bluuebunny/crossref_metadata_2025 huggingface dataset:
B‐spline active rays segmentation of microcalcifications in mammography
Authors: Arikidis Nikolaos S. , Skiadopoulos Spyros , Karahaliou Anna , Likaki Eleni , Panayiotakis George , Costaridou Lena
Published: November 2008

Accurate segmentation of microcalcifications in mammography is crucial for the quantification of morphologic properties by features incorporated in computer‐aided diagnosis schemes. A novel segmentation method is proposed implementing active rays (polar‐transformed active contours) on B‐spline wavelet representation to identify microcalcification contour point estimates in a coarse‐to‐fine strategy at two levels of analysis. An iterative region growing method is used to delineate the final microcalcification contour curve, with pixel aggregation constrained by the microcalcification contour point estimates. A radial gradient‐based method was also implemented for comparative purposes. The methods were tested on a dataset consisting of 149 mainly pleomorphic microcalcification clusters originating from of the DDSM database. Segmentation accuracy of both methods was evaluated by three radiologists, based on a five‐point rating scale. The radiologists’ average accuracy ratings were , , and for the proposed method, and , , and for the radial gradient‐based method, respectively, while the differences in accuracy ratings between the two segmentation methods were statistically significant (Wilcoxon signed‐ranks test, ). The effect of the two segmentation methods in the classification of benign from malignant microcalcification clusters was also investigated. A least square minimum distance classifier was employed based on cluster features reflecting three morphological properties of individual microcalcifications (area, length, and relative contrast). Classification performance was evaluated by means of the area under ROC curve . The area and length morphologic features demonstrated a statistically significant (Mann‐Whitney U‐test, ) higher patient‐based classification performance when extracted from microcalcifications segmented by the proposed method ( and , respectively), as compared to segmentation by the radial gradient‐based method ( and ). The proposed method demonstrates improved segmentation accuracy, fulfilling human visual criteria, and enhances the ability of morphologic features to characterize microcalcification clusters.
A procedure for calculation of monitor units for passively scattered proton radiotherapy beams
Authors: Sahoo Narayan , Zhu X. Ronald , Arjomandy Bijan , Ciangaru George , Lii MingFwu , Amos Richard , Wu Richard , Gillin Michael T.
Published: November 2008

The purpose of this study is to validate a monitor unit (MU) calculation procedure for passively scattered proton therapy beams. The output dose per MU (d/MU) of a therapeutic radiation beam is traditionally calibrated under specific reference conditions. These conditions include beam energy, field size, suitable depth in water or water equivalent phantom in a low dose gradient region with known relative depth dose, and source to point of calibration distance. Treatment field settings usually differ from these reference conditions leading to a different d/MU that needs to be determined for delivering the prescribed dose. For passively scattered proton beams, the proton specific parameters, which need to be defined, are related to the energy, lateral scatterers, range modulating wheel, spread out Bragg peak (SOBP) width, thickness of any range shifter, the depth dose value relative to the normalization point in the SOBP, and scatter both from the range compensator and inhomogeneity in the patient. Following the custom for photons or electrons, a set of proton dosimetry factors, representing the changes in the d/MU relative to a reference condition, can be defined as the relative output factor (ROF), SOBP factor (SOBPF), range shifter factor (RSF), SOBP off‐center factor (SOBPOCF), off‐center ratio (OCR), inverse square factor (ISF), field size factor (FSF), and compensator and patient scatter factor (CPSF). The ROF, SOBPF, and RSF are the major contributors to the d/MU and were measured using an ion chamber in water tank during the clinical commissioning of each beam to create a dosimetry beam data table to be used for calculating the monitor units. The following simple formula is found to provide an independent method to determine the d/MU at the point of interest (POI) in the patient, namely, . The monitor units for delivering the intended dose to the POI can be obtained from . The accuracy and robustness of the above formula were validated by calculating the d/MU in water for many different combinations of beam parameters and comparing it with the corresponding measured d/MU by an ion chamber in a water or water/plastic phantom. This procedure has been in use for MU calculation for patient treatment fields at our facility since May 2006. The differences in the calculated and measured values of the d/MU for 623 distinct fields used for patient treatment during the period of May 2006 to February 2007 are within 2% for 99% of these fields. The authors conclude that an intuitive formula similar to the one used for monitor unit calculation of therapeutic photon beams can be used to compute the monitor units of passively scattered proton therapy beams.
Dosimetric characteristics of linear accelerator photon beams with small monitor unit settings
Authors: Kang Sei‐Kwon , Cheong Kwang‐Ho , Hwang Taejin , Cho Byung Chul , Kim Su SSan , Kim Kyoung Ju , Oh Do Hoon , Bae Hoonsik , Suh Tae‐Suk
Published: November 2008

