bluuebunny/crossref_metadata_2025 huggingface dataset:
Flavopiridol displays preclinical activity in acute lymphoblastic leukemia
Authors: Jackman Kelly M. , Frye Carole B. , Hunger Stephen P.
Published: November 2007

Background

New agents are needed for treatment of children with relapsed acute lymphoblastic leukemia (ALL). Based on altered expression of cell cycle regulatory proteins, including frequent p16 (INK4A) and p15 (INK4B) deletions, flavopiridol (FP; Alvocidib) is an attractive agent for relapsed ALL.

Procedure

We evaluated the efficacy of FP in ALL cell lines using cell proliferation assays, determined the effects of FP treatment on cell growth and viability in cell lines and patient samples, examined cell cycle kinetics, and evaluated the effect of FP on endogenous cyclin‐dependent kinase (CDK) activity, Mcl‐1 expression, and RNA polymerase II expression and phosphorylation.

Results

ALL cell lines are sensitive to FP. At lower concentrations, FP induces transient G1‐S cell cycle arrest and modest levels of apoptosis in cell lines. In contrast, a sustained G1‐S and G2‐M arrest and substantial apoptosis are observed following exposure to higher FP concentrations. After treatment with FP, ALL cell lines have decreased expression of retinoblastoma protein phosphorylated at serines 795 and 807/811, indicating reduced CDK activity. We also show that ALL cell lines are sensitive to clinically achievable concentrations of FP in medium supplemented with human serum and that FP reduces the expression of Mcl‐1 and phosphorylated forms of the C‐terminal domain of RNA polymerase II. FP also increases cell death by approximately twofold over baseline in primary ALL blasts.

Conclusions

These data provide a biological rationale for testing FP in relapsed ALL. Pediatr Blood Cancer 2008;50:772–778. © 2007 Wiley‐Liss, Inc.
Fetal arterial and venous Doppler pulsatility index and time averaged velocity ranges
Authors: Parra‐Cordero M. , Lees C. , Missfelder‐Lobos H. , Seed P. , Harris C.
Published: November 2007

Objectives

The aim of this study was to determine the fetal arterial and venous Doppler pulsatility index and time averaged velocity ranges for women undergoing third trimester ultrasound.

Methods

One hundred and seventy‐two women with singleton pregnancy and clinical indication underwent biometry and fetal Doppler assessment at 23 to 41 weeks. Umbilical artery, middle cerebral artery, thoracic aorta and ductus venosus pulsatility index and time averaged velocity measurements were performed and corrected statistically based on the distribution of estimated fetal weight at the time of the scan.

Results

The tables and figures of the several vessels published in this study are broadly comparable to other publications and unlike others, are adjusted for the estimated fetal weight distribution.

Conclusions

We present the values of the commonly measured Doppler indices in fetuses with normal growth at the time of scan. The ranges, therefore, have potential utility in the setting where referrals to a fetal assessment unit are made. Copyright © 2007 John Wiley & Sons, Ltd.
Neuroendocrine differentiation in the 12T‐10 transgenic prostate mouse model mimics endocrine differentiation of pancreatic beta cells
Authors: Gupta Aparna , Wang Yongqing , Browne Christopher , Kim Susan , Case Tom , Paul Manik , Wills Marcia L. , Matusik Robert J.
Published: November 2007

BACKGROUND

Neuroendocrine (NE) prostate cancer develops as an aggressive disease that does not respond to androgen ablation therapy. It has been demonstrated that the paracrine action of NE cells facilitates the progression of androgen dependent adenocarcinoma to an androgen independent state, suggesting a significant role for NE cells during failure of androgen ablation therapy.

METHODS

To investigate the pathways that are involved in NE differentiation of prostate cancer, we have looked at the expression of genes known to be involved in endocrine differentiation of β‐cells in the pancreas. This study has been performed using the NE prostate cancer mouse model (12T‐10) and the derivative allograft model (NE‐10).

RESULTS

Immunohistochemical studies have shown that the neuroendocrine prostate tumors express the transcription factors Foxa2, mouse achaete‐scute homolog‐1 (mash‐1), neurogenin3 (Ngn3) and Nkx2.2. These tumors show a loss of hairy/enhancer of split (Hes‐1), a gene that inhibits NE differentiation. Human NE prostate cancers also express Foxa2 and human achaete‐scute homolog‐1 (HASH‐1). These genes are expressed in NE prostate tumors in the similar sequential manner as they appear in a pancreatic β‐cell endocrine differentiation. Foxa2 expression is detected in early prostatic intraepithelial neoplasia (PIN). Mash‐1 expression is detected in a few clusters within low grade PIN lesions and Nkx2.2 expression is rarely detected in individual scattered cells within the PIN lesion. Ngn3 and Nkx2.2 frequently appear in the invasive NE cancer. Subsequent NE metastasis to lung and liver show a distinct gene expression pattern. The lung metastasis expresses Ngn3 but does not express Nkx2.2 whereas liver metastases do not express Ngn3 but express Nkx2.2.

