bluuebunny/crossref_metadata_2025 huggingface dataset:
COUNTERPARTY RISK FOR CREDIT DEFAULT SWAPS: IMPACT OF SPREAD VOLATILITY AND DEFAULT CORRELATION
Authors: BRIGO DAMIANO , CHOURDAKIS KYRIAKOS
Published: November 2009

We consider counterparty risk for Credit Default Swaps (CDS) in presence of correlation between default of the counterparty and default of the CDS reference credit. Our approach is innovative in that, besides default correlation, which was taken into account in earlier approaches, we also model credit spread volatility. Stochastic intensity models are adopted for the default events, and defaults are connected through a copula function. We find that both default correlation and credit spread volatility have a relevant impact on the positive counterparty-risk credit valuation adjustment to be subtracted from the counterparty-risk free price. We analyze the pattern of such impacts as correlation and volatility change through some fundamental numerical examples, analyzing wrong-way risk in particular. Given the theoretical equivalence of the credit valuation adjustment with a contingent CDS, we are also proposing a methodology for valuation of contingent CDS on CDS.
VALUATION OF CREDIT DEFAULT SWAPTIONS AND CREDIT DEFAULT INDEX SWAPTIONS
Authors: RUTKOWSKI MAREK , ARMSTRONG ANTHONY
Published: November 2009

The paper provides simple and rigorous, albeit fairly general, derivations of valuation formulae for credit default swaptions and credit default index swaptions. Results of this work cover as special cases the pricing formulae derived previously by Jamshidian [Finance and Stochastics8 (2004) 343–371], Pedersen [Quantitative Credit Research (2003)], Brigo and Morini (2005), and Morini and Brigo (2007). Most results presented in this work are completely independent of a particular convention regarding the specification of the fee and protection legs and thus they can also be used for valuation of other credit derivatives that exhibit similar features (for instance, options on CDO tranches). The main tools are a judicious choice of the reference filtration and a suitable specification of the risk-neutral dynamics for the pre-default (loss-adjusted) fair market spread.
ALIGNMENT OF CARBON NANOTUBES USING MAGNETIC NANOPARTICLES
Authors: ALDAJAH S. , CHATTERJEE J. , ALRAWADEH M. , KOSURI A. , HAIK Y.
Published: November 2009

Carbon nanotubes are driving scientific research nowadays. This field has several important directions in basic research, including chemistry, electronic transport, mechanical, and field emission properties. The most eye-catching features of carbon nanotubes are their electronic, mechanical, optical, and chemical characteristics, which open a way to future applications. One of the most important applications of nanotubes based on their properties will be as reinforcements in composite materials. One of the biggest concerns to nanotube industry is the alignment problem which has limited the usage and utilizations of carbon nanotubes in composites. The ability to impose a preferred alignment of carbon nanotubes in a composite will increase the effectiveness of utilizing nanotubes in composite applications. The alignment of nanotubes will maximize the interfacial bonding across the nanotube matrix interface.

In this research, we developed a methodology and a process to align nanotubes in polymer nanocomposites by means of a magnetic field. By doing so, we will get a very strong nanocomposite that can be used in the composites industry. The proposed mechanism aims at aligning the carbon nanotubes by means of nanomagnetic particles that are adsorbed on the nanotube surfaces and by applying an external magnetic field. SEM analysis have shown that nanomagnetic particles with the assistance of the magnetic field were able to align the carbon nanotubes in the desired direction.
CONTINUOUS-WAVE PHOTOLUMINESCENCE AND NANOSTRUCTURAL PROPERTIES OF POROUS SILICON
Authors: Al-AJILI ADWAN
Published: November 2009

The photoluminescence (PL) emitted by porous silicon has been investigated by using the continuous tuneable UV Synchrotron Radiation Source. One sample was investigated for orange PL emission wavelength at temperatures 77–295 K. The PL peak is found to shift to higher frequency with decreasing temperature. Information about the nanostructure of porous silicon has been determined from PL and Extended X-ray Absorption Fine Structure (EXAFS), as well as from electron microscopy. In particular, the optical properties of silicon-based nanostructured materials, obtained from PL and photoluminescence excitation measurements, have been correlated with structural information from Si –K-edge EXAFS. Electron microscopy was used to study the relation between the nanostructure and PL of porous Si , and to investigate porous Si structure. Platelet Si and Si crystallites in porous Si layers were observed. The size of crystallites ranged from 4 to 6.5 nm. Diffraction patterns show these porous Si samples have a crystalline structure.
FABRICATION AND EVALUATION OF HUMAN SERUM ALBUMIN (HSA) NANOPARTICLES FOR DRUG DELIVERY APPLICATION
Authors: MEHRAVAR R. , JAHANSHAHI M. , SAGHATOLESLAMI N.
Published: November 2009

Human Serum Albumin (HSA) nanoparticles represent promising drug carrier systems. Particle size is a crucial parameter in particular for the in vivo behavior of nanoparticles after intravenous injection. The object of present study was to characterize the desolvation process of HSA for preparation of nanoparticles. Two process parameters were examined to achieve a suitable size of nanoparticles such as the pH value and the amount of glutaraldehyde concentration (%). The smallest size of nanoparticles achieved was 91 nm and the largest size was 388 nm which is suitable for drug delivery. The pH value of the HSA solution prior to the desolvation procedure was identified as the major factor determining particle size and the amount of crosslinker showed that it has less effect on produced nanoparticle size. The nanoparticle sample was purified by five cycles' centrifugation (20 000× g, 8 min) and redispersion of the pellet to the original volume in 10 mM NaCl at pH values of 7.5–9, respectively, and then analyzed by particle size analyzer (PCS).
FABRICATION OF ARRAY MICROSTRUCTURES USING SERIAL AND PARALLEL LOCALIZED ELECTRODEPOSITION
Authors: SAID RA'A , ALSHWAWREH NIDAL , HAIK YOUSEF
Published: November 2009

