bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECTS OF INTRADAY PATTERNS ON ANALYSIS OF STOCK MARKET INDEX AND TRADING VOLUME
Authors: CHOI HYUNG WOOC , MAENG SEONG EUN , LEE JAE WOO
Published: August 2012

We review the stylized properties of the stock market and consider effects of the intraday patterns on the analysis of the time series for the stock index and the trading volume in Korean stock market. In the stock market the probability distribution function (pdf) of the return and volatility followed the power law for the stock index and the change of the volume traded. The volatility of the stock index showed the long-time memory and the autocorrelation function followed a power law. We applied two eliminating methods of the intraday patterns: the intraday patterns of the time series itself, and the intraday patterns of the absolute return for the index or the absolute volume change. We scaled the index and return by two types of the intraday patterns. We considered the probability distribution function and the autocorrelation function (ACF) for the time series scaled by the intraday patterns. The cumulative probability distribution function of the returns scaled by the intraday patterns showed a power law, P>(r) ~ r-α±, where α± corresponds to the exponent of the positive and negative fat tails. The pdf of the return scaled by intraday patterns by the absolute return decayed much steeper than that of the return scaled by intraday patterns of the index itself. The pdf for the volume change also followed the power law for both methods of eliminating intraday patterns. However, the exponents of the power law at fat tails do not depend on the intraday patterns. The ACF of the absolute return showed long-time correlation and followed the power law for the scaled index and for the scaled volume. The daily periodicity of the ACF was removed for scaled time series by the intraday patterns of the absolute return or the absolute volume change.
POWER LAWS IN REAL ESTATE PRICES DURING BUBBLE PERIODS
Authors: OHNISHI TAKAAKI , MIZUNO TAKAYUKI , SHIMIZU CHIHIRO , WATANABE TSUTOMU
Published: August 2012

How can we detect real estate bubbles? In this paper, we propose making use of information on the cross-sectional dispersion of real estate prices. During bubble periods, prices tend to go up considerably for some properties, but less so for others, so that price inequality across properties increases. In other words, a key characteristic of real estate bubbles is not the rapid price hike itself but a rise in price dispersion. Given this, the purpose of this paper is to examine whether developments in the dispersion in real estate prices can be used to detect bubbles in property markets as they arise, using data from Japan and the U.S. First, we show that the land price distribution in Tokyo had a power-law tail during the bubble period in the late 1980s, while it was very close to a lognormal before and after the bubble period. Second, in the U.S. data we find that the tail of the house price distribution tends to be heavier in those states which experienced a housing bubble. We also provide evidence suggesting that the power-law tail observed during bubble periods arises due to the lack of price arbitrage across regions.
TIME EVOLUTION OF FINANCIAL CROSS-CORRELATION COEFFICIENTS ACROSS MARKET CRISIS
Authors: TACCHELLA ANDREA , CRISTELLI MATTHIEU , ZACCARIA ANDREA , PIETRONERO LUCIANO
Published: August 2012

We investigate the time evolution of financial cross-correlation coefficients during financial crises and compare them to what is observed in periods of stability. We choose three main events, the Dot.Com Bubble, the market crisis which followed the attacks at the Twin Towers in 2001 and the recent subprime crisis. Each of them has a different nature and a different impact on the market, which we analyze by studying separately different economic sectors. As a general trend, we observe an increase of correlation during these high volatility periods and a broadening of the distributions of correlation coefficients. We then compare the spectra of the cross-correlation matrices, calculated in different periods of three years, with the distribution of eigenvalues predicted by the Random Matrix Theory. We find that these spectra are markedly perturbated during crisis periods. Finally we show how a simple stochastic model can produce similar results.
MUSICAL MARKOV CHAINS
Authors: VOLCHENKOV DIMA , DAWIN JEAN RENÉ
Published: August 2012

A system for using dice to compose music randomly is known as the musical dice game. The discrete time MIDI models of 804 pieces of classical music written by 29 composers have been encoded into the transition matrices and studied by Markov chains. Contrary to human languages, entropy dominates over redundancy, in the musical dice games based on the compositions of classical music. The maximum complexity is achieved on the blocks consisting of just a few notes (8 notes, for the musical dice games generated over Bach's compositions). First passage times to notes can be used to resolve tonality and feature a composer.
LTL over description logic axioms
Authors: Baader Franz , Ghilardi Silvio , Lutz Carsten
Published: August 2012

Most of the research on temporalized Description Logics (DLs) has concentrated on the case where temporal operators can be applied to concepts, and sometimes additionally to TBox axioms and ABox assertions. The aim of this article is to study temporalized DLs where temporal operators on TBox axioms and ABox assertions are available, but temporal operators on concepts are not. While the main application of existing temporalized DLs is the representation of conceptual models that explicitly incorporate temporal aspects, the family of DLs studied in this article addresses applications that focus on the temporal evolution of data and of ontologies. Our results show that disallowing temporal operators on concepts can significantly decrease the complexity of reasoning. In particular, reasoning with rigid roles (whose interpretation does not change over time) is typically undecidable without such a syntactic restriction, whereas our logics are decidable in elementary time even in the presence of rigid roles. We analyze the effects on computational complexity of dropping rigid roles, dropping rigid concepts, replacing temporal TBoxes with global ones, and restricting the set of available temporal operators. In this way, we obtain a novel family of temporalized DLs whose complexity ranges from 2- ExpTime-complete via NExpTime-complete to ExpTime-complete.
Algorithmic analysis of array-accessing programs
Authors: Alur Rajeev , Černý Pavol , Weinstein Scott
Published: August 2012

