bluuebunny/crossref_metadata_2025 huggingface dataset:
The geometry of slip surfaces beneath landslides: predictions from surface measurements
Authors: Carter M. , Bentley S. P.
Published: May 2010

A knowledge of the slip surface profile beneath a landslip is essential for stability analysis and for the design of remedial works. This note sets out to demonstrate the accuracy of a technique that utilizes the measurement of surface displacements to predict the position and shape of the slip surface. The proposed technique is tested in model studies of all major classes of landslip and is used on three large landslips for which corroboratory evidence of the position of the slip surface, located by traditional site investigation methods, is available. The results indicate that, from a knowledge of ground surface displacements alone, the depth of the slip surface can be confidently predicted to within 2% of the distance between ground stations. The usefulness of this technique for planning and costing-feasibility studies, site investigation programmes, and prospective remedial measures is also discussed.
Slope of consolidation lines
Authors: Chakrabarti S. , Horvath R. G.
Published: May 2010

Slopes of normal consolidation lines in one-dimensional and isotropic consolidation tests done on isotropically prepared samples of two soils are compared. It has been observed that the consolidation lines are not necessarily parallel. The ratios between the two slopes have been found to be 0.53 and 0.884 for kaolin and Dundas soil respectively. It is suggested that the value of this ratio may be dependent on the percentage and the type of clay in the soil. Key words: normally consolidated, one-dimensional, isotropic, Cc-line, λ-line.
ROBUST PARAMETER SELECTION FOR PARALLEL TEMPERING
Authors: HAMZE FIRAS , DICKSON NEIL , KARIMI KAMRAN
Published: May 2010

This paper describes an algorithm for selecting parameter values (e.g. temperature values) at which to measure equilibrium properties with Parallel Tempering Monte Carlo simulation. Simple approaches to choosing parameter values can lead to poor equilibration of the simulation, especially for Ising spin systems that undergo first-order phase transitions. However, starting from an initial set of parameter values, the careful, iterative respacing of these values based on results with the previous set of values greatly improves equilibration. Example spin systems presented here appear in the context of Quantum Monte Carlo.
EVOLUTION OF EXTREMIST OPINIONS IN A POPULATION OF INTERACTING AGENTS
Authors: BOCCARA NINO
Published: May 2010

We have studied various spatial models of temporal evolution of opinions of a population of agents, located in a finite closed space, in which, at each time step, a given agent adopts, subject to a probability condition, a new opinion which depends upon the opinions of some of its neighbors. Moreover, at each time step each agent moves to a random neighboring location distributed according to a normal distribution with zero mean and a small standard deviation. The purpose of the paper is to find which types of interactions reduce the number of extremists.
NUMERICAL APPROACH OF THE MICROSCOPIC–MACROSCOPIC METHOD
Authors: MOHAMMED-AZIZI B.
Published: May 2010

A numerical method close to the Strutinsky procedure (but better) is proposed to calculate the deformation energy of nuclei. Quadrupole (triaxial) deformations are considered. Theoretical as well as practical aspects of the method are reviewed in this paper. A complete FORTRAN program illustrates the feasibility of the method. The numerical method employed in this paper avoids the main drawback of the Strutinsky method, that is to say the well known dependency of the results on the inherent two free parameters.
Prunella vulgaris L. Upregulates eNOS Expression in Human Endothelial Cells
Authors: Xia Ning , Bollinger Larissa , Steinkamp-Fenske Katja , Förstermann Ulrich , Li Huige
Published: May 2010

The purported effects of "circulation-improving" herbs used in traditional Chinese medicine (TCM) show striking similarities with the vascular actions of nitric oxide (NO) produced by the endothelial NO synthase (eNOS). We have previously reported that Salviae miltiorrhizae radix and Zizyphi spinosae semen upregulate eNOS expression. In the present study, we studied the effect on eNOS gene expression of 15 Chinese herbs with potential effects on the vasculature, and identified Prunella vulgaris L. (PVL) (flowering spike) as a potent eNOS-upregulating agent. In EA.hy 926 cells, a cell line derived from human umbilical vein endothelial cells (HUVEC), an aqueous extract of PVL increased eNOS promoter activity, eNOS mRNA and protein expressions, as well as NO production in concentration- and time-dependent manners. We have previously shown that ursolic acid (a constituent of Salviae miltiorrhizae radix), betulinic acid (a compound present in Zizyphi spinosae semen), luteolin and cynaroside (ingredients of artichoke, Cynara scolymus L.) are capable of enhancing eNOS gene expression. These compounds are also present in significant quantities in PVL. Thus, PVL contains active principles that stimulate human eNOS gene expression, and such compounds may have therapeutic potential against cardiovascular diseases.
ESTIMATING BIVARIATE GARCH-JUMP MODEL BASED ON HIGH FREQUENCY DATA: THE CASE OF REVALUATION OF THE CHINESE YUAN IN JULY 2005
Authors: LU XINHONG , KAWAI KEN-ICHI , MAEKAWA KOICHI
Published: May 2010

