bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs
Authors: Von Klopmann T. , Rambeck B. , Tipold A.
Published: February 2007

Objectives: Investigation of the efficacy of zonisamide as an add‐on therapy in dogs with refractory epilepsy.

Methods: Thirteen dogs fulfilled the inclusion criteria of poor seizure control despite adequate serum levels of phenobarbital, potassium bromide or both. One further dog was treated with zonisamide as monotherapy because of severe blood dyscrasia due to phenobarbital treatment. Various seizure parameters were evaluated retrospectively for a four month period without zonisamide and prospectively for the same time period under zonisamide add‐on therapy. The study time period was extended by up to 17 months to evaluate long‐term outcome.

Results: Data of 11 dogs could be evaluated: nine of them were responders. The median reduction of seizure frequency of all dogs on zonisamide add‐on therapy was 70 per cent (range 14 to 100 per cent). Only transient central nervous system side effects were reported. No further increase of liver enzymes occurred. In three of the responder dogs, seizure control subsided after individual time periods (between 69 days and seven months).

Clinical Significance: In dogs with refractory epilepsy, zonisamide may have a beneficial effect on seizure control. In three responder dogs, seizure activity relapsed possibly because of an induction of tolerance. Limiting factors are the high costs.
China's State Security in a Time of Peaceful Development: A New Issue on Research Agenda
Authors: Wang Yizhou
Published: February 2007

This paper holds that China's national security during its peaceful rise is a new issue on the research agenda, which requires new counter‐measures and collective wisdom. The paper discusses five of China's objectives in addressing national security; namely, from highest to lowest priority, friction among big powers, the Taiwan issue, disputes over sovereignty, protection of interests overseas, and undertaking international responsibilities. Systematically achieving these objectives is of major importance for building up national defence and China's international image. China's state security in the current period of peaceful development is a new issue on the research agendum, for politicians, the military, scholars and researchers alike. Extensive and in‐depth discussion is needed. Global security commitments made by a big power might conflict with its own security interests and objectives. Judging by any standard, China's tasks are heavy and the road ahead is long.

(Edited by Xinyu Fan)
Benchmarking BrachyDose: Voxel based EGSnrc Monte Carlo calculations of TG‐43 dosimetry parameters
Authors: Taylor R. E. P. , Yegin G. , Rogers D. W. O.
Published: February 2007

In this study, BrachyDose, a recently developed EGSnrc Monte Carlo code for rapid brachytherapy dose calculations, has been benchmarked by reproducing previously published dosimetry parameters for three brachytherapy seeds with varied internal structure and encapsulation. Calculations are performed for two seeds (Source Tech Medical Model STM1251 and Imagyn isoSTAR model 12501) and one source (Theragenics Model 200). Voxel size effects were investigated with dose distribution calculations for three voxel sizes: , , and . In order to minimize the impact of voxel size effects, tabulated dosimetry data for this study consist of a combination of the three calculations: voxels for distances in the range of , voxels for and voxels for . Dosimetry parameters from this study are compared with values calculated by other authors using Williamson's PTRAN code and to measured values. Overall, calculations made with Brachydose show good agreement with calculations made with PTRAN although there are some exceptions.
Complexity curve and grey level co‐occurrence matrix in the texture evaluation of breast tumor on ultrasound images
Authors: Alvarenga André Victor , Pereira Wagner C. A. , Infantosi Antonio Fernando C. , Azevedo Carolina M.
Published: February 2007

This work aims at investigating texture parameters in distinguishing malign and benign breast tumors on ultrasound images. A rectangular region of interest (ROI) containing the tumor and its neighboring was defined for each image. Five parameters were extracted from the complexity curve (CC) of the ROI. Another five parameters were calculated from the grey‐level co‐occurrence matrix (GLCM) also for the ROI. The same was carried out for internal tumor region, hence, totaling 20 parameters. The linear discriminant analysis was applied to sets of up to five parameters and then the performances were assessed. The most relevant individual parameters were the contrast (con) (from the GLCM over the ROI) and the maximum value from the CC just for the tumor internal region). When they were taken together, a correct classification slightly over 80% of the breast tumors was achieved. The highest performance (, , and ) was obtained with , con, the standard deviation of the pixel pairs and the entropy, both for GLCM, and the internal region contrast also from GLCM. Parameters extracted from the internal region generally performed better and were more significant than those from the ROI. Moreover, parameters calculated only from CC or GLCM resulted in no statistically significant performance difference. These findings suggest that the texture parameters can be useful to help radiologist in distinguishing between benign or malign breast tumors on ultrasound images.
Technical note: Overprediction of dose with default PRESTA‐I boundary crossing in DOSXYZnrc and BEAMnrc
Authors: Walters B. R. B. , Kawrakow I.
Published: February 2007

Use of the PRESTA‐I (current default) boundary crossing algorithm for charged particles in DOSXYZnrc and BEAMnrc is shown to result in dose overprediction by up to 2.5% in photon and electron beams (less in high‐energy electron beams). The effect is most pronounced when charged particle equilibrium does not exist or when the phantom is not divided into uniform voxels throughout. As a result, the default boundary crossing algorithm in BEAMnrc will be changed to “exact” (single scattering).
Radiation attenuation by lead and nonlead materials used in radiation shielding garments
Authors: McCaffrey J. P. , Shen H. , Downton B. , Mainegra‐Hing E.
Published: February 2007

