bluuebunny/crossref_metadata_2025 huggingface dataset:
DISAMBIGUATION OF GREEK POLYSEMOUS WORDS USING HIERARCHICAL PROBABILISTIC NETWORKS AND A CHI-SQUARE FEATURE SELECTION STRATEGY
Authors: FRAGOS KOSTAS , PANETSOS SPIROS
Published: September 2008

In this paper, we present a robust classification technique to disambiguate Greek polysemous words based on hierarchical probabilistic networks. Assuming that the linguistic data of a polysemous word is classified to equivalent classes according to the number of its senses, we try to disambiguate them by using a hierarchical mixture of experts' probabilistic model — a soft version of neural networks that permits overlapping between classes and which is successfully applied in classification tasks. The model is used in combination with an effective feature selection strategy based on a Chi-square test that enhances disambiguation performance. Due to the absence of previous similar work on Greek linguistic data, for comparison we also implement and apply the very popular naïve Bayes classifier to the same data. Comparing the two systems, we find that the Hierarchical Mixtures-of-Experts (HME) model is superior to the naïve Bayes classifier, mainly because of its ability to permit overlapping and the capture of non-linearity among the data. We believe that the system can be successfully applied on real linguistic data after training on a small amount of data.
A SPACE-EFFICIENT BACKTRACK-FREE REPRESENTATION FOR CONSTRAINT SATISFACTION PROBLEMS
Authors: BECK J. CHRISTOPHER , CARCHRAE TOM , FREUDER EUGENE C. , RINGWELSKI GEORG
Published: September 2008

In this paper we present a radical approach to obtaining a backtrack-free representation for a constraint satisfaction problem: remove values that lead to dead-ends. This technique does not require additional space but has the drawback of removing solutions. We investigate a number of variations on the basic algorithm including the use of seed solutions, consistency techniques, and a variety of pruning heuristics. Our experimental results indicate that a significant proportion of the solutions to the original problem can be retained especially when an optimization algorithm that specifically searches for such “good” backtrack-free representations is employed. Further extensions increase solution retention by searching for high-coverage backtrack-free representations, by removing tuples rather than values, and by combining multiple backtrack-free representations. Our approach elucidates, for the first time, a three-way trade-off between space complexity, potential backtracks, and solution loss and enables algorithms that can actively reason about the trade-off between space, backtracks, and solution loss.
ON FINDING MINIMALLY UNSATISFIABLE CORES OF CSPs
Authors: GRÉGOIRE ÉRIC , MAZURE BERTRAND , PIETTE CÉDRIC
Published: September 2008

When a Constraint Satisfaction Problem (CSP) admits no solution, it can be useful to pinpoint which constraints are actually contradicting one another and make the problem infeasible. In this paper, a recent heuristic-based approach to compute infeasible minimal subparts of discrete CSPs, also called Minimally Unsatisfiable Cores (MUCs), is improved. The approach is based on the heuristic exploitation of the number of times each constraint has been falsified during previous failed search steps. It appears to enhance the performance of the initial technique, which was the most efficient one until now.
FUZZY C-MEANS ALGORITHM WITH LOCAL THRESHOLDING FOR GRAY-SCALE IMAGES
Authors: NG HSIAO PIAU , ONG SIM HENG , FOONG KELVIN WENG CHIONG , GOH POH SUN , NOWINSKI WIESLAW L.
Published: September 2008

An improved fuzzy C-means (FCM) clustering method is proposed. It incorporates Otsu thresholding with conventional FCM to reduce FCM's susceptibility to local minima, as well as its tendency to derive a threshold that is biased towards the component with larger probability, and derive threshold values with greater accuracy. Thresholding is performed at the cluster boundary region in feature space. A comparison of the results produced by improved and conventional algorithms confirms the superior performance of the former.
CONSERVED WATER MOLECULES IN X-RAY STRUCTURES HIGHLIGHT THE ROLE OF WATER IN INTRAMOLECULAR AND INTERMOLECULAR INTERACTIONS
Authors: AKSIANOV EVGENIY , ZANEGINA OLGA , GRISHIN ALEXANDER , SPIRIN SERGEY , KARYAGINA ANNA , ALEXEEVSKI ANDREI
Published: September 2008

Water molecules immobilized on a protein or DNA surface are known to play an important role in intramolecular and intermolecular interactions. Comparative analysis of related three-dimensional (3D) structures allows to predict the locations of such water molecules on the protein surface. We have developed and implemented the algorithm WLAKE detecting "conserved" water molecules, i.e. those located in almost the same positions in a set of superimposed structures of related proteins or macromolecular complexes. The problem is reduced to finding maximal cliques in a certain graph. Despite exponential algorithm complexity, the program works appropriately fast for dozens of superimposed structures. WLAKE was used to predict functionally significant water molecules in enzyme active sites (transketolases) as well as in intermolecular (ETS–DNA complexes) and intramolecular (thiol–disulfide interchange protein) interactions. The program is available online at .
MANY-ATOM VAN DER WAALS INTERACTIONS LEAD TO DIRECTION-SENSITIVE INTERACTIONS OF COVALENT BONDS
Authors: FINKELSTEIN ALEXEI V. , LOBANOV MICHAEL Y. , DOVIDCHENKO NIKITA V. , BOGATYREVA NATALIA S.
Published: September 2008