To add to the development efforts in enhancing the capabilities of localized electrodeposition (LED) fabrication technique, this paper presents serial and parallel deposition algorithms to fabricate array microstructures. Such arrays can be implemented as microsensors in neural recording applications or as antenna arrays in ultra high frequency applications. Also, magnetic tip microarrays for tissue engineering can be realized. In the case of serial fabrication, an array of high aspect ratio microstructures is realized using the conventional single-tip microelectrode while implementing a multistep fabrication algorithm. In this algorithm, the fabricated microstructure elements within the array are realized one at a time. In the parallel deposition algorithm, the array is realized using a multitip array microelectrode while implementing a single step fabrication algorithm. In this algorithm, the microstructure elements within the array are fabricated simultaneously. The proposed algorithms are compared through a demonstration of fabricated array microstructures.
MICROWAVE SINTERING OF NANOCRYSTALLINE 8YSZ: EFFECT OF HEATING SCHEDULE ON MICROSTRUCTURE, IONIC CONDUCTIVITY, AND MECHANICAL PROPERTIES
Authors: VALEFI MAHDIAR , FALAMAKI CAVUS , FATTAHI AHAD , EBADZADEH TOURAJ
Published: November 2009

Nanocrystalline 8 mol.% yttria-stabilized zirconia powder prepared from a combustion synthesis route has been sintered using microwave (MW) energy by two routes: Conventional one-step and a novel two-step method. The final products from the two routes have been compared regarding their microstructure, ion-conductivity, and mechanical properties. It is shown that it is possible to produce highly dense compacts with significant smaller grains using the novel two-step MW sintering method with significant smaller energy consumption with respect to conventional one-step MW assisted sintering. The novel method is able to produce sintered samples with near similar ionic conductivity at temperatures higher than 700°C and slightly lower mechanical properties at room temperature.
PARAMETRIC STUDY ON THE SYNTHESIS OF SINGLE WALL CARBON NANOTUBE BY GAS ARC-DISCHARGE METHOD WITH MULTIPLE LINEAR REGRESSIONS AND ARTIFICIAL NEURAL NETWORK
Authors: SERESHT RAZIEH JABARI , JAHANSHAHI MOHSEN , YAZDANI MASOUD
Published: November 2009

Carbon nanotube, a new form of carbon element. The arc-discharge method is one of the most efficient techniques for this purpose. Arc-discharge is very simple and has merit to make massive and elongated single wall carbon nanotubes (SWCNTs). Synthesis of SWCNTs are affected with some parameters. In this paper, a predictive model has performed for prediction diameter of SWCNTs based on these factors. In this study, a linear model were established by subjecting the transformed values of independent variables to multiple linear regression (MLR) analysis. In order to examine the correctness of predicted linear model, a predictive artificial neural network (ANN) model was utilized. The optimized models developed by both ANN and regression were validated by comparing the results by a paired t test. These findings demonstrate that ANN provides more accurate prediction and is quite useful in the optimization of diameter SWCNT when compared with the MLR analysis method.
STRUCTURAL AND MAGNETIC PROPERTIES OF HEMATITE NANOCRYSTALLINE OBTAINED BY BALL MILLING
Authors: LEMINE O. M. , MSALAM R. , ALYAMANI A. , SAJIEDDINE M. , MUFTI S. , ZIQ Kh. , SALEM A. F. , BOUOUDINA M.
Published: November 2009

α-Fe2O3 nanoparticles were obtained by a mechanical alloying of micrometer-sized powder at different milling times. Samples were characterized by X-ray powder diffraction, scanning electron microscope (SEM), Mössbauer spectrometry, and vibrating sample magnetometer (VSM). A qualitative and quantitative phase analyses using the Rietveld method have been performed based on the XRD data. The results did not reveal any phase change during the milling. The average particle size decreases with a prolongation of milling times, while the lattice parameters, unit cell volume, and microstrain increase. Mössbauer measurement shows that there are two components, one nanometric and other micrometric. The magnetic hysteresis loops shows that the samples are typical of ferromagnet with superparamagnetic fraction in the material.
SYNTHESIS AND CHARACTERIZATION OF ZnO NANORODS AND NANOWIRES USING PVP AS CAPPING
Authors: ESKANDARI M. , AHMADI V. , AHMADI Sh.
Published: November 2009

In this study, ZnO nanowires are synthesized via ZnO nanorods at low temperature by using zinc acetate dehydrate and polyvinylpyrrolidone as precursor and capping, respectively. We use chemical solution method for synthesis of ZnO nanowires. Samples are characterized by means of scanning electron microscopy and X-ray diffraction. First, the nanorods are prepared at 300°C temperature, and then they are put into the furnace under air atmosphere at 450°C for 2 h. It is observed that nanowires with 20 nm diameter are produced. Photoluminescence spectra of nanorods and nanowires are compared. It shows that intensity of ultraviolet peak in the nanowires decreases but in contrast the intensity of green emission part increases. This is because, the surface effects such as oxygen vacancies increase in the structures of ZnO .
SYNTHESIS OF Cu–Al2O3 METAL MATRIX NANOCOMPOSITE POWDER FROM CuO AND Al POWDERS BY USING HIGH ENERGY PLANETARY FAST MILLING
Authors: MOTAMAN ASHKAN , SALAHI ESMAEIL
Published: November 2009