The attenuating properties of several types of lead (Pb)‐based and non‐Pb radiation shielding materials were studied and a correlation was made of radiation attenuation, materials properties, calculated spectra and ambient dose equivalent. Utilizing the well‐characterized x‐ray and gamma ray beams at the National Research Council of Canada, air kerma measurements were used to compare a variety of commercial and pre‐commercial radiation shielding materials over mean energy ranges from 39 to . The EGSnrc Monte Carlo user code, cavity.cpp was extended to provide computed spectra for a variety of elements that have been used as a replacement for Pb in radiation shielding garments. Computed air kerma values were compared with experimental values and with the SRS‐30 catalogue of diagnostic spectra available through the Institute of Physics and Engineering in Medicine Report 78. In addition to garment materials, measurements also included pure Pb sheets, allowing direct comparisons to the common industry standards of 0.25 and “lead equivalent.” The parameter “lead equivalent” is misleading, since photon attenuation properties for all materials (including Pb) vary significantly over the energy spectrum, with the largest variations occurring in the diagnostic imaging range. Furthermore, air kerma measurements are typically made to determine attenuation properties without reference to the measures of biological damage such as ambient dose equivalent, which also vary significantly with air kerma over the diagnostic imaging energy range. A single material or combination cannot provide optimum shielding for all energy ranges. However, appropriate choice of materials for a particular energy range can offer significantly improved shielding per unit mass over traditional Pb‐based materials.
Estimation of the focal spot size and shape for a medical linear accelerator by Monte Carlo simulation
Authors: Wang Lilie L. W. , Leszczynski Konrad
Published: February 2007

The focal spot size and shape of a medical linac are important parameters that determine the dose profiles, especially in the penumbral region. A relationship between the focal spot size and the dose profile penumbra has been studied and established from simulation results of the EGSnrc Monte Carlo code. A simple method is proposed to estimate the size and the shape of a linac's focal spot from the measured dose profile data.
Patient dose and image quality from mega‐voltage cone beam computed tomography imaging
Authors: Gayou Olivier , Parda David S. , Johnson Mark , Miften Moyed
Published: February 2007

The evolution of ever more conformal radiation delivery techniques makes the subject of accurate localization of increasing importance in radiotherapy. Several systems can be utilized including kilo‐voltage and mega‐voltage cone‐beam computed tomography (MV‐CBCT), CT on rail or helical tomography. One of the attractive aspects of mega‐voltage cone‐beam CT is that it uses the therapy beam along with an electronic portal imaging device to image the patient prior to the delivery of treatment. However, the use of a photon beam energy in the mega‐voltage range for volumetric imaging degrades the image quality and increases the patient radiation dose. To optimize image quality and patient dose in MV‐CBCT imaging procedures, a series of dose measurements in cylindrical and anthropomorphic phantoms using an ionization chamber, radiographic films, and thermoluminescent dosimeters was performed. Furthermore, the dependence of the contrast to noise ratio and spatial resolution of the image upon the dose delivered for a cylindrical phantom was evaluated. Depending on the anatomical site and patient thickness, we found that the minimum dose deposited in the irradiated volume was and the maximum dose was between 9 and for our clinical MV‐CBCT imaging protocols. Results also demonstrated that for high contrast areas such as bony anatomy, low doses are sufficient for image registration and visualization of the three‐dimensional boundaries between soft tissue and bony structures. However, as the difference in tissue density decreased, the dose required to identify soft tissue boundaries increased. Finally, the dose delivered by MV‐CBCT was simulated using a treatment planning system (TPS), thereby allowing the incorporation of MV‐CBCT dose in the treatment planning process. The TPS‐calculated doses agreed well with measurements for a wide range of imaging protocols.
Novel approach to evaluating breast density utilizing ultrasound tomography
Authors: Glide Carri , Duric Nebojsa , Littrup Peter
Published: February 2007

Women with high mammographic breast density have a four‐ to fivefold increased risk of developing breast cancer compared to women with fatty breasts. Many preventative strategies have attempted to correlate changes in breast density with response to interventions including drugs and diet. The purpose of this work is to investigate the feasibility of assessing breast density with acoustic velocity measurements with ultrasound tomography, and to compare the results with existing measures of mammographic breast density. An anthropomorphic breast tissue phantom was first imaged with our computed ultrasound tomography clinical prototype. Strong positive correlations were observed between sound speed and material density, and sound speed and computed tomography number (Pearson correlation and 0.91, respectively). A cohort of 48 women was then imaged. Whole breast acoustic velocity was determined by creating image stacks and evaluating the sound speed frequency distribution. The acoustic measures of breast density were evaluated by comparing these results to two mammographic density measures: (1) qualitative estimates determined by a certified radiologist using the BI‐RADS Categorical Assessment based on a 1 (fatty) to 4 (dense) scale, and (2) quantitative measurements via digitization and computerized analysis of archival mammograms. A one‐way analysis of variance showed that a significant difference existed between the mean values of sound speed according to BI‐RADS category, while post hoc analyses using the Scheffé criterion for significance indicated that BI‐RADS 4 (dense) patients had a significantly higher sound speed than BI‐RADS 1, 2, and 3 at an alpha level of 0.05. Using quantitative measures of breast density, a direct correlation between the mean acoustic velocity and calculated mammographic percent breast density was demonstrated with correlation coefficients ranging from 0.75 to 0.89. The results presented here support the hypothesis that sound speed can be used as an indicator of breast tissue density. Noninvasive, nonionizing monitoring of dietary and chemoprevention interventions that affect breast density are now possible.
The prediction of radiation‐induced liver dysfunction using a local dose and regional venous perfusion model
Authors: Cao Yue , Platt Joel F. , Francis Isaac R , Balter James M. , Pan Charlie , Normolle Daniel , Ben‐Josef Edgar , Ten Haken Randall K. , Lawrence Theodore S.
Published: February 2007