For programs whose data variables range over Boolean or finite domains, program verification is decidable, and this forms the basis of recent tools for software model checking. In this article, we consider algorithmic verification of programs that use Boolean variables, and in addition, access a single read-only array whose length is potentially unbounded, and whose elements range over an unbounded data domain. We show that the reachability problem, while undecidable in general, is (1) Pspace-complete for programs in which the array-accessing for-loops are not nested, (2) decidable for a restricted class of programs with doubly nested loops. The second result establishes connections to automata and logics defining languages over data words.
Atomic-level computing
Authors: Goth Gregory
Published: August 2012

Thanks to the University of New South Wales and IBM Research, scientists are moving closer to the junction of quantum and digital computing.
Garbage in, info out
Authors: Krakovsky Marina
Published: August 2012

Security researchers used malware to investigate large-scale Internet censorship in Egypt and Libya.
In honor of Alan Turing
Authors: Hyman Paul
Published: August 2012

Thirty-two of the 39 living A.M. Turing Award laureates gathered in San Francisco to pay tribute to "the father of CS" and discuss the past, present, and future of computing.
The need to balance innovation and implementation in broadening participation
Authors: Ladner Richard E. , Litzler Elizabeth
Published: August 2012

Seeking to improve the process for writing and reviewing proposals for new educational programs.
All your database are belong to us
Authors: Meijer Erik
Published: August 2012

In the big open world of the cloud, highly available distributed objects will rule.
Questioning naturalism in 3D user interfaces
Authors: Bowman Doug A. , McMahan Ryan P. , Ragan Eric D.
Published: August 2012

3D UIs are uniquely able to achieve superior interaction fidelity, and this naturalism can be a huge advantage.
Q&A: What women want
Authors: Hoffmann Leah
Published: August 2012

Harvey Mudd College president Maria Klawe talks about increasing the number of women who study computer science.
On Lyapunov Inequalities and Subsolutions for Efficient Importance Sampling
Authors: Blanchet Jose , Glynn Peter , Leder Kevin
Published: August 2012

In this article we explain some connections between Lyapunov methods and subsolutions of an associated Isaacs equation for the design of efficient importance sampling schemes. As we shall see, subsolutions can be derived by taking an appropriate limit of an associated Lyapunov inequality. They have been recently proposed in several works of Dupuis, Wang, and others and applied to address several important problems in rare-event simulation. Lyapunov inequalities have been used for testing the efficiency of state-dependent importance sampling schemes in heavy-tailed or discrete settings in a variety of works by Blanchet, Glynn, and others. While subsolutions provide an analytic criterion for the construction of efficient samplers, Lyapunov inequalities are useful for finding more precise information, in the form of bounds, for the behavior of the coefficient of variation of the associated importance sampling estimator in the prelimit. In addition, Lyapunov inequalities provide insight into the various mollification procedures that are often required in constructing associated subsolutions. Our aim is to demonstrate that applying Lyapunov inequalities for verification of efficiency can help both guide the selection of various mollification parameters and sharpen the information on the efficiency gain induced by the sampler.
Simulating Lévy Processes from Their Characteristic Functions and Financial Applications
Authors: Chen Zisheng , Feng Liming , Lin Xiong
Published: August 2012

The simulation of a discrete sample path of a Lévy process reduces to simulating from the distribution of a Lévy increment. For a general Lévy process with exponential moments, the inverse transform method proposed in Glasserman and Liu [2010] is reliable and efficient. The values of the cumulative distribution function (cdf) are computed by inverting the characteristic function and tabulated on a uniform grid. The inverse of the cumulative distribution function is obtained by linear interpolation. In this article, we apply a Hilbert transform method for the characteristic function inversion. The Hilbert transform representation for the cdf can be discretized using a simple rule highly accurately. Most importantly, the error estimates admit explicit and computable expressions, which allow us to compute the cdf to any desired accuracy. We present an explicit bound for the estimation bias in terms of the range of the grid where probabilities are tabulated, the step size of the grid, and the approximation error for the probabilities. The bound can be computed from the characteristic function directly and allows one to determine the size and fineness of the grid and numerical parameters for evaluating the Hilbert transforms for any given bias tolerance level in one-dimensional problems. For multidimensional problems, we present a procedure for selecting the grid and the numerical parameters that is shown to converge theoretically and works well practically. The inverse transform method is attractive not only for Lévy processes that are otherwise not easy to simulate, but also for processes with special structures that could be simulated in different ways. The method is very fast and accurate when combined with quasi-Monte Carlo schemes and variance reduction techniques. The main results we derived are not limited to Lévy processes and can be applied to simulating from tabulated cumulative distribution functions in general and characteristic functions in our analytic class in particular.
Simulating Multivariate Nonhomogeneous Poisson Processes Using Projections
Authors: Saltzman Evan A. , Drew John H. , Leemis Lawrence M. , Henderson Shane G.
Published: August 2012

Established techniques for generating an instance of a multivariate NonHomogeneous Poisson Process (NHPP) such as thinning can become highly inefficient as the dimensionality of the process is increased, particularly if the defining intensity (or rate) function has a pronounced peak. To overcome this inefficiency, we propose an alternative approach where one first generates a projection of the NHPP onto a lower-dimensional space, and then extends the generated points to points in the original space by generating from appropriate conditional distributions. One version of this algorithm replaces a high-dimensional problem with a series of one-dimensional problems. Several examples are presented.
A Framework for Selecting a Selection Procedure
Authors: Waeber Rolf , Frazier Peter I. , Henderson Shane G.
Published: August 2012