Several studies on the effect of tumor cell killing by dose rate variation have implied that the use of a shorter treatment time is more favorable for intensity modulated radiation therapy (IMRT). Aiming at step‐and‐shoot IMRT with higher dose rates, the stabilities of beam output and profiles with small monitor unit (MU) settings were investigated for various dose rates. With the use of a Varian 21EX (Varian Medical Systems Inc., Palo Alto, CA), static and step‐and‐shoot IMRT beam output along with profiles were measured by use of an ion chamber and a two‐dimensional diode array detector as a function of monitor units and dose rates. For a static case, as the MU approached 1, the beam output increased up to 2% for and 4.5% for , showing a larger overdose as the dose rate increased. Deterioration of the beam symmetry and flatness were also observed as the MU decreased to 1 monitor unit. For the step‐and‐shoot IMRT case, a large dosimetric error of more than 10% was also detected with the use of a small MU segment. However, no definite correlation with the dose rate was observed due to the combined beam start‐up effects by the grid pulse and finite communication time between the machine console and multileaf collimator (MLC) controller. For step‐and‐shoot IMRT with higher dose rates, beam output and beam profile stability with small MU needs to be checked, and adequate MU limitation where segments are not allowed need to be reflected in the step‐and‐shoot IMRT planning.
Impact of wavelet based denoising of ‐PK11195 time activity curves on accuracy and precision of kinetic analysis
Authors: Yaqub Maqsood , Boellaard Ronald , Schuitemaker Alie , van Berckel Bart N. M. , Lammertsma Adriaan A.
Published: November 2008

The purpose of the present study was to investigate the use of various wavelets based techniques for denoising of ‐PK11195 time activity curves (TACs) in order to improve accuracy and precision of PET kinetic parameters, such as volume of distribution and distribution volume ratio with reference region (DVR). Simulated and clinical TACs were filtered using two different categories of wavelet filters: (1) wave shrinking thresholds using a constant or a newly developed time varying threshold and (2) “statistical” filters, which filter extreme wavelet coefficients using a set of “calibration” TACs. PET pharmacokinetic parameters were estimated using linear models (plasma Logan and reference Logan analyses). For simulated noisy TACs, optimized wavelet based filters improved the residual sum of squared errors with the original noise free TACs. Furthermore, both clinical results and simulations were in agreement. Plasma Logan values increased after filtering, but no differences were seen in reference Logan DVR values. This increase in plasma Logan suggests a reduction of noise induced bias by wavelet based denoising, as was seen in the simulations. Wavelet denoising of TACs for ‐PK11195 PET studies is therefore useful when parametric Logan based is the parameter of interest.
Dosimetric investigation of high dose rate, gated IMRT
Authors: Lin Teh , Chen Yan , Hossain Murshed , Li Jinsheng , Ma C.‐M.
Published: November 2008