CONCLUSIONS

These results suggest that Ngn3 and Nkx2.2 expression are markers for site‐specific metastasis and/or transcriptionally regulated genes that are required for organ‐specific metastasis. This study indicates that a pathway similar to pancreatic β‐cell differentiation is involved in NE differentiation of prostate cancer. Prostate 68: 50–60, 2008. © 2007 Wiley‐Liss, Inc.
Information and discrimination in pairwise contact potentials
Authors: Solis Armando D. , Rackovsky S.
Published: November 2007

We examine the information‐theoretic characteristics of statistical potentials that describe pairwise long‐range contacts between amino acid residues in proteins. In our work, we seek to map out an efficient information‐based strategy to detect and optimally utilize the structural information latent in empirical data, to make contact potentials, and other statistically derived folding potentials, more effective tools in protein structure prediction. Foremost, we establish fundamental connections between basic information‐theoretic quantities (including the ubiquitous Z‐score) and contact “energies” or scores used routinely in protein structure prediction, and demonstrate that the informatic quantity that mediates fold discrimination is the total divergence. We find that pairwise contacts between residues bear a moderate amount of fold information, and if optimized, can assist in the discrimination of native conformations from large ensembles of native‐like decoys. Using an extensive battery of threading tests, we demonstrate that parameters that affect the information content of contact potentials (e.g., choice of atoms to define residue location and the cut‐off distance between pairs) have a significant influence in their performance in fold recognition. We conclude that potentials that have been optimized for mutual information and that have high number of score events per sequence–structure alignment are superior in identifying the correct fold. We derive the quantity “information product” that embodies these two critical factors. We demonstrate that the information product, which does not require explicit threading to compute, is as effective as the Z‐score, which requires expensive decoy threading to evaluate. This new objective function may be able to speed up the multidimensional parameter search for better statistical potentials. Lastly, by demonstrating the functional equivalence of quasi‐chemically approximated “energies” to fundamental informatic quantities, we make statistical potentials less dependent on theoretically tenuous biophysical formalisms and more amenable to direct bioinformatic optimization. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Use of L‐asparagine and N‐phosphonacetyl‐L‐asparagine to investigate the linkage of catalysis and homotropic cooperativity in E. coli aspartate transcarbomoylase
Authors: Cardia James P. , Eldo Joby , Xia Jiarong , O'Day Elizabeth M. , Tsuruta Hiro , Gryncel Kimberly R. , Kantrowitz Evan R.
Published: November 2007

The mechanism of domain closure and the allosteric transition of Escherichia coli aspartate transcarbamoylase (ATCase) are investigated using L‐Asn, in the presence of carbamoyl phosphate (CP), and N‐phosphonacetyl‐L‐asparagine (PASN). ATCase was found to catalyze the carbamoylation of L‐Asn with a Km of 122 mM and a maximal velocity 10‐fold lower than observed with the natural substrate, L‐Asp. As opposed to L‐Asp, no cooperativity was observed with respect to L‐Asn. Time‐resolved small‐angle X‐ray scattering (SAXS) and fluorescence experiments revealed that the combination of CP and L‐Asn did not convert the enzyme from the T to the R state. PASN was found to be a potent inhibitor of ATCase exhibiting a KD of 8.8 μM. SAXS experiments showed that PASN was able to convert the entire population of molecules to the R state. Analysis of the crystal structure of the enzyme in the presence of PASN revealed that the binding of PASN was similar to that of the R‐state complex of ATCase with N‐phosphonaceyl‐L‐aspartate, another potent inhibitor of the enzyme. The linking of CP and L‐Asn into one molecule, PASN, correctly orients the asparagine moiety in the active site to induce domain closure and the allosteric transition. This entropic effect allows for the high affinity binding of PASN. However, the binding of L‐Asn, in the presence of a saturating concentration of CP, does not induce the closure of the two domains of the catalytic chain, nor does the enzyme undergo the transition to the high‐activity high‐ affinity R structure. These results imply that Arg229, which interacts with the β‐carboxylate of L‐Asp, plays a critical role in the orientation of L‐Asp in the active site and demonstrates the requirement of the β‐carboxylate of L‐Asp in the mechanism of domain closure and the allosteric transition in E. coli ATCase. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Probing ligand binding modes of human cytochrome P450 2J2 by homology modeling, molecular dynamics simulation, and flexible molecular docking
Authors: Li Weihua , Tang Yun , Liu Hong , Cheng Jiagao , Zhu Weiliang , Jiang Hualiang
Published: November 2007

Cytochrome P450 (P450) 2J2 catalyzes epoxidation of arachidonic acid to eicosatrienoic acids, which are related to a variety of diseases such as coronary artery disease, hypertension, and carcinogenesis. Recent experimental data also suggest that P450 2J2 could be a novel biomarker and a potential target for cancer therapy. However, the active site topology and substrate specificity of this enzyme remain unclear. In this study, a three‐dimensional model of human P450 2J2 was first constructed on the basis of the crystal structure of human P450 2C9 in complex with a substrate using homology modeling method, and refined by molecular dynamics simulation. Flexible docking approaches were then employed to dock four ligands into the active site of P450 2J2 in order to probe the ligand‐binding modes. By analyzing the results, active site architecture and certain key residues responsible for substrate specificity were identified on the enzyme, which might be very helpful for understanding the enzyme's biological role and providing insights for designing novel inhibitors of P450 2J2. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Using scores derived from statistical coupling analysis to distinguish correct and incorrect folds in de‐novo protein structure prediction
Authors: Bartlett Gail J. , Taylor William R.
Published: November 2007