Strict physical theory and numerical calculations show that a specific coupling of many-atom van der Waals interactions with covalent bonding can significantly (half as much) increase the strength of attractive dispersion interactions when the direction of interaction coincides with the direction of the covalent bond, and decrease this strength when the direction of interaction is perpendicular to the direction of the covalent bond. The energy effect is comparable to that caused by the replacement of atoms (e.g. N by C or O ) in conventional pairwise van der Waals interactions. Analysis of protein structures shows that they bear an imprint of this effect. This means that many-atom van der Waals interactions cannot be ignored in refinement of protein structures, in simulations of their folding, and in prediction of their binding affinities.
COMPACTNESS DETERMINES PROTEIN FOLDING TYPE
Authors: GALZITSKAYA OXANA V. , BOGATYREVA NATALYA S. , IVANKOV DMITRY N.
Published: September 2008

We have demonstrated here that protein compactness, which we define as the ratio of the accessible surface area of a protein to that of the ideal sphere of the same volume, is one of the factors determining the mechanism of protein folding. Proteins with multi-state kinetics, on average, are more compact (compactness is 1.49 ± 0.02 for proteins within the size range of 101–151 amino acid residues) than proteins with two-state kinetics (compactness is 1.59 ± 0.03 for proteins within the same size range of 101–151 amino acid residues). We have shown that compactness for homologous proteins can explain both the difference in folding rates and the difference in folding mechanisms.
SEARCH FOR FOLDING INITIATION SITES FROM AMINO ACID SEQUENCE
Authors: GALZITSKAYA OXANA V.
Published: September 2008

A crucial event in protein folding is the formation of a folding nucleus, which is a structured part of the protein chain in the transition state. We demonstrate a correlation between locations of residues involved in the folding nuclei and locations of predicted amyloidogenic regions. The average Φ-values are significantly greater inside amyloidogenic regions than outside them. We have found that fibril formation and normal folding involve many of the same key residues, giving an opportunity to outline the folding initiation site in protein chains. The search for folding initiation sites for apomyoglobin and ribonuclease. A coincides with the predictions made by other approaches.
GENE ONTOLOGY-BASED SEMANTIC ALIGNMENT OF BIOLOGICAL PATHWAYS BY EVOLUTIONARY SEARCH
Authors: GAMALIELSSON JONAS , OLSSON BJÖRN
Published: September 2008

A large number of biological pathways have been elucidated recently, and there is a need for methods to analyze these pathways. One class of methods compares pathways semantically in order to discover parts that are evolutionarily conserved between species or to discover intraspecies similarities. Such methods usually require that the topologies of the pathways being compared are known, i.e. that a query pathway is being aligned to a model pathway. However, sometimes the query only consists of an unordered set of gene products. Previous methods for mapping sets of gene products onto known pathways have not been based on semantic comparison of gene products using ontologies or other abstraction hierarchies. Therefore, we here propose an approach that uses a similarity function defined in Gene Ontology (GO) terms to find semantic alignments when comparing paths in biological pathways where the nodes are gene products. A known pathway graph is used as a model, and an evolutionary algorithm (EA) is used to evolve putative paths from a set of experimentally determined gene products. The method uses a measure of GO term similarity to calculate a match score between gene products, and the fitness value of each candidate path alignment is derived from these match scores. A statistical test is used to assess the significance of evolved alignments. The performance of the method has been tested using regulatory pathways for S. cerevisiae and M. musculus.
KINETIC MODEL OF PHOSPHOFRUCTOKINASE-1 FROMESCHERICHIA COLI
Authors: PESKOV KIRILL , GORYANIN IGOR , DEMIN OLEG
Published: September 2008

This paper presents a kinetic model of phosphofructokinase-1 from Escherichia coli. A complete catalytic cycle has been reconstructed based on available information on the oligomeric structure of the enzyme and kinetic mechanism of its monomer. Applying the generalization of the Monod–Wyman–Changeux approach proposed by Popova and Sel'kov35–37to the reconstructed catalytic cycle rate equation has been derived. Dependence of the reaction rate on pH , magnesium, and effectors has been taken into account. Kinetic parameters have been estimated via fitting the rate equation against experimentally measured dependencies of initial rate on substrates, products, effectors, and pH available from the literature. The model of phosphofructokinase-1 predicts (1) cooperativity of binding both fructose-6-phosphate and ATPMg2-, (2) significant inhibition of the enzyme resulting from an increase in total concentration of ATP under the condition of fixed concentration of Mg2+ions, and (3) dual effect of ADP consisting of allosteric activation and product inhibition of the enzyme. Moreover, the model developed can be used in the kinetic modeling of biochemical pathways containing phosphofructokinase-1.
LARGE-SCALE STRUCTURAL MODELING OF PROTEIN COMPLEXES AT LOW RESOLUTION
Authors: ZHU ZHENGWEI , TOVCHIGRECHKO ANDREY , BARONOVA TATIANA , GAO YING , DOUGUET DOMINIQUE , O'TOOLE NICHOLAS , VAKSER ILYA A.
Published: September 2008

Structural aspects of protein–protein interactions provided by large-scale, genome-wide studies are essential for the description of life processes at the molecular level. A methodology is developed that applies the protein docking approach (GRAMM), based on the knowledge of experimentally determined protein–protein structures (DOCKGROUND resource) and properties of intermolecular energy landscapes, to genome-wide systems of protein interactions. The full sequence-to-structure-of-complex modeling pipeline is implemented in the Genome Wide Docking Database (GWIDD) resource. Protein interaction data are imported to GWIDD from external datasets of experimentally determined interaction networks. Essential information is extracted and unified to form the GWIDD database. Structures of individual interacting proteins in the database are retrieved (if available) or modeled, and protein complex structures are predicted by the docking program. All protein sequence, structure, and docking information is conveniently accessible through a Web interface.
WAVE PACKET MOTIONS COUPLED TO ELECTRON TRANSFER IN REACTION CENTERS OF CHLOROFLEXUS AURANTIACUS
Authors: YAKOVLEV ANDREI G. , SHKUROPATOVA TATIANA A. , VASILIEVA LYUDMILA G. , YA. SHKUROPATOV ANATOLI , SHUVALOV VLADIMIR A.
Published: September 2008