For many discrete simulation optimization applications, it is often difficult to decide which Ranking and Selection (R&S) procedure to use. To efficiently compare R&S procedures, we present a three-layer performance evaluation process. We show that the two most popular performance formulations, namely the Bayesian formulation and the indifference zone formulation, have a common representation analogous to convex risk measures used in mathematical finance. We then specify how a decision maker can impose a performance requirement on R&S procedures that is more adequate for her risk attitude than the indifference zone or the Bayesian performance requirements. Such a performance requirement partitions the space of R&S procedures into acceptable and nonacceptable procedures. The minimal computational budget required for a procedure to become acceptable introduces an easy-to-interpret preference order on the set of R&S policies. We demonstrate with a numerical example how the introduced framework can be used to guide the choice of selection procedure in practice.
Bayesian Kriging Analysis and Design for Stochastic Simulations
Authors: Ng Szu Hui , Yin Jun
Published: August 2012

Kriging is an increasingly popular metamodeling tool in simulation due to its flexibility in global fitting and prediction. In the fitting of this metamodel, the parameters are often estimated from the simulation data, which introduces parameter estimation uncertainties into the overall prediction error. Traditional plug-in estimators usually ignore these uncertainties, which can be substantial in stochastic simulations. This typically leads to an underestimation of the total variability and an overconfidence in the results. In this article, a Bayesian metamodeling approach for kriging prediction is proposed for stochastic simulations to more appropriately account for the parameter uncertainties. We derive the predictive distribution under certain assumptions and also provide a general Markov Chain Monte Carlo analysis approach to handle more general assumptions on the parameters and design. Numerical results indicate that the Bayesian approach has better coverage and better predictive variance than a previously proposed modified nugget effect kriging model, especially in cases where the stochastic variability is high. In addition, we further consider the important problem of planning the experimental design. We propose a two-stage design approach that systematically balances the allocation of computing resources to new design points and replication numbers in order to reduce the uncertainties and improve the accuracy of the predictions.
Teacher Preparation Trends
Authors: Williamson Amy M.
Published: August 2012

Online learning can no longer be considered a "fad" that may quickly pass. Instead, teachers and teacher educators alike must prepare themselves for the increasingly technological learning of the 21st century. This article focuses specifically on the benefits of YouTube as a means of reflection, modeling, and assessment for online education courses.
Galactic Stellar Populations in the Era of the Sloan Digital Sky Survey and Other Large Surveys
Authors: Ivezić Željko , Beers Timothy C. , Jurić Mario
Published: August 2012

Studies of stellar populations, understood to mean collections of stars with common spatial, kinematic, chemical, and/or age distributions, have been reinvigorated during the past decade by the advent of large-area sky surveys such as the Sloan Digital Sky Survey, the Two-Micron All Sky Survey, the Radial Velocity Experiment, and others. We review recent analyses of these data that, together with theoretical and modeling advances, are revolutionizing our understanding of the nature of the Milky Way and galaxy formation and evolution in general. The formation of galaxies like the Milky Way was long thought to be a steady process leading to a smooth distribution of stars. However, the abundance of substructure in the multidimensional space of various observables, such as position, kinematics, and metallicity, is now proven beyond doubt and demonstrates the importance of mergers in the growth of galaxies. Unlike smooth models that involve simple components, the new data reviewed here clearly exhibit many irregular structures, such as the Sagittarius dwarf tidal stream and the Virgo and Pisces overdensities in the halo and the Monoceros stream closer to the Galactic plane. These recent developments have made it clear that the Milky Way is a complex and dynamic structure, one that is still being shaped by the merging of neighboring smaller galaxies. We also briefly discuss the next generation of wide-field sky surveys, such as SkyMapper, Panoramic Survey Telescope & Rapid Response System, Global Astrometric Interferometer for Astrophysics, and the Large Synoptic Survey Telescope, which will improve measurement precision manyfold and include billions of individual stars. The ultimate goal, development of a coherent and detailed story of the assembly and evolutionary history of the Milky Way and other large spirals like it, now appears well within reach.
The Formation and Early Evolution of Low-Mass Stars and Brown Dwarfs
Authors: Luhman Kevin L.
Published: August 2012

The discovery of large numbers of young low-mass stars and brown dwarfs over the past decade has made it possible to investigate star formation and early evolution in a previously unexplored mass regime. In this review, we begin by describing surveys for low-mass members of nearby associations, open clusters, star-forming regions, and the methods used to characterize their stellar properties. We then use observations of these populations to test theories of star formation and evolution at low masses. For comparison to the formation models, we consider the initial mass function, stellar multiplicity, circumstellar disks, protostellar characteristics, and kinematic and spatial distributions at birth for low-mass stars and brown dwarfs. To test the evolutionary models, we focus on measurements of dynamical masses and empirical Hertzsprung-Russell diagrams for young brown dwarfs and planetary companions.
Strong Convergence Theorems for a Countable Family of Total Quasi‐ϕ‐Asymptotically Nonexpansive Nonself Mappings
Authors: Zhao Liang-cai , Chang Shih-sen
Published: August 2012