Cu–Al2O3 metal matrix nanocomposite powder has been synthesized from CuO and Al powders using high energy planetary fast milling. Mechanical alloying was used to produce 20% Vol. Alumina as a reinforcement phase in copper matrix. Reactive milling between Cu ( Al ) solid solution and CuO powders lead to formation of Cu–Al2O3 metal matrix composite. To obtain Cu ( Al ) solid solution, Cu and Al powders with Cu:Al atomic ratio of six were mechanically alloyed for 50 h.

XRD analysis showed that during the reaction of Cu ( Al ) solid solution and CuO , Al solute is extracted from Cu ( Al ) solid solution and reacted with oxygen of CuO to form alumina particles while copper turning back to pure Cu . Presence of alumina particles with sizes smaller than 50 nm was observed in TEM micrographs.
SYNTHESIS OF MONODISPERSE Mn3O4 NANOCRYSTALS
Authors: SALAVATI-NIASARI MASOUD , DAVAR FATEMEH
Published: November 2009

Mn3O4 nanocrystals have been prepared using [bis(2-hydroxyacetophenato)manganese(II)] as precursor. Transmission electron microscopy analysis demonstrated nanocrystals Mn3O4 with an average diameter of about 20 nm. The structural study by X-ray diffraction indicates that these nanocrystals have pure tetragonal phase. The phase pure samples were characterized using X-ray Photoelectron Spectroscopy for Mn 2p level. The values of binding energies are consistent with the relative values reported in the literature.
SYNTHESIS AND CHARACTERIZATION OF CARBON NANOTUBES REINFORCED POLYMER NANOCOMPOSITES
Authors: ETMAN MOHAMED A. , RASHAD R. M. , BEDEWY M. K.
Published: November 2009

An experimental program was designed to synthesize and characterize carbon nanotubes (CNTs) and CNTs reinforced polymeric matrix nanocomposites. PMMA, and PS, matrices were adopted for this investigation using different percents of CNTs loading of 0, 1, 3, and 5 and wt%. Morphological characterization was carried out using SEM, TEM, and TEDM microscopy. Mechanical properties were also measured to evaluate the enhancement effect of the CNTs loading percent. The results revealed a remarkable enhancement of the strength and ductility of the matrix material at 3 wt% of reasonably dispersed CNTs.
Life-Cycle Finance and the Design of Pension Plans
Authors: Bodie Zvi , Detemple Jérôme , Rindisbacher Marcel
Published: November 2009

This article reviews recent scientific literature on consumer financial decisions over the life cycle, outlining its implications for the design of pension plans. It begins with a review of advances in the theory of rational financial planning and wealth management. It then summarizes the recent empirical literature on the actual behavior of households regarding saving, investing, and insuring their consumption in old age. Finally, it briefly comments on the practical implications of the theory for the design of pension systems and outlines areas of future research.
Never Waste a Good Crisis: An Historical Perspective on Comparative Corporate Governance
Authors: Morck Randall , Yeung Bernard
Published: November 2009

Different economies at different times use different institutional arrangements to constrain the people entrusted with allocating capital and other resources. Comparative financial histories show these corporate governance regimes to be largely stable through time, but capable of occasional dramatic change in response to a severe crisis. Legal origin, language, culture, religion, accidents of history (path dependence), and other factors affect these changes because they affect how people and societies solve problems.
Volatility Derivatives
Authors: Carr Peter , Lee Roger
Published: November 2009

Volatility derivatives are a class of derivative securities where the payoff explicitly depends on some measure of the volatility of an underlying asset. Prominent examples of these derivatives include variance swaps and VIX futures and options. We provide an overview of the current market for these derivatives. We also survey the early literature on the subject. Finally, we provide relatively simple proofs of some fundamental results related to variance swaps and volatility swaps.
Financial Crises: Theory and Evidence
Authors: Allen Franklin , Babus Ana , Carletti Elena
Published: November 2009

Financial crises have occurred for many centuries. They are often preceded by a credit boom and a rise in real estate and other asset prices, as in the current crisis. They are also often associated with severe disruption in the real economy. This paper surveys the theoretical and empirical literature on crises. The first explanation of banking crises is that they are a panic. The second is that they are part of the business cycle. Modeling crises as a global game allows the two to be unified. With all the liquidity problems in interbank markets that have occurred during the current crisis, there is a growing literature on this topic. Perhaps the most serious market failure associated with crises is contagion, and there are many papers on this important topic. The relationship between asset price bubbles, particularly in real estate, and crises is discussed at length.
Estimating and Testing Continuous-Time Models in Finance: The Role of Transition Densities
Authors: Aït-Sahalia Yacine
Published: November 2009

This article surveys recent developments to estimate and test continuous-time models in finance using discrete observations on the underlying asset price or derivative securities' prices. Both parametric and nonparametric methods are described. All these methods share a common focus on the transition density as the central object for inference and testing of the model.
An Enjoyable Life Puzzling Over Modern Finance Theory
Authors: Samuelson Paul A.
Published: November 2009