Transient absorption difference spectroscopy with ~20 femtosecond (fs) resolution was applied to study the time and spectral evolution of low-temperature (90 K) absorbance changes in isolated reaction centers (RCs) of Chloroflexus (C.) aurantiacus. In RCs, the composition of the B-branch chromophores is different with respect to that of purple bacterial RCs by occupying the BB binding site of accessory bacteriochlorophyll by bacteriopheophytin molecule (ΦB). It was found that the nuclear wave packet motion induced on the potential energy surface of the excited state of the primary electron donor P* by ~20 fs excitation leads to a coherent formation of the states [Formula: see text] and [Formula: see text] (BA is a bacteriochlorophyll monomer in the A-branch of cofactors). The processes were studied by measuring coherent oscillations in kinetics of the absorbance changes at 900 nm and 940 nm (P* stimulated emission), at 750 nm and 785 nm (ΦB absorption bands), and at 1,020–1028 nm ([Formula: see text] absorption band). In RCs, the immediate bleaching of the P band at 880 nm and the appearance of the stimulated wave packet emission at 900 nm were accompanied (with a small delay of 10–20 fs) by electron transfer from P* to the B-branch with bleaching of the ΦB absorption band at 785 nm due to [Formula: see text] formation. These data are consistent with recent measurements for the mutant HM182L Rb. sphaeroides RCs (Yakovlev et al., Biochim Biophys Acta1757:369–379, 2006). Only at a delay of 120 fs was the electron transfer from P* to the A-branch observed with a development of the [Formula: see text] absorption band at 1028 nm. This development was in phase with the appearance of the P* stimulated emission at 940 nm. The data on the A-branch electron transfer in C. aurantiacus RCs are consistent with those observed in native RCs of Rb. sphaeroides. The mechanism of charge separation in RCs with the modified B-branch pigment composition is discussed in terms of coupling between the nuclear wave packet motion and electron transfer from P* to ΦB and BA primary acceptors in the B-branch and A-branch, respectively.
ORTHOFOCUS: PROGRAM FOR IDENTIFICATION OF ORTHOLOGS IN MULTIPLE GENOMES IN FAMILY-FOCUSED STUDIES
Authors: IVLIEV ALEXANDER E. , SERGEEVA MARINA G.
Published: September 2008

The identification of orthologs to a set of known genes is often the starting point for evolutionary studies focused on gene families of interest. To date, the existing orthology detection tools (COG, InParanoid, OrthoMCL, etc.) are aimed at genome-wide ortholog identification and lack flexibility for the purposes of case studies. We developed a program OrthoFocus, which employs an extended reciprocal best hit approach to quickly search for orthologs in a pair of genomes. A group of paralogs from the input genome is used as the start for the forward search and the criterion for the reverse search, which allows handling many-to-one and many-to-many relationships. By pairwise comparison of genomes with the input species genome, OrthoFocus enables quick identification of orthologs in multiple genomes and generates a multiple alignment of orthologs so that it can further be used in phylogenetic analysis. The program is available at .
KULLBACK–LEIBLER MARKOV CHAIN MONTE CARLO — A NEW ALGORITHM FOR FINITE MIXTURE ANALYSIS AND ITS APPLICATION TO GENE EXPRESSION DATA
Authors: TATARINOVA TATIANA , BOUCK JOHN , SCHUMITZKY ALAN
Published: September 2008

In this paper, we study Bayesian analysis of nonlinear hierarchical mixture models with a finite but unknown number of components. Our approach is based on Markov chain Monte Carlo (MCMC) methods. One of the applications of our method is directed to the clustering problem in gene expression analysis. From a mathematical and statistical point of view, we discuss the following topics: theoretical and practical convergence problems of the MCMC method; determination of the number of components in the mixture; and computational problems associated with likelihood calculations. In the existing literature, these problems have mainly been addressed in the linear case. One of the main contributions of this paper is developing a method for the nonlinear case. Our approach is based on a combination of methods including Gibbs sampling, random permutation sampling, birth-death MCMC, and Kullback–Leibler distance.
JUDGMENT ALGORITHM FOR PERIODICITY OF TIME SERIES DATA BASED ON BAYESIAN INFORMATION CRITERION
Authors: TOMINAGA DAISUKE , HORIMOTO KATSUHISA
Published: September 2008

Judgment periodicity of biological time series data is important and done widely to find the circadian expression of genes, monthly change of hormones, etc. To keep complete reproducibility of judgment is a problem because popular judgment methods such as curve fitting, Fourier analysis, etc. need judgment criteria determined by analysts considering experimental conditions and results (level, S/N, distribution, etc.) based on their experience. Judgment results are often affected by analysts' subjects. Reproducible criterion determination is therefore strongly needed. We propose introducing the information criterion to replace analysts' criteria. A judgment algorithm by combining Bayesian information criterion (BIC) and discrete Fourier transform (DFT) has been developed and has proved its ability through application to mice microarray data and finding of circadian genes. Our method, named "Piccolo", shows higher sensitivity than the simple DFT (without BIC) method with reproducibility, and can be fully automated.
Evolutionary Ecology of Figs and Their Associates: Recent Progress and Outstanding Puzzles
Authors: Herre Edward Allen , Jandér K. Charlotte , Machado Carlos Alberto
Published: September 2008