We have shown that high dose conformal radiation combined with chemotherapy appears to prolong the survival of patients with unresectable intrahepatic cancers. The ability to safely deliver higher doses is primarily limited by the development of radiation‐induced liver disease, characterized by venous occlusion. In this study, we investigated whether portal venous perfusion measured prior to the end of radiation therapy (RT) together with dose could predict liver venous perfusion dysfunction after treatment. Ten patients with unresectable intrahepatic cancer participated in an IRB‐approved computer tomography (CT) perfusion study. Hepatic arterial and portal vein perfusion distributions were estimated by using dynamic contrast enhanced CT and the single compartmental model. Scans were obtained at four time points: prior to treatment, after 15 and 30 fractions of treatments, and one month following the completion of RT. Multivariant linear regression was used to determine covariances among the first three time point measurements plus dose for prediction of the post RT measurement. The reduction in the regional venous perfusion one month following RT was predicted by the local accumulated dose and the change in the regional venous perfusion after fractions . Each Gy produced an approximately 1.2% of reduction in the venous perfusion. This local dose and venous perfusion model has the potential to predict individual sensitivity to radiation. This is the first step toward developing a method to deliver higher and potentially more curative radiation doses to the patients who can safely receive these higher doses.
Energy optimization procedure for treatment planning with laser‐accelerated protons
Authors: Fourkal E. , Velchev I. , Fan J. , Luo W. , Ma C.‐M.
Published: February 2007

A simple analytical model is found that predicts the exact proton spectrum needed to obtain a spread‐out‐Bragg peak (SOBP) distribution for laser‐accelerated proton beams. The theory is based on the solution to the Boltzmann kinetic equation for the proton distribution function. The resulting analytical expression allows one to calculate the SOBP proton energy spectra for the different beamlet sizes and modulation depths that can be readily implemented in the calculation of energy and intensity modulated proton dose distributions. Since the practical implementation of energy modulation for proton beams is realized through the discrete superposition of individual Bragg peaks, it is shown that there exists an optimal relationship between the energy sampling size and the width of the initial proton energy distribution.
Brachytherapy dosimetry parameters calculated for a source
Authors: Rivard Mark J.
Published: February 2007

A comprehensive analysis of the IsoRay Medical model CS‐1 Rev2 brachytherapy source was performed. Dose distributions were simulated using Monte Carlo methods (MCNP5) in liquid water, Solid Water™, and Virtual Water™ spherical phantoms. From these results, the in‐water brachytherapy dosimetry parameters have been determined, and were compared with those of Murphy et al. [Med. Phys. 31, 1529–1538 (2004)] using measurements and simulations. Our results suggest that calculations obtained using erroneous cross‐section libraries should be discarded as recommended by the 2004 AAPM TG‐43U1 report. Our value of is within 1.3% of that measured by Chen et al. [Med. Phys. 32, 3279–3285 (2005)] using TLDs and the calculated results of Wittman and Fisher [Med. Phys., 49–54 (2007)] using MCNP5. Using the discretized energy approach of Rivard [Appl. Radiat. Isot. 55, 775–782 (2001)] to ascertain the impact of individual photons on radial dose function and anisotropy functions, there was virtual equivalence of results for and for a mono‐energetic photon source. Comparisons of radial dose function and 2D anisotropy function data are also included, and an analysis of material composition and cross‐section libraries was performed.
Compartmental Pharmacokinetic Analysis of Oral Amprenavir with Secondary Peaks
Authors: Okusanya Olanrewaju , Forrest Alan , DiFrancesco Robin , Bilic Sanela , Rosenkranz Susan , Para Michael F. , Adams Elizabeth , Yarasheski Kevin E. , Reichman Richard C. , Morse Gene D.
Published: February 2007

Amprenavir is a protease inhibitor that has been shown to have secondary peaks postulated to be due to enterohepatic recycling. We propose a model to describe the pharmacokinetics of amprenavir which accommodates the secondary peak(s). A total of 82 healthy human immunodeficiency virus (HIV)-seronegative subjects were administered a single 600-mg dose of amprenavir as part of adult AIDS Clinical Trials Group protocol A5043. Serial blood samples were obtained over 24 h. Samples were analyzed for amprenavir and fit to a compartmental model using ADAPT II software, with all relevant parameters conditional with respect to bioavailability. The model accommodated secondary peaks by incorporating clearance out of the central compartment with delayed instantaneous release back into the gut compartment. The data were weighted by the inverse of the estimated measurement error variance; model discrimination was determined using Akaike's Information Criteria. A total of 76 subjects were evaluable in the study analysis. The data were best fit by a two-compartment model, with 98.7% of the subjects demonstrating a secondary peak. Amprenavir had a mean total clearance of 1.163 liters/h/kg of body weight (0.7), a central volume of distribution of 1.208 liters/kg (0.8), a peripheral volume of distribution of 8.2 liters/kg (0.81), and distributional clearance of 0.04 liters/h/kg (0.81). The time to the secondary peak was 7.86 h (0.17), and clearance into a recycling compartment was 0.111 liters/kg/h (0.74). Amprenavir pharmacokinetics has been well described using a two-compartment model with clearance to a recycling compartment and release back into the gut. The nature of the secondary peaks may be an important consideration for the interpretation of amprenavir plasma concentrations during therapeutic drug monitoring.
Fluoroquinolone Resistance in
Haemophilus influenzae
Is Associated with Hypermutability
Authors: Pérez-Vázquez María , Román Federico , García-Cobos Silvia , Campos José
Published: February 2007