This paper analyzes the behavior of one-minute high-frequency time-series data of exchange rates for five currencies (Japanese Yen, Australian Dollar, Canadian Dollar, Euro, and Pound Sterling) against the US Dollar when the Chinese Yuan was revalued on July 21st, 2005. The data show the following distinctive features: (1) There is a large jump in the exchange rates time series at the time of the Yuan revaluation. (2) Large volatility in the returns of exchange rates is observed for a while after the jump. (3) There are many other jumps, possibly correlated, in each exchange rate time series. To capture these features we fit the following models to the data: (i) a univariate GARCH-Jump model with a large jump that is influential on volatility, and (ii) a bivariate GARCH-Jump model with correlated Poisson jumps. For comparison, we also estimate these GARCH models without the associated jumps. The model performance is evaluated based on Value-at-Risk (VaR).
TOPOLOGICAL ORIGIN OF THE COUPLING CONSTANTS HIERARCHY IN KALUZA–KLEIN APPROACH
Authors: EFREMOV VLADIMIR N. , HERNÁNDEZ MAGDALENO ALFONSO M. , MORENO CLAUDIA
Published: May 2010

We consider an Abelian BF-model in the frame of ten-dimensional Kaluza–Klein approach on the space T2×X×M, where X belongs to the class of four-dimension decorated plumbed cobordisms (dp-cobordisms) and M is an An-1-singularity resolution manifold homeomorphic to a compactified ALE space. These four-dimensional manifolds with boundaries possess nontrivial cohomology properties that lead to a specific generalization of the Dirac quantization conditions and enables us to express classical partition functions in terms of 4-form fluxes through the direct product of nontrivial 2-cycles associated with the manifolds X and M. The intersection matrices of these manifolds play the role of coupling constants for the fluxes. We build several examples of dp-cobordisms containing in their intersection matrices the hierarchy of dimensionless low-energy coupling constants of interactions which are available in the real universe. We also consider the phenomenon of "running coupling constants," in particular the cosmological constant evolution induced by the topology changes of internal space X.
HIGHER DIMENSIONAL MODELS OF CROSS-COUPLED OSCILLATORS AND APPLICATION TO DESIGN
Authors: ELWAKIL A. S. , SALAMA K. N.
Published: May 2010

We present four-dimensional and five-dimensional models for classical cross-coupled LC oscillators. Using these models, sinusoidal oscillation condition, frequency and amplitude can be found. Further, undesired behaviors such as relaxation-mode oscillations and latchup can be explained and detected. A simple graphical design procedure is also described.
A VARIABILITY-TOLERANT FEEDBACK TECHNIQUE FOR THROUGHPUT MAXIMIZATION OF TRBGs WITH PREDEFINED ENTROPY
Authors: ADDABBO T. , ALIOTO M. , FORT A. , ROCCHI S. , VIGNOLI V.
Published: May 2010

In this paper a probabilistic feedback technique to maximize the throughput of a generic True Random Bit Generator (TRBG) circuit, under a given constraint on the entropy, is discussed. In the proposed solution, the throughput of the device is dynamically and adaptively varied by an on-line entropy detector, such to obtain, with an arbitrary confidence level, an entropy greater than a given worst-case value. The approach, which has a general validity, introduces a method for making maximum use of the TRBG random bit generation capabilities, maximizing the generation throughput while preserving its entropy. It is different from the classical "open loop" TRBG design approach, in which the circuit parameter variability determines an uncertainty about the actual entropy of the device, with the proposed techniques the TRBG generation speed is varied under a given constraint on the entropy. The method can be applied to all those integrated TRBG circuits proposed in the literature and based on the uniform sampling of, e.g., random physical processes or chaotic dynamical systems.
STATISTICAL TESTING OF A CHAOS BASED CMOS TRUE-RANDOM NUMBER GENERATOR
Authors: PARESCHI FABIO , SETTI GIANLUCA , ROVATTI RICCARDO
Published: May 2010

As faster Random Number Generators become available, the possibility to improve the accuracy of randomness tests through the analysis of a larger number of generated bits increases. In this paper we first introduce a high-performance true-random number generator designed by authors, which use a set of discrete-time piecewise-linear chaotic maps as its entropy source. Then, we present by means of suitably improved randomness tests, the validation of this generator and the comparison with other high-end solutions. We consider the NIST test suite SP 800-22 and we show that, as suggested by NIST itself, to increase the so-called power of the test, a more in-depth analysis should be performed using the outcomes of the suite over many generated sequences. With this approach we build a framework for RNG high quality testing, with which we are able to show that the designed prototype has a comparable quality with respect to the other high-quality commercial solutions, with a working speed that is one order of magnitude faster.
TORSIONAL POTENTIALS AND FULL-DIMENSIONAL SIMULATION OF ELECTRONIC ABSORPTION SPECTRA OF para-PHENYLENEVINYLENE OLIGOMERS USING SEMIEMPIRICAL HAMILTONIANS
Authors: LUKEŠ VLADIMÍR , ŠOLC ROLAND , BARBATTI MARIO , LISCHKA HANS , KAUFFMANN HARALD-FRIEDRICH
Published: May 2010

A systematic study of torsional potential curves in electronic ground state based on second-order Møller–Plesset energy (MP2), density functional theory (DFT), and Austin mode 1 (AM1) methods is presented for para-phenylenevinylene oligomers constructed from two to four aromatic rings. The semiempirical AM1 approach gives the correct location of potential energy minima in comparison with the reference MP2 calculations and literature data. However, the semiempirical AM1 energy barriers at perpendicular orientation are ca. 30% smaller than the MP2 ones. The DFT calculations indicate optimal planar structures and the barriers are three times higher than MP2 values. Excited-state potential energy curves evaluated from vertical excitations at the time-dependent density functional theory (TD-DFT) and ab initio CI levels exhibit much steeper increase of values in the vicinity of perpendicular orientation than in the semiempirical Zerner's intermediate neglect of differential overlap (ZINDO) and ab initio RI-CC2 cases. The effects of vibrational motion of phenylene rings on the torsional broadening of absorption spectra were estimated from semi-classical molecular dynamics simulations and harmonic oscillator sampling. The simulated spectra agree well with the experiment and allow estimating the conformer distribution of the molecules.
GK BASED FUZZY CLUSTERING FOR THE DIAGNOSIS OF CARDIAC ARRHYTHMIA
Authors: MEHDI AHMED M. , ZAYEGH ALADIN , BEGG REZAUL , ALI RUBBIYA
Published: May 2010