Over the past decade a proliferation of research has enriched and dramatically altered our understanding of the biology of figs, their pollinator wasps, and the myriad of other organisms that depend on them. Ecologically, this work underscores the crucial role that fig fruits play in sustaining and shaping tropical frugivore communities. More generally, this work addresses several key issues in evolutionary ecology, including evolution of breeding systems (shifts between monoecy and dioecy), factors that promote the stability of mutualisms, precision of adaptation, and trajectories of community assembly and coevolution in systems with multiple interacting partners. Moreover, both the pollinating and nonpollinating wasps associated with figs provide unparalleled opportunities for examining how different population structures can differentially affect sex allocation, kin selection, the evolution of parasite virulence, and many fundamental parameters of population genetics (e.g., levels of genetic variation and rates of silent and nonsilent base substitutions).
Herbivory from Individuals to Ecosystems
Authors: Schmitz Oswald J.
Published: September 2008

Herbivores not only consume resources, but they are resources for other consumers. Consequently, they have much potential to mediate effects that cascade up and down trophic chains in ecosystems. The way those effects are mediated depends on individual-scale properties of herbivores including constraints determining resource limitation, herbivore feeding mode, the adaptive trade-off to balance nutrient intake and predation risk avoidance, and the need to maintain homeostatic balance of elemental chemistry in the face of widely varying elemental composition of plant resources. These factors determine the rates of ecosystem functions such as production, decomposition and nutrient cycling. This review integrates those factors to build a conceptual framework for looking at herbivore-mediated effects in ecosystems. The framework systematically resolves how herbivores and carnivores directly and indirectly interact with plants to shape ecosystem functions. It can be used to motivate new field experimentation aimed at elucidating mechanisms of trophic control of ecosystem function.
Revisiting the Impact of Inversions in Evolution: From Population Genetic Markers to Drivers of Adaptive Shifts and Speciation?
Authors: Hoffmann Ary A. , Rieseberg Loren H.
Published: September 2008

There is a growing appreciation that chromosome inversions affect rates of adaptation, speciation, and the evolution of sex chromosomes. Comparative genomic studies have identified many new paracentric inversion polymorphisms. Population models suggest that inversions can spread by reducing recombination between alleles that independently increase fitness, without epistasis or coadaptation. Areas of linkage disequilibrium extend across large inversions but may be interspersed by areas with little disequilibrium. Genes located within inversions are associated with a variety of traits including those involved in climatic adaptation. Inversion polymorphisms may contribute to speciation by generating underdominance owing to inviable gametes, but an alternative view gaining support is that inversions facilitate speciation by reducing recombination, protecting genomic regions from introgression. Likewise, inversions may facilitate the evolution of sex chromosomes by reducing recombination between sex determining alleles and alleles with sex-specific effects. However, few genes within inversions responsible for fitness effects or speciation have been identified.
Role of Endothelin Receptor Antagonists in the Treatment of Pulmonary Arterial Hypertension
Authors: Abman Steven H.
Published: September 2008

Pulmonary arterial hypertension (PAH) is a severe disease with marked morbidity and mortality for which therapeutic strategies have been limited. Basic research in vascular biology has implicated endothelin-1 (ET-1) and its receptors (ETAand ETB) in diverse preclinical models of PAH, and ET-1 has been shown to contribute significantly to PAH in human patients. Despite the complexity of roles of the ET receptors in the development or reversal of PAH in the laboratory, the introduction of endothelin receptor antagonists (ETRAs) to clinical medicine has substantially expanded our therapeutic approach toward severe PAH. This article briefly reviews preclinical data and the current status of ETRAs in the clinical management of PAH.
Conceptual Consumption
Authors: Ariely Dan , Norton Michael I.
Published: September 2008

As technology has simplified meeting basic needs, humans have cultivated increasingly psychological avenues for occupying their consumption energies, moving from consuming food to consuming concepts; we propose that consideration of such “conceptual consumption” is essential for understanding human consumption. We first review how four classes of conceptual consumption—consuming expectancies, goals, fluency, and regulatory fit—impact physical consumption. Next, we benchmark the power of conceptual consumption against physical consumption, reviewing research in which people forgo positive physical consumption—and even choose negative physical consumption–in order to engage in conceptual consumption. Finally, we outline how conceptual consumption informs research examining both preference formation and virtual consumption, and how it may be used to augment efforts to enhance consumer welfare.
Oxytocin and vasopressin gene expression and RNA splicing patterns in the rat supraoptic nucleus
Authors: Yue Chunmei , Ponzio Todd A. , Fields Raymond L. , Gainer Harold
Published: September 2008

