bluuebunny/crossref_metadata_2025 huggingface dataset:
Broadening of transgenic adenocarcinoma of the mouse prostate (TRAMP) model to represent late stage androgen depletion independent cancer
Authors: Jeet Varinder , Ow Kim , Doherty Eboney , Curley Ben , Russell Pamela J. , Khatri Aparajita
Published: February 2008

BACKGROUND

The transgenic adenocarcinoma of the mouse prostate (TRAMP) model closely mimics PC‐progression as it occurs in humans. However, the timing of disease incidence and progression (especially late stage) makes it logistically difficult to conduct experiments synchronously and economically. The development and characterization of androgen depletion independent (ADI) TRAMP sublines are reported.

METHODS

Sublines were derived from androgen‐sensitive TRAMP‐C1 and TRAMP‐C2 cell lines by androgen deprivation in vitro and in vivo. Epithelial origin (cytokeratin) and expression of late stage biomarkers (E‐cadherin and KAI‐1) were evaluated using immunohistochemistry. Androgen receptor (AR) status was assessed through quantitative real time PCR, Western blotting, and immunohistochemistry. Coexpression of AR and E‐cadherin was also evaluated. Clonogenicity and invasive potential were measured by soft agar and matrigel invasion assays. Proliferation/survival of sublines in response to androgen was assessed by WST‐1 assay. In vivo growth of subcutaneous tumors was assessed in castrated and sham‐castrated C57BL/6 mice.

RESULTS

The sublines were epithelial and displayed ADI in vitro and in vivo. Compared to the parental lines, these showed (1) significantly faster growth rates in vitro and in vivo independent of androgen depletion, (2) greater tumorigenic, and invasive potential in vitro. All showed substantial downregulation in expression levels of tumor suppressor, E‐cadherin, and metastatis suppressor, KAI‐1. Interestingly, the percentage of cells expressing AR with downregulated E‐cadherin was higher in ADI cells, suggesting a possible interaction between the two pathways.

CONCLUSIONS

The TRAMP model now encompasses ADI sublines potentially representing different phenotypes with increased tumorigenicity and invasiveness. Prostate 68: 548–562, 2008. © 2008 Wiley‐Liss, Inc.
MUSTER: Improving protein sequence profile–profile alignments by using multiple sources of structure information
Authors: Wu Sitao , Zhang Yang
Published: February 2008

We develop a new threading algorithm MUSTER by extending the previous sequence profile–profile alignment method, PPA. It combines various sequence and structure information into single‐body terms which can be conveniently used in dynamic programming search: (1) sequence profiles; (2) secondary structures; (3) structure fragment profiles; (4) solvent accessibility; (5) dihedral torsion angles; (6) hydrophobic scoring matrix. The balance of the weighting parameters is optimized by a grading search based on the average TM‐score of 111 training proteins which shows a better performance than using the conventional optimization methods based on the PROSUP database. The algorithm is tested on 500 nonhomologous proteins independent of the training sets. After removing the homologous templates with a sequence identity to the target >30%, in 224 cases, the first template alignment has the correct topology with a TM‐score >0.5. Even with a more stringent cutoff by removing the templates with a sequence identity >20% or detectable by PSI‐BLAST with an E‐value <0.05, MUSTER is able to identify correct folds in 137 cases with the first model of TM‐score >0.5. Dependent on the homology cutoffs, the average TM‐score of the first threading alignments by MUSTER is 5.1–6.3% higher than that by PPA. This improvement is statistically significant by the Wilcoxon signed rank test with a P‐value < 1.0 × 10−13, which demonstrates the effect of additional structural information on the protein fold recognition. The MUSTER server is freely available to the academic community at http://zhang.bioinformatics.ku.edu/MUSTER. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Protein thermal stabilization by charged compatible solutes: Computational studies in rubredoxin from Desulfovibrio gigas
Authors: Micaelo Nuno M. , Victor Bruno L. , Soares Cláudio M.
Published: February 2008

Molecular dynamics simulation studies of rubredoxin from Desulfovibrio gigas (RDG) were used to characterize the molecular mechanism of thermal stabilization by the compatible solute (CS) diglycerol‐phospate (DGP). DGP is a negatively charged CS that accumulates under salt stress in Archaeoglobus fulgidus. Experimental results show that a 100 mM DGP solution exerts a strong protection effect in the half‐life of RDG at 363 K (Lamosa et al., Appl Environ Microbiol 2000;66:1974–1979). RDG was simulated in four aqueous solutions at 300 and 363 K: pure aqueous media, 100 mM DGP, 100 mM NaCl, and 500 mM DGP. Our work shows that the 100 mM DGP solution is able to maintain the average protein structure when the temperature is increased, preventing the occurrence of large‐scale deviation of a mobile loop involved in the first steps of RDG unfolding. The molecular mechanism of thermal denaturation protection by DGP seems to involve the direct interaction between the protein and the CS by hydrogen bond interactions near the mobile loop. Several clusters of DGP molecules are formed and preferentially localized at neutral electrostatic regions of the surface. The increase of DGP concentration to 500 mM did not yield better stabilization of the protein suggesting that the thermal protective role of this charged CS is achieved at low concentrations, as shown experimentally. Proteins 2008. © 2008 Wiley‐Liss, Inc.
The peroxidase–cyclooxygenase superfamily: Reconstructed evolution of critical enzymes of the innate immune system
Authors: Zamocky Marcel , Jakopitsch Christa , Furtmüller Paul G. , Dunand Christophe , Obinger Christian
Published: February 2008