Forty-three percent (12/28) of ciprofloxacin (CIP)-nonsusceptible respiratory isolates of
Haemophilus influenzae
were hypermutable, compared with 8.5% (3/35) in the CIP-susceptible control group (
P
= 0.002). CIP-nonsusceptible mutants were obtained with hypermutable strains only; these mutants developed three resistance mechanisms in a step-by-step process: target modifications, loss of a porin protein, and increased efflux.
Screening of an Antigen Target for Immunocontraceptives from Cross-Reactive Antigens between Human Sperm andUreaplasma urealyticum
Authors: Shi Jianli , Yang Zhengmin , Wang Min , Cheng Guoyan , Li Ding , Wang Yifei , Zhou Yuancong , Liu Xiaolong , Xu Chen
Published: February 2007

Epidemiologic studies indicated that some infertile men who were infected withUreaplasma urealyticumdisplayed positive antisperm antibodies in their serum and/or semen. The purpose of this study was to investigate the possible mechanism of antisperm antibodies production after infection withU. urealyticumand to analyze the relationship betweenU. urealyticumand infertility. The existence of cross-reactive antigens (61, 50, and 25 kDa) betweenU. urealyticumand human sperm membrane proteins was confirmed. Among the cross-reactive antigens, the urease complex component UreG ofU. urealyticumwas determined. By searching the Swiss-Prot protein database, a pentapeptide identity (IERLT) between UreG and human nuclear autoantigenic sperm protein (NASP) was found. Furthermore, using Western blot analysis and enzyme-linked immunosorbent assay, the cross-reaction between the NASP and UreG was verified. Both anti-rUreG antibody and the antiserum against the synthetic peptide NASP393-408 containing the pentapeptide inhibited mouse sperm egg binding and fusion. After immunization by rUreG or the synthetic peptide, 81.2 and 75% female mice became sterile, respectively. The effect on fertility in mice immunized with the synthetic peptide was reversible. These findings proved for the first time that it was feasible to screen antigens for immunocontraceptives from cross-reactive antigens between sperm and microorganisms which induce infertility.
The Genome of Non-O1
Vibrio cholerae
NRT36S Demonstrates the Presence of Pathogenic Mechanisms That Are Distinct from Those of O1
Vibrio cholerae
Authors: Chen Yuansha , Johnson Judith A. , Pusch Gordon D. , Morris J. Glenn , Stine O. Colin
Published: February 2007

Vibrio cholerae
NRT36S is a non-cholera toxin-producing, non-O1 strain that causes diarrhea in volunteers. The genome of NRT36S was sequenced to create a draft containing 174 contigs plus the superintegron region. Our analysis of the draft genome revealed several putative toxin genes and colonization factors. Besides confirming the existence of nonagglutinable heat-stable toxin, we also identified the genes for a type three secretion system, a putative exotoxin, two different RTX toxins, and four pilus systems.
Blind Identification of FIR Channels in the Presence of Unknown Noise
Authors: He Xiaojuan , Wong Kon Max
Published: February 2007

Blind channel identification techniques based on second-order statistics (SOS) of the received data have been a topic of active research in recent years. Among the most popular is the subspace method (SS) proposed by Moulines et al. (1995). It has good performance when the channel output is corrupted by white noise. However, when the channel noise is correlated and unknown as is often encountered in practice, the performance of the SS method degrades severely. In this paper, we address the problem of estimating FIR channels in the presence of arbitrarily correlated noise whose covariance matrix is unknown. We propose several algorithms according to the different available system resources: (1) when only one receiving antenna is available, by upsampling the output, we develop the maximum a posteriori (MAP) algorithm for which a simple criterion is obtained and an efficient implementation algorithm is developed; (2) when two receiving antennae are available, by upsampling both the outputs and utilizing canonical correlation decomposition (CCD) to obtain the subspaces, we present two algorithms (CCD-SS and CCD-ML) to blindly estimate the channels. Our algorithms perform well in unknown noise environment and outperform existing methods proposed for similar scenarios.
Decision Analysis via Granulation Based on General Binary Relation
Authors: Abd El-Monsef M. M. E. , Kilany N. M.
Published: February 2007

Decision theory considers how best to make decisions in the light of uncertainty about data. There are several methodologies that may be used to determine the best decision. In rough set theory, the classification of objects according to approximation operators can be fitted into the Bayesian decision-theoretic model, with respect to three regions (positive, negative, and boundary region). Granulation using equivalence classes is a restriction that limits the decision makers. In this paper, we introduce a generalization and modification of decision-theoretic rough set model by using granular computing on general binary relations. We obtain two new types of approximation that enable us to classify the objects into five regions instead of three regions. The classification of decision region into five areas will enlarge the range of choice for decision makers.
Block Iterative Methods for a Finite Family of Relatively Nonexpansive Mappings in Banach Spaces
Authors: Kohsaka Fumiaki , Takahashi Wataru
Published: February 2007