Abstract-Cardiac arrhythmia is one of the major causes of human death, and most of the time it cannot be predicted well in advance at the right time. Computational intelligence algorithms can help in extracting the hidden patterns of biological datasets. This paper explores the use of advanced and intelligent computational algorithms for automated detection, classification and clustering of cardiac arrhythmia (CA). Application of Fuzzy C-Mean and Extended Fuzzy C-Mean method to the arrhythmia dataset (165 normal healthy and 138 with CA) demonstrated their good CA classification capabilities. Fuzzy C Mean algorithm was able to classify the two group of data set with an overall accuracy of 97.2% [sensitivity 96.4%, specificity 98.12% and area under the receiver operating curve (AUC-ROC = 0.963)]. The classification accuracy improved significantly when GK-based extended Fuzzy was employed, and an overall accuracy of 99.14% was achieved (sensitivity 97.11%, specificity 99.18% and AUC-ROC = 0.995). These accuracy results were respectively, 19.02%, 7%, 9.14% and 11.06% higher when compared to multi-input single layer perceptron (SLP), feed forward back propagation (FFBP), self organizing maps (SOM) and support vector machine (SVM). The performance measures of fuzzy techniques were found to be better if a Principal Component Analysis (PCA) technique was used to preprocess the arrhythmia datasets.
DESIGN OF EXPERIMENTS IN NEURO-FUZZY SYSTEMS
Authors: ZANCHETTIN CLEBER , MINKU LEANDRO L. , LUDERMIR TERESA B.
Published: May 2010

Interest in hybrid methods that combine artificial neural networks and fuzzy inference systems has grown in recent years. These systems are robust solutions that search for representations of domain knowledge, reasoning on uncertainty, automatic learning and adaptation. However, the design and definition of the parameter effectiveness of such systems is still a hard task. In the present work, we perform a statistical analysis to verify interactions and interrelations between parameters in the design of neuro-fuzzy systems. The analysis is carried out using a powerful statistical tool, namely, Design of Experiments (DOE), in two neuro-fuzzy models — Adaptive Neuro Fuzzy Inference System (ANFIS) and Evolving Fuzzy Neural Networks (EFuNN). The results show that, for ANFIS, input MFs number and output MFs shape are usually the factors with the largest influence on the system's RMSE. For EFFuNN, the MF shape and the interaction between MF shape and number usually have the largest effect size.
KNOWLEDGE-BASED METHODS FOR OPTIMUM APPROXIMATION OF GEOMETRIC DILUTION OF PRECISION
Authors: MOSAVI M. R.
Published: May 2010

Global Positioning System (GPS) satellites signal processing to obtain all in view satellite measurements and to use them to find a solution and to do integrity monitoring forms a major component of the load on the receiver's processing element. If processing capability is limited there is restriction on the number of measurements which can be obtained and processed. Alternatively, the number of measurements can be restricted and the resulting saving in load on the processor can be used to offer more spare processing time which can be used for other user specific requirements. Thus if m visible satellites can provide measurements only n measurements can be used (n < m). The arrangement and the number of GPS satellites influence measurement accuracy. Dilution of Precision (DOP) is an index evaluating the arrangement of satellites. Geometric DOP (GDOP) is, in effect, the amplification factor of pseudo-range measurement errors into user errors due to the effect of satellite geometry. The GDOP approximation is an essential feature in determining the performance of a positioning system. In this paper, knowledge-based methods such as neural networks and evolutionary adaptive filters are presented for optimum approximation of GDOP. Without matrix inversion required, the knowledge-based approaches are capable of evaluating all subsets of satellites and hence reduce the computational burden. This would enable the use of a high-integrity navigation solution without the delay required for many matrix inversions. Models validity is verified with test data. The results are highly effective techniques for GDOP approximation.
LOWER BOUNDS FOR THE NORMALIZED HEIGHT AND NON-DENSE SUBSETS OF SUBVARIETIES OF ABELIAN VARIETIES
Authors: VIADA EVELINA
Published: May 2010

This work is the third part of a series of papers. In the first two, we considered curves and varieties in a power of an elliptic curve. Here, we deal with subvarieties of an abelian variety in general.

Let V be a proper irreducible subvariety of dimension d in an abelian variety A, both defined over the algebraic numbers. We say that V is weak-transverse if V is not contained in any proper algebraic subgroup of A, and transverse if it is not contained in any translate of such a subgroup.