The authors have reconstructed the phylogenetic relationships of the main evolutionary lines of mammalian heme containing peroxidases. The sequences of intensively investigated human myeloperoxidase, eosinophil peroxidase, and lactoperoxidase, which participate in host defence against infections, were aligned together with newly found open reading frames coding for highly similar putative peroxidase domains in all kingdoms of life. The evolutionary relationships were reconstructed using neighbor‐joining, maximum parsimony, and maximum likelihood methods. It is demonstrated that this enzyme superfamily obeys the rules of birth‐and‐death model of multigene family evolution and contains proteins with a variety of function that could be grouped in seven subfamilies. On the basis of occurrence and the fact that two main enzymatic activities are related with these metalloproteins, they propose the name peroxidase–cyclooxygenase superfamily for this widely spread group of heme‐containing oxidoreductases. Well known structure–function relationships in mammalian peroxidases formed the basis for the critical inspection of all subfamilies. The presented data unequivocally suggest that predecessor genes of mammalian heme peroxidases have segregated very early in evolution. Before organisms developed an acquired immunity, their antimicrobial defence depended on enzymes that were recruited upon pathogen invasion and could produce antimicrobial reaction products. Thus, these peroxidatic heme proteins evolved to important components in the innate immune defence system. This work shows that even in certain prokaryotic organisms, genes encoding putative antimicrobial enzymes are found providing a group of bacteria with an evolutionary advantage over the others. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Biotinoyl domain of human acetyl‐CoA carboxylase: Structural insights into the carboxyl transfer mechanism
Authors: Lee Chung‐Kyung , Cheong Hae‐Kap , Ryu Kyoung‐Seok , Lee Jae Il , Lee Weontae , Jeon Young Ho , Cheong Chaejoon
Published: February 2008

Acetyl‐CoA carboxylase (ACC) catalyzes the first step in fatty acid biosynthesis: the synthesis of malonyl‐CoA from acetyl‐CoA. As essential regulators of fatty acid biosynthesis and metabolism, ACCs are regarded as therapeutic targets for the treatment of metabolic diseases such as obesity. In ACC, the biotinoyl domain performs a critical function by transferring an activated carboxyl group from the biotin carboxylase domain to the carboxyl transferase domain, followed by carboxyl transfer to malonyl‐CoA. Despite the intensive research on this enzyme, only the bacterial and yeast ACC structures are currently available. To explore the mechanism of ACC holoenzyme function, we determined the structure of the biotinoyl domain of human ACC2 and analyzed its characteristics and interaction with the biotin ligase, BirA using NMR spectroscopy. The 3D structure of the hACC2 biotinoyl domain has a similar folding topology to the earlier determined domains from E. coli and P. shermanii. However, the local structures near the biotinylation sites have notable differences that include the geometry of the consensus “Met‐Lys‐Met” (MKM) motif and the absence of “thumb” structure in the hACC2 biotinoyl domain. Observations of the NMR signals upon the biotinylation indicate that the biotin group of hACC2 does not affect the structure of the biotinoyl domain, while the biotin group for E. coli ACC interacts directly with the thumb residues that are not present in the hACC2 structure. These results imply that, in the E. coli ACC reaction, the biotin moiety carrying the carboxyl group from BC to CT can pause at the thumb of the BCCP domain. The human biotinoyl domain, however, lacks the thumb structure and does not have additional noncovalent interactions with the biotin moiety; thus, the flexible motion of the biotinylated lysine residue must underlie the “swinging arm” motion. The chemical shift perturbation and the cross saturation experiments of the human ACC2 holo‐biotinoyl upon the addition of the biotin ligase (BirA) showed the interaction surface near the MKM motif, the two glutamic acids (Glu 926, Glu 953), and the positively charged residues (several lysine and arginine residues). This study provides insight into the mechanism of ACC holoenzyme function and supports the swinging arm model in human ACCs. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Quantitative expression of protein heterogeneity: Response of amino acid side chains to their local environment
Authors: Bandyopadhyay Debashree , Mehler Ernest L.
Published: February 2008