Using the convex combination based on Bregman distances due to Censor and Reich, we define an operator from a given family of relatively nonexpansive mappings in a Banach space. We first prove that the fixed-point set of this operator is identical to the set of all common fixed points of the mappings. Next, using this operator, we construct an iterative sequence to approximate common fixed points of the family. We finally apply our results to a convex feasibility problem in Banach spaces.
An Iteration Method for Nonexpansive Mappings in Hilbert Spaces
Authors: Wang Lin
Published: February 2007

In real Hilbert space "Equation missing", from an arbitrary initial point "Equation missing", an explicit iteration scheme is defined as follows: "Equation missing", where "Equation missing", "Equation missing" is a nonexpansive mapping such that "Equation missing" is nonempty, "Equation missing" is a "Equation missing"-strongly monotone and "Equation missing"-Lipschitzian mapping, "Equation missing", and "Equation missing". Under some suitable conditions, the sequence "Equation missing" is shown to converge strongly to a fixed point of "Equation missing" and the necessary and sufficient conditions that "Equation missing" converges strongly to a fixed point of "Equation missing" are obtained.
Selective Modulators of PPAR-γActivity: Molecular Aspects Related to Obesity and Side-Effects
Authors: Zhang Fang , Lavan Brian E. , Gregoire Francine M.
Published: February 2007

Peroxisome proliferator-activated receptorγ(PPAR-γ) is a key regulator of lipid metabolism and energy balance implicated in the development of insulin resistance and obesity. The identification of putative natural and synthetic ligands and activators of PPAR-γhas helped to unravel the molecular basis of its function, including molecular details regarding ligand binding, conformational changes of the receptor, and cofactor binding, leading to the emergence of the concept of selective PPAR-γmodulators (SPPARγMs). SPPARγMs bind in distinct manners to the ligand-binding pocket of PPAR-γ, leading to alternative receptor conformations, differential cofactor recruitment/displacement, differential gene expression, and ultimately differential biological responses. Based on this concept, new and improved antidiabetic agents for the treatment of diabetes are in development. This review summarizes the current knowledge on the mechanism of action and biological effects of recently characterized SPPARγMs, including metaglidasen/halofenate, PA-082, and the angiotensin receptor antagonists, recently characterized as a new class of SPPARγMs.
Hereditary Portfolio Optimization with Taxes and Fixed Plus Proportional Transaction Costs—Part II
Authors: Chang Mou-Hsiung
Published: February 2007

This paper is the continuation of the paper entitled “Hereditary portfolio optimization with taxes and fixed plus proportional transaction costs I” that treats an
infinite-time horizon hereditary portfolio optimization problem in a market
that consists of one savings account and one stock account. Within the solvency region, the investor is allowed to consume from the savings account and can make transactions between the two assets subject to paying capital-gain taxes as well as a fixed plus proportional transaction cost. The investor is to seek an optimal consumption-trading strategy in order to maximize the expected utility from the total discounted consumption.
The portfolio optimization problem is formulated as an infinite dimensional
stochastic classical impulse control problem due to the hereditary nature
of the stock price dynamics and inventories. This paper
contains the verification theorem for the optimal strategy. It also proves
that the value function is a viscosity solution of the QVHJBI.
Influence of Lanthanide(III) Ions on the Reaction System Tryptophan—H2O2–Fe(II)
Authors: Kaczmarek M. , Lis S.
Published: February 2007

Chemiluminescence (CL) studies were carried out with luminescent lanthanide ions as probes to a tryptophan-oxidation reaction at pH∼6. The redox system consisted of tryptophan, hydrogen peroxide, and Fe(II) ions (catalysts ofH2O2decomposition). The luminescent lanthanide(III) ions used were Eu(III), Tb(III), Gd(III), and Dy(III). In the case of the reaction system with the Tb(III) ion a significant increase in the chemiluminescence intensity and its duration was observed over the other Ln(III) ions. The CL spectrum registered for this system shows emission bands typical of Tb(III) ions with maxima atλ∼490 and 550 nm, corresponding to the electronic transitions of5D4→7F6and5D4→7F5, respectively. The presence of emission bands characteristic of the Ln(III) ions was also observed in the systems containing Eu(III) and Dy(III) ions. These studies revealed a strong influence of the chemiluminescence intensity associated with the tryptophan oxidation, on the concentration of Ln(III) ions. On the basis of the results obtained, a possible mechanism is proposed for reaction of the systemml: Ln(III)—tryptophan—H2O2–Fe(II), taking into consideration an energy transfer process from the tryptophan oxidation products to the Tb(III), Dy(III), or Eu(III) ions.
Protein Coevolution and Isoexpression in Yeast Macromolecular Complexes
Authors: Ettwiller Laurence , Veitia Reiner A.
Published: February 2007