Assume a conjectural lower bound for the normalized height of V. Then, for V transverse, we prove that the algebraic points of bounded height of V which lie in the union of all algebraic subgroups of A of codimension at least d + 1 translated by the points close to a subgroup Γ of finite rank, are non-Zariski-dense in V. If Γ has rank zero, it is sufficient to assume that V is weak-transverse. The notion of closeness is defined using a height function.
ON THE RANK OF ABELIAN VARIETIES OVER AMPLE FIELDS
Authors: FEHM ARNO , PETERSEN SEBASTIAN
Published: May 2010

A field K is called ample if every smooth K-curve that has a K-rational point has infinitely many of them. We prove two theorems to support the following conjecture, which is inspired by classical infinite rank results: Every non-zero Abelian variety A over an ample field K which is not algebraic over a finite field has infinite rank. First, the ℤ(p)-module A(K) ⊗ ℤ(p) is not finitely generated, where p is the characteristic of K. In particular, the conjecture holds for fields of characteristic zero. Second, if K is an infinite finitely generated field and S is a finite set of local primes of K, then every Abelian variety over K acquires infinite rank over certain subfields of the maximal totally S-adic Galois extension of K. This strengthens a recent infinite rank result of Geyer and Jarden.
RAMANUJAN'S CUBIC CONTINUED FRACTION AND AN ANALOG OF HIS "MOST BEAUTIFUL IDENTITY"
Authors: CHAN HEI-CHI
Published: May 2010

In this paper, we prove an analog of Ramanujan's "Most Beautiful Identity". This analog is closely related to Ramanujan's beautiful results involving the cubic continued fraction.
OUT-OF-THE-BOX THOUGHTS ABOUT THE INTERNATIONAL FINANCIAL ARCHITECTURE
Authors: EICHENGREEN BARRY
Published: May 2010

This paper contemplates ambitious reforms of the international financial architecture. It proposes routinising the expansion of IMF quotas and the conduct of exchange rate surveillance. It contemplates an expanded role for the SDR in international transactions, which would require someone — like the IMF — to act as market maker. It considers proposals for reimposing Glass–Steagall-like restrictions on commercial and investment banking, something that will have to be coordinated internationally to be feasible. All this of course presupposes meaningful IMF governance reform so that the institution has the legitimacy and efficiency to assume these additional responsibilities.
THE SLOW SPREAD OF THE GLOBAL CRISIS
Authors: LIANG PRISCILLA , WILLETT THOMAS D. , ZHANG NAN
Published: May 2010

We argue that the depth and breadth of the spread of the current crisis from the US subprime market across the globe was due more to the buildup of substantial financial vulnerabilities prior to the crisis than to irrational panic during the crisis. We examine how these developments explain the belated recognition of the severity of the crisis and its slow spread through various channels of contagion. We also discuss lessons for policy and research.
Increased fat mass, decreased myofiber size, and a shift to glycolytic muscle metabolism in adolescent male transgenic mice overexpressing IGFBP-2
Authors: Rehfeldt Charlotte , Renne Ulla , Sawitzky Mandy , Binder Gerhard , Hoeflich Andreas
Published: May 2010

To elucidate the functional role of insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) for in vivo skeletal muscle growth and function, skeletal muscle cellularity and metabolism, expression of signal molecules, and body growth and composition were studied in a transgenic mouse model overexpressing IGFBP-2. Postnatal growth rate of transgenic mice was reduced from day 21 of age by 6–8% compared with nontransgenic controls. At 10 wk of age body lean protein and moisture percentages were lower, whereas fat percentage was higher in IGFBP-2 transgenic mice. Muscle weights were reduced (−13% on day 30 of age, −14% on day 72), which resulted from slower growth of myofibers in size but not from decreases in myofiber number. The reduction in muscle mass was associated with lower total DNA, RNA, and protein contents as well as greater DNA/RNA and protein/RNA ratios. The percentage of proliferating (Ki-67-positive) nuclei within myofibers was reduced (3.4 vs. 5.8%) in 30-day-old transgenic mice. These changes were accompanied by slight reductions in specific p44/42 MAPK activity (−18% on day 72) and, surprisingly, by increased levels of phosphorylated Akt (Ser473) (+25% on day 30, +66% on day 72). The proportion of white glycolytic fibers (55.9 vs. 53.5%) and the activity of lactate dehydrogenase (+8%) were elevated in 72-day-old transgenic mice. Most of the differences observed between transgenic and nontransgenic mice were more pronounced in males. The results suggest that IGFBP-2 significantly inhibits postnatal skeletal myofiber growth by decreasing myogenic proliferation and protein accretion and enhances glycolytic muscle metabolism.
Carbachol-Induced Long-Term Synaptic Depression Is Enhanced During Senescence at Hippocampal CA3–CA1 Synapses
Authors: Kumar Ashok
Published: May 2010

Dysregulation of the cholinergic transmitter system is a hallmark of Alzheimer's disease and contributes to an age-associated decline in memory performance. The current study examined the influence of carbachol, a cholinergic receptor agonist, on synaptic transmission over the course of aging. Extracellular excitatory postsynaptic field potentials were recorded from CA3–CA1 synapses in acute hippocampal slices obtained from young adult (5–8 mo) and aged (22–24 mo) male Fischer 344 rats. Bath application of carbachol elicited a transient depression of synaptic transmission, which was followed by a long-lasting depression (CCh-LTD) observed 90 min after carbachol cessation in both age groups. However, the magnitude of CCh-LTD was significantly larger in senescent animals and was attenuated by N-methyl-d-aspartate receptor blockade in aged animals. Blockade of L-type Ca2+ channels inhibited CCh-LTD to a greater extent in aged animals compared to young adults. Finally, the expression of CCh-LTD was dependent on protein synthesis. The results indicate that altered Ca2+ homeostasis or muscarinic activation of Ca2+ signaling contribute to the enhanced CCh-LTD during senescence.
Temporal Selectivity in Midbrain Electrosensory Neurons Identified by Modal Variation in Active Sensing
Authors: Pluta Scott R. , Kawasaki Masashi
Published: May 2010