Distinguishing native from non‐native folds remains a challenging problem for protein structure prediction. We describe a method, SCA‐distance scoring, based on results from statistical coupling analysis which discriminates between native and non‐native folds produced by a de novo protein structure prediction method for four out of five test proteins. The method is particularly good at discriminating non‐native folds which are close in RMSD to the true fold but contain a change in an internal structural element. SCA‐distance scoring is a useful addition to the tools available for distinguishing native from non‐native folds in protein structure prediction. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Analysis of the protein kinome of Entamoeba histolytica
Authors: Anamika K. , Bhattacharya A. , Srinivasan N.
Published: November 2007

Protein kinases play important roles in almost all major signaling and regulatory pathways of eukaryotic organisms. Members in the family of protein kinases make up a substantial fraction of eukaryotic proteome. Analysis of the protein kinase repertoire (kinome) would help in the better understanding of the regulatory processes. In this article, we report the identification and analysis of the repertoire of protein kinases in the intracellular parasite Entamoeba histolytica. Using a combination of various sensitive sequence search methods and manual analysis, we have identified a set of 307 protein kinases in E. histolytica genome. We have classified these protein kinases into different subfamilies originally defined by Hanks and Hunter and studied these kinases further in the context of noncatalytic domains that are tethered to catalytic kinase domain. Compared to other eukaryotic organisms, protein kinases from E. histolytica vary in terms of their domain organization and displays features that may have a bearing in the unusual biology of this organism. Some of the parasitic kinases show high sequence similarity in the catalytic domain region with calmodulin/calcium dependent protein kinase subfamily. However, they are unlikely to act like typical calcium/calmodulin dependent kinases as they lack noncatalytic domains characteristic of such kinases in other organisms. Such kinases form the largest subfamily of kinases in E. histolytica. Interestingly, a PKA/PKG‐like subfamily member is tethered to pleckstrin homology domain. Although potential cyclins and cyclin‐dependent kinases could be identified in the genome the likely absence of other cell cycle proteins suggests unusual nature of cell cycle in E. histolytica. Some of the unusual features recognized in our analysis include the absence of MEK as a part of the Mitogen Activated Kinase signaling pathway and identification of transmembrane region containing Src kinase‐like kinases. Sequences which could not be classified into known subfamilies of protein kinases have unusual domain architectures. Many such unclassified protein kinases are tethered to domains which are Cysteine‐rich and to domains known to be involved in protein–protein interactions. Our kinome analysis of E. histolytica suggests that the organism possesses a complex protein phosphorylation network that involves many unusual kinases. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Clustering orthologous proteins across phylogenetically distant species
Authors: Kim Sunshin , Kang Jaewoo , Chung Yong Je , Li Jinyan , Ryu Keun Ho
Published: November 2007

The quality of orthologous protein clusters (OPCs) is largely dependent on the results of the reciprocal BLAST (basic local alignment search tool) hits among genomes. The BLAST algorithm is very efficient and fast, but it is very difficult to get optimal solution among phylogenetically distant species because the genomes with large evolutionary distance typically have low similarity in their protein sequences. To reduce the false positives in the OPCs, thresholding is often employed on the BLAST scores. However, the thresholding also eliminates large numbers of true positives as the orthologs from distant species likely have low BLAST scores. To rectify this problem, we introduce a new hybrid method combining the Recursive and the Markov CLuster (MCL) algorithms without using the BLAST thresholding. In the first step, we use InParanoid to produce n(n−1)/2 ortholog tables from n genomes. After combining all the tables into one, our clustering algorithm clusters ortholog pairs recursively in the table. Then, our method employs MCL algorithm to compute the clusters and refines the clusters by adjusting the inflation factor. We tested our method using six different genomes and evaluated the results by comparing against Kegg Orthology (KO) OPCs, which are generated from manually curated pathways. To quantify the accuracy of the results, we introduced a new intuitive similarity measure based on our Least‐move algorithm that computes the consistency between two OPCs. We compared the resulting OPCs with the KO OPCs using this measure. We also evaluated the performance of our method using InParanoid as the baseline approach. The experimental results show that, at the inflation factor 1.3, we produced 54% more orthologs than InParanoid sacrificing a little less accuracy (1.7% less) than InParanoid, and at the factor 1.4, produced not only 15% more orthologs than InParanoid but also a higher accuracy (1.4% more) than InParanoid. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Unstructured intermediate states in single protein force experiments
Authors: Junier Ivan , Ritort Felix
Published: November 2007