This is a terse account of group creation of modern finance theory; and a sampling of my prosaic autobiographical investing and consulting for nonprofit academies. Eschewing 1900 Bachelier and 1905 Einstein white noise randomness, my martingale version of market micro efficiency invoked no violation of economic law. My attempts to establish pricing theory for options fell a bit short of the Black-Scholes-Merton Holy Grail. For life cycle investing, mathematicians’ maximum growth Kelly criterion was debunked, as were vulgar notions that necessarily riskiness is averaged downward for long-term investors. Popular Markowitz-Tobin quadratic programming was shown to hold generically only for smallest price variations or for unrealistic risk-aversion functions. Because economic history at best obeys only quasi-stationary probabilities, no sure-thing formulas will ever be definable. Excess returns—excess “alphas”—can result only from early new “insider” knowledge, however acquired—legally or illegally. Boo hoo.
What Decision Neuroscience Teaches Us About Financial Decision Making
Authors: Bossaerts Peter
Published: November 2009

Financial decision making is the outcome of complex neurophysiological processes involving, among others, constant re-evaluation of the statistics of the problem at hand, balancing of the various emotional aspects, and computation of the very value signals that are at the core of modern economic thinking. The evidence suggests that emotions play a crucial supporting role in the mathematical computations needed for reasoned choice, rather than interfering with it, even if emotions (and their mathematical counterparts) may not always be balanced appropriately. Decision neuroscience can be expected in the near future to provide a number of effective tools for improved financial decision making.
Predicting metabolic adaptation, body weight change, and energy intake in humans
Authors: Hall Kevin D.
Published: November 2009

Complex interactions between carbohydrate, fat, and protein metabolism underlie the body's remarkable ability to adapt to a variety of diets. But any imbalances between the intake and utilization rates of these macronutrients will result in changes in body weight and composition. Here, I present the first computational model that simulates how diet perturbations result in adaptations of fuel selection and energy expenditure that predict body weight and composition changes in both obese and nonobese men and women. No model parameters were adjusted to fit these data other than the initial conditions for each subject group (e.g., initial body weight and body fat mass). The model provides the first realistic simulations of how diet perturbations result in adaptations of whole body energy expenditure, fuel selection, and various metabolic fluxes that ultimately give rise to body weight change. The validated model was used to estimate free-living energy intake during a long-term weight loss intervention, a variable that has never previously been measured accurately.
Galois Field Instructions in the Sandblaster 2.0 Architectrue
Authors: Moudgill Mayan , Iancu Andrei , Iancu Daniel
Published: November 2009

This paper presents a novel approach to implementing multiplication of Galois Fields with . Elements of GF() can be represented as polynomials of degree less than N over GF(2). Operations are performed modulo an irreducible polynomial of degree n over GF(2). Our approach splits a Galois Field multiply into two operations, polynomial-multiply and polynomial-remainder over GF(2). We show how these two operations can be implemented using the same hardware. Further, we show that in many cases several polynomial-multiply operations can be combined before needing to a polynomial-remainder. The Sandblaster 2.0 is a SIMD architecture. It has SIMD variants of the poly-multiply and poly-remainder instructions. We use a Reed-Solomon encoder and decoder to demonstrate the performance of our approach. Our new approach achieves speedup of 11.5x compared to the standard SIMD processor of 8x.
Myelofibrosis-Associated Lymphoproliferative Disease: Retrospective Study of 16 Cases and Literature Review
Authors: Etienne A. , Gruson B. , Chatelain D. , Garidi R. , Royer B. , Sevestre H. , Marolleau J. P. , Damaj G.
Published: November 2009

Background. To better describe the clinical, biological, and the outcome of non-Hodgkin's lymphoma (NHL) with, at the initial presentation, bone marrow fibrosis (MF).Patients and Methods. From January 2001 to January 2007, 16 eligible patients with NHL and MF were retrieved from the Pathology Department of the University hospital of Amiens. Median age of patients was 62 years (range 16–74) with a sex ratio male/female of 3.Results. MF is associated with all types of lymphoma predominantly with B-cell phenotype and it seems to be more associated with low-grade NHL. B-symptoms are more frequent at diagnosis and more patients presented with an elevated LDH level. JAK-2 was negative in the 10 patients analysed. Two patients presented with features of primary MF with no evidence of lymphoma. Overall response rate was 94% after the first line of therapy with regression or improvement of MF. Relapse occurred in 8 patients (47%) with recurrence of MF in all of them. After a median follow-up of 42 months, 12 patients were alive with an overall survival rate for the entire group of 75%.Conclusions. MF-associated NHL is a rare manifestation which may be associated with all types of NHL and its presence does not seem to confer a poor prognosis. A search for lymphoproliferation should be considered when the cause of MF is not apparent.
Approximate Implicitization of Parametric Curves Using Cubic Algebraic Splines
Authors: Zhang Xiaolei , Wu Jinming
Published: November 2009

This paper presents an algorithm to solve the approximate implicitization of planar parametric curves using cubic algebraic splines. It applies piecewise cubic algebraic curves to give a global G2 continuity approximation to planar parametric curves. Approximation error on approximate implicitization of rational curves is given. Several examples are provided to prove that the proposed method is flexible and efficient.
Functional Dyes, and Some Hi‐Tech Applications
Authors: El-Shishtawy Reda M.
Published: November 2009