Increasing the dose rate offers time saving for IMRT delivery but the dosimetric accuracy is a concern, especially in the case of treating a moving target. The objective of this work is to determine the effect of dose rate associated with organ motion and gated treatment using step‐and‐shoot IMRT delivery. Both measurements and analytical simulation on clinical plans are performed to study the dosimetric differences between high dose rate and low dose rate gated IMRT step‐and‐shoot delivery. Various sites of IMRT plans for liver, lung, pancreas, and breast cancers were delivered to a custom‐made motorized phantom, which simulated sinusoidal movement. Repeated measurements were taken for gated and nongated delivery with different gating settings and three dose rates, 100, 500, and using ion chambers and extended dose range films. For the study of the residual motion effect for individual segment dose and composite dose of IMRT plans, our measurements with 30%–60% phase gating and without gating for various dose rates were compared. A small but clinically acceptable difference in delivered dose was observed between 1000, 500, and at 30%–60% phase gating. A simulation is presented, which can be used for predicting dose profiles for patient cases in the presence of motion and gating to confirm that IMRT step‐and‐shoot delivery with gating for are not much different from . Based on the authors sample plan analyses, our preliminary results suggest that using dose rate is dosimetrically accurate and efficient for IMRT treatment delivery with gating. Nonetheless, for the concern of patient care and safety, a patient specific QA should be performed as usual for IMRT plans for high dose rate deliveries.
In vivo measurement of bone aluminum in population living in southern Ontario, Canada
Authors: Davis K. , Aslam  , Pejović‐Milić A. , Chettle D. R.
Published: November 2008

The harmful biological effect of excessive aluminum (Al) load in humans has been well documented in the literature. Al stored in bone, for instance due to dialysis treatment or occupational exposure, can interfere with normal bone remodeling leading to osteodystrophy, osteoarthritis, or osteomalacia. On the other hand, the relationship between chronic Al exposure and the risk of Alzheimer's disease remains controversial. In this work, the feasibility of in vivo neutron activation analysis (IVNAA) for measuring Al levels in the human hand bone, using the thermal neutron capture reaction , is reported. This noninvasive diagnostic technique employs a high beam current Tandetron accelerator based neutron source, an irradiation/shielding cavity, a NaI(Tl) detector system, and a new set of hand bone phantoms. The photon spectra of the irradiated phantom closely resemble those collected from the hands of nonexposed healthy subjects. A protocol was developed using the newly developed hand phantoms, which resulted in a minimum detectable limit (MDL) of Al in the human hand. Using the ratio of Al to Ca as an index of Al levels per unit bone mass, the MDL was determined as , which is within the range of the measured levels of [ICRP, Report of the Task Group on Reference Man, Publication 23 (Pergamon, Oxford, 1975)] found in other in vivo and in vitro studies. Following the feasibility studies conducted with phantoms, the diagnostic technique was used to measure Al levels in the hand bones of 20 healthy human subjects. The mean hand bone Al concentration was determined as . The average standard error in the is , which corresponds to an average relative error of 50% in the measured levels of . These results were achieved with a dose equivalent of to a hand and an effective dose of . This effective dose is approximately half of that received in a chest radiograph examination. It is recommended to investigate the use of the bone Al IVNAA diagnostic technique for in vivo measurements of patients with documented overload of Al in bone.
Totally Accessible MRI: A User's Guide to Principles, Technology, and Applications
Authors: Jacobs Michael
Published: November 2008

Totally Accessible MRI: A User's Guide to Principles, Technology, and Applications Lipton Michael L. Kanal Emanuel MD, FACR, FISMRM, AANG Springer Science+Business Media, LLC, New York, NY, 2008. Price: $59.95. Softcover 384p. ISBN 978‐0‐387‐48895‐0.
Monte Carlo Treatment Planning—An Introduction: Report 16 of the Netherlands Commission on Radiation Dosimetry
Authors: Chetty Indrin
Published: November 2008