A general method has been developed to characterize the hydrophobicity or hydrophilicity of the microenvironment (MENV), in which a given amino acid side chain is immersed, by calculating a quantitative property descriptor (QPD) based on the relative (to water) hydrophobicity of the MENV. Values of the QPD were calculated for a test set of 733 proteins to analyze the modulating effects on amino acid residue properties by the MENV in which they are imbedded. The QPD values and solvent accessibility were used to derive a partitioning of residues based on the MENV hydrophobicities. From this partitioning, a new hydrophobicity scale was developed, entirely in the context of protein structure, where amino acid residues are immersed in one or more “MENVpockets.” Thus, the partitioning is based on the residues “sampling” a large number of “solvents” (MENVs) that represent a very large range of hydrophobicity values. It was found that the hydrophobicity of around 80% of amino acid side chains and their MENV are complementary to each other, but for about 20%, the MENV and their imbedded residue can be considered as mismatched. Many of these mismatches could be rationalized in terms of the structural stability of the protein and/or the involvement of the imbedded residue in function. The analysis also indicated a remarkable conservation of local environments around highly conserved active site residues that have similar functions across protein families, but where members have relatively low sequence homology. Thus, quantitative evaluation of this QPD is suggested, here, as a tool for structure–function prediction, analysis, and parameter development for the calculation of properties in proteins. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Insect growth regulator effects of azadirachtin and neem oil on survivorship, development and fecundity of Aphis glycines (Homoptera: Aphididae) and its predator, Harmonia axyridis (Coleoptera: Coccinellidae)
Authors: Kraiss Heidi , Cullen Eileen M
Published: February 2008

BACKGROUND: Aphis glycines Matsumura, an invasive insect pest in North American soybeans, is fed upon by a key biological control agent, Harmonia axyridis Pallas. Although biological control is preferentially relied upon to suppress insect pests in organic agriculture, approved insecticides, such as neem, are periodically utilized to reduce damaging pest populations. The authors evaluated direct spray treatments of two neem formulations, azadirachtin and neem seed oil, under controlled conditions for effects on survivorship, development time and fecundity in A. glycines and H. axyridis.

RESULTS: Both azadirachtin and neem seed oil significantly increased aphid nymphal mortality (80 and 77% respectively) while significantly increasing development time of those surviving to adulthood. First‐instar H. axyridis survival to adulthood was also significantly reduced by both neem formulations, while only azadirachtin reduced third‐instar survivorship. Azadirachtin increased H. axyridis development time to adult when applied to both instars, while neem oil only increased time to adult when applied to first instar. Neither neem formulation affected the fecundity of either insect.

CONCLUSIONS: Results are discussed within the context of future laboratory and field studies aimed at clarifying if neem‐derived insecticides can be effectively integrated with biological control for soybean aphid management in organic soybeans. Copyright © 2008 Society of Chemical Industry
Pressure‐ and orientation‐dependent linear optical absorption spectra of radially deformed single‐walled carbon nanotubes
Authors: Liu Guogao , Wang Xiao , Chen Jiangwei , Lu Huaixian
Published: February 2008

Based upon the Slater–Koster tight‐binding model and the gradient approximation, we investigate the linear optical properties of radially deformed single‐walled carbon nanotubes (SWNTs). It is found that, for the armchair tubes, the radial pressure may make the absorption peaks exhibited in the perfect tube shift to lower energy and eventually vanish, which is consistent with the experimental results observed in the optical spectra of squashed SWNT films. In addition, a lot of new and pressure‐ and orientation‐dependent absorption peaks emerge in the optical spectra of the radially deformed tubes. Finally, for comparison, the dependence of optical properties of deformed tubes on chirality is discussed simply. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Compton profiles of p‐Si and n‐Si in an external electric field
Authors: Demir D. , Sahin Y.
Published: February 2008

The Compton profiles of p‐Si and n‐Si have been measured in an external electric field with 59.54 keV gamma radiation from an Am‐241 source. The external electric field of intensities +167 kV/m and –167 kV/m were used to change the surface charge density of the samples. Comparison of the profiles of p‐Si and n‐Si in the same magnitude but opposite direction of the electric field gives information about the Compton scattering of gamma rays from holes. Furthermore, the Compton profile experiments in an external electric field can be used to identify the type of semiconductor. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Investigations of spin‐Hamiltonian parameters and defect structure for Mn4+ in Al2O3 from a two‐mechanism model
Authors: Wu Xiao‐Xuan , Feng Wen‐Lin , Fang Wang , Zheng Wen‐Chen
Published: February 2008

The complete high‐order perturbation formulas based on a two‐mechanism model for the spin‐Hamiltonian (SH) parameters (g ‐factors g||, g⊥, and zero‐field splitting D) of 3d3 ions in trigonal octahedral sites are derived. In the model, not only the conventional contribution to SH parameters from the crystal‐field (CF) mechanism, but also that from the charge‐transfer (CT) mechanism (which is omitted in the CF theory) are included. From these formulas, the SH parameters of Mn4+ replacing Al3+ in Al2O3 crystal are calculated by using the parameters related to the optical spectral data and the defect structure of the studied system. The results (including the relative importance of the CT mechanism on the SH parameters and the defect structure of Mn4+ impurity center) are discussed. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Supramolecular structure of perylene tetracarboxdiimides
Authors: Marcon V. , Kirkpatrick J. , Pisula W. , Andrienko D.
Published: February 2008

Using atomistic molecular dynamics (MD) simulations we study the columnar phases of perylene tetracarboxdiimides (PDI) and establish correlations between the molecular structure, packing, and dynamical properties of these materials. Combining electronic structure calculations, MD and kinetic Monte Carlo simulations, a correlation is then established between molecular structure and charge mobility of columnar mesophases of perylene tetracarboxdiimide derivatives. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The low velocity impact response of auxetic carbon fibre laminates
Authors: Alderson K. L. , Coenen V. L.
Published: February 2008