Previous studies in the yeastSaccharomyces cerevisiaehave shown that genes encoding subunits of macromolecular complexes have similar evolutionary rates (K) and expression levels (E). Besides, it is known that the expression of a gene is a strong predictor of its rate of evolution (i.e., E and K are correlated). Here we show that intracomplex variation of subunit expression correlates with intracomplex variation of their evolutionary rates (using two different measures of dispersion). However, a similar trend was observed for randomized complexes. Therefore, using a mathematical transformation, we created new variables capturing intracomplex variation of both E and K. The values of these new compound variables were smaller for real complexes than for randomized ones. This shows that proteins in complexes tend to have closer expressivities (E) and K's simultaneously than in the randomly grouped genes. We speculate about the possible implications of this finding.
Extensions of Some Parametric Families ofD(16)-Triples
Authors: Filipin Alan
Published: February 2007

Letnbe an integer. A set ofmpositive integers is called aD(n)-m-tuple if the product of any two of them increased bynis a perfect square. In this paper, we consider extensions of some parametric families ofD(16)-triples. We prove that if{k−4,k+4,4k,d},fork≥5,is aD(16)-quadruple, thend=k3−4k. Furthermore, if{k−4,4k,9k−12}, fork>5, is aD(16)-quadruple, thend=9k3−48k2+76k−32. But fork=5, this statement is not valid. Namely, theD(16)-triple{1,20,33}has exactly two extensions to aD(16)-quadruple:{1,20,33,105}and{1,20,33,273}.
Love and Rayleigh Correction Terms and Padé Approximants
Authors: Andrianov I. , Awrejcewicz J.
Published: February 2007

Simplified theories governing behavior of beams and plates keeping the fundamental characteristics of the being modeled objects are proposed and discussed. By simplification, we mean decrease of order of partial differential equations (PDEs) with respect to spatial coordinates. Our approach is used for both discrete and continuous models. An advantage of Padé approximation is addressed. First part of this report deals with approximation of a beam equation by string-like one, and plate equation by membrane-like one. Second part is devoted to the construction of Love-type theory for rods vibrations and Rayleigh-type theory for beams vibrations.
Bounds on coefficients of reciprocals of formal power series with rapidly decreasing coefficients
Authors: Berenhaut Kenneth S. , Allen Edward E. , Fraser Sam J.
Published: February 2007

This paper studies reciprocals of formal power series whose coefficients
are monotone and bounded by a geometrically decaying sequence. Explicit
and applicable, optimal decay rates are provided for the coefficients of the reciprocal
series in terms of the parameters of the geometric bound. The results imply a
best possible lower bound on the zeros of the series being considered.
On (s, S) inventory system with random lead time and repeateddemands
Authors: Ushakumari P. V.
Published: February 2007

We consider an (s, S) inventory system with random lead time and repeated demands of unsatisfied demands from the orbit. Whenever the inventory level falls to the level s, an order is placed to bring the level to S. The quantity ordered is M = S − s. Demands to the system are served immediately if there is a positive inventory. Otherwise it will go to a pool of unsatisfied customers called orbit. After a random amount of time, that demand is retried for service. We assume a Markovian setup for the time between consecutive arrivals, replenishments, and retrials. We obtained the condition for ergodicity of the system, steady state system size probabilities, expected length of the busy period of the system, expected inventory level, expected number of customers waiting in the orbit, expected waiting
times, and so forth. A control problem is studied and some numerical illusrtations are provided.
Inhibition of Fatty Acid Synthase Induces Endoplasmic Reticulum Stress in Tumor Cells
Authors: Little Joy L. , Wheeler Frances B. , Fels Diane R. , Koumenis Constantinos , Kridel Steven J.
Published: February 2007

Fatty acid synthase (FAS), the cellular enzyme that synthesizes palmitate, is expressed at high levels in tumor cells and is vital for their survival. Through the synthesis of palmitate, FAS primarily drives the synthesis of phospholipids in tumor cells. In this study, we tested the hypothesis that the FAS inhibitors induce endoplasmic reticulum (ER) stress in tumor cells. Treatment of tumor cells with FAS inhibitors induces robust PERK-dependent phosphorylation of the translation initiation factor eIF2α and concomitant inhibition of protein synthesis. PERK-deficient transformed mouse embryonic fibroblasts and HT-29 colon carcinoma cells that express a dominant negative PERK (ΔC-PERK) are hypersensitive to FAS inhibitor–induced cell death. Pharmacologic inhibition of FAS also induces the processing of X-box binding protein-1, indicating that the IRE1 arm of the ER stress response is activated when FAS is inhibited. Induction of ER stress is further confirmed by the increased expression of the ER stress–regulated genes CHOP, ATF4, and GRP78. FAS inhibitor–induced ER stress is activated prior to the detection of caspase 3 and PARP cleavage, primary indicators of cell death, whereas orlistat-induced cell death is rescued by coincubation with the global translation inhibitor cycloheximide. Lastly, FAS inhibitors cooperate with the ER stress inducer thapsigargin to enhance tumor cell killing. These results provide the first evidence that FAS inhibitors induce ER stress and establish an important mechanistic link between FAS activity and ER function. [Cancer Res 2007;67(3):1262–9]
Identification of Pancreatic Cancer Stem Cells
Authors: Li Chenwei , Heidt David G. , Dalerba Piero , Burant Charles F. , Zhang Lanjing , Adsay Volkan , Wicha Max , Clarke Michael F. , Simeone Diane M.
Published: February 2007