In this study, we test the hypothesis that there are differential splicing patterns between the expressed oxytocin (OT) and vasopressin (VP) genes in the rat supraoptic nucleus (SON). We quantify the low abundance, intron-containing heteronuclear RNAs (hnRNAs) and the higher abundance mRNAs in the SON using two-step, quantitative SYBR Green real-time reverse transcription (RT)-PCR and external standard curves constructed using synthetic 90 nt sense-strand oligonucleotides. The levels of OT and VP mRNA in the SON were found to be similar, ∼108 copies/SON pair, whereas the copy numbers of VP hnRNAs containing intron 1 or 2 and the OT hnRNA containing intron 1 are much lower, i.e., ∼102–103 copies/rat SON pair. However, the estimated copy number of the intron 2-containing OT hnRNA is much larger, ∼106 copies/SON pair. The relative distributions of all the OT and VP RNA species were invariant and independent of the physiological status of the rats (e.g., osmotically stimulated or lactating rats). Using intron-specific riboprobes against hnRNAs, we demonstrate by fluorescence in situ hybridization strong signals of OT hnRNA containing intron 2 predominantly in the cytoplasm, in contrast to the localization of the VP hnRNA found only in the nuclei. Taken together, these data support the view that the splicing patterns between OT and VP gene transcripts are different and show that there is a selective cytoplasmic retention of OT intron 2.
Effects of fluoxetine on the reproductive axis of female goldfish (Carassius auratus)
Authors: Mennigen Jan A. , Martyniuk Christopher J. , Crump Kate , Xiong Huiling , Zhao E. , Popesku Jason , Anisman Hymie , Cossins Andrew R. , Xia Xuhua , Trudeau Vance L.
Published: September 2008

We investigated the effects of fluoxetine, a selective serotonin reuptake inhibitor, on neuroendocrine function and the reproductive axis in female goldfish. Fish were given intraperitoneal injections of fluoxetine twice a week for 14 days, resulting in five injections of 5 μg fluoxetine/g body wt. We measured the monoamine neurotransmitters serotonin, dopamine, and norepinephrine in addition to their metabolites with HPLC. Homovanillic acid, a metabolite in the dopaminergic pathway, increased significantly in the hypothalamus. Plasma estradiol levels were measured by radioimmunoassay and were significantly reduced approximately threefold after fluoxetine treatment. We found that fluoxetine also significantly reduced the expression of estrogen receptor (ER)β1 mRNA by 4-fold in both the hypothalamus and the telencephalon and ERα mRNA by 1.7-fold in the telencephalon. Fluoxetine had no effect on the expression of ERβ2 mRNA in the hypothalamus or telencephalon. Microarray analysis identified isotocin, a neuropeptide that stimulates reproductive behavior in fish, as a candidate gene affected by fluoxetine treatment. Real-time RT-PCR verified that isotocin mRNA was downregulated approximately sixfold in the hypothalamus and fivefold in the telencephalon. Intraperitoneal injection of isotocin (1 μg/g) increased plasma estradiol, providing a potential link between changes in isotocin gene expression and decreased circulating estrogen in fluoxetine-injected fish. Our results reveal targets of serotonergic modulation in the neuroendocrine brain and indicate that fluoxetine has the potential to affect sex hormones and modulate genes involved in reproductive function and behavior in the brain of female goldfish. We discuss these findings in the context of endocrine disruption because fluoxetine has been detected in the environment.
Vanishing Waves on Closed Intervals and Propagating Short‐Range Phenomena
Authors: Toma Ghiocel , Doboga Flavia
Published: September 2008

This study presents mathematical aspects of wave equation
considered on closed space intervals. It is shown that a solution of this
equation can be represented by a certain superposition of traveling waves
with null values for the amplitude and for the time derivatives of the resulting
wave in the endpoints of this interval. Supplementary aspects
connected with the possible existence of initial conditions for a secondorder
differential system describing the amplitude of these localized oscillations
are also studied, and requirements necessary for establishing
a certain propagation direction for the wave (rejecting the possibility of
reverse radiation) are also presented. Then it is shown that these aspects
can be extended to a set of adjacent closed space intervals, by considering
that a certain traveling wave propagating from an endpoint to the
other can be defined on each space interval and a specific mathematical
law (which can be approximated by a differential equation) describes the
amplitude of these localized traveling waves as related to the space coordinates
corresponding to the middle point of the interval. Using specific
differential equations, it is shown that the existence of such propagating
law for the amplitude of localized oscillations can generate periodical
patterns and can explain fracture phenomena inside materials as well.
Relativistic Short Range Phenomena and Space‐Time Aspects of Pulse Measurements
Authors: Bakhoum Ezzat G. , Toma Cristian
Published: September 2008

Particle physics is increasingly being linked to engineering applications via electron microscopy, nuclear instrumentation, and numerous other applications. It is well known that relativistic particle equations notoriously fail over very short space‐time intervals. This paper introduces new versions of Dirac_s equation and of the Klein‐Gordon equation that are suitable for
short‐range phenomena. Another objective of the paper is to demonstrate
that pulse measurement methods that are based on the wave nature of matter
do not necessarily correlate with physical definitions that are based on
the corpuscular nature of particles.
Incremental Nonnegative Matrix Factorization for Face Recognition
Authors: Chen Wen-Sheng , Pan Binbin , Fang Bin , Li Ming , Tang Jianliang
Published: September 2008

Nonnegative matrix factorization (NMF) is a promising approach for local feature extraction in face recognition tasks. However, there are two major drawbacks in almost all existing NMF‐based methods. One shortcoming is that the computational cost is expensive for large matrix decomposition. The other is that it must conduct repetitive learning, when the training samples or classes are updated. To overcome these two limitations, this paper proposes a novel incremental nonnegative matrix factorization (INMF) for face representation and recognition. The proposed INMF approach is based on a novel constraint criterion and our previous block strategy. It thus has some good properties, such as low computational complexity, sparse coefficient matrix. Also, the coefficient column vectors between different classes are orthogonal. In particular, it can be applied to incremental learning. Two face databases, namely FERET and CMU PIE face databases, are selected for evaluation. Compared with PCA and some state‐of‐the‐art NMF‐based methods, our INMF approach gives the best performance.
Thyroid Function and Cognition during Aging
Authors: Bégin M. E. , Langlois M. F. , Lorrain D. , Cunnane S. C.
Published: September 2008