The low velocity impact resistance of auxetic carbon fibre laminates has been compared to that of laminates with matched through‐the‐thickness modulus, but with Poisson's ratios of near zero and positive values. Four impact loads corresponding to major events in the static indentation response were examined and damage was assessed by ultrasonic C‐scans, detailed fractography and measurement of residual properties. It was found that enhancements were seen in resistance to low velocity for the auxetic laminates, but only at low energy levels, indicating some degree of rate dependency. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Estimates for the localised stiffness and heterogeneity of auxetic foams
Authors: Gaspar N.
Published: February 2008

In the task to accurately model auxetic foams, a number of details must be correctly accounted for. Firstly, the microstructure is not simple and can only be qualitatively described by traditional, regular, cellular models. Computed tomography (CT) data has been used to begin to describe the details of the complex geometry of the foams' microstructure and to describe it in a manner suitable for advanced models. Using these modelling techniques that are able to capture difficult geometries, values of the local and global mechanical properties are calculated. These mechanical calculations are based on a linear elastic core and global properties are a mean strain estimate. The latter is shown to be inadequate, highlighting the need for a heterogeneous basis for accurate modelling. The significant mechanical anisotropy of the material is reported and mechanical results are recast according to axis of major and minor principal stiffness demonstrating the elastic symmetry of the foam and a requirement of an objective methodology in modelling an inherently anisotropic material. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Quantitative chiral analysis of phthaloylglutamic acid and related analogs by a single ratio kinetic method using electrospray ionization and matrix‐assisted laser desorption techniques
Authors: Ramagiri Suma , Gupte Renuka , Rakov Igor , Yates Charles R. , Miller Duane D.
Published: February 2008

A rapid method for quantitative chiral analysis of phthaloylglutamic acid and its dimethyl ester by Cook's kinetic method is demonstrated using electrospray ionization (ESI) and matrix‐assisted laser desorption techniques. Transition‐metal‐bound complex ions containing the chiral phthaloylglutamic acid and its dimethyl ester are generated by ESI mass spectrometry and subjected to collision‐induced dissociation. The ratio of the two competitive dissociation rates is related to the enantiomeric composition of the drug mixture. A seven‐point calibration curve, derived from the kinetic method, allowed rapid quantitation of the enantiomeric excess of drug mixtures. In this paper, matrix‐assisted laser desorption/ionization (MALDI) coupled with the linear ion trap (LIT) technique is evaluated for its applicability as a complementary technique to ESI for chiral discrimination and quantitation. Copyright © 2008 John Wiley & Sons, Ltd.
On the impacts of low rate DoS attacks on VoIP traffic
Authors: Shevtekar A. , Stille J. , Ansari N.
Published: February 2008

Low rate TCP DoS (Shrew) and reduction of quality (RoQ) attacks have been proven to be detrimental to TCP traffic in the Internet. In this paper, we investigate the effect of these attacks on QoS sensitive, real time UDP traffic, like VoIP. Both of these attacks are difficult to detect, as the average attack traffic is low. These stealthy RoQ attacks are especially hard to detect as their periodicity is not well‐defined, and the attacks can contain spoofed source as well as destination IP addresses. Extensive ns2 simulations have been performed under realistic scenarios to validate the effects of these attacks on real time VoIP traffic using the G711 and G729a audio codecs. Forward Error Correction (FEC) is also considered in our analysis to recover packets from the packet loss caused by attacks. Without FEC, these attacks can drastically reduce the quality of VoIP traffic, leading to denial of service. To evaluate the perceptual quality of voice under attacks, the network losses are mapped to user's quality perception by using the ITU E‐model. The MOS range of the E‐model decreases frombesttomediumdue to the low rate TCP DoS and RoQ attacks even when FEC is deployed. In some of the attack scenarios, the packet losses are bursty, which can lead to dropped calls. In addition, the stealthy RoQ attacks with higher burst lengths are as effective as the shrew attack in impairing VoIP traffic. We have also evaluated the effects of the attack on the VoIP traffic on the DETERLAB testbed, which has specifically been built for conducting network security research, and the results are consistent with the ns2 simulation results. We believe our investigation is important to remove the misconception about low rate TCP DoS and RoQ attacks that they affect only TCP traffic in the Internet. Copyright © 2008 John Wiley & Sons, Ltd.
In situ structural analysis of corrosion products formed on the surfaces of iron‐based alloys
Authors: Suzuki Shigeru , Suzuki Shinya , Inoue Katsuya , Matsubara Eiichiro , Waseda Yoshio
Published: February 2008