Mormyrid weakly electric fish actively sense their surroundings by continuously emitting discrete pulses of electricity separated by varying intervals of silence. The temporal pattern of this pulsing behavior is related to context. While resting in the absence of an overt stimulus, baseline interpulse intervals (IPIs) mostly range 200–450 ms, and sequential variation is relatively high. Spontaneously, or following the presentation of a novel stimulus, IPIs transiently shorten during the performance of an electromotor “burst” display. We made intracellular whole cell recordings in vivo from neurons in the lateral nucleus of the torus semicircularis while the fish's dynamic pulsing behavior modified the temporal pattern of stimulation. Stimulation was designed to simulate the spatial patterns of AM that occur during the electrolocation of a resistive object. We discovered that toral neurons selectively respond to stimulation during a particular mode of electromotor activity. Two types of temporally selective neurons were discovered: baseline-selective neurons that displayed significantly higher postsynaptic potential (PSP) amplitude and spike count per electric organ discharge (EOD) during baseline electromotor activity and burst-selective neurons that displayed significantly higher PSP amplitude and spike count per EOD during electromotor burst displays. Interval-dependent changes in the strength of excitation and inhibition contributed to their selectivity.
Role of the renin angiotensin system on bone marrow-derived stem cell function and its impact on skeletal muscle angiogenesis
Authors: de Resende Micheline M. , Stodola Timothy J. , Greene Andrew S.
Published: May 2010

Autologous bone marrow cell (BMC) transplantation has been shown as a potential approach to treat various ischemic diseases. However, under many conditions BMC dysfunction has been reported, leading to poor cell engraftment and a failure of tissue revascularization. We have previously shown that skeletal muscle angiogenesis induced by electrical stimulation (ES) is impaired in the SS/Mcwi rats and that this effect is related to a dysregulation of the renin angiotensin system (RAS) that is normalized by the replacement of chromosome 13 derived from the Brown Norway rat (SS-13BN/Mcwi consomic rats). The present study explored bone marrow-derived endothelial cell (BM-EC) function in the SS/Mcwi rat and its impact on skeletal muscle angiogenesis induced by ES. SS/Mcwi rats were randomized to receive BMC from: SS/Mcwi; SS-13BN/Mcwi; SS/Mcwi rats infused with saline or ANG II (3 ng·kg−1·min−1). BMC were injected in the stimulated tibialis anterior muscle of SS/Mcwi rats. Vessel density was evaluated in unstimulated and stimulated muscles after 7 days of ES. BMC isolated from SS/Mcwi or SS/Mcwi rats infused with saline failed to restore angiogenesis induced by ES. However, BMC isolated from SS-13BN/Mcwi and SS/Mcwi rats infused with ANG II effectively restored the angiogenesis response in the SS/Mcwi recipient. Furthermore, ANG II infusion increased the capacity of BM-EC to induce endothelial cell tube formation in vitro and slightly increased VEGF protein expression. This study suggests that dysregulation of the RAS in the SS/Mcwi rat contributes to impaired BM-EC function and could impact the angiogenic therapeutic potential of BMC.
Optimization of the Fermentation Process of Actinomycete Strain Hhs.015T
Authors: Wang Xinxuan , Huang Lili , Kang Zhensheng , Buchenauer Heinrich , Gao Xiaoning
Published: May 2010

StrainHhs.015T(Saccharothrix yanglingensissp. nov.), an antagonistic endophyticSaccharothrixactinomycete isolated from roots of cucumber plants, exhibited a broad antimicrobial spectrum in vitro and was active as a biocontrol against plant diseases in field trials. The SSY medium was used for production of antimicrobial metabolites by strainHhs.015T. However, this medium is too expensive for large-scale production. In this study, an alternative culture medium, based on agricultural waste products (e.g., apple pomace), was optimized. The results showed that the alternative medium contained 15 g apple pomace, 4 g rapeseed meal, 0.1 gKH2PO4, and 0.6 gMgSO4·7H2Oin 1 L distilled water. This medium reduced the material costs by 91.5% compared to SSY medium. Response surface methodology (RSM) was used to investigate the influence of environmental variables on production of compounds of antimicrobial metabolites. The optimal conditions achieved were initial pH 7.0, medium volume of 90 mL in 250 mL flasks, rotary speed of 100 rpm, temperature 25C, and inoculation volume of 15.8%. The antimicrobial activity was increased by 20% by optimizing the environmental parameters. The results obtained allow an efficient production of components with antimicrobial activity by strainHhs.015Ton a large scale at low costs.
A Family of Sixth-Order Compact Finite-Difference Schemes for the Three-Dimensional Poisson Equation
Authors: Kyei Yaw , Roop John Paul , Tang Guoqing
Published: May 2010

We derive a family of sixth-order compact finite-difference schemes for the three-dimensional Poisson's equation. As opposed to other research regarding higher-order compact difference schemes, our approach includes consideration of the discretization of the source function on a compact finite-difference stencil. The schemes derived approximate the solution to Poisson's equation on a compact stencil, and thus the schemes can be easily implemented and resulting linear systems are solved in a high-performance computing environment. The resulting discretization is a one-parameter family of finite-difference schemes which may be further optimized for accuracy and stability. Computational experiments are implemented which illustrate the theoretically demonstrated truncation errors.
What the CERAD Battery Can Tell Us about Executive Function as a Higher-Order Cognitive Faculty
Authors: Tractenberg Rochelle E. , Fillenbaum Gerda , Aisen Paul S. , Liebke David E. , Yumoto Futoshi , Kuchibhatla Maragatha N.
Published: May 2010