Recent single‐molecule force measurements on single‐domain proteins have highlighted a three‐state folding mechanism where a stabilized intermediate state ($ {\cal I} $) is observed on the folding trajectory between the stretched state and the native state. Here we investigate on‐lattice protein‐like heteropolymer models that lead to a three‐state mechanism and show that force experiments can be useful to determine the structure of $ {\cal I} $. We have mostly found that $ {\cal I} $ is composed of a core stabilized by a high number of native contacts, plus an unstructured extended chain. The lifetime of $ {\cal I} $ is shown to be sensitive to modifications of the protein that spoil the core. We then propose three types of modifications–point mutations, cuts, and circular permutations–aiming at: (1) confirming the presence of the core and (2) determining its location, within one amino acid accuracy, along the polypeptide chain. We also propose force jump protocols aiming to probe the on/off‐pathway nature of $ {\cal I} $. Proteins 2008. © 2007 Wiley‐Liss, Inc.
New insights of membrane environment effects on MscL channel mechanics from theoretical approaches
Authors: Debret Gaëlle , Valadié Hélène , Stadler Andreas Maximilian , Etchebest Catherine
Published: November 2007

The prokaryotic mechanosensitive channel of large conductance (MscL) is a remarkable integral membrane protein. During hypo‐osmotic shock, it responses to membrane tension through large conformational changes, that lead to an open state of the pore. The structure of the channel from Mycobacterium tuberculosis has been resolved in the closed state. Numerous experiments have attempted to trap the channel in its open state but they did not succeed in obtaining a structure. A gating mechanism has been proposed based on different experimental data but there is no experimental technique available to follow this process in atomic details. In addition, it has been shown that a decrease of the lipid bilayer thickness lowered MscL activation energy and stabilized a structurally distinct closed channel intermediate. Here, we use atomistic molecular dynamics simulations to investigate the effect of the lipid bilayer thinning on our model of the structure of the Escherichia coli. We thoroughly analyze simulations of the channel embedded in two pre‐equilibrated membranes differing by their hydrophobic tail length (DMPE and POPE). The MscL structure remains stable in POPE, whereas a distinct structural state is obtained in DMPE in response to hydrophobic mismatch. This latter is obtained by tilts and kinks of the transmembrane helices, leading to a widening and a diminution of the channel height. Part of these motions is guided by a competition between solvent and lipids for the interaction with the periplasmic loops. We finally conduct a principal component analysis of the simulation and compare anharmonic motions with harmonic ones, previously obtained from a coarse‐grained normal mode analysis performed on the same structural model. Significant similarities exist between low‐frequency harmonic motions and those observed with essential dynamics in DMPE. In summary, change in membrane thickness permits to accelerate the conformational changes involved in the mechanics of the E. coli channel, providing a closed structural intermediate en route to the open state. These results give clues for better understanding why the channel activation energy is lowered in a thinner membrane. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Crystal structure of a secondary vitamin D3 binding site of milk β‐lactoglobulin
Authors: Yang Ming‐Chi , Guan Hong‐Hsiang , Liu Ming‐Yih , Lin Yih‐Hung , Yang Jinn‐Moon , Chen Wen‐Liang , Chen Chun‐Jung , Mao Simon J. T.
Published: November 2007

β‐lactoglobulin (β‐LG), one of the most investigated proteins, is a major bovine milk protein with a predominantly β structure. The structural function of the only α‐helix with three turns at the C‐terminus is unknown. Vitamin D3 binds to the central calyx formed by the β‐strands. Whether there are two vitamin D binding‐sites in each β‐LG molecule has been a subject of controversy. Here, we report a second vitamin D3 binding site identified by synchrotron X‐ray diffraction (at 2.4 Å resolution). In the central calyx binding mode, the aliphatic tail of vitamin D3 clearly inserts into the binding cavity, where the 3‐OH group of vitamin D3 binds externally. The electron density map suggests that the 3‐OH group interacts with the carbonyl of Lys‐60 forming a hydrogen bond (2.97 Å). The second binding site, however, is near the surface at the C‐terminus (residues 136–149) containing part of an α‐helix and a β‐strand I with 17.91 Å in length, while the span of vitamin D3 is about 12.51 Å. A remarkable feature of the second exosite is that it combines an amphipathic α‐helix providing nonpolar residues (Phe‐136, Ala‐139, and Leu‐140) and a β‐strand providing a nonpolar (Ile‐147) and a buried polar residue (Arg‐148). They are linked by a hydrophobic loop (Ala‐142, Leu‐143, Pro‐144, and Met‐145). Thus, the binding pocket furnishes strong hydrophobic force to stabilize vitamin D3 binding. This finding provides a new insight into the interaction between vitamin D3 and β‐LG, in which the exosite may provide another route for the transport of vitamin D3 in vitamin D3 fortified dairy products. Atomic coordinates for the crystal structure of β‐LG‐vitamin D3 complex described in this work have been deposited in the PDB (access code 2GJ5). Proteins 2008. © 2007 Wiley‐Liss, Inc.
Protein model quality assessment prediction by combining fragment comparisons and a consensus Cα contact potential
Authors: Zhou Hongyi , Skolnick Jeffrey
Published: November 2007