Monte Carlo Treatment Planning—An Introduction: Report 16 of the Netherlands Commission on Radiation Dosimetry Netherlands Commission on Radiation Dosimetry, Subcommittee Monte Carlo Treatment Planning. N. Reynaert (Chairman). Delft, Netherlands, June 2006. Price: 30.00 EURO, ISBN: 90‐78522‐01‐1.
A new formalism for reference dosimetry of small and nonstandard fields
Authors: Alfonso R. , Andreo P. , Capote R. , Huq M. Saiful , Kilby W. , Kjäll P. , Mackie T. R. , Palmans H. , Rosser K. , Seuntjens J. , Ullrich W. , Vatnitsky S.
Published: November 2008

The use of small fields in radiotherapy techniques has increased substantially, in particular in stereotactic treatments and large uniform or nonuniform fields that are composed of small fields such as for intensity modulated radiation therapy (IMRT). This has been facilitated by the increased availability of standard and add‐on multileaf collimators and a variety of new treatment units. For these fields, dosimetric errors have become considerably larger than in conventional beams mostly due to two reasons; (i) the reference conditions recommended by conventional Codes of Practice (CoPs) cannot be established in some machines and (ii) the measurement of absorbed dose to water in composite fields is not standardized. In order to develop standardized recommendations for dosimetry procedures and detectors, an international working group on reference dosimetry of small and nonstandard fields has been established by the International Atomic Energy Agency (IAEA) in cooperation with the American Association of Physicists in Medicine (AAPM) Therapy Physics Committee. This paper outlines a new formalism for the dosimetry of small and composite fields with the intention to extend recommendations given in conventional CoPs for clinical reference dosimetry based on absorbed dose to water. This formalism introduces the concept of two new intermediate calibration fields: (i) a static machine‐specific reference field for those modalities that cannot establish conventional reference conditions and (ii) a plan‐class specific reference field closer to the patient‐specific clinical fields thereby facilitating standardization of composite field dosimetry. Prior to progressing with developing a CoP or other form of recommendation, the members of this IAEA working group welcome comments from the international medical physics community on the formalism presented here.
Identification ofMannheimia haemolyticaAdhesins Involved in Binding to Bovine Bronchial Epithelial Cells
Authors: Kisiela Dagmara I. , Czuprynski Charles J.
Published: November 2008

Mannheimia haemolytica, a commensal organism of the upper respiratory tract in cattle, is the principal bacterial pathogen associated with the bovine respiratory disease complex. Adherence to the respiratory mucosa is a crucial event in its pathogenesis. However, the bacterial components that contribute to this process are not fully characterized. In this study, we demonstrated thatM. haemolyticaadhered to bovine bronchial epithelial cells (BBEC) in vitro and that adherence was inhibited by anti-M. haemolyticaantibody. Western blot analysis ofM. haemolyticaproteins that bind to BBEC showed a dominant protein band with an apparent molecular mass of ∼30 kDa. Peptide sequences for the 30-kDa BBEC-binding proteins, as determined by liquid chromatography-tandem mass spectrometry, matched twoM. haemolyticasurface proteins: heat-modifiable outer membrane protein A (OmpA) and lipoprotein 1 (Lpp1). Western blotting showed that the 30-kDa protein band is recognized by both anti-M. haemolyticaOmpA and anti-Lpp1 antibodies. Furthermore, incubation with anti-OmpA and anti-Lpp1 antibodies significantly inhibitedM. haemolyticabinding to BBEC monolayers. In summary, these results suggest that OmpA and Lpp1 contribute to adherence ofM. haemolyticato bovine respiratory epithelial cells.
Identification of an Essential
Francisella tularensis
subsp.
tularensis
Virulence Factor
Authors: Qin Aiping , Scott David W. , Thompson Jennifer A. , Mann Barbara J.
Published: November 2008