The purpose of this paper is to introduce a class of total quasi‐ϕ‐asymptotically nonexpansive‐nonself mappings and to study the strong convergence under a limit condition only in the framework of Banach spaces. As an application, we utilize our results to study the approximation problem of solution to a system of equilibrium problems. The results presented in the paper extend and improve the corresponding results announced by some authors recently.
On the Study of Local Solutions for a Generalized Camassa‐Holm Equation
Authors: Wu Meng
Published: August 2012

The pseudoparabolic regularization technique is employed to study the local well‐posedness of strong solutions for a nonlinear dispersive model, which includes the famous Camassa‐Holm equation. The local well‐posedness is established in the Sobolev space Hs(R) with s > 3/2 via a limiting procedure.
Robust Exponential Stability for LPD Discrete‐Time System with Interval Time‐Varying Delay
Authors: Mukdasai Kanit
Published: August 2012

This paper investigates the problem of robust exponential stability for uncertain linear‐parameter dependent (LPD) discrete‐time system with delay. The delay is of an interval type, which means that both lower and upper bounds for the time‐varying delay are available. The uncertainty under consideration is norm‐bounded uncertainty. Based on combination of the linear matrix inequality (LMI) technique and the use of suitable Lyapunov‐Krasovskii functional, new sufficient conditions for the robust exponential stability are obtained in terms of LMI. Numerical examples are given to demonstrate the effectiveness and less conservativeness
of the proposed methods.
Functional Reconstruction of Sarcoma Defects Utilising Innervated Free Flaps
Authors: Grinsell Damien , Di Bella Claudia , Choong Peter F. M.
Published: August 2012

Soft-tissue reconstruction following preoperative radiotherapy and wide resection of soft tissue sarcoma remains a challenge. Pedicled and free tissue transfers are an essential part of limb sparing surgery. We report 22 cases of sarcoma treated with radiotherapy and wide excision followed by one-stage innervated free or pedicled musculocutaneous flap transfers. The resection involved the upper limb in 3 cases, the lower limb in 17, and the abdominal wall in 2. The flaps used for the reconstruction were mainly latissimus dorsi and gracilis. The range of motion was restored fully in 14 patients. The muscle strength of the compartment reconstructed was of grades 4 and 5 in all patients except one. The overall function was excellent in all the cases with functional scores of 71.2% in the upper limb and 84% in the lower limb. The only 2 major complications were flap necrosis, both revised with another flap, one of which was innervated with restoration of function. Innervated flaps are valuable alternatives for reconstruction after sarcoma resection in the extremity and in the abdominal wall. The excellent functional results are encouraging, and we believe that innervated muscle reconstruction should be encouraged in the treatment of sarcoma after radiotherapy and wide resection.
CoFe2O4−Fe3O4Magnetic Nanocomposites as Photocatalyst for the Degradation of Methyl Orange Dye
Authors: Mishra Debabrata , Senapati Kula Kamal , Borgohain Chandan , Perumal A.
Published: August 2012

We report the investigation of temperature-dependent magnetic properties and photocatalytic activity ofCoFe2O4−Fe3O4magnetic nanocomposites (MNCs) synthesized by hydrothermal process. Room-temperature magnetic hysteresis (M-H) loops result enhanced saturation magnetization of 90 emu/g and coercivity (HC) of 530 Oe forCoFe2O4−Fe3O4MNCs. With decreasing temperature to 20 K,HCincreases from 500 Oe to 6800 Oe, and the M-H loops exhibit exchange coupling feature betweenCoFe2O4andFe3O4. Low- and high-temperature-dependent magnetization measurements confirm that the blocking temperature lies above 300 K and the presence of two magnetic phase transitions corresponding toCoFe2O4andFe3O4, respectively. The photocatalytic activity of the MNCs has been examined on the reduction of methyl orange (MO), a colored compound used in dyeing and printing textiles. The observed results suggest that theCoFe2O4−Fe3O4MNCs act as an excellent photocatalyst on the degradation of organic contaminants and degrade 93% of MO in 5 hours of UV irradiation. The photocatalytic activity of MNCs is attributed to remarkably high band gap energy and small particle size. Also, the MNCs with a reproducible photocatalytic activity are well separable from water media by applying external magnetic field and acts as a promising catalyst for the remediation of textile wastewater.
Cluster Anti‐Synchronization of Complex Networks with Nonidentical Dynamical Nodes
Authors: Wang Shuguo , He Chunyuan , Yao Hongxing
Published: August 2012

This paper investigates a new cluster antisynchronization scheme in the time‐varying delays coupled complex dynamical networks with nonidentical nodes. Based on the community structure of the networks, the controllers are designed differently between the nodes in one community that have direct connections to the nodes in other communities and the nodes without direct connections with the nodes in other communities strategy; some sufficient criteria are derived to ensure cluster anti‐synchronization of the network model. Particularly, the weight configuration matrix is not assumed to be irreducible. The numerical simulations are performed to verify the effectiveness of the theoretical results.
Multiple Pulp Stones in Primary and Developing Permanent Dentition: A Report of 4 Cases
Authors: Marwaha Mohita , Chopra Radhika , Chaudhuri Payal , Gupta Atul , Sachdev Jayna
Published: August 2012