Executive function (EF) is believed to control or influence the integration and application of cognitive functions such as attention and memory and is an important area of research in cognitive aging. Recent studies and reviews have concluded that there is no single test for EF. Results from first-order latent variable modeling have suggested that little, if any, variability in cognitive performance can be directly (and uniquely) attributed to EF; so instead, we modeled EF, as it is conceptualized, as a higher-order function, using elements of the CERAD neuropsychological battery. Responses to subtests from two large, independent cohorts of nondemented elderly persons were modeled with three theoretically plausible structural models using confirmatory factor analysis. Robust fit statistics, generated for the two cohorts separately, were consistent and support the conceptualization of EF as a higher-order cognitive faculty. Although not specifically designed to assess EF, subtests of the CERAD battery provide theoretically and empirically robust evidence about the nature of EF in elderly adults.
Rumor Propagation Model: An Equilibrium Study
Authors: Piqueira José Roberto C.
Published: May 2010

Compartmental epidemiological models have been developed since the 1920s and successfully applied to study the propagation of infectious diseases. Besides, due to their structure, in the 1960s an interesting version of these models was developed to clarify some aspects of rumor propagation, considering that spreading an infectious disease or disseminating
information is analogous phenomena. Here, in an analogy with the SIR (Susceptible‐Infected‐Removed) epidemiological model, the ISS (Ignorant‐Spreader‐Stifler) rumor spreading model is studied. By using concepts from the Dynamical Systems Theory, stability of equilibrium points is established, according to propagation parameters and initial conditions. Some numerical experiments are conducted in order to validate the model.
Immune Infiltration of Spontaneous Mouse Astrocytomas Is Dominated by Immunosuppressive Cells from Early Stages of Tumor Development
Authors: Tran Thang Nhu Nam , Derouazi Madiha , Philippin Géraldine , Arcidiaco Séverine , Di Berardino-Besson Wilma , Masson Frédérick , Hoepner Sabine , Riccadonna Cristina , Burkhardt Karim , Guha Abhijit , Dietrich Pierre-Yves , Walker Paul R.
Published: May 2010

Immune infiltration of advanced human gliomas has been shown, but it is doubtful whether these immune cells affect tumor progression. It could be hypothesized that this infiltrate reflects recently recruited immune cells that are immediately overwhelmed by a high tumor burden. Alternatively, if there is earlier immune detection and infiltration of the tumor, the question arises as to when antitumor competency is lost. To address these issues, we analyzed a transgenic mouse model of spontaneous astrocytoma (GFAP-V12HA-ras mice), which allows the study of immune interactions with developing glioma, even at early asymptomatic stages. T cells, including a significant proportion of Tregs, are already present in the brain before symptoms develop, followed later by macrophages, natural killer cells, and dendritic cells. The effector potential of CD8 T-cells is defective, with the absence of granzyme B expression and low expression of IFN-γ, tumor necrosis factor, and interleukin 2. Overall, our results show an early defective endogenous immune response to gliomas, and local accumulation of immunosuppressive cells at the tumor site. Thus, the antiglioma response is not simply overwhelmed at advanced stages of tumor growth, but is counterbalanced by an inhibitory microenvironment from the outset. Nevertheless, we determined that effector molecule expression (granzyme B, IFN-γ) by brain-infiltrating CD8 T-cells could be enhanced, despite this unfavorable milieu, by strong immune stimuli. This potential to modulate the strong imbalance in local antiglioma immunity is encouraging for the development and optimization of future glioma immunotherapies. Cancer Res; 70(12); 4829–39. ©2010 AACR.
Breast Cancer Dormancy Can Be Maintained by Small Numbers of Micrometastases
Authors: Willis Lisa , Alarcón Tomas , Elia George , Jones J. Louise , Wright Nick A. , Tomlinson Ian P.M. , Graham Trevor A. , Page Karen M.
Published: May 2010

Late relapse of breast cancer can occur more than 25 years after primary diagnosis. During the intervening years between initial treatment and relapse, occult cancers are maintained in an apparent state of dormancy that is poorly understood. In this study, we applied a probabilistic mathematical model to long-term follow-up studies of postresection patients to investigate the factors involved in mediating breast cancer dormancy. Our results suggest that long-term dormancy is maintained most often by just one growth-restricted dangerous micrometastasis. Analysis of the empirical data by Approximate Bayesian Computation indicated that patients in dormancy have between 1 and 5 micrometastases at 10 years postresection, when they escape growth restriction with a half-life of <69 years and are >0.4 mm in diameter. Before resection, primary tumors seed at most an average of 6 dangerous micrometastases that escape from growth restriction with a half-life of at least 12 years. Our findings suggest that effective preventive treatments will need to eliminate these small numbers of micrometastases, which may be preangiogenic and nonvascularized until they switch to growth due to one oncogenic mutation or tumor suppressor gene inactivation. In summary, breast cancer dormancy seems to be maintained by small numbers of sizeable micrometastases that escape from growth restriction with a half-life exceeding 12 years. Cancer Res; 70(11); 4310–7. ©2010 AACR.
Downregulation of MicroRNA miR-520h by E1A Contributes to Anticancer Activity
Authors: Su Jen-Liang , Chen Poshen B. , Chen Ya-Huey , Chen Shang-Chih , Chang Yi-Wen , Jan Yi-Hua , Cheng Xiaoyun , Hsiao Michael , Hung Mien-Chie
Published: May 2010