In situ X‐ray diffraction measurements were performed for analyzing the constituent species of corrosion products freshly formed on the surfaces of pure iron and iron‐based alloys, namely, iron − 0.58 mass% phosphorus and iron − 3.2 mass% molybdenum. As these elements are often added into corrosion‐resistant steels, their influence on the constituent species of the corrosion products was studied. The sample surfaces were corroded by dropping an NaCl aqueous solution and cyclically exposing them to wet and dry atmospheres. The results revealed that γ‐FeOOH was formed as the main corrosion product on the surface of the iron‐based alloys, and small amounts of species such as green rust (GR), and magnetite were formed depending on the addition of the alloying elements. It is considered that the formation of different constituent species of the corrosion products is influenced by the alloying elements in the corrosion products. It was shown that in situ X‐ray diffraction measurements enable us to obtain information on different species in the corrosion products formed under various conditions. Copyright © 2008 John Wiley & Sons, Ltd.
Numerical modelling of the electrochemical behaviour of 316 stainless steel based upon static and dynamic experimental microcapillary‐based techniques: effect of electrolyte flow and capillary size
Authors: Krawiec Halina , Vignal Vincent , Akid Robert
Published: February 2008

The objective of this work was to determine the parameters that affect the mass transport and the distribution of species in microcapillaries close to the specimen surface. Local experiments were carried out under static and flow conditions on type 316L stainless steel in 1.7 M NaCl, pH = 3, by means of the electrochemical microcell and the scanning droplet cell technique. The polarisation behaviour of pure iron (used as a model system) in an aqueous environment was calculated adopting a finite element approach and was compared to the experimental results. The corrosion system consists of three parallel electrochemical reactions: the oxygen reduction reaction (ORR), the hydrogen evolution reaction (HER) and iron dissolution. Copyright © 2008 John Wiley & Sons, Ltd.
Fragmentation of molecular compounds on silicon wafers and low dielectric constant materials studied by time‐of‐flight secondary ion mass spectrometry using a polyatomic ion source
Authors: Ravanel X. , Trouiller C. , Juhel M. , Wyon C. , Kwakman L. F. T. , Léonard D.
Published: February 2008

Recent time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) studies using primary cluster ion sources such as Aun+, SFn+, Bin+ or C60+ have shown polyatomic ions to be more appropriate for the detection of high mass molecular secondary ions than monoatomic ion sources like Ga+, thanks to secondary ion yield and ion formation efficiency enhancements.

This work is part of a study aiming at improving molecular compound quantification at the surface of microelectronics industry substrates by taking advantage of a polyatomic ion source in ToF‐SIMS analysis. It focuses on the case of a phthalate‐related contamination. Fundamental parameters like secondary ion yield, damage cross section and secondary ion efficiency were studied as a function of the size and the energy of the primary ions. The substrate composition influence on the ToF‐SIMS results was also studied by comparing several substrates of interest in the microelectronics industry such as silicon wafers and low dielectric constant materials SiOxCyHz.

Phthalate‐related secondary ions detected at the surface of the contaminated surfaces were compared and a fragmentation pathway of the di‐isononyl phthalate (DNP) molecule was determined. A drastic improvement of the secondary ion yield was provided when using a polyatomic ion source. Furthermore, a clear increase in damage cross section was observed as a function of the secondary ion size for a given Bin primary ion as well as an increase for a given fragment as a function of the number of Bi atoms in the Bin aggregate. This led to a lower static limit when taking into account higher phthalate fragments and primary ions of larger size. Copyright © 2008 John Wiley & Sons, Ltd.
Film morphology and orientation of N‐cyclohexyl‐γ‐aminopropyl polydimethylsiloxane
Authors: Li Mingtao , An Qiufeng , Huang Lianxian
Published: February 2008

A novel polysiloxane softener bearing N‐cyclohexyl‐γ‐aminopropyl side groups (ASO‐702) is synthesized by copolymerization of octamethylcyclotetrasiloxane with N‐cyclohexyl‐γ‐aminopropyl methyldimethoxylsilane and hexamethyldisiloxane. Chemical structure and film morphology of the synthesized polysiloxane are characterized and investigated by IR, 1H NMR, 13C NMR, SEM and atomic force microscope (AFM). The results of the experiment indicate that ASO‐702 can form a hydrophobic film on both a cotton fiber and a silicon‐wafer surface. At scales > 100 nm, the ASO‐702 shows a relative smooth‐resin film on the treated fabric/fiber surface. But as the observation rule decreases to 2 nm, the molecular scale, the ASO‐702 film exhibits an inhomogeneous structure and uneven morphology in its AFM images. There are many low or high peaks in ASO‐702 topography. Consequently in 2 µm2 scanning field, the root mean square roughness of ASO‐702 film is 0.246 nm, which is 3.05 times rougher as compared with that of polydimethylsiloxane (PDMS) film. Copyright © 2008 John Wiley & Sons, Ltd.
Adaptive dose finding based on t‐statistic for dose–response trials
Authors: Ivanova Anastasia , Bolognese James A. , Perevozskaya Inna
Published: February 2008

The goals of phase II dose–response studies are to prove that the treatment is effective and to choose the dose for further development. Randomized designs with equal allocation to either a high dose and placebo or to each of several doses and placebo are typically used. However, in trials where response is observed relatively quickly, adaptive designs might offer an advantage over equal allocation. We propose an adaptive design for dose–response trials that concentrates the allocation of subjects in one or more areas of interest, for example, near a minimum clinically important effect level, or near some maximal effect level, and also allows for the possibility to stop the trial early if needed. The proposed adaptive design yields higher power to detect a dose–response relationship, higher power in comparison with placebo, and selects the correct dose more frequently compared with a corresponding randomized design with equal allocation to doses. Copyright © 2008 John Wiley & Sons, Ltd.
Magnetic Force Microscopy of Superparamagnetic Nanoparticles
Authors: Schreiber Sharon , Savla Mayur , Pelekhov Denis V. , Iscru Daniel F. , Selcu Camelia , Hammel P. Chris , Agarwal Gunjan
Published: February 2008