Pulp stones are foci of calcification or discrete calcifications in the dental pulp. They are frequently found on bitewing and periapical radiographs, but their occurrence in entire dentition is unusual. We are reporting four cases in which the occurrence of pulp stones ranged from their presence in just primary teeth (Cases 1 and 2) to involvement of young permanent teeth also (Case 3) and even unerupted permanent teeth (Case 4). In all the cases, dental, medical, and family histories as well as the findings from the clinical examination of the patient were not contributory. Histopathological report revealed true denticle. Metabolic evaluation of patients through liver function test, kidney function test, and blood investigation did not show any metabolic disorders. Patients were also evaluated for any systemic, syndromic, or genetic involvement, but this was also noncontributing. Therefore, it is suggested that these unusual cases may be of idiopathic origin.
Elimination of Tumor Cells Using Folate Receptor Targeting by Antibody‐Conjugated, Gold‐Coated Magnetite Nanoparticles in a Murine Breast Cancer Model
Authors: Krystofiak Evan S. , Matson Vyara Z. , Steeber Douglas A. , Oliver Julie A.
Published: August 2012

Background. The chemotherapeutic treatment of cancer suffers from poor specificity for targeting the tumor cells and often results in adverse effects such as systemic toxicity, damage to nontarget tissues, and development of drug‐resistant tumors in patients. Increasingly, drug nanocarriers have been explored as a way of lessening or overcoming these problems. In this study, antibody‐conjugated Au‐coated magnetite nanoparticles, in conjunction with inductive heating produced by exposure to an oscillating magnetic field (OMF), were evaluated for their effects on the viability of tumor cells in a murine model of breast cancer. Treatment effects were evaluated by light microscopy and SEM. Results. 4T1 mammary epithelial carcinoma cells overexpressing the folate receptor were targeted with an anti‐folate receptor primary antibody, followed by labeling with secondary antibody‐conjugated Au‐coated magnetite nanoparticles. In the absence of OMF exposure, nanoparticle labeling had no effect on 4T1 cell viability. However, following OMF treatment, many of the labeled 4T1 cells showed extensive membrane damage by SEM analysis, and dramatically reduced viability as assessed using a live/dead staining assay. Conclusions. These results demonstrate that Au‐coated magnetite targeted to tumor cells through binding to an overexpressed surface receptor, in the presence of an OMF, can lead to tumor cell death.
A Very Robust AlGaN/GaN HEMT Technology to High Forward Gate Bias and Current
Authors: Christiansen Bradley D. , Heller Eric R. , Coutu Ronald A. , Vetury Ramakrishna , Shealy Jeffrey B.
Published: August 2012

Reports to date of GaN HEMTs subjected to forward gate bias stress include varied extents of degradation. We report an extremely robust GaN HEMT technology that survived—contrary to conventional wisdom—high forward gate bias (+6 V) and current (>1.8 A/mm) for >17.5 hours exhibiting only a slight change in gate diode characteristic, little decrease in maximum drain current, with only a 0.1 V positive threshold voltage shift, and, remarkably, a persisting breakdown voltage exceeding 200 V.
Insurance and Banking Interconnectedness in Europe: The Opinion of Equity Markets
Authors: Nyholm Ken
Published: August 2012

Conditional expected shortfalls calculated for European insurance companies and banks under stressed market conditions are shown to be of similar magnitudes. Measured at 95% and 99% stress levels, on data covering the period from 1995 to 2011, the equity-return tail losses of insurance undertakings and banks are indistinguishable. Granger causality analysis, on all pairs of banks and insurance companies included in the sample, shows that banks and insurance companies have equal propensity to cause each others price movements. Even though the business model of insurance undertakings is different from the business model typically applied by banks, and even though insurance companies are not depending to a similar degree on short term funding as banks, the empirical results indicate that the financial equity markets in Europe do not differentiate their trading of banks and insurance
companies in periods of stress.
Effects of Palm Vitamin E on Bone-Formation-Related Gene Expression in Nicotine-Treated Rats
Authors: Abukhadir Seham Salem Ahmed , Mohamed Norazlina , Makpol Suzana , Muhammad Norliza
Published: August 2012

The study determines the effects of palm vitamin E on the gene expression of bone-formation-related genes in nicotine-treated rats. Male rats were divided into three groups: normal saline olive oil (NSO), nicotine olive oil (NO), and nicotine palm vitamin E (NE). The treatment was carried out in 2 phases. During the first 2 months, the NSO group received normal saline while the NO and NE groups received nicotine 7 mg/kg, 6 days a week, intraperitoneally. The following 2 months, normal saline and nicotine administration was stopped and was replaced with oral supplementation of olive oil for the NSO and NO groups and oral supplementation of palm vitamin E (60 mg/kg) for the NE group. Both femurs were harvested to determine the gene expression of bone morphogenetic protein-2 (BMP-2), Osterix (OSX), and Runt-related transcription factor 2 (RUNX2). Nicotine significantly downregulated the gene expression. This effect was reversed by palm vitamin E treatment. In conclusion, palm vitamin E may play a role in osteoblast differentiation and can be considered as an anabolic agent to treat nicotine-induced osteoporosis.
Photocatalytic Activity of Nanostructured Titanium Dioxide Thin Films
Authors: Michalcik Zdenek , Horakova Marta , Spatenka Petr , Klementova Sarka , Zlamal Martin , Martin Nicolas
Published: August 2012

The aim of this paper is to investigate the properties and photocatalytic activity of nanostructured TiO2layers. The glancing angle deposition method with DC sputtering at low temperature was applied for deposition of the layers with various columnar structures. The thin-film structure and surface morphology were analyzed by XRD, SEM, and AFM analyses. The photocatalytic activity of the films was determined by the rate constant of the decomposition of the Acid Orange 7. In dependence on the glancing angle deposition parameters, three types of columnar structures were obtained. The films feature anatase/rutile and/or amorphous structures depending on the film architecture and deposition method. All the films give the evidence of the photocatalytic activity, even those without proved anatase or rutile structure presence. The impact of columnar boundary in perspective of the photocatalytic activity of nanostructured TiO2layers was discussed as the possible factor supporting the photocatalytic activity.
Obstructive Sleep Apnea in a Patient with CHARGE Syndrome
Authors: Trider Carrie-Lee , Blake Kim
Published: August 2012