An overview of the recent developments in functional dyes, which are useful for hi‐tech applications for those based on optoelectronics, such as dye sensitized solar cells, photochromic dyes and biomedical applications, such as photodynamic therapy for the treatment of cancer and fluorescent sensors is presented.
Antifungal Activity of Selected IndigenousPseudomonasandBacillusfrom the Soybean Rhizosphere
Authors: León M. , Yaryura P. M. , Montecchia M. S. , Hernández A. I. , Correa O. S. , Pucheu N. L. , Kerber N. L. , García A. F.
Published: November 2009

The purpose of this study was to isolate and select indigenous soilPseudomonasandBacillusbacteria capable of developing multiple mechanisms of action related to the biocontrol of phytopathogenic fungi affecting soybean crops. The screening procedure consisted of antagonism tests against a panel of phytopathogenic fungi, taxonomic identification, detection by PCR of several genes related to antifungal activity, in vitro detection of the antifungal products, and root colonization assays. Two isolates, identified and designated asPseudomonas fluorescensBNM296 andBacillus amyloliquefaciensBNM340, were selected for further studies. These isolates protected plants against the damping-off caused byPythium ultimumand were able to increase the seedling emergence rate after inoculation of soybean seeds with each bacterium. Also, the shoot nitrogen content was higher in plants when seeds were inoculated with BNM296. The polyphasic approach of this work allowed us to select two indigenous bacterial strains that promoted the early development of soybean plants.
Presence of Autoimmune Antibody in Chikungunya Infection
Authors: Maek-a-nantawat Wirach , Silachamroon Udomsak
Published: November 2009

Chikungunya infection has recently re-emerged as an important arthropod-borne disease in Thailand. Recently, Southern Thailand was identified as a potentially endemic area for the chikungunya virus. Here, we report a case of severe musculoskeletal complication, presenting with muscle weakness and swelling of the limbs. During the investigation to exclude autoimmune muscular inflammation, high titers of antinuclear antibody were detected. This is the report of autoimmunity detection associated with an arbovirus infection. The symptoms can mimic autoimmune polymyositis disease, and the condition requires close monitoring before deciding to embark upon prolonged specific treatment with immunomodulators.
Mechanisms of the Regulation of the IntestinalNa+/H+Exchanger NHE3
Authors: He Peijian , Yun C. Chris
Published: November 2009

A major ofNa+absorptive process in the proximal part of intestine and kidney is electroneutral exchange ofNa+andH+byNa+/H+exchanger type 3 (NHE3). During the past decade, significant advance has been achieved in the mechanisms of NHE3 regulation. A bulk of the current knowledge onNa+/H+exchanger regulation is based on heterologous expression of mammalianNa+/H+exchangers inNa+/H+exchanger deficient fibroblasts, renal epithelial, and intestinal epithelial cells. Based on the reductionist's approach, an understanding of NHE3 regulation has been greatly advanced. More recently, confirmations of in vitro studies have been made using animals deficient in one or more proteins but in some cases unexpected findings have emerged. The purpose of this paper is to provide a brief overview of recent progress in the regulation and functions of NHE3 present in the luminal membrane of the intestinal tract.
Multicamera Real-Time 3D Modeling for Telepresence and Remote Collaboration
Authors: Petit Benjamin , Lesage Jean-Denis , Menier Clément , Allard Jérémie , Franco Jean-Sébastien , Raffin Bruno , Boyer Edmond , Faure François
Published: November 2009

We present a multicamera real-time 3D modeling system that aims at enabling new immersive and interactive environments. This system, called Grimage, allows to retrieve in real-time a 3D mesh of the observed scene as well as the associated textures. This information enables a strong visual presence of the user into virtual worlds. The 3D shape information is also used to compute collisions and reaction forces with virtual objects, enforcing the mechanical presence of the user in the virtual world. The innovation is a fully integrated system with both immersive and interactive capabilities. It embeds a parallel version of the EPVH modeling algorithm inside a distributed vision pipeline. It also adopts the hierarchical component approach of the FlowVR middleware to enforce software modularity and enable distributed executions. Results show high refresh rates and low latencies obtained by taking advantage of the I/O and computing resources of PC clusters. The applications we have developed demonstrate the quality of the visual and mechanical presence with a single platform and with a dual platform that allows telecollaboration.
The Core‐Cusp Problem
Authors: de Blok W. J. G.
Published: November 2009

This paper gives an overview of the attempts to determine the distribution of dark matter in low surface
brightness disk and gas‐rich dwarf galaxies, both through observations and computer simulations. Observations
seem to indicate an approximately constant dark matter density in the inner parts of galaxies, while
cosmological computer simulations indicate a steep power‐law‐like behaviour. This difference has become
known as the “core/cusp problem,” and it remains one of the unsolved problems in small‐scale cosmology.
Prognostic Significance of Growth Kinetics in Newly Diagnosed Glioblastomas Revealed by Combining Serial Imaging with a Novel Biomathematical Model
Authors: Wang Christina H. , Rockhill Jason K. , Mrugala Maciej , Peacock Danielle L. , Lai Albert , Jusenius Katy , Wardlaw Joanna M. , Cloughesy Timothy , Spence Alexander M. , Rockne Russ , Alvord Ellsworth C. , Swanson Kristin R.
Published: November 2009

