Preferences for the Provision of Genetic Services for Hearing Loss
Authors: Withrow Kara A. , Burton Sarah , Arnos Kathleen S. , Kalfoglou Andrea , Pandya Arti
Published: February 2008

Genetic services for deafness are being increasingly sought due to the introduction of early hearing detection and intervention programs, as well as the rapid progress in the identification of deafness genes. This study aimed to assess the motivations of consumers for pursuing genetic testing as well as their preferences for provision of these services. We conducted 5 focus groups consisting of hearing parents of deaf children, deaf parents, and unmarried deaf adults. Motivations for pursuing genetic testing included determining the etiology, helping to alleviate the guilt associated with the diagnosis of hearing loss in a child, and acquiring information to help them and other family members prepare for the future. Most participants thought that a genetic counselor/geneticist would be the most appropriate professional to provide genetics services. For culturally Deaf individuals, the communication method was seen as more important than the type of professional. Parents preferred that genetic evaluation, including testing, occur either immediately at or a few months after the audiologic diagnosis of hearing loss.
Triplane ankle fracture with deltoid ligament tear and syndesmotic disruption
Authors: Cummings Robert Jay
Published: February 2008

In patients with immature skeletons, ligamentous injuries rarely accompany ankle fractures. In this article, we report about deltoid ligament tears and syndesmotic disruptions accompanying triplane ankle fractures in two children, and make recommendations as to the evaluation and treatment of children with such injuries.
Efficacy and tolerability of adding an angiotensin receptor blocker in patients with heart failure already receiving an angiotensin‐converting inhibitor plus aldosterone antagonist, with or without a beta blocker. Findings from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)‐Added trial
Authors: Weir R.A.P. , McMurray John J.V. , Puu Margareta , Solomon Scott D. , Olofsson Bertil , Granger Christopher B. , Yusuf Salim , Michelson Eric L. , Swedberg Karl , Pfeffer Marc A. ,   CHARM Investigators
Published: February 2008

Background:

The efficacy and safety of adding an angiotensin receptor blocker (ARB) in heart failure (HF) patients already taking an angiotensin‐converting enzyme‐inhibitor (ACE‐I) plus an aldosterone antagonist is uncertain (especially if taking a beta blocker as well). The CHARM‐Added trial describes the largest experience of using multiple inhibitors of the renin–angiotensin–aldosterone system (RAAS) together.

Methods and results:

2548 HF patients, taking an ACE‐I (936 no spironolactone/no beta blocker; 1175 no spironolactone/beta blocker; 199 spironolactone/no beta blocker; 238 sprionolactone/beta blocker), were randomized to placebo or candesartan and followed for 41 months (median). The primary outcome was cardiovascular death or HF hospitalization. In patients taking both a beta blocker and spironolactone (in addition to an ACE‐I) at baseline, the candesartan:placebo hazard ratio was 0.85(95% CI 0.56, 1.29), compared to 0.85(95% CI 0.75, 0.96) in all randomized patients (interaction p value 0.49).

The relative risk of discontinuation of candesartan (compared to placebo) because of hypotension, increased serum creatinine or hyperkalemia was not increased in patients taking spironolactone at baseline.

Conclusions:

An ARB may provide added benefit, at acceptable risk, in HF patients already taking spironolactone as well as an ACE‐I and beta blocker. These findings must be confirmed in a prospective randomized trial before this approach can be recommended, routinely.
Catalpol protects primary cultured astrocytes from in vitro ischemia‐induced damage
Authors: Li Yachen , Bao Yongming , Jiang Bo , Wang Zhuo , Liu Yuxin , Zhang Cen , An Lijia
Published: February 2008

Catalpol, an iridoid glycoside abundant in the roots of Rehmannia glutinosa, has been previously found to prevent the loss of CA1 hippocampal neurons and to reduce working errors in gerbils after ischemia‐reperfusion injury. In the present study, we investigated the effects of catalpol on astrocytes in an ischemic model to further characterize its neuroprotective mechanisms. Primary cultured astrocytes exposed to oxygen‐glucose deprivation (OGD) followed by reperfusion (adding back oxygen and glucose, OGD‐R), were used as an in vitro ischemic model. Treatment of the astrocytes with catalpol during ischemia‐reperfusion increased astrocyte survival significantly in a concentration‐dependent manner, as demonstrated by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release and morphological observation. In addition, catalpol prevented the decrease in mitochondrial membrane potential, inhibited the formation of reactive oxygen species (ROS) and the production of nitric oxide (NO), decreased the level of lipid peroxide and the activity of inducible nitric oxide synthase (iNOS), and elevated the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and the content of glutathione (GSH). Our results suggest that catalpol exerts the most significant cytoprotective effect on astrocytes by suppressing the production of free radicals and elevating antioxidant capacity.