Francisella tularensis
, the highly virulent etiologic agent of tularemia, is a low-dose intracellular pathogen that is able to escape from the phagosome and replicate in the cytosol. Although there has been progress in identifying loci involved in the pathogenicity of this organism, analysis of the genome sequence has revealed few obvious virulence factors. We previously reported isolation of an
F. tularensis
subsp.
tularensis
strain Schu S4 transposon insertion mutant with a mutation in a predicted hypothetical lipoprotein, FTT1103, that was deficient in intracellular replication in HepG2 cells. In this study, a mutant with a defined nonpolar deletion in FTT1103 was created, and its phenotype, virulence, and vaccine potential were characterized. A phagosomal integrity assay and lysosome-associated membrane protein 1 colocalization revealed that ΔFTT1103 mutant bacteria were defective in phagosomal escape. FTT1103 mutant bacteria were maximally attenuated in the mouse model; mice survived, without visible signs of illness, challenge by more than 10
10
CFU when the intranasal route was used and challenge by 10
6
CFU when the intraperitoneal, subcutaneous, or intravenous route was used. The FTT1103 mutant bacteria exhibited dissemination defects. Mice that were infected by the intranasal route had low levels of bacteria in their livers and spleens, and these bacteria were cleared by 3 days postinfection. Mutant bacteria inoculated by the subcutaneous route failed to disseminate to the lungs. BALB/c or C57BL/6 mice that were intranasally vaccinated with 10
8
CFU of FTT1103 mutant bacteria were protected against subsequent challenge with wild-type strain Schu S4. These experiments identified the FTT1103 protein as an essential virulence factor and also demonstrated the feasibility of creating defined attenuated vaccines based on a type A strain.
Immunization with Recombinant
Brucella
Species Outer Membrane Protein Omp16 or Omp19 in Adjuvant Induces Specific CD4
+
and CD8
+
T Cells as Well as Systemic and Oral Protection against
Brucella abortus
Infection
Authors: Pasquevich Karina A. , Estein Silvia M. , Samartino Clara García , Zwerdling Astrid , Coria Lorena M. , Barrionuevo Paula , Fossati Carlos A. , Giambartolomei Guillermo H. , Cassataro Juliana
Published: November 2008

Available vaccines against
Brucella
spp. are live attenuated
Brucella
strains. In order to engineer a better vaccine to be used in animals and humans, our laboratory aims to develop an innocuous subunit vaccine. Particularly, we are interested in the outer membrane proteins (OMPs) of
B. abortus
: Omp16 and Omp19. In this study, we assessed the use of these proteins as vaccines against
Brucella
in BALB/c mice. Immunization with lipidated Omp16 (L-Omp16) or L-Omp19 in incomplete Freund's adjuvant (IFA) conferred significant protection against
B. abortus
infection. Vaccination with unlipidated Omp16 (U-Omp16) or U-Omp19 in IFA induced a higher degree of protection than the respective lipidated versions. Moreover, the level of protection induced after U-Omp16 or U-Omp19 immunization in IFA was similar to that elicited by live
B. abortus
S19 immunization. Flow cytometric analysis showed that immunization with U-Omp16 or U-Omp19 induced antigen-specific CD4
+
as well as CD8
+
T cells producing gamma interferon. In vivo depletion of CD4
+
or CD8
+
T cells in mice immunized with U-Omp16 or U-Omp19 plus IFA resulted in a loss of the elicited protection, indicating that both cell types are mediating immune protection. U-Omp16 or U-Omp19 vaccination induced a T helper 1 response, systemic protection in aluminum hydroxide formulation, and oral protection with cholera toxin adjuvant against
B. abortus
infection. Both immunization routes exhibited a similar degree of protection to attenuated
Brucella
vaccines (S19 and RB51, respectively). Overall these results indicate that U-Omp16 or U-Omp19 would be a useful candidate for a subunit vaccine against human and animal brucellosis.
The effect of prolonged endurance exercise upon blood pressure regulation during a postexercise orthostatic challenge
Authors: Privett S E , George K P , Middleton N , Whyte G P , Cable N T
Published: November 2008

Objective

To investigate the regulation of blood pressure in response to an orthostatic challenge in athletes running a marathon.