The use of magnetic force microscopy (MFM) to detect probe–sample interactions from superparamagnetic nanoparticles in vitro in ambient atmospheric conditions is reported here. By using both magnetic and nonmagnetic probes in dynamic lift‐mode imaging and by controlling the direction and magnitude of the external magnetic field applied to the samples, it is possible to detect and identify the presence of superparamagnetic nanoparticles. The experimental results shown here are in agreement with the estimated sensitivity of the MFM technique. The potential and challenges for localizing nanoscale magnetic domains in biological samples is discussed.
Nanoscale Detection of Ionizing Radiation Damage to DNA by Atomic Force Microscopy
Authors: Ke Changhong , Jiang Yong , Mieczkowski Piotr A. , Muramoto Garrett G. , Chute John P. , Marszalek Piotr E.
Published: February 2008

The detection and quantification of ionizing radiation damage to DNA at a single‐molecule level by atomic force microscopy (AFM) is reported. The DNA damage‐detection technique combining supercoiled plasmid relaxation assay with AFM imaging is a direct and quantitative approach to detect gamma‐ray‐induced single‐ and double‐strand breaks in DNA, and its accuracy and reliability are validated through a comparison with traditional agarose gel electrophoresis. In addition, the dependence of radiation‐induced single‐strand breaks on plasmid size and concentration at a single‐molecule level in a low‐dose (1 Gy) and low‐concentration range (0.01 ng µL−1–10 ng µL−1) is investigated using the AFM‐based damage‐detection assay. The results clearly show that the number of single‐strand breaks per DNA molecule is linearly proportional to the plasmid size and inversely correlated to the DNA concentration. This assay can also efficiently detect DNA damage in highly dilute samples (0.01 ng µL−1), which is beyond the capability of traditional techniques. AFM imaging can uniquely supplement traditional techniques for sensitive measurements of damage to DNA by ionizing radiation.
ANTLRWorks: an ANTLR grammar development environment
Authors: Bovet Jean , Parr Terence
Published: February 2008

Programmers tend to avoid using language tools, resorting toad hocmethods, because tools can be hard to use, their parsing strategies can be difficult to understand and debug, and their generated parsers can be opaque black‐boxes. In particular, there are two very common difficulties encountered by grammar developers: understanding why a grammar fragment results in a parser non‐determinism and determining why a generated parser incorrectly interprets an input sentence. This paper describes ANTLRWorks, a complete development environment for ANTLR grammars that attempts to resolve these difficulties and, in general, make grammar development more accessible to the average programmer. The main components are a grammar editor with refactoring and navigation features, a grammar interpreter, and a domain‐specific grammar debugger. ANTLRWorks' primary contributions are a parser non‐determinism visualizer based on syntax diagrams and a time‐traveling debugger that pays special attention to parser decision‐making by visualizing lookahead usage and speculative parsing during backtracking. Copyright © 2008 John Wiley & Sons, Ltd.
Cost modeling of distributed team processes for global development and Software‐Intensive Systems of Systems
Authors: Madachy Raymond J.
Published: February 2008

Distributed team processes are becoming more pervasive because of geographically distributed development and complex Software‐Intensive Systems of Systems (SISOS) with many layers of breadth and depth. Software is developed collaboratively in multiple locations around the world, and projects are being contracted out in whole or in part for economic leverage. Systems are becoming larger and more complex, leading to distributed processes at many levels. Projects are often split among distributed teams, where the teams contribute different portions of work per phase to take advantage of their skill sets and rates. Thus there is a need for new parametric cost estimation models where effort multipliers are phase sensitive. Working with industrial partners, a set of constructive cost models have been extended to better estimate distributed teams where work is allocated by phase, rather than just along the lines of specific functionality. The distributed development models allow for work distribution by phase per team (and per module), different environmental characteristics of the teams, localized labor categories, calendars, compensation rates, and currencies for costing. They also use a generalized scheme for user‐defined global life‐cycle processes that include calibrated effort and schedule distributions. Representative examples show the models being used for global development and SISOS scenarios. Copyright © 2008 John Wiley & Sons, Ltd.
Evaluating the impact of requirements analysis tools using simulation
Authors: Raffo David , Ferguson Robert , Setamanit Siri‐on , Sethanandha Bhuricha
Published: February 2008

Adopting new tools and technologies on a development process can be a risky endeavor. Will the project accept the new technology? What will be the impact? Far too often the project is forced to adopt the new technology without planning how it will be applied on the project or evaluating the technology's potential impact. In this article, we provide a case study evaluating a new technology. Specifically we assess the merits of an automated requirements analysis tool. First, we provide a background on automated requirements analysis tool technology. Then, using Process Simulation (P‐SIM), we find situations where the use of this new technology is useful and situations where the use of this new technology is useless for large‐scale NASA projects that utilize a process similar to the IEEE 12207 systems development life cycle. The method can be applied in assessing the impact (including Return on Investment), breakeven point, and the overall value of applying any tool on a project. Copyright © 2008 John Wiley & Sons, Ltd.
Estimating fixing effort and schedule based on defect injection distribution
Authors: Wang Qing , Gou Lang , Jiang Nan , Che Meiru , Zhang Ronghui , Yang Yun , Li Mingshu
Published: February 2008