We summarize here the studies examining the association between thyroid function and cognitive performance from an aging perspective. The available data suggest that there may be a continuum in which cognitive dysfunction can result from increased or decreased concentrations of thyroid hormones. Clinical and subclinical hypothyroidism as well as hyperthyroidism in middle-aged and elderly adults are both associated with decreased cognitive functioning, especially memory, visuospatial organization, attention, and reaction time. Mild variations of thyroid function, even within normal limits, can have significant consequences for cognitive function in the elderly. Different cognitive deficits possibly related to thyroid failure do not necessarily follow a consistent pattern, and L-thyroxine treatment may not always completely restore normal functioning in patients with hypothyroidism. There is little or no consensus in the literature regarding how thyroid function is associated with cognitive performance in the elderly.
Detection of Short‐Step Pulses Using Practical Test‐Functions and Resonance Aspects
Authors: Toma Alexandru , Morarescu Cristian
Published: September 2008

An important aspect in modeling dynamic phenomena consists in measuring
with higher accuracy some physical quantities corresponding to the
dynamic system. Yet for measurements performed on limited time interval
at high working frequency, certain intelligent methods should be added. The
high working frequency requires that the measurement and data processing
time interval should be greater than the time interval when the step input is
received, so as to allow an accurate measurement. This paper will show that
an intelligent processing method based on oscillating second‐order systems
working on limited time interval can differentiate between large step inputs
(which are active on the whole limited time interval) and short step inputs
(which are active on a time interval shorter than the limited working period).
Some resonance aspects (appearing when the input frequency is close
to the working frequency of the oscillating second‐order system) will be also
presented.
Surveillance as an Option for the Treatment of Small Renal Masses
Authors: Klaver S. , Joniau S. , Van Poppel H.
Published: September 2008

Objectives. To review the natural history and biological potential of small renal masses in order to evaluate surveillance as a treatment option.Methods. Literature search of Medline and additional references from non-Medline-indexed publications concerning surveillance of small renal masses.Results. The natural history and biological potential of small renal masses can still not be unambiguously predicted at present. There seems to be no clear correlation between tumour size and presence of benign histology. The majority of small renal masses grow and the majority are cancer, but one cannot safely assume that a lack of growth on serial CT scans is the confirmation of absence of malignancy. Needle core biopsies could be used to help in decision making. They show a high accuracy for histopathological tumour type but are less accurate in evaluating Fuhrman grade.Conclusions. At present, surveillance of small renal masses should only be considered in elderly and/or infirm patients with competing health risks, in those with a limited life expectancy, and in those for whom minimal invasive treatment or surgery is not an option. In all other patients, active surveillance should only be considered in the context of a study protocol. Long-term, prospective studies are needed to provide a more accurate assessment of the natural history and metastastic potential of small renal masses.
PPARα‐ and DEHP‐Induced Cancers
Authors: Ito Yuki , Nakajima Tamie
Published: September 2008

Di(2‐ethylhexyl)phthalate (DEHP) is a widely used plasticizer and a potentially nongenotoxic carcinogen. Its mechanism had been earlier proposed based on peroxisome proliferator‐activated receptor α (PPARα) because metabolites of DEHP are agonists. However, recent evidence also suggests the involvement of non‐PPARα multiple pathway in DEHP‐induced carcinogenesis. Since there are differences in the function and constitutive expression of PPARα among rodents and humans, species differences are also thought to exist in the carcinogenesis. However, species differences were also seen in the lipase activity involved in the first step of the DEHP metabolism, which should be considered in DEHP‐induced carcinogenesis. Taken together, it is very difficult to extrapolate the results from rodents to humans in the case of DEHP carcinogenicity. However, PPARα‐null mice or mice with human PPARα gene have been developed, which may lend support to make such a difficult extrapolation. Overall, further mechanical study on DEHP‐induced carcinogenicity is warranted using these mice.
5‐ALA Mediated Fluorescence Detection of Gastrointestinal Tumors
Authors: Borisova Ekaterina , Vladimirov Borislav , Avramov Latchezar
Published: September 2008

Delta‐aminolevulinic acid/protoporphyrin IX is applied for fluorescent tumor detection in the upper part of gastrointestinal tract. The 5‐ALA is administered per os six hours before measurements at dose 20 mg/kg weight. High‐power light‐emitting diode at 405 nm is used as an excitation source. Special opto‐mechanical device is built to use the light guide of standard video‐endoscopic system. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. In such way, 1D detection and 2D visualization of the lesions′ fluorescence are received, and both advantages and limitations of these methodologies are discussed in relation to their clinical applicability. Comparison of the spectra received from normal mucosa, inflammatory, and tumor areas is applied to evaluate the feasibility for development of simple but effective algorithm based on dimensionless ratio of the fluorescence signals at 560 and 635 nm, for differentiation of normal/abnormal gastrointestinal tissues.
Solving Ratio‐Dependent Predator‐Prey System with Constant Effort Harvesting Using Homotopy Perturbation Method
Authors: Ghotbi Abdoul R. , Barari A. , Ganji D. D.
Published: September 2008