In this work, we develop a fully automated method for the quality assessment prediction of protein structural models generated by structure prediction approaches such as fold recognition servers, or ab initio methods. The approach is based on fragment comparisons and a consensus Cα contact potential derived from the set of models to be assessed and was tested on CASP7 server models. The average Pearson linear correlation coefficient between predicted quality and model GDT‐score per target is 0.83 for the 98 targets, which is better than those of other quality assessment methods that participated in CASP7. Our method also outperforms the other methods by about 3% as assessed by the total GDT‐score of the selected top models. Proteins 2008. © 2007 Wiley‐Liss, Inc.
X‐ray reflectivity study of a transcription‐activating factor‐derived peptide penetration into the model phospholipid monolayers
Authors: Tae Giyoong , Yang Hosung , Shin Kwanwoo , Satija Sushil K. , Torikai Naoya
Published: November 2007

The penetration of a transcription‐activating factor (TAT)‐derived, cell‐penetration peptide onto 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine (DPPC) or 1,2‐dipalmitoyl‐sn‐glycero‐3‐[phospho‐L‐serine] (DPPS) monolayer on phosphate‐buffered saline subphase was characterized. The surface area at the target pressure increased noticeably by the peptide penetration from the subphase to the phospholipid monolayer, which might suggest a direct penetration of the peptide across the pure phospholipid bilayer membrane. Interestingly, the more significant area increase at 35 mN/m was monitored from DPPC monolayer, contrary to the simple charge interaction: the net neutral DPPC, the net‐negative DPPS, and the positive TAT‐derived peptides (TDP). X‐ray reflectivity measurements as well as the molecular area from π (surface pressure)‐A (area) isotherms suggest that the packing density of DPPS at the target pressure is too high to allow the effective penetration of the peptide into the monolayer and the positively charged peptides can be entrapped at the negative electrostatic well of DPPS headgroup layer, leading to the simple adsorption on the DPPS monolayer instead of penetration into it. Thus, more penetration with less adsorption of the peptide is induced by DPPC monolayer than DPPS monolayer. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
Intersubband transitions in a biased superlattice: THz gain and surface mode
Authors: Vasko F. T. , Hernandez‐Cabrera A. , Aceituno P.
Published: November 2007

Intersubband response in a biased superlattice with equipopulated levels is studied within the tight‐binding approximation and the complex dielectric permittivity is calculated beyond the Born approximation for a wide spectral region. The low‐frequency enhancement of the dispersion of permittivity is found and the conditions to obtain the stimulated emission regime is estimated. The enhancement of the emission due to the THz waveguide effect is also considered for the cases of the BSL placed between ideal metallic mirrors, the free‐standing BSL, and BSL at a vacuum‐dielectric interface. An appearance of the localized THz mode is described for the last case. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Femtosecond pump‐probe studies of carrier transport and gain dynamics in quantum cascade lasers
Authors: Choi Hyunyong , Diehl Laurent , Giovannini Marcella , Faist Jérôme , Capasso Federico , Norris Theodore B.
Published: November 2007

Time‐resolved pump‐probe differential transmission measurements have been performed on various sets of quantum cascade lasers below and above threshold. Bias‐, temperature‐, and polarization dependent studies enable a comprehensive understanding of the gain dynamics to be possible in terms of tunneling, transport, and coupling with the intra‐cavity photon density. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Simulation of the charge transport in DNA
Authors: Yamanaka T. , Dutta M. , Stroscio M. A.
Published: November 2007

In this research, charge transport characteristics in a double‐stranded DNA are discussed. Based on the polaron drift model, DNA was characterized by a 1D quantum wire model and the phonon scattering rates were calculated by deformation potential theory. Furthermore, using the calculated pho‐ non scattering rates, the carrier dynamics in DNA were characterized by the Monte Carlo simulation technique. The simulation result shows a rapid charge transport from the initial point. The validity of our modeling is also discussed. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Carrier density dependence of nonresonant carrier tunneling in GaAs double quantum wells – effect of exciton and free carrier thermodynamic
Authors: Lu S. L. , Ushiyama T. , Tackeuchi A. , Muto S.
Published: November 2007

Nonresonant carrier tunneling dynamics in GaAs/AlGaAs double quantum wells as a function of carrier density was investigated by using time‐resolved pump and probe measurements. At low temperatures, tunneling time increases with increasing carrier density. At high temperatures, no dependence of tunneling time on carrier density was shown. This unique behavior is well explained by the thermodynamic effect be‐ tween excitons and free carriers as a function of carrier density on the tunneling process. At low temperatures, a larger fraction of excitons at a higher carrier density, which have a relatively slow tunneling time in contrast to free electrons, leads to a slow tunneling time. The independence of the tunneling time at high temperatures is attributed to the insensitivity of the exciton population to the increased carrier density. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Multiple Linear Regression Analysis and Optimal Descriptors: Predicting the Cholesteryl Ester Transfer Protein Inhibition Activity
Authors: Rasulev Bakhtiyor F. , Toropov Andrey A. , Hamme Ashton T. , Leszczynski Jerzy
Published: November 2007