CHARGE syndrome is a genetic disorder characterized by choanal atresia, coloboma of the eye, and ear and cranial nerve abnormalities. We report a child with CHARGE syndrome and obstructive sleep apnea. We highlight difficulties in discerning obstructive sleep apnea-related symptoms from typical features of CHARGE syndrome. Treatment options are discussed with regard to our patient. Tonsillectomy and adenoidectomy improved physical symptoms of obstructive sleep apnea in the patient.
Synthesis, Spectral Characterization, andIn VitroCytotoxicity of N-2′-Hydroxyethyl-Substituted Azacholestanes Prepared from 6-Oxocholestanes by Modified Schmidt Reaction
Authors: Nami Shahab A. A. , Khan Suraiya , Alam Mahboob , Mushfiq M. , Lee Dong-Ung , Park Soonheum
Published: August 2012

The present paper reports the synthesis and spectroscopic characterization of few N-2′-hydroxyethyl-substituted azacholestanes using BF3-OEt2, TiCl4, SnCl4, and H2SO4as catalysts in moderate yields by a modified version of Schmidt reaction. A notable feature is the passivity of SnCl4in case of 3β-acetoxy-N-2′-hydroxyethyl-6-aza-B-homo-5α-cholestan-7-one and 3β-chloro-N-2′-hydroxyethyl-6-aza-B-homo-5α-cholestan-7-one. However, the reaction was unsuccessful in case of N-2′-Hydroxyethyl-6-aza-B-homo-5α-cholestan-7-one. Another striking aspect is the attainment of high yield in case of H2SO4as catalyst. The semisolid compounds are characterized using various spectroscopic techniques such as FT-IR,1H-NMR and mass spectra, and microanalytical data. A reaction mechanism has been proposed on the basis of previous studies. Moreover, the compounds have also been screened for theirin vitrocytotoxicity against human colon carcinoma cell line, HCT116, and human liver hepatocellular carcinoma cell line, HepG2, using doxorubicin as standard. On the basis of IC50values, 3β-chloro-N-2′-hydroxyethyl-6-aza-B-homo-5α-cholestan-7-one (5) was found to inhibit the cancer cells most effectively.
Extractive Spectrophotometric Method for Determination of Molybdenum in Steels and Environmental Samples
Authors: Dass Rameshwar , Kapoor Jitander K. , Gambhir Sunita
Published: August 2012

An extractive spectrophotometric method has been developed for microdetermination of molybdenum. At room temperature Mo(VI) was reduced to Mo(V) in 2 M H2SO4 using ascorbic acid as a reductant. The Mo(V) formed a yellow‐coloured (1 : 2) complex with 6‐chloro‐3‐hydroxy‐2‐(3′‐hydroxyphenyl)‐4‐oxo‐4H‐1‐benzopyran (CHHB). The complex was quantitatively extracted into toluene and absorbed maximum at λmax 404 nm. Beer’s law was obeyed over the concentration range of 2.31 μg Mo ml−1 with a molar absorptivity and Sandell′s sensitivity of 5.62 × 104 L mol−1 cm−1 and 0.0016 μg Mo cm−2, respectively. The relative standard deviation was 0.0025 (in absorbance units) for 10 replicate determinations of 1 μg Mo ml−1. The method was free from the interference of large number of analytically important elements. Molybdenum has been determined satisfactorily in different technical, synthetic, and environmental samples with improved accuracy and precision.
Electroimpedance Spectroscopy for the Measurement of the Dielectric Properties of Sodium Chloride Solutions at Different Glucose Concentrations
Authors: Sbrignadello Stefano , Tura Andrea , Ravazzani Paolo
Published: August 2012

We investigated possible variations of impedance values in samples of sodium chloride solution (sodium chloride 0.9%) with glucose at different concentrations, ranging from 5000 to around 75 mg/dL. The sodium chloride solution (either saline physiological solution) was chosen since it has similarities to blood but no cell components, which may be confounding factors in this study. Special focus was on the effect of stirring and of temperature variations on the impedance spectrum of samples at different glucose concentrations. We found that variations in glucose concentration directly affect the impedance modulus of the sample both in static conditions and in dynamic conditions due to stirring, as well as at both room temperature and at increased temperature. In fact, even if the impedance variations were often small (around 3-4 mΩper mg/dL), they were usually clearly measurable. These findings may be the basis for possible development of a new approach, based on impedance technology, for the noninvasive monitoring of glycaemia.
Mammalian Sterile 20–like Kinase 1 Suppresses Lymphoma Development by Promoting Faithful Chromosome Segregation
Authors: Kim Tae-Shin , Lee Da-Hye , Kim Sang Kyum , Shin So Youn , Seo Eul-Ju , Lim Dae-Sik
Published: August 2012