Due to wide range of interest in use of bioeconomic models to gain insight into the scientific management of renewable resources like fisheries and forestry, homotopy perturbation method is employed to approximate the solution of the ratio‐dependent predator‐prey system with constant effort prey harvesting. The results are compared with the results obtained by Adomian decomposition method. The results show that, in new model, there are less computations needed in comparison to Adomian decomposition method.
Tribochemistry and EP Activity Assessment of Mo‐S Complexes in Lithium‐Base Greases
Authors: Singh Tarunendr
Published: September 2008

The blends of bis(1,5‐diaryl‐2,4‐dithiomalonamido)dioxomolybdenum(VI) complexes in lithium‐base grease are evaluated for their extreme pressure activity in a “four‐ball test” using 12.7 mm diameter alloy steel ball specimen. The additive, bis(1,5‐di‐p‐methoxyphenyl‐2,4‐dithiomalonamido)dioxomolybdenum(VI) and bis(1,5‐di‐p‐chloro‐phenyl‐2,4‐dithiomalonamido)dioxomolybdenum(VI) exhibited lower values of wear‐scar diameter at higher load and higher values of weld load, flash temperature parameter, and pressure wear index as compared with lithium‐base grease without additives. The greases fortified with the developed additives prevent rusting and corrosion of bearings while grease containing no additives did not pass these tests as per the standard tests. These greases have also better oxidation protection as compared to the grease that has no additive. The topography and tribochemistry of the wear‐scar surface are carried out by means of scanning electron microscopy and Auger electron spectroscopy techniques, respectively.
Matrilysin(MMP-7) Is a Novel Broadly Expressed Tumor Antigen Recognized by Antigen-Specific T Cells
Authors: Yokoyama Yuko , Grünebach Frank , Schmidt Susanne M. , Heine Annkristin , Häntschel Maik , Stevanovic Stefan , Rammensee Hans-Georg , Brossart Peter
Published: September 2008

Purpose: A prerequisite for the development of vaccination strategies is the identification and characterization of relevant tumor-associated antigen. Using microarray and reverse transcription-PCR analysis, we found matrix metalloproteinase (MMP)-7 to be extensively up-regulated in renal cell carcinomas and expressed in a broad variety of malignant cells. MMP-7 can promote cancer invasion and angiogenesis by proteolytic cleavage of extracellular matrix and basement membrane proteins, thus making it a promising target in the context of immunotherapies.

Experimental Design: To analyze the possible use of MMP-7 as a tumor-associated antigen, specific CTLs were induced using monocyte-derived dendritic cells electroporated with MMP-7-mRNA. In addition, to better characterize the fine specificity of these CTLs, MMP-7 MHC class I ligands were isolated and characterized in renal cell carcinoma tissue, which overexpressed MMP-7, by mass spectrometry–based peptide sequencing. Using this approach, we identified a novel HLA-A3–binding antigenic MMP-7 peptide. CTLs generated from healthy donors by in vitro priming with dendritic cells, pulsed with the novel peptide, were used as effectors in 51Cr-release assays.

Results: The induced CTLs elicited an antigen-specific and HLA-restricted cytolytic activity against tumor cells endogenously expressing the MMP-7 protein. Furthermore, we were able to induce MMP-7–specific CTLs using peripheral blood mononuclear cells from a patient with acute lymphoblastic leukemia capable of recognizing the autologous leukemic blasts while sparing nonmalignant cells.

Conclusions: Our study describes the identification of a novel broadly expressed T-cell epitope derived from the MMP-7 protein that represents an interesting candidate to be applied in immunotherapies of human malignancies targeting both tumor cells and neovascularization.
Effective CpG Immunotherapy of Breast Carcinoma Prevents but Fails to Eradicate Established Brain Metastasis
Authors: Xiong Zhengming , Gharagozlou Soheila , Vengco Isabelita , Chen Wei , Ohlfest John R.
Published: September 2008

Purpose: Breast cancer patients with brain metastasis have a dismal prognosis. We determined the ability of immunostimulatory CpG oligodeoxynucleotides (ODN) to treat or prevent brain metastasis in a mouse model.

Experimental Design: Mice bearing orthotopic breast carcinoma with or without concurrent i.c. tumors were treated by injections of CpG ODN at the primary tumor. Immunologic memory was tested by tumor rechallenge and immune responses were assessed by flow cytometry, delayed-type hypersensitivity, and CTL assays.

Results: Orthotopic tumors regressed in treated mice regardless of whether concurrent i.c. disease was present. In mice bearing only orthotopic tumors, CpG ODN rendered 50% tumor-free and they rejected tumor rechallenge in breast and brain. In mice with concurrent i.c. disease, there was no difference in brain tumor growth compared with saline controls, despite regression of the primary tumor. Flow cytometry revealed that treated mice that died from i.c. disease exhibited a significant increase in brain-infiltrating T and natural killer cells relative to saline controls. CTLs from these mice were able to kill tumor in vitro and extend survival of naive mice bearing less-established brain tumors by adoptive transfer.