Glioblastomas are the most aggressive primary brain tumors, characterized by their rapid proliferation and diffuse infiltration of the brain tissue. Survival patterns in patients with glioblastoma have been associated with a number of clinicopathologic factors including age and neurologic status, yet a significant quantitative link to in vivo growth kinetics of each glioma has remained elusive. Exploiting a recently developed tool for quantifying glioma net proliferation and invasion rates in individual patients using routinely available magnetic resonance images (MRI), we propose to link these patient-specific kinetic rates of biological aggressiveness to prognostic significance. Using our biologically based mathematical model for glioma growth and invasion, examination of serial pretreatment MRIs of 32 glioblastoma patients allowed quantification of these rates for each patient's tumor. Survival analyses revealed that even when controlling for standard clinical parameters (e.g., age and Karnofsky performance status), these model-defined parameters quantifying biological aggressiveness (net proliferation and invasion rates) were significantly associated with prognosis. One hypothesis generated was that the ratio of the actual survival time after whatever therapies were used to the duration of survival predicted (by the model) without any therapy would provide a therapeutic response index (TRI) of the overall effectiveness of the therapies. The TRI may provide important information, not otherwise available, about the effectiveness of the treatments in individual patients. To our knowledge, this is the first report indicating that dynamic insight from routinely obtained pretreatment imaging may be quantitatively useful in characterizing the survival of individual patients with glioblastoma. Such a hybrid tool bridging mathematical modeling and clinical imaging may allow for stratifying patients for clinical studies relative to their pretreatment biological aggressiveness. [Cancer Res 2009;69(23):9133–40]
In vivo Administration of Artificial Antigen-Presenting Cells Activates Low-Avidity T Cells for Treatment of Cancer
Authors: Ugel Stefano , Zoso Alessia , De Santo Carmela , Li Yu , Marigo Ilaria , Zanovello Paola , Scarselli Elisa , Cipriani Barbara , Oelke Mathias , Schneck Jonathan P. , Bronte Vincenzo
Published: November 2009

The development of effective antitumor immune responses is normally constrained by low-avidity, tumor-specific CTLs that are unable to eradicate the tumor. Strategies to rescue antitumor activity of low-avidity melanoma-specific CTLs in vivo may improve immunotherapy efficacy. To boost the in vivo effectiveness of low-avidity CTLs, we immunized mice bearing lung melanoma metastases with artificial antigen-presenting cells (aAPC), made by covalently coupling pepMHC-Ig dimers and B7.1-Ig molecules to magnetic beads. aAPC treatment induced significant tumor reduction in a mouse telomerase antigen system, and complete tumor eradication in a mouse TRP-2 antigen system, when low-avidity CTLs specific for these antigens were adoptively transferred. In addition, in an in vivo treatment model of subcutaneous melanoma, aAPC injection also augmented the activity of adoptively transferred CTLs and significantly delayed tumor growth. In vivo tumor clearance due to aAPC administration correlated with in situ proliferation of the transferred CTL. In vitro studies showed that aAPC effectively stimulated cytokine release, enhanced CTL-mediated lysis, and TCR downregulation in low-avidity CTLs. Therefore, in vivo aAPC administration represents a potentially novel approach to improve cancer immunotherapy. [Cancer Res 2009;69(24):9376–84]
Circulating Carotenoids, Mammographic Density, and Subsequent Risk of Breast Cancer
Authors: Tamimi Rulla M. , Colditz Graham A. , Hankinson Susan E.
Published: November 2009

Mammographic density is one of the strongest predictors of breast cancer risk. Recently, it has been suggested that reactive oxygen species may influence breast cancer risk through its influence on mammographic density. In the current study, we addressed this hypothesis and also assessed if the association between carotenoids and breast cancer risk varies by mammographic density. We conducted a nested case-control study consisting of 604 breast cancer cases and 626 controls with prospectively measured circulating carotenoid levels and mammographic density in the Nurses' Health Study. Circulating levels of α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein/zeaxanthin were measured. We used a computer-assisted thresholding method to measure percent mammographic density. We found no evidence that circulating carotenoids are inversely associated with mammographic density. However, mammographic density significantly modified the association between total circulating carotenoids and breast cancer (P heterogeneity = 0.008). Overall, circulating total carotenoids were inversely associated with breast cancer risk (P trend = 0.01). Among women in the highest tertile of mammographic density, total carotenoids were associated with a 50% reduction in breast cancer risk (odds ratio, 0.5; 95% confidence interval, 0.3–0.8). In contrast, there was no inverse association between carotenoids and breast cancer risk among women with low mammographic density. Similarly, among women in the highest tertile of mammographic density, high levels of circulating α-carotene, β-cryptoxanthin, lycopene, and lutein/zeaxanthin were associated with a significant 40% to 50% reduction in breast cancer risk (P trend < 0.05). Our results suggest that plasma levels of carotenoids may play a role in reducing breast cancer risk, particularly among women with high mammographic density. [Cancer Res 2009;69(24):9323–9]
Heat Shock Factor 1–Mediated Aneuploidy Requires a Defective Function of p53
Authors: Kim Eun-Ho , Lee Yoon-Jin , Bae Sangwoo , Lee Jae Seon , Kim Joon , Lee Yun-Sil
Published: November 2009