Quantitative structure–activity relationships have been developed for a set of 40 halogenated substituted N‐benzyl‐N‐phenyl aminoalcohol compounds. IC50 values for Cholesteryl Ester Transfer Protein (CETP) inhibition activity for these compounds expressed in log units have been modeled by Multiple Linear Regression Analysis (MLRA) based on descriptors generated by DRAGON software and optimal descriptors approach. Forty benzene derivatives have been divided into training (n=20) and test (n=20) sets. In the case of the MLRA, the three‐variable model has the best predictive potential. Comparison of the quality of MLRA and optimal descriptor models shows that the predictive potential of the one‐variable model, based on the optimal descriptor, provides a low correlation coefficient in the training set. However, this one‐variable model performs better for the test set when compared to the two‐ and three‐variable MLRA models.
Pronounced Effect of DNA Hybridization on Click Reaction Efficiency
Authors: Wirges Christian T. , Gramlich Philipp M. E. , Gutsmiedl Katrin , Gierlich Johannes , Burley Glenn A. , Carell Thomas
Published: November 2007

We report about the efficiency of the click reaction directly on PCR products containing alkyne‐modified uridine nucleosides. Galactose azide was clicked onto single‐stranded and double‐stranded 300mer DNA in order to investigate the efficiency of sugar labeling of DNA under various conditions. Single‐stranded alkyne‐modified DNA was prepared by selective lambda exonuclease digestion of 5′‐phosphate‐labeled double strands. A comparison of the click reaction efficiency on modified single and double stranded 300mers under identical conditions shows a pronounced effect of the strandedness on the yield of the click reaction.
Peptoids on Steroids: Precise Multivalent Estradiol–Peptidomimetic Conjugates Generated via Azide–Alkyne [3+2] Cycloaddition Reactions
Authors: Holub Justin M. , Garabedian Michael J. , Kirshenbaum Kent
Published: November 2007

We have developed a family of functionalized peptidomimetic oligomers for the multivalent display of bioactive ligands in a site‐directed manner. Sequence‐specific N‐substituted glycine peptoid oligomer scaffolds were synthesized on solid phase to include up to six azidoalkyl sidechains. These constructs were used as substrates for Cu(I)‐catalyzed azide–alkyne [3+2] cycloaddition reactions. 17α‐ethynylestradiol was conjugated at up to six positions along the peptoid backbone, generating estradiol–peptidomimetic conjugates in good yield. We evaluate how the binding avidities of these compounds to the estrogen receptor are enhanced when the valency of hormone ligand presentation is increased.
Click Chemistry‐Led Advances in High Content Functional Proteomics
Authors: Salisbury Cleo M. , Cravatt Benjamin F.
Published: November 2007

The availability of complete genome sequences for numerous eukaryotic and prokaryotic organisms has inspired the advent of new methods to functionally characterize proteins on a global scale. Chemical approaches, in particular, have emerged as a powerful way to investigate the proteome, providing small‐molecule probes that report on protein activity and Post‐Translational Modification (PTM) state directly in complex biological samples. Many of the key advances made in chemical proteomics can be attributed to the development of efficient bio‐orthogonal reactions such as the copper (I)‐catalyzed Huisgen's azide–alkyne cycloaddition, a reaction commonly known as “Click Chemistry” (CC). The generation of “clickable” proteomics probes has removed the requirement for bulky reporter tags, thereby allowing access to more biologically relevant systems such as live cells or animals. The versatility of CC has also allowed for greater experimental efficiency, as different reporter tags (i.e., a fluorophore for detection or biotin for enrichment) can be appended to a single probe. Such advances have enabled researchers to identify protein activities dysregulated in disease states, assess the selectivity of enzyme inhibitors in vivo, and inventory specific PTMs on a proteome‐wide scale.
Characterization of glutathione conjugates of chloroacetanilide pesticides using ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry and liquid chromatography/ion trap mass spectrometry
Authors: Pérez Sandra , Farkas Michael , Barceló Damià , Aga Diana S.
Published: November 2007

Glutathione S‐transferases (GSTs) isolated from maize were used to catalyze the conjugation of glutathione (GSH) with chloroacetanilide herbicides, producing stable conjugates that were structurally characterized using ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry (UPLC/QqToF‐MS) and liquid chromatography/ion trap mass spectrometry (LC/IT‐MS). Enzyme‐mediated dechlorination of alachlor, metolachlor, and propachlor resulted during GSH conjugation as revealed by the mass spectra of the conjugates, which was confirmed by the loss of the chlorine isotopic signature and from high accurate mass measurements. Several fragmentation patterns in the mass spectra of the chloroacetanilide‐GSH conjugates can be used to verify the identities of the enzyme reaction products, such as characteristic ions corresponding to the neutral loss of glutamic acid residue (129 Da) and water (18 Da) observed in the product ion spectrum. For the first time, data are presented showing detection of chloroacetanilides that are conjugated with two GSH molecules, in addition to the known single GSH conjugates. Copyright © 2007 John Wiley & Sons, Ltd.
Data flow language DFC: Design and implementation
Authors: Shimada Toshio , Sekiguchi Satoshi , Hiraki Kei
Published: November 2007

This paper presents the basic idea in the design of the data‐flow language DFC and problems and their solutions in its implementation on the data‐flow computer SIGMA‐1. DFC is a data‐flow language designed with consideration of the compatibility to C language. In the first part of the paper, a design to integrate the functional properties while maintaining the compatibility to C language is shown for the conditional and loop sentences, which are the major components of DFC, as well as the data structure. Then the conversion procedure from DFC to the code of SIGMA‐1 is described together with the problems and their solutions.