The leading cause of death in cancer patients is cancer metastasis, for which there is no effective treatment. MicroRNAs (miRNA) have been shown to play a significant role in cancer metastasis through regulation of gene expression. The adenovirus type 5 E1A (E1A) is associated with multiple tumor-suppressing activities including the inhibition of metastasis, and E1A gene therapies have been tested in several clinical trials. However, the mechanisms involved in E1A-mediated tumor-suppressing activities are not yet completely defined. Here, we showed that E1A downregulated the expression of the miRNA miR-520h, which was critical for E1A-mediated cancer cell mobility and in vitro invasion activity. In addition, we identified a signal cascade, namely, E1A→miRNA-520h→PP2A/C→IκB kinase→NF-κB→Twist, in which E1A inhibited the expression of Twist through downregulation of miR-520h and the signal cascade. Our results indicated a functional link between miR-520h and tumorigenicity/invasive ability and provided a new insight into the role of E1A-mediated miRNA regulation in tumor suppression. Therefore, the results identified a new cascade of E1A-mediated tumor suppression activity via downregulation of miRNA-520h expression. Cancer Res; 70(12); 5096–108. ©2010 AACR.
PTPL1/PTPN13 Regulates Breast Cancer Cell Aggressiveness through Direct Inactivation of Src Kinase
Authors: Glondu-Lassis Murielle , Dromard Mathilde , Lacroix-Triki Magali , Nirdé Philippe , Puech Carole , Knani Dora , Chalbos Dany , Freiss Gilles
Published: May 2010

The protein tyrosine phosphatase PTPL1/PTPN13, the activity of which is decreased through allelic loss, promoter methylation, or somatic mutations in some tumors, has been proposed as a tumor suppressor gene. Moreover, our recent clinical study identified PTPL1 expression level as an independent prognostic indicator of a favorable outcome for patients with breast cancer. However, how PTPL1 can affect tumor aggressiveness has not been characterized. Here, we first show that PTPL1 expression, assessed by immunohistochemistry, is decreased in breast cancer and metastasis specimens compared with nonmalignant tissues. Second, to evaluate whether PTPL1 plays a critical role in breast cancer progression, RNA interference experiments were performed in poorly tumorigenic MCF-7 breast cancer cells. PTPL1 inhibition drastically increased tumor growth in athymic mice and also enhanced several parameters associated with tumor progression, including cell proliferation on extracellular matrix components and cell invasion. Furthermore, the inhibition of Src kinase expression drastically blocked the effects of PTPL1 silencing on cell growth. In PTPL1 knockdown cells, the phosphorylation of Src on tyrosine 419 is increased, leading to the activation of its downstream substrates Fak and p130cas. Finally, substrate-trapping experiments revealed that Src tyrosine 419 is a direct target of the phosphatase. Thus, by identification of PTPL1 as the first phosphatase able to inhibit Src through direct dephosphorylation in intact cells, we presently describe a new mechanism by which PTPL1 inhibits breast tumor aggressiveness. Cancer Res; 70(12); 5116–26. ©2010 AACR.
βIII-Tubulin Is a Multifunctional Protein Involved in Drug Sensitivity and Tumorigenesis in Non–Small Cell Lung Cancer
Authors: McCarroll Joshua A. , Gan Pei Pei , Liu Marjorie , Kavallaris Maria
Published: May 2010

Advanced non–small cell lung cancer (NSCLC) has a dismal prognosis. βIII-Tubulin, a protein highly expressed in neuronal cells, is strongly associated with drug-refractory and aggressive NSCLC. To date, the role of this protein in in vivo drug resistance and tumorigenesis has not been determined. NSCLC cells stably expressing βIII-tubulin short hairpin RNA displayed reduced growth and increased chemotherapy sensitivity when compared with control clones. In concordance with these results, stable suppression of βIII-tubulin reduced the incidence and significantly delayed the growth of tumors in mice relative to controls. Our findings indicate that βIII-tubulin mediates not only drug sensitivity but also the incidence and progression of lung cancer. βIII-Tubulin is a cellular survival factor that, when suppressed, sensitizes cells to chemotherapy via enhanced apoptosis induction and decreased tumorigenesis. Findings establish that upregulation of a neuronal tubulin isotype is a key contributor to tumor progression and drug sensitivity in lung adenocarcinoma. Cancer Res; 70(12); 4995–5003. ©2010 AACR.
Histone Methyltransferase Gene SETD2 Is a Novel Tumor Suppressor Gene in Clear Cell Renal Cell Carcinoma
Authors: Duns Gerben , van den Berg Eva , van Duivenbode Inge , Osinga Jan , Hollema Harry , Hofstra Robert M.W. , Kok Klaas
Published: May 2010

Sporadic clear cell renal cell carcinoma (cRCC) is genetically characterized by the recurrent loss of the short arm of chromosome 3, with a hotspot for copy number loss in the 3p21 region. We applied a method called “gene identification by nonsense-mediated mRNA decay inhibition” to a panel of 10 cRCC cell lines with 3p21 copy number loss to identify biallelic inactivated genes located at 3p21. This revealed inactivation of the histone methyltransferase gene SETD2, located on 3p21.31, as a common event in cRCC cells. SETD2 is nonredundantly responsible for trimethylation of the histone mark H3K36. Consistent with this function, we observed loss or a decrease of H3K36me3 in 7 out of the 10 cRCC cell lines. Identification of missense mutations in 2 out of 10 primary cRCC tumor samples added support to the involvement of loss of SETD2 function in the development of cRCC tumors. Cancer Res; 70(11); 4287–91. ©2010 AACR.
Mechanism by Which Mcl-1 Regulates Cancer-Specific Apoptosis Triggered by mda-7/IL-24, an IL-10–Related Cytokine
Authors: Dash Rupesh , Richards Joanna E. , Su Zhao-zhong , Bhutia Sujit K. , Azab Belal , Rahmani Mohamed , Dasmahapatra Girija , Yacoub Adly , Dent Paul , Dmitriev Igor P. , Curiel David T. , Grant Steven , Pellecchia Maurizio , Reed John C. , Sarkar Devanand , Fisher Paul B.
Published: May 2010

Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24), a cytokine belonging to the IL-10 family, selectively induces apoptosis in cancer cells without harming normal cells by promoting an endoplasmic reticulum (ER) stress response. The precise molecular mechanism by which the ER stress response culminates in cell death requires further clarification. The present study shows that in prostate carcinoma cells, the mda-7/IL-24–induced ER stress response causes apoptosis by translational inhibition of the antiapoptotic protein myeloid cell leukemia-1 (Mcl-1). Forced expression of Mcl-1 blocked mda-7/IL-24 lethality, whereas RNA interference or gene knockout of Mcl-1 markedly sensitized transformed cells to mda-7/IL-24. Mcl-1 downregulation by mda-7/IL-24 relieved its association with the proapoptotic protein Bak, causing oligomerization of Bak and leading to cell death. These observations show the profound role of the Bcl-2 protein family member Mcl-1 in regulating cancer-specific apoptosis induced by this cytokine. Thus, our studies provide further insights into the molecular mechanism of ER stress–induced cancer-selective apoptosis by mda-7/IL-24. As Mcl-1 is overexpressed in the majority of prostate cancers, mda-7/IL-24 might provide an effective therapeutic for this disease. Cancer Res; 70(12); 5034–45. ©2010 AACR.
Control of Tumorigenesis and Chemoresistance by the DEK Oncogene
Authors: Riveiro-Falkenbach Erica , Soengas María S.
Published: May 2010

Slight modifications of chromatin dynamics can translate into small- and large-scale changes in DNA replication and DNA repair. Similarly, promoter usage and accessibility are tightly dependent on chromatin architecture. Consequently, it is perhaps not surprising that factors controlling chromatin organization are frequently deregulated (directly or indirectly) in cancer cells. DEK is emerging as a novel class of DNA topology modulators that can be both targets and effectors of protumorigenic events. The locus containing DEK at chromosome 6p22.3 is amplified or reorganized in multiple cancer types. In addition, DEK can be subject to a variety of tumor-associated transcriptional and post-translational modifications. In turn, DEK can favor cell transformation, at least in part by inhibiting cell differentiation and premature senescence. More recently, DEK has also been linked to the resistance of malignant cells to apoptotic inducers. Interestingly, a fraction of DEK can also bind RNA and affect alternative splicing, further illustrating the pleiotropic roles that this protein may exert in cancer cells. Here we will summarize the current literature about the regulation and function(s) of DEK as a proto-oncogene. In addition, the translational relevance of DEK as a putative diagnostic marker and candidate for drug development will be discussed. Clin Cancer Res; 16(11); 2932–8. ©2010 AACR.
A Phase I Study of 5-Fluorouracil/Leucovorin and Arsenic Trioxide for Patients with Refractory/Relapsed Colorectal Carcinoma
Authors: Ardalan Bach , Subbarayan Pochi R. , Ramos Yipsel , Gonzalez Michael , Fernandez Anthony , Mezentsev Dmitry , Reis Isildinha , Duncan Robert , Podolsky Lisa , Lee Kelvin , Lima Mayra , Ganjei-Azar Parvin
Published: May 2010

Purpose: This Phase I study was designed to determine a safe combination dose of 5-fluorouracil (5-FU) and arsenic trioxide (ATO) to treat 5-FU–resistant relapsed/refractory colorectal cancer patients. We studied the effect of ATO in the downregulation of thymidylate synthase (TS) in peripheral blood mononuclear cells and in tumor biopsies.

Experimental Design: ATO was administered for 5 consecutive days during the first week and twice during weeks 2 to 3 and once on week 4. 5-FU/leucovorin (LV) was administered on days 8, 15, and 22. A modified accelerated titration design was used. 5-FU was dose escalated first followed by a planned dose increase for ATO.

Results: No dose-limiting toxicities were seen in seven patients who received 0.15 mg/kg ATO; grade 3 toxicities were as follows: neutropenia 1, diarrhea 1, and bowel obstruction 1. In patients receiving 0.20 mg/kg ATO, grade 3 toxicities were QTc prolongation 1, fatigue 4, alkaline phosphatase elevation 2, diarrhea 2, and peripheral edema 1. TS gene expression in peripheral blood mononuclear cell decreased in all patients. Eight tumors were biopsied, four showed TS downregulation, three showed upregulations, and one did not change. Estimated median progression-free survival and overall survival were 3.1 and 13.9 months, respectively. In patients who showed TS increase or no change versus TS reduction, estimated median progression-free survival was 2.6 versus 7.9 months (P = 0.188) and overall survival was 8.6 versus 11.7 months (P = 0.44), respectively.

Conclusions: Thus, we determined 0.20 mg/kg ATO, 2,600 mg/m2 5-FU, and 500 mg/m2 leucovorin (LV) to be the recommended phase II dose. Clin Cancer Res; 16(11); 3019–27. ©2010 AACR.