Because heat shock factor 1 (HSF1) phosphorylation by Plk1 has been previously reported to be involved in mitotic regulation and p53 function may be involved in this mitotic regulation, we have further examined HSF1 functions in mitotic regulation according to p53 status. Nocodazole-mediated aneuploidy was increased in p53-defective (p53Mut) cells; however, it was not increased in p53 wild-type (p53WT) cells. Phosphorylation of HSF1 at Ser216 was increased in p53Mut cells with increased stability of securin and cyclin B1 in mitosis compared with p53WT cells. The interaction of p53 with Plk1 that was shown in p53WT cells and that induced normal mitotic checkpoint function was not observed in p53Mut cells; instead, the binding of HSF1 with Plk1 and HSF1 phosphorylation at Ser216 were seen in p53Mut cells, which resulted in increased aneuploidy production. Moreover, the interaction affinity of Cdc20 with Mad2 was inhibited in p53Mut cells, whereas the interaction between Cdc20 and HSF1 was increased. From the data, it was suggested that HSF1-mediated aneuploidy was more facilitated in p53-defective cells, indicating the importance of novel mechanisms for p53 function in HSF1-mediated mitotic regulation and genomic instability. [Cancer Res 2009;69(24):9404–12]
Hypoxia-Regulated Delta-like 1 Homologue Enhances Cancer Cell Stemness and Tumorigenicity
Authors: Kim Yuri , Lin Qun , Zelterman Daniel , Yun Zhong
Published: November 2009

Reduced oxygenation, or hypoxia, inhibits differentiation and facilitates stem cell maintenance. Hypoxia commonly occurs in solid tumors and promotes malignant progression. Hypoxic tumors are aggressive and exhibit stem cell–like characteristics. It remains unclear, however, whether and how hypoxia regulates cancer cell differentiation and maintains cancer cell stemness. Here, we show that hypoxia increases the expression of the stem cell gene DLK1, or delta-like 1 homologue (Drosophila), in neuronal tumor cells. Inhibition of DLK1 enhances spontaneous differentiation, decreases clonogenicity, and reduces in vivo tumor growth. Overexpression of DLK1 inhibits differentiation and enhances tumorigenic potentials. We further show that the DLK1 cytoplasmic domain, especially Tyrosine339 and Serine355, is required for maintaining both clonogenicity and tumorigenicity. Because elevated DLK1 expression is found in many tumor types, our observations suggest that hypoxia and DLK1 may constitute an important stem cell pathway for the regulation of cancer stem cell–like functionality and tumorigenicity. [Cancer Res 2009;69(24):9271–80]
EZH2 Is Essential for Glioblastoma Cancer Stem Cell Maintenance
Authors: Suvà Mario-Luca , Riggi Nicolò , Janiszewska Michalina , Radovanovic Ivan , Provero Paolo , Stehle Jean-Christophe , Baumer Karine , Le Bitoux Marie-Aude , Marino Denis , Cironi Luisa , Marquez Victor E. , Clément Virginie , Stamenkovic Ivan
Published: November 2009

Overexpression of the polycomb group protein enhancer of zeste homologue 2 (EZH2) occurs in diverse malignancies, including prostate cancer, breast cancer, and glioblastoma multiforme (GBM). Based on its ability to modulate transcription of key genes implicated in cell cycle control, DNA repair, and cell differentiation, EZH2 is believed to play a crucial role in tissue-specific stem cell maintenance and tumor development. Here, we show that targeted pharmacologic disruption of EZH2 by the S-adenosylhomocysteine hydrolase inhibitor 3-deazaneplanocin A (DZNep), or its specific downregulation by short hairpin RNA (shRNA), strongly impairs GBM cancer stem cell (CSC) self-renewal in vitro and tumor-initiating capacity in vivo. Using genome-wide expression analysis of DZNep-treated GBM CSCs, we found the expression of c-myc, recently reported to be essential for GBM CSCs, to be strongly repressed upon EZH2 depletion. Specific shRNA-mediated downregulation of EZH2 in combination with chromatin immunoprecipitation experiments revealed that c-myc is a direct target of EZH2 in GBM CSCs. Taken together, our observations provide evidence that direct transcriptional regulation of c-myc by EZH2 may constitute a novel mechanism underlying GBM CSC maintenance and suggest that EZH2 may be a valuable new therapeutic target for GBM management. [Cancer Res 2009;69(24):9211–8]
Invasion of Human Breast Cancer Cells In vivo Requires Both Paracrine and Autocrine Loops Involving the Colony-Stimulating Factor-1 Receptor
Authors: Patsialou Antonia , Wyckoff Jeffrey , Wang Yarong , Goswami Sumanta , Stanley E. Richard , Condeelis John S.
Published: November 2009

Colony-stimulating factor-1 (CSF-1) and its receptor (CSF-1R) have been implicated in the pathogenesis and progression of various types of cancer, including breast cancer. This is based on high levels of circulating CSF-1 in patient sera with aggressive disease and increased CSF-1R staining in the tumor tissues. However, there have been no direct in vivo studies to determine whether a CSF-1 autocrine signaling loop functions in human breast cancer cells in vivo and whether it contributes to invasion. Recently, in mouse and rat models, it has been shown that invasion and metastasis are driven by an epidermal growth factor (EGF)/CSF-1 paracrine loop between tumor cells and host macrophages. In this macrophage-dependent invasion, tumor cells secrete CSF-1 and sense EGF, whereas the macrophages secrete EGF and sense CSF-1. Here, we test the hypothesis that in human breast tumors, the expression of both the CSF-1 ligand and its receptor in tumor cells leads to a CSF-1/CSF-1R autocrine loop which contributes to the aggressive phenotype of human breast tumors. Using MDA-MB-231 cell–derived mammary tumors in severe combined immunodeficiency mice, we show here for the first time in vivo that invasion in a human mammary tumor model is dependent on both paracrine signaling with host macrophages as well as autocrine signaling involving the tumor cells themselves. In particular, we show that the autocrine contribution to invasion is specifically amplified in vivo through a tumor microenvironment–induced upregulation of CSF-1R expression via the transforming growth factor-β1. [Cancer Res 2009;69(24):9498–506]
Activating Peroxisome Proliferator-Activated Receptor γ Mutant Promotes Tumor Growth In vivo by Enhancing Angiogenesis
Authors: Tian Lifeng , Zhou Jie , Casimiro Mathew C. , Liang Bing , Ojeifo John O. , Wang Min , Hyslop Terry , Wang Chenguang , Pestell Richard G.
Published: November 2009