Conclusions: The lack of survival benefit in mice with appreciable brain metastasis was not explained by a deficit in lymphocyte trafficking or function because CTLs from these mice killed tumor and inhibited microscopic brain metastasis by adoptive transfer. These results indicate that CpG ODN might be beneficial as a preventative adjuvant to initial therapy preceding brain metastasis or to inhibit progression of microscopic brain metastases.
Oncostatin M Induces Bone Loss and Sensitizes Rat Osteosarcoma to the Antitumor Effect of MidostaurinIn vivo
Authors: Brounais Bénédicte , Chipoy Céline , Mori Kanji , Charrier Céline , Battaglia Séverine , Pilet Paul , Richards Carl D. , Heymann Dominique , Rédini Françoise , Blanchard Frédéric
Published: September 2008

Purpose: In cultures, the cytokine oncostatin M (OSM) reduces the growth and induces differentiation of osteoblasts and osteosarcoma cells into glial/osteocytic cells. Moreover, OSM sensitizes these cells to apoptosis driven by various death inducers such as the kinase inhibitor staurosporine. Here, we asked whether OSM would have similar effects in vivo.

Experimental Design: Adenoviral gene transfer of OSM (AdOSM) was done in naive and osteosarcoma-bearing rats, alone or in combination with Midostaurin (PKC412), a derivative of staurosporine currently used in cancer clinical trials. Bone variables were analyzed by micro-computed tomography scanner, by histology, and by the levels of various serum bone markers. Osteosarcoma progression was analyzed by the development of the primary bone tumor, evolution of pulmonary metastasis, histology (necrosis and fibrosis), and animal survival.

Results: In naive rats, AdOSM reduced serum osteoblastic and osteoclastic markers in correlation with a reduced trabecular bone volume. In an osteosarcoma rat model, the combination of AdOSM with PKC412 reduced the progression of the primary bone tumor, pulmonary metastatic dissemination, and increased overall survival, whereas these agents alone had no antitumor effect. Increased tumor necrosis and tissue repair (fibrosis) were observed with this combination.

Conclusion: These in vivo experiments confirm that systemic OSM overexpression alters osteoblast/osteosarcoma activity. Because OSM sensitizes rat osteosarcoma to apoptosis/necrosis, the use of kinase inhibitors such as Midostaurin in association with OSM could represent new adjuvant treatments for this aggressive malignancy.
Oncogenic NOTCH1 Control of MYC and PI3K: Challenges and Opportunities for Anti-NOTCH1 Therapy in T-Cell Acute Lymphoblastic Leukemias and Lymphomas
Authors: Palomero Teresa , Ferrando Adolfo
Published: September 2008

The identification of activating mutations in NOTCH1 in the majority of T-cell acute lymphoblastic leukemias and lymphomas (T-ALL) has brought much interest in inhibiting NOTCH1 signaling as therapeutic target in this disease. Small-molecule inhibitors of the γ-secretase complex, which mediates a critical proteolytic cleavage required for NOTCH1 activation, hold the promise of becoming an effective molecular therapy against relapsed and refractory T-ALL. Recent progress in the elucidation of the transcriptional regulatory networks downstream of oncogenic NOTCH1 has uncovered a central role of NOTCH1 signaling in promoting leukemic cell growth and revealed an intricate circuitry that connects NOTCH1 signaling with MYC and the PI3K-AKT signaling pathway. The identification of the downstream effector pathways controlled by NOTCH1 should pave the way for the rational design of anti-NOTCH1 therapies for the treatment of T-ALL.
Targeting Aurora Kinase with MK-0457 Inhibits Ovarian Cancer Growth
Authors: Lin Yvonne G. , Immaneni Anand , Merritt William M. , Mangala Lingegowda S. , Kim Seung Wook , Shahzad Mian M.K. , Tsang Yvonne T.M. , Armaiz-Pena Guillermo N. , Lu Chunhua , Kamat Aparna A. , Han Liz Y. , Spannuth Whitney A. , Nick Alpa M. , Landen Charles N. , Wong Kwong K. , Gray Michael J. , Coleman Robert L. , Bodurka Diane C. , Brinkley William R. , Sood Anil K.
Published: September 2008

Purpose: The Aurora kinase family plays pivotal roles in mitotic integrity and cell cycle. We sought to determine the effects of inhibiting Aurora kinase on ovarian cancer growth in an orthotopic mouse model using a small molecule pan-Aurora kinase inhibitor, MK-0457.

Experimental Design: We examined cell cycle regulatory effects and ascertained the therapeutic efficacy of Aurora kinase inhibition both alone and combined with docetaxel using both in vitro and in vivo ovarian cancer models.

Results: In vitro cytotoxicity assays with HeyA8 and SKOV3ip1 cells revealed >10-fold greater docetaxel cytotoxicity in combination with MK-0457. After in vivo dose kinetics were determined using phospho-histone H3 status, therapy experiments with the chemosensitive HeyA8 and SKOV3ip1 as well as the chemoresistant HeyA8-MDR and A2780-CP20 models showed that Aurora kinase inhibition alone significantly reduced tumor burden compared with controls (P values < 0.01). Combination treatment with docetaxel resulted in significantly improved reduction in tumor growth beyond that afforded by docetaxel alone (P ≤ 0.03). Proliferating cell nuclear antigen immunohistochemistry revealed that MK-0457 alone and in combination with docetaxel significantly reduced cellular proliferation (P values < 0.001). Compared with controls, treatment with MK-0457 alone and in combination with docetaxel also significantly increased tumor cell apoptosis by ∼3-fold (P < 0.01). Remarkably, compared with docetaxel monotherapy, MK-0457 combined with docetaxel resulted in significantly increased tumor cell apoptosis.

Conclusions: Aurora kinase inhibition significantly reduces tumor burden and cell proliferation and increases tumor cell apoptosis in this preclinical orthotopic model of ovarian cancer. The role of Aurora kinase inhibition in ovarian cancer merits further investigation in clinical trials.