Detecting and fixing defects are key activities in a testing process, which consume two kinds of skill sets. Unfortunately, many current leading software estimation methods, such as COCOMO II, mainly estimate the effort depending on the size of software, and allocate testing effort proportionally among various activities. Both efforts on detecting and fixing defects, are simply counted into software testing process/phase and cannot be estimated and managed satisfactorily. In fact, the activities for detecting defects and fixing them are quite different and need differently skilled people. The inadequate effort estimation leads to the difficulty of test process management. It is also the main problem which causes software project delays. In this article, we propose a method onQuantitativelyManagingTesting (TestQM) process including identifying performance objectives, establishing a performance baseline, establish a process‐performance model for fixing effort, and establishing a process‐performance model for fixing the schedule, which supports high‐level process management mentioned in Capability Maturity Model Integration (CMMI). In our method, defect injection distribution (DID) is used to derive estimation of fixing effort and schedule. The TestQM method has been successfully applied to a software organization for their quantitative management of testing process and proved to be helpful in estimating and controlling defects, effort and schedule of the testing process. Copyright © 2008 John Wiley & Sons, Ltd.
Providing value to customers in software development through lean principles
Authors: Mehta Merwan , Anderson David , Raffo David
Published: February 2008

Lean thinking has created substantial benefits for a variety of industries. Although it is not easily apparent, the same principles can be utilized in reducing lead times for software development. Fundamentally, lean principles leverage the benefits of software engineering best practices to improve the work flow and the tactical management of the project. By managing the project more efficiently and reducing waste, tremendous performance benefits can be achieved.

This article seeks to present and articulate a number of key lean principles in the context of software development. The goal is to provide insight into practical strategies for making trade‐offs between the core lean principles of providing the highest possible customer value, maximizing work flow, and eliminating waste in the context of specific real world software development situations. Copyright © 2008 John Wiley & Sons, Ltd.
Robotics and science literacy: Thinking skills, science process skills and systems understanding
Authors: Sullivan Florence R.
Published: February 2008

This paper reports the results of a study of the relationship of robotics activity to the use of science literacy skills and the development of systems understanding in middle school students. Twenty‐six 11–12‐year‐olds (22 males and 4 females) attending an intensive robotics course offered at a summer camp for academically advanced students participated in the research. This study analyzes how students utilized thinking skills and science process skills characteristic of scientifically literate individuals to solve a robotics challenge. In addition, a pre/post test revealed that course participants increased their systems understanding, t (21) = 22.47, p < .05. It is argued that the affordances of the robotics environment coupled with a pedagogical approach emphasizing open‐ended, extended inquiry prompts the utilization of science literacy‐based thinking and science process skills and leads to increased systems understanding. © 2008 Wiley Periodicals, Inc. J Res Sci Teach 45: 373–394, 2008
Impact of degradation products of sulfamethoxazole on mammalian cultured cells
Authors: Yargeau Viviane , Huot Jennifer Caitlin , Rodayan Angela , Rouleau Leonie , Roy Ranjan , Leask Richard L.
Published: February 2008

Sulfamethoxazole (SMX) is a widely used antibiotic which has been detected in surface water samples in the ng/L range and also detected in drinking water samples. To limit the environmental impact, ozonation treatment of waste streams has been proposed. However, the degradation products created by ozonation as well as their toxicity have not been reported. In this study, we investigated the degradation products of SMX formed during ozonation and the effects of these products on mammalian cultured cells. In addition to alcohols and nitrates, sulfanilamide was identified as the larger molecular weight compound of the degradation products detected. Cells exposed to the degradation products of SMX maintained their polyhedral geometry longer than the control cells. Proliferation of the cells exposed to the degradation products was not negatively affected when compared with the control cells. The results of this study show that bioactive degradation products can be formed by ozonation of SMX. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Microcystin concentrations and genetic diversity of Microcystis in the lower Great Lakes
Authors: Dyble Julianne , Fahnenstiel Gary L. , Litaker R. Wayne , Millie David F. , Tester Patricia A.
Published: February 2008