Especially, the generation of a graph is discussed in detail, which enables the resource reclamation in execution with the data‐flow computer SIGMA‐1.
Association‐based parser for speech understanding systems—framework design on cognitive exploration
Authors: Hori Masahiro , Mizoguchi Riichiro , Kawachi Masaaki , Uehara Kuniaki , Toyoda Jun'Ichi , Kakusho Osamu
Published: November 2007

It is well known that the use of the high‐level information data such as language information is indispensable in the speech understanding system. Because the human speech understanding process is executed unconsciously, sufficient knowledge is not yet available concerning what kind of high‐level information data are utilized and in what ways. We made two kinds of studies from the viewpoint of cognitive science to acquire knowledge about the use of high‐level information. Based on the result of study, an association based parser ASP was realized for the speech understanding system. ASP receives a large number of phrase candidate sequences as the input, and identifies the correct phrase sequence by examining successively the available syntactic, semantic and associative information. Especially, the topic is extracted first from the input candidates as a whole, and an association mechanism is employed where the vocabulary associated from the topic is processed with priority, being considered as an active word. The study in this paper is described from the viewpoint of cognitive science, and the framework of the language processing system obtained from the study is presented.
Membership problem for head languages and multiple context‐free languages
Authors: Kasami Tadao , Seki Hiroyuki , Fujii Mamoru
Published: November 2007

This paper considers multiple context‐free grammars (mcfg's) which inherit the basic properties of context‐free grammars with generative capacity stronger than that of context‐free grammars but weaker than that of context‐sensitive grammars. It is shown that the time complexity of the membership problem for languages generated by mcfg's is polynomial. It is shown also that head grammars introduced by Pollard for describing the syntax of natural language correspond to a special subclass of mcfg's and, as a corollary, the time complexity of the membership problem for languages generated by head grammars is of order n6.* This is an improvement by one order of magnitude, compared with the result by Pollard.
Bi‐directional current‐mode basic circuits for the multilevel signed‐digit arithmetic and their evaluation
Authors: Kameyama Michitaka , Kawahito Shoji , Higuchi Tatsuo
Published: November 2007

For highly parallel operation, use of a radix‐4 signed‐digit (SD) number system is attractive. Since the SD number system uses more than three values in each digit, multivalued coding is suitable for the implementation of the high‐speed compact arithmetic integrated circuits. We have already proposed the basic idea of multivalued bidirectional current‐mode circuits which are essentially suitable for the SD arithmetic implementation. This paper describes the experimental results of the basic SD arithmetic integrated circuits by means of the bidirectional current‐mode circuits and their evaluation. A parallel SD adder is implemented with 2‐μm CMOS technology and the addition time is estimated to be about 10 ns. The addition time of the SD adder is 14 times faster than that of the conventional ripple‐carry adder and is three times faster than that of the block carry lookahead adder.
A high‐speed rotation method for binary images based on coordinate operation of run data
Authors: Shima Yoshihiro , Kashioka Seiji , Higashino Jun'Ichi
Published: November 2007

The rotation of an image is one of the fundamental functions in image processing and is applied to document image processing in the office or for industrial use with industrial robots. A method of image rotation based on digital image data has been developed. This paper assumes the binary digital data, and proposes a method which is different from the traditional one based on pixel data. This method can execute a high‐speed rotation of the binary image based on coordinate data for the start and the end of the run. Using the proposed method, the image rotation at an arbitrary angle can be realized by the real number operation on the run data, which is suited to the general‐purpose processor. It is a practically useful method since the processing is fast and less memory capacity is required. In this paper, a discussion is made first on the format of the run data, the number of runs and the data complexity for the binary data. Then the newly devised rotation for the binary image is described. The rotation method is used to perform successively the skew coordinate transformations in the vertical and horizontal directions, to determine the rotated image. Finally, a document image is actually rotated on a large‐scale computer. The processing time was examined to demonstrate experimentally the usefulness of the proposed method.
Efficient distributed algorithms solving problems about the connectivity of network
Authors: Park Jungho , Tokura Nobuki , Masuzawa Toshimitsu , Hagihara Ken'Ichi
Published: November 2007

This paper presents efficient distributed algorithms on an asynchronous network for the following problems: finding bi‐connected components, finding cutpoints, finding bridges, testing for bi‐connectedness and finding strongly connected components of a directed graph defined on a network. All these distributed algorithms use a depth‐first search tree having an arbitrary processor in the network as its root. The communication complexity of these algorithms is O(nlogn+e) and their ideal‐time complexity is O(nG(n)), where n and e represent the numbers of processors and links, respectively, and G(n) is almost a constant. It is shown also that a lower bound for the communication complexity of the five problems is O(e) and a lower bound for their ideal‐time complexity is O(n).
Performance analysis of multiprocessor systems with bus architecture
Authors: Matsunaga Toshio , Fukumura Yoshimi
Published: November 2007

The performance of bus‐architecture multiprocessor systems is discussed in this paper. The goal is to clarify the effective organizations of future computer systems by analyzing the total system performance of tightly coupled multiprocessors (TCMP) and loosely coupled multiprocessors (LCMP). For the purpose of comparing TCMP and LCMP designs, queueing models for hardware processing and software processing are introduced and system performance is evaluated. As a result, limitations on the TCMP model and the conditions under which it is more profitable than the LCMP model are shown. Further, the influence of multimedia communication on system performance is indicated.
A parallel processing architecture for image understanding
Authors: Watanabe Masaki , Ohta Yuichi , Ikeda Katsuo
Published: November 2007

General‐purpose image understanding requires that an image understanding system be built that will accommodate multiple image understanding algorithms and thereby provide the system with flexibility and robustness. This paper proposes a mechanism whereby multiple modules can cooperate with each other and process in parallel, each of which modules is designed to execute a dedicated image understanding algorithm.