The mammalian Hippo signaling pathway has been implicated in oncogenesis in the context of solid tumors such as hepatocellular carcinoma. Mammalian sterile 20–like kinase 1 (MST1), the core component of the Hippo signaling pathway, is highly expressed in hematopoietic cells. However, its possible impact on tumorigenesis in this setting is unknown. In this study, we provide evidence that Mst1 loss in the mouse enhances chemically and genetically induced lymphoma development by inducing chromosomal instability. Mst1 deficiency increased susceptibility to T-cell acute lymphoblastic leukemia induced by mutagen exposure. Notably, before transformation Mst1−/− normal thymocytes showed no changes in proliferation or apoptosis in vitro and in vivo, but they displayed elevated levels of abnormal mitotic chromosomes and aneuploidy, conditions known to promote tumorigenesis. Mst1−/− mice also showed accelerated formation of spontaneous lymphomas in a p53-deficient background, accompanied by severe aneuploidy. In clinical specimens of lymphoma and leukemia, we documented frequent downregulation of MST1 expression, consistent with our findings. Taken together, our findings reveal a tumor suppressive function of Mst1 based on its ability to prevent chromosomal instability in lymphocytes. Cancer Res; 72(20); 5386–95. ©2012 AACR.
An NMR Metabolomics Approach for the Diagnosis of Leptomeningeal Carcinomatosis
Authors: Cho Hye Rim , Wen He , Ryu Young Jin , An Yong Jin , Kim Hyo Cheol , Moon Woo Kyung , Han Moon Hee , Park Sunghyouk , Choi Seung Hong
Published: August 2012

Leptomeningeal carcinomatosis (LC) is the third most common metastatic complication of the central nervous system. However, the current modalities to reliably diagnose this condition are not satisfactory. Here, we report a preclinical proof of concept for a metabolomics-based diagnostic strategy using a rat LC model incorporating glioma cells that stably express green fluorescent protein. Cytologic diagnoses gave 66.7% sensitivity for the 7-day LC group and 0% for the 3-day LC group. MR imaging could not diagnose LC at these stages. In contrast, nuclear magnetic resonance–based metabolomics on cerebrospinal fluid detected marked differences between the normal and LC groups. Predictions based on the multivariate model provided sensitivity, specificity, and overall accuracy of 88% to 89% in both groups for LC diagnosis. Further statistical analyses identified lactate, acetate, and creatine as specific for the 7-day LC group, with glucose a specific marker of the normal group. Overall, we showed that the metabolomics approach provided both earlier and more accurate diagnostic results than cytology and MR imaging in current use. Cancer Res; 72(20); 5179–87. ©2012 AACR.
Phase I Study of the Antiangiogenic Antibody Bevacizumab and the mTOR/Hypoxia-Inducible Factor Inhibitor Temsirolimus Combined with Liposomal Doxorubicin: Tolerance and Biological Activity
Authors: Moroney John , Fu Siqing , Moulder Stacy , Falchook Gerald , Helgason Thorunn , Levenback Charles , Hong David , Naing Aung , Wheler Jennifer , Kurzrock Razelle
Published: August 2012

Purpose: Preclinical data suggest that combining the mTOR/hypoxia-inducible factor (HIF) inhibitor temsirolimus and the antiangiogenesis antibody bevacizumab may augment antitumor activity as well as resensitize cells to anthracyclines.

Experimental Design: We initiated a phase I study of bevacizumab and temsirolimus plus liposomal doxorubicin in patients with advanced malignancies. Patients (N = 136) were enrolled according to a modified 3 + 3 design plus dose expansion in responsive tumor types.

Results: The most common cancers were breast (n = 29), epithelial ovarian (n = 23), and colorectal cancer (n = 17). The median number of prior chemotherapy regimens was four (range: 0–16). Grade 3 or higher adverse events (> 5%) included pancytopenia, mucositis, hand–foot syndrome, hypertension, and fistula. This regimen led to a 21% (n = 28) stable disease (SD) ≥ 6 months and 21% (n = 29) rate of partial or complete remission [PR/CR; (total SD ≥ 6 months/PR/CR = 42% (n = 57)]. PR/CR was most common in parotid gland adenocarcinoma (4/6, 67%), metaplastic breast cancer (5/12, 42%), endometrial endometrioid carcinoma (6/15, 40%), and in patients with a PIK3CA mutation and/or a PTEN mutation/loss (11/28, 39%). The maximum tolerated dose was liposomal doxorubicin 30 mg/m2 and bevacizumab 15 mg/kg every three weeks with temsirolimus 25 mg weekly.

Conclusions: Patients tolerated bevacizumab and temsirolimus together with liposomal doxorubicin. Further evaluation, especially in patients with parotid, metaplastic breast, and endometrial endometrioid cancer, and in patients with PIK3CA and/or PTEN aberrations is warranted. Clin Cancer Res; 18(20); 5796–805. ©2012 AACR.
Inhibition of TGF-β Enhances the In Vivo Antitumor Efficacy of EGF Receptor–Targeted Therapy
Authors: Bedi Atul , Chang Xiaofei , Noonan Kimberly , Pham Vui , Bedi Rishi , Fertig Elana J. , Considine Michael , Califano Joseph A. , Borrello Ivan , Chung Christine H. , Sidransky David , Ravi Rajani
Published: August 2012