The resurgence of Microcystis blooms in the lower Great Lakes region is of great concern to public and ecosystem health due to the potential for these colonial cyanobacteria to produce hepatotoxic microcystins. A survey of Microcystis cell densities and microcystin concentrations during August 2004 showed particularly high concentrations of both cells and toxin in the nearshore regions of Saginaw Bay (Lake Huron) and western Lake Erie, often exceeding the World Health Organization's recommended drinking water limit of 1 μg L−1. The dominant congener of microcystin in both basins was microcystin‐LR (MC‐LR), whereas the second most abundant congeners, accounting for up to 20–25% of the total microcystin concentrations, were MC‐LA in Saginaw Bay and MC‐RR in western Lake Erie. Multiplex PCR assays of Microcystis colonies isolated from these two regions showed that a much greater percentage of the Microcystis colonies from Saginaw Bay carried the mcyB gene necessary for microcystin production, in comparison with those from western Lake Erie. The mcyB genotypes sequenced separated into two distinct phylogenetic clusters, with Microcystis originating from Lake Erie predominantly in one branch and from Saginaw Bay present in both branches. These results indicate that the genetic composition of the bloom could impact the concentrations and congeners of microcystin produced and that the cell count methods currently being used to gauge public health threats posed by Microcystis blooms may not sufficiently assess actual bloom toxicity. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Levels of transaminases, alkaline phosphatase, and protein in tissues of Clarias gariepienus fingerlings exposed to sublethal concentrations of cadmium chloride
Authors: Velmurugan Babu , Selvanayagam Mariadoss , Cengiz Elif I. , Uysal Ersin
Published: February 2008

The freshwater fish, Clarias gariepienus fingerlings, were exposed to sublethal concentrations (1.7 and 3.4 mg/L) of cadmium chloride for 12 days. Aspartate aminotransferase (AAT), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total protein levels were assayed in the gill, brain, and muscle of the fish at regular intervals of 6 and 12 days. The activities of AAT, ALT, and ALP of the treated fishes increased significantly in all the tissues compared with the control fish. Protein level in all the tissues showed a significant decrease in comparison to unexposed controls throughout the experimental periods. These results revealed that cadmium chloride effects the intermediary metabolism of C. gariepienus fingerlings and that the assayed enzymes can work as good biomarkers of contamination. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.
Serial uterine artery Doppler velocity parameters and human uterine receptivity in IVF/ICSI cycles
Authors: Hoozemans D. A. , Schats R. , Lambalk N. B. , Homburg R. , Hompes P. G. A.
Published: February 2008

Objective

To evaluate the predictive value of serial uterine artery Doppler ultrasound for embryo implantation in in‐vitro fertilization (IVF)‐intracytoplasmic sperm injection (ICSI) cycles.

Methods

This was a prospective observational study at the VU University Medical Center, Amsterdam. Patients with an indication for IVF or IVF‐ICSI according to departmental protocol underwent controlled ovarian hyperstimulation followed by IVF or IVF‐ICSI and embryo transfer and had serial Doppler ultrasound performed during this treatment cycle. Patient and cycle characteristics, number of conceptions and ongoing pregnancies and pulsatility index (PI) of both uterine arteries on different cycle days were assessed and results were compared between patients who conceived and those who did not.

Results

Of the 102 patients enrolled into the study, 83 underwent embryo transfer. Of these, 41 became pregnant and 42 did not (Group 1). Of the 41 pregnancies, 30 were ongoing (Group 2) and 11 miscarried (Group 3). Between Groups 1, 2 and 3, linear regression revealed no significant difference between any of the variables examined except in the quality of transferred embryos. There was no significant difference in the mean PI of the left and right uterine arteries on any day of the cycle, or in the change in PI during the cycle. Receiver–operating characteristics curves derived to determine the performance of PI to predict pregnancy outcome supported our findings that the uterine artery PI is not a suitable marker for identifying patients with implantation failure. Multivariate analysis showed no relationship between pregnancy and PI between groups, but it did show a relationship between pregnancy and some patient and cycle characteristics.

Conclusion

In an unselected group of patients undergoing IVF or IVF‐ICSI and embryo transfer, serial Doppler ultrasound examination of the uterine artery does not discriminate between cycles resulting in ongoing pregnany, miscarriage and no pregnancy. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.
Fetal biometry in ethnic Chinese: biparietal diameter, head circumference, abdominal circumference and femur length
Authors: Leung T. N. , Pang M. W. , Daljit S. S. , Leung T. Y. , Poon C. F. , Wong S. M. , Lau T. K.
Published: February 2008

Objectives

To construct new reference charts and equations for fetal biometry in the Hong Kong ethnic Chinese population, and to compare them with existing references from different populations.

Methods

This was a prospective observational study involving 709 women with singleton pregnancies and confirmed gestational age. For the purposes of this study, each woman was scanned once only, between 12 and 40 completed weeks of gestation, and the following fetal biometric measurements were recorded: biparietal diameter, head circumference, abdominal circumference and femur length. For each measurement, regression models were fitted to estimate the mean and SD at each gestational age. For comparison, the fetal biometric measurements of other populations at each gestation were expressed as Z‐scores calculated with our reference equations. Results were presented graphically across the different gestational ages to allow visual comparison.

Results

New charts and reference equations are reported in this Hong Kong Chinese population for fetal outer–inner and outer–outer biparietal diameter, head circumference, abdominal circumference and femur length. Equations for dating of pregnancy are presented. Our charts were very similar to those of the Singaporean population for most parameters. The main difference in our fetal biometric measurements compared with those of the UK and French populations was in FL.

Conclusions

Our new set of reference centiles for fetal biometric measurements and equations for dating of pregnancy in a Hong Kong Chinese population are ready for clinical use and research in appropriate ethnic Chinese groups. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.