Peroxisome proliferator-activated receptor γ (PPARγ) is expressed in a variety of cancer cells. The addition of ligand activates the receptor by inducing a conformational change in the receptor, which can be recapitulated by mutation. To investigate the role of activated PPARγ signaling in breast cancer, we compared the function of a constitutively active PPARγ (PγCA) mutant with the wild-type PPARγ in ErbB2-induced mammary tumorigenesis in vivo. Tumor cells transduced with either PPARγ or PγCA were implanted into immunocompetent FVB mice. Enhanced tumor growth was observed in PγCA-transduced cells, which was associated with increased angiogenesis and endothelial stem cells as evidenced by increased number of cells stained with von Willebrand factor, c-Kit, CD133, and CD31. Genome-wide expression profiling identified a group of genes within the angiogenesis pathway, including Angptl4, as targets of activated PPARγ; PγCA also induced Angptl4 protein secretion in ErbB2-transformed mammary epithelial cells. Angptl4 promoted vascular endothelial cell migration; conversely, immunodepletion of Angptl4 reduced PγCA-mediated cellular migration. Collectively, these studies suggest that activated PPARγ induces Angptl4 to promote tumor growth through enhanced angiogenesis in vivo. [Cancer Res 2009;69(24):9236–44]
Disruption of Sphingosine 1-Phosphate Lyase Confers Resistance to Chemotherapy and Promotes Oncogenesis through Bcl-2/Bcl-xL Upregulation
Authors: Colié Sandra , Van Veldhoven Paul P. , Kedjouar Blandine , Bedia Carmen , Albinet Virginie , Sorli Sonia-Caroline , Garcia Virginie , Djavaheri-Mergny Mojgan , Bauvy Chantal , Codogno Patrice , Levade Thierry , Andrieu-Abadie Nathalie
Published: November 2009

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in cancer development through stimulation of cell survival, proliferation, migration, and angiogenesis. Irreversible degradation of S1P is catalyzed by S1P lyase (SPL). The human SGPL1 gene that encodes SPL maps to a region often mutated in cancers. To investigate the effect of SPL deficiency on cell survival and transformation, the susceptibility to anticancer drugs of fibroblasts generated from SPL-deficient mouse embryos (Sgpl1−/−) was compared with that of cells from heterozygous (Sgpl1+/−) or wild-type (Sgpl1+/+) embryos. First, loss of SPL caused resistance to the toxic effects of etoposide and doxorubicin. Interestingly, heterozygosity for the Sgpl1 gene resulted in partial resistance to apoptosis. Secondly, doxorubicin-induced apoptotic signaling was strongly inhibited in Sgpl1−/− cells (phosphatidylserine externalization, caspase activation, and cytochrome c release). This was accompanied by a strong increase in Bcl-2 and Bcl-xL protein content. Whereas correction of SPL deficiency in Sgpl1−/− cells led to downregulation of antiapoptotic proteins, Bcl-2 and Bcl-xL small interfering RNA–mediated knockdown in SPL-deficient cells resulted in increased sensitivity to doxorubicin, suggesting that Bcl-2 upregulation mediates SPL protective effects. Moreover, SPL deficiency led to increased cell proliferation, anchorage-independent cell growth, and formation of tumors in nude mice. Finally, transcriptomic studies showed that SPL expression is downregulated in human melanoma cell lines. Thus, by affecting S1P metabolism and the expression of Bcl-2 members, the loss of SPL enhances cell resistance to anticancer regimens and results in an increased ability of cells to acquire a transformed phenotype and become malignant. [Cancer Res 2009;69(24):9346–53]
Natural Sphingadienes Inhibit Akt-Dependent Signaling and Prevent Intestinal Tumorigenesis
Authors: Fyrst Henrik , Oskouian Babak , Bandhuvula Padmavathi , Gong Yaqiong , Byun Hoe Sup , Bittman Robert , Lee Andrew R. , Saba Julie D.
Published: November 2009

Sphingolipid metabolites regulate cell proliferation, migration, and stress responses. Alterations in sphingolipid metabolism have been proposed to contribute to carcinogenesis, cancer progression, and drug resistance. We identified a family of natural sphingolipids called sphingadienes and investigated their effects in colon cancer. We find that sphingadienes induce colon cancer cell death in vitro and prevent intestinal tumorigenesis in vivo. Sphingadienes exert their influence by blocking Akt translocation from the cytosol to the membrane, thereby inhibiting protein translation and promoting apoptosis and autophagy. Sphingadienes are orally available, are slowly metabolized through the sphingolipid degradative pathway, and show limited short-term toxicity. Thus, sphingadienes represent a new class of therapeutic and/or chemopreventive agents that blocks Akt signaling in neoplastic and preneoplastic cells. [Cancer Res 2009;69(24):9457–64]