EGF receptor (EGFR)–targeted monoclonal antibodies (mAb), such as cetuximab, execute their antitumor effect in vivo via blockade of receptor–ligand interactions and engagement of Fcγ receptors on immune effector cells that trigger antibody-dependent cell-mediated cytotoxicity (ADCC). We show that tumors counteract the in vivo antitumor activity of anti-EGFR mAbs by increasing tumor cell-autonomous expression of TGF-β. We show that TGF-β suppresses the expression of key molecular effectors of immune cell–mediated cytotoxicity, including Apo2L/TRAIL, CD95L/FasL, granzyme B, and IFN-γ. In addition to exerting an extrinsic inhibition of the cytotoxic function of immune effectors, TGF-β–mediated activation of AKT provides an intrinsic EGFR-independent survival signal that protects tumor cells from immune cell–mediated apoptosis. Treatment of mice-bearing xenografts of human head and neck squamous cell carcinoma with cetuximab resulted in emergence of resistant tumor cells that expressed relatively higher levels of TGF-β compared with untreated tumor-bearing mice. Although treatment with cetuximab alone forced the natural selection of TGF-β–overexpressing tumor cells in nonregressing tumors, combinatorial treatment with cetuximab and a TGF-β–blocking antibody prevented the emergence of such resistant tumor cells and induced complete tumor regression. Therefore, elevated levels of TGF-β in the tumor microenvironment enable tumor cells to evade ADCC and resist the antitumor activity of cetuximab in vivo. Our results show that TGF-β is a key molecular determinant of the de novo and acquired resistance of cancers to EGFR-targeted mAbs, and provide a rationale for combinatorial targeting of TGF-β to improve anti-EGFR–specific antibody therapy of EGFR-expressing cancers. Mol Cancer Ther; 11(11); 2429–39. ©2012 AACR.
The Combination of Tamoxifen and the Rexinoid LG100268 Prevents ER-Positive and ER-Negative Mammary Tumors in p53-Null Mammary Gland Mice
Authors: Mazumdar Abhijit , Medina Daniel , Kittrell Francis S. , Zhang Yun , Hill Jamal L. , Edwards David E. , Bissonnette Reid P. , Brown Powel H.
Published: August 2012

In pursuit of effective therapeutic agents for the estrogen receptor (ER)-negative breast cancer, we previously showed that bexarotene reduced mammary tumor development by 75% in ErbB2 mice. To further improve the effectiveness of breast cancer prevention, we have now investigated the effects of a combinatorial therapy consisting of two cancer preventive drugs. On the basis of the hypothesis, rexinoid LG100268 plus tamoxifen would more effectively prevent the development of both ER-positive and ER-negative breast cancer. We treated p53-null mammary gland mice with tamoxifen and LG100268, individually and in combination. By 60 weeks of age, vehicle-treated mice developed tumors in 52% of transplanted mammary glands, whereas mice treated with tamoxifen and LG100268 developed tumors in only 13% of transplanted mammary glands. To further define the mechanistic effects of this combinatorial treatment, we investigated the effects of tamoxifen and LG100268 on mammary tissue biomarkers. In mammary tissue harvested before tumor development, the proliferation markers Ki67 and cyclin D1 were significantly reduced in mice treated with the combination therapy. In addition, the rexinoid target genes ABCA1 and ABCG1 were induced in both the rexinoid and combination treatment groups, whereas expression remained constant in tamoxifen group. These results show that tamoxifen-LG100268 combinatorial treatment is more effective in preventing mammary tumors than either agent alone. In addition, these studies have identified relevant tissue biomarkers that can be used to show the effect of these agents on mammary tissue. These results support the development of clinical trials of antiestrogen and rexinoid combinatorial therapy for the prevention of patients with high-risk breast cancer. Cancer Prev Res; 5(10); 1195–202. ©2012 AACR.
Orally Active Vitamin D for Potential Chemoprevention of Posttransplant Malignancy
Authors: Obi Yoshitsugu , Ichimaru Naotsugu , Hamano Takayuki , Tomida Kodo , Matsui Isao , Fujii Naohiko , Okumi Masayoshi , Kaimori Jun-ya , Yazawa Koji , Kokado Yukito , Tsubakihara Yoshiharu , Nonomura Norio , Rakugi Hiromi , Takahara Shiro , Isaka Yoshitaka
Published: August 2012

Posttransplant malignancy (PTM) is a limiting factor both for patient and allograft survival in kidney transplant recipients (KTRs). We hypothesized that active vitamin D compounds (AVD) could reduce PTM development in KTRs. Ambulatory KTRs in a Japanese prospective cohort were followed from August 2007 to November 2010. The outcome of interest was newly diagnosed PTM. A propensity score (PS) of having received AVDs was estimated using 26 clinically relevant factors. We used the Cox proportional hazards model with stratification by PS tertiles on the assumption that baseline hazard functions differ among tertiles. As sensitivity analyses, we used inverse probability weighting and PS matching. Among 218 participants, the median age was 50 (interquartile range [IQR], 40 to 59) years, 63.3% were male, median time since transplantation was 11.2 (IQR, 5.2 to 17.1) years, and mean estimated GFR was 41.3 (SD, 15.6) mL/min per 1.73 m2. At baseline, 42.2% had been treated with AVDs mainly for glucocorticoid-induced osteoporosis. AVDs used were calcitriol (58.7%) and alfacalcidol (41.3%). During follow-up, PTM developed in 5.4% of 92 AVD users and 8.7% of 126 nonusers. Poor vitamin D status was common in the participants, but the serum 25-hydroxyvitamin D level was not significantly associated with PTM in Cox regression analysis. After stratifying patients by PS tertiles, we found that AVDs were significantly associated with a lower risk of PTM (HR 0.25 [0.07 to 0.82]). Sensitivity analyses yielded similar results. AVDs are potential chemopreventive agents against PTM in KTRs. Cancer Prev Res; 5(10); 1229–35. ©2012 AACR.