Emerging evidence has suggested that the capability of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. Although data have been provided to support this theory in human blood, brain, and breast cancers, the identity of pancreatic cancer stem cells has not been determined. Using a xenograft model in which primary human pancreatic adenocarcinomas were grown in immunocompromised mice, we identified a highly tumorigenic subpopulation of pancreatic cancer cells expressing the cell surface markers CD44, CD24, and epithelial-specific antigen (ESA). Pancreatic cancer cells with the CD44+CD24+ESA+ phenotype (0.2–0.8% of pancreatic cancer cells) had a 100-fold increased tumorigenic potential compared with nontumorigenic cancer cells, with 50% of animals injected with as few as 100 CD44+CD24+ESA+ cells forming tumors that were histologically indistinguishable from the human tumors from which they originated. The enhanced ability of CD44+CD24+ESA+ pancreatic cancer cells to form tumors was confirmed in an orthotopic pancreatic tail injection model. The CD44+CD24+ESA+ pancreatic cancer cells showed the stem cell properties of self-renewal, the ability to produce differentiated progeny, and increased expression of the developmental signaling molecule sonic hedgehog. Identification of pancreatic cancer stem cells and further elucidation of the signaling pathways that regulate their growth and survival may provide novel therapeutic approaches to treat pancreatic cancer, which is notoriously resistant to standard chemotherapy and radiation. [Cancer Res 2007;67(3):1030–7]
Changes in DNA Methylation Patterns in Subjects Exposed to Low-Dose Benzene
Authors: Bollati Valentina , Baccarelli Andrea , Hou Lifang , Bonzini Matteo , Fustinoni Silvia , Cavallo Domenico , Byun Hyang-Min , Jiang Jiayi , Marinelli Barbara , Pesatori Angela C. , Bertazzi Pier A. , Yang Allen S.
Published: February 2007

Aberrant DNA methylation patterns, including global hypomethylation, gene-specific hypermethylation/hypomethylation, and loss of imprinting (LOI), are common in acute myelogenous leukemia (AML) and other cancer tissues. We investigated for the first time whether such epigenetic changes are induced in healthy subjects by low-level exposure to benzene, a widespread pollutant associated with AML risk. Blood DNA samples and exposure data were obtained from subjects with different levels of benzene exposure, including 78 gas station attendants, 77 traffic police officers, and 58 unexposed referents in Milan, Italy (personal airborne benzene range, <6–478 μg/m3). Bisulfite-PCR pyrosequencing was used to quantitate DNA methylation in long interspersed nuclear element-1 (LINE-1) and AluI repetitive elements as a surrogate of genome-wide methylation and examine gene-specific methylation of MAGE-1 and p15. Allele-specific pyrosequencing of the H19 gene was used to detect LOI in 96 subjects heterozygous for the H19 imprinting center G/A single-nucleotide polymorphism. Airborne benzene was associated with a significant reduction in LINE-1 (−2.33% for a 10-fold increase in airborne benzene levels; P = 0.009) and AluI (−1.00%; P = 0.027) methylation. Hypermethylation in p15 (+0.35%; P = 0.018) and hypomethylation in MAGE-1 (−0.49%; P = 0.049) were associated with increasing airborne benzene levels. LOI was found only in exposed subjects (4 of 73, 5.5%) and not in referents (0 of 23, 0.0%). However, LOI was not significantly associated with airborne benzene (P > 0.20). This is the first human study to link altered DNA methylation, reproducing the aberrant epigenetic patterns found in malignant cells, to low-level carcinogen exposure. [Cancer Res 2007;67(3):876–80]
In vivoEffects of Vaccination with Six-Transmembrane Epithelial Antigen of the Prostate: A Candidate Antigen for Treating Prostate Cancer
Authors: Garcia-Hernandez Maria de la Luz , Gray Andrew , Hubby Bolyn , Kast W. Martin
Published: February 2007

Immunotherapy may provide an alternative treatment for cancer patients, especially when tumors overexpress antigens that can be recognized by immune cells. The identification of markers and therapeutic targets that are up-regulated in prostate cancer has been important to design new potential treatments for prostate cancer. Among them, the recently identified six-transmembrane epithelial antigen of the prostate (STEAP) is considered attractive due to its overexpression in human prostate cancer tissues. Our study constitutes the first assessment of the in vivo effectiveness of STEAP-based vaccination in prophylactic and therapeutic mouse models. Two delivery systems, cDNA delivered by gene gun and Venezuelan equine encephalitis virus-like replicon particles (VRP), both encoding mouse STEAP (mSTEAP) and three vaccination strategies were used. Our results show that mSTEAP-based vaccination was able to induce a specific CD8 T-cell response against a newly defined mSTEAP epitope that prolonged the overall survival rate in tumor-challenged mice very significantly. This was achieved without any development of autoimmunity. Surprisingly, CD4 T cells that produced IFNγ, tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2) played the main role in tumor rejection in our model as shown by using CD4- and CD8-deficient mice. In addition, the presence of high IL-12 levels in the tumor environment was associated with a favorable antitumor response. Finally, the therapeutic effect of STEAP vaccination was also assessed and induced a modest but significant delay in growth of established, 31 day old tumors. Taken together, our data suggest that vaccination against mSTEAP is a viable option to delay tumor growth. [Cancer Res 2007;67(3):1344–51]
The Androgen Receptor Negatively Regulates the Expression of c-Met: Implications for a Novel Mechanism of Prostate Cancer Progression
Authors: Verras Meletios , Lee Jane , Xue Hui , Li Tzu-Huey , Wang Yuzhuo , Sun Zijie
Published: February 2007

The precise molecular mechanisms by which prostate cancer cells progress from androgen-sensitive to androgen-insensitive status still remain largely unclear. The hepatocyte growth factor/scatter factor (HGF/SF) plays a critical role in the regulation of cell growth, cell motility, morphogenesis, and angiogenesis. The aberrant expression of HGF/SF and its receptor, c-Met, often correlates with poor prognosis in a variety of human malignancies, including prostate cancer. Here, we investigate a potential link between androgen signaling and c-Met expression in prostate cancer cells. First, we showed that the androgen receptor (AR) represses the expression of c-Met in a ligand-dependent manner. Using different c-Met promoter/reporter constructs, we identified that Sp1 induces the transcription of c-Met and that AR can repress the Sp1-induced transcription in prostate cancer cells. Moreover, the data from electrophoretic mobility shift assay showed that AR interferes with the interaction between Sp1 and the functional Sp1 binding site within the c-Met promoter. Furthermore, we tested the effect of AR on c-Met expression in an androgen-insensitive prostate cancer cell line, CWR22Rv1. Finally, the repressive role of androgen signaling on c-Met expression was confirmed in prostate cancer xenografts. The above data indicate a dual role of AR in transcriptional regulation. Although the current androgen ablation therapy can repress the expression of growth-promoting genes that are activated by the AR, it may also attenuate the repressive role of AR on c-Met expression. Therefore, the therapeutic strategies to inhibit the activation of the HGF/c-Met pathway may be of benefit when combined with current androgen ablation treatment. [Cancer Res 2007;67(3):967–75]
TSP50 Encodes a Testis-Specific Protease and Is Negatively Regulated by p53
Authors: Xu Haopeng , Shan Jidong , Jurukovski Vladimir , Yuan Liming , Li Jianhua , Tian Kegui
Published: February 2007

Earlier studies suggested that TSP50 is a testis-specific gene that encodes a protein, which is homologous to serine proteases but differs in that threonine replaces serine in its catalytic triad. Most importantly, it was abnormally reactivated in many breast cancer biopsies tested. While further investigating its biochemical and cell biological natures, we found that TSP50 exhibited enzyme activity and was located in the endoplasmic reticulum and cytosol membrane. During our studies to elucidate the regulatory mechanisms related to its differential expression, we discovered a putative p53-binding site and several Sp1-binding sites in the TSP50 promoter, which led us to test if it was regulated by the p53 gene. We found that the p53 transgene negatively regulated the TSP50 promoter in diverse types of cell lines. This result was consistent with other observations: (a) p53 overexpression reduced endogenous TSP50 expression; and (b) breast cancer cell lines containing mutated p53, such as MCF7/Adr, or normal p53, such as MCF7, produced high or low levels of TSP50 transcripts, which was consistent with the fact that TSP50 promoter activity was much higher in MCF7/Adr than that in MCF7 cells. We also found that the quantity of Sp1 transcription factor was lower in MCF7/Adr than in MCF7 cells, which suggested that another mechanism (i.e., transcription factor modulation) was also involved in TSP50 differential expression. [Cancer Res 2007;67(3):1239–45]
Molecular and Cytogenetical Alterations Induced by Environmental Cigarette Smoke in Mice Heterozygous for Fhit
Authors: De Flora Silvio , D'Agostini Francesco , Izzotti Alberto , Zanesi Nicola , Croce Carlo M. , Balansky Roumen
Published: February 2007

Previous studies in humans and animal models provided evidence that the Fhit gene is an early target for cigarette smoke. We compared the induction of a variety of molecular and cytogenetical alterations in B6-129(F1) mice, either wild type or Fhit+/−, after whole-body exposure to environmental cigarette smoke (ECS) for 15 consecutive days. Both mouse genotypes responded to ECS with a loss of Fhit protein in the bronchial epithelium, accompanied by induction of apoptosis and stimulation of cell proliferation. ECS induced formation of bulky DNA adducts in whole lung. In addition, ECS caused cytogenetical damage both in the respiratory tract and at a systemic level, as shown by a significant increase of micronucleus frequency in pulmonary alveolar macrophages, bone marrow polychromatic erythrocytes, and peripheral blood normochromatic erythrocytes of both wild-type and Fhit+/− mice. These results are compared with those generated in other species, strains, and genotypes of rodents exposed to ECS that we investigated previously. Although the loss of Fhit protein in the bronchial epithelium of ECS-exposed B6-129(F1) mice provides further evidence that the Fhit gene is an early molecular target for ECS, heterozygosity for Fhit does not seem to confer an increased susceptibility of mice in terms of the investigated early biomarkers. [Cancer Res 2007;67(3):1001–6]
Giyoo Hatano’s Analysis of Psychological Tools
Authors: Cole Michael
Published: February 2007

This paper focuses on the relation between two areas of research which owe a great debt to the work of Giyoo Hatano: the ways in which the use of the abacus mediates arithmetic problem solving and the way in which the use of the kanji writing system mediates the interpretation of unfamiliar words. These examples are related to L.S. Vygotsky’s ideas about the ways in which particular kinds of mediational means can serve as psychological tools for accomplishing culturally valued problem solving. They also urge upon us the need to be cautious when we are tempted to order culturally valued mediational means in terms of a unilinear evolutionary sequence.