Methods

10 experienced male runners (mean (SD) age 29 (4) years) were tested on the day prior to the 2004 London Marathon, and again immediately postrace (race time 210 (36) min). In addition, 6 of the subjects were retested 24 h postrace. During each examination, beat-to-beat systolic arterial blood pressure (SBP) and heart rate (HR) were measured, and stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were estimated via arterial transmural pressure waveforms during 3 min in a supine position and then during 3 min of upright, unsupported standing. Data were averaged over 20 s epochs, and the final 20 s of each posture were compared prerace and postrace via repeated measures 2-way ANOVA.

Results

Prerace SBP in standing increased only moderately when compared with supine values (2 (9) mm Hg, NS). This was accompanied by an increase in HR (13 (7) beats/min, p<0.05), as well as a decrease in SV (16 (9) ml, p<0.05). However, there was little change in CO (−0.13 (0.97) litres/min, NS) or TPR (0.047 (0.280) medical units (MU), NS). Postrace SBP significantly decreased from supine to standing (−15 (20) mm Hg, p<0.05). The change in SBP was accompanied by an increase in HR (19 (6) beats/min, p<0.05) and a reduction in SV (26 (14) ml, p<0.05) and CO (−1.02 (1.39) litres/min, p = 0.05). Postrace there was no change in TPR (0.366 (0.607) MU, NS) upon standing. The orthostatic adjustments in SBP, HR and CO were greater than at prerace (p<0.05). The postrace orthostatic challenge resulted in only one subject experiencing presyncopal symptoms. At 24 h postrace, cardiovascular responses to an orthostatic challenge mirrored those at prerace.

Conclusions

Following prolonged exercise, a fall in systolic blood pressure during orthostasis results from an inadequately compensated decrease in SV and resultant CO during standing.
COLLISION AVOIDANCE IN COMMERCIAL AIRCRAFT FREE FLIGHT VIA NEURAL NETWORKS AND NON-LINEAR PROGRAMMING
Authors: CHRISTODOULOU MANOLIS A. , KONTOGEORGOU CHRYSA
Published: November 2008

In recent years there has been a great effort to convert the existing Air Traffic Control system into a novel system known as Free Flight. Free Flight is based on the concept that increasing international airspace capacity will grant more freedom to individual pilots during the enroute flight phase, thereby giving them the opportunity to alter flight paths in real time. Under the current system, pilots must request, then receive permission from air traffic controllers to alter flight paths. Understandably the new system allows pilots to gain the upper hand in air traffic. At the same time, however, this freedom increase pilot responsibility. Pilots face a new challenge in avoiding the traffic shares congested air space. In order to ensure safety, an accurate system, able to predict and prevent conflict among aircraft is essential. There are certain flight maneuvers that exist in order to prevent flight disturbances or collision and these are graded in the following categories: vertical, lateral and airspeed. This work focuses on airspeed maneuvers and tries to introduce a new idea for the control of Free Flight, in three dimensions, using neural networks trained with examples prepared through non-linear programming.
DOCUMENT IMAGE BINARISATION USING A SUPERVISED NEURAL NETWORK
Authors: KHASHMAN ADNAN , SEKEROGLU BORAN
Published: November 2008

Advances in digital technologies have allowed us to generate more images than ever. Images of scanned documents are examples of these images that form a vital part in digital libraries and archives. Scanned degraded documents contain background noise and varying contrast and illumination, therefore, document image binarisation must be performed in order to separate foreground from background layers. Image binarisation is performed using either local adaptive thresholding or global thresholding; with local thresholding being generally considered as more successful. This paper presents a novel method to global thresholding, where a neural network is trained using local threshold values of an image in order to determine an optimum global threshold value which is used to binarise the whole image. The proposed method is compared with five local thresholding methods, and the experimental results indicate that our method is computationally cost-effective and capable of binarising scanned degraded documents with superior results.
COMPUTER ALGEBRA REEXAMINATION OF THE SCALED PARTICLE THEORY