An architecture to implement the mechanism onto a parallel computer is also presented. Knowledge regarding the execution of an algorithm and the results obtained by the execution are stored in each separate module. These results are accessed when the modules communicate with each other. Intra‐module parallel processing can be done by executing in parallel processes that are dynamically generated with query by query coming to each module to reply. This intra‐module processing makes it possible to concurrently apply the same algorithm to different local parts of a single image.

A stereo matching system, one application of the mechanism, is introduced and some experimental results obtained on a parallel computer are shown.
Efficient facsimile data reduction by thinning process
Authors: Mizuno Shoji
Published: November 2007

Picture preprocessing and encoding methods that can greatly reduce the facsimile picture signal information are presented here. Preprocessing consists of smoothing and thinning lines before encoding in a transmitter. Lines are thickened by postprocessing after decoding in a receiver. Because the post‐processed picture quality is lower than that for the original picture, it is important to prove whether entropy reduction by thinning is still great. To do so requires considering picture quality degradation caused by preprocessing. Proof of high entropy reduction involves a comparison of the entropy for a preprocessed picture with that for a reduced‐size picture. The picture quality of the latter when enlarged back to its original size is comparable with that for the post‐processed picture. This comparison reveals that entropy reduction by preprocessing is 5 percent for printed Japanese and 19 to 24 percent for handwritten English and Japanese, as well as for typewritten English.

An encoding scheme called predictive MH coding, which takes advantage of the feature wherein line width in a preprocessed picture is almost a single picture element, is applied to encode preprocessed pictures. As already predicted by entropy measurement, it was found that the compression ratio for the proposed method is 1.04 times as high as that for the CCITT‐standard MR coding for printed Japanese. Furthermore, it is from 1.3 to 1.4 times as high as that for the CCITT‐standard MR coding for handwritten English and Japanese, as well as for typewritten English.
Construction and evaluation of the identity transformers for cryptographic key distribution
Authors: Matsumoto Tsutomu , Takashima Youichi , Iraai Hideki
Published: November 2007

This paper describes the key predistribution system (KPS) which simplifies the use of public key cryptography in a large‐scale complex network. The identity (ID) transformer R, which is needed in the realization of KPS by a linear scheme, is proposed and evaluated; R is an algorithm which transforms a short vector into a long vector. It is desired that R be executed in a simple way by an IC card and can realize a one‐way and random injective function; a method to realize such R is discussed fully in this paper. An example R1 with the specified parameters is realized using 8 bit CPU, and it is verified that the ID transformer algorithm can be executed in approximately 0.4 s, using the one‐way algorithm with the processing speed of approximately 50 kbit/s. As a result of evaluation of the statistical randomness, it is verified that the random condition is satisfied.
A condition matching algorithm for high‐cost rules in production systems: Effectiveness measurements
Authors: Kimura Haruhiko , Kobayashi Shin‐Ya , Sumiyoshi Kazuyuki , Takebe Tsuyoshi
Published: November 2007

Production systems are well known as the most essential tools for developing expert systems. The most important problem to solve in a production system is that of speeding up its condition matching process. A production system quite often requires excessive matching time. This excessive computational time is normally caused by so‐called high‐cost rules that require a great deal of computational time. The objective of this paper is to develop an algorithm that can reduce the condition matching times of these high‐cost rules.

An algorithm is presented here that can efficiently handle the high‐cost rules by reducing the worst case computational time for condition matching compared with the conventional Rete or Treat algorithms. An experiment was performed to demonstrate the effectiveness of the proposed algorithm high‐cost rules.
Computer graphic model of walking quadruped animal
Authors: Mizuno Hironori , Muraoka Yoichi
Published: November 2007

No animation method has ben established which makes flexible and pliant the walk of an animal keeping a balance of its body parts with joints. This paper proposes a computer graphic model of a quadruped animal (e.g., a dog) which walks and runs naturally and autonomously. The model is based on: (1) calculation of shift of the position of the animal over frames using “speed function”; (2) balancing the motions of four legs and the vertebra with their joints. The speed is obtained from analyses of actual animal motions. A smooth natural action of the animal over frames is achieved by allocating the speed function to spatial shifts of the body and its joints. To obtain a real time operation, “kinematic control” is used, ensuring smooth motions as in a “dynamic control.” Motions of an animal body in an image are controlled by specifying the path and speed of the body. The effect of the proposed model has been evaluated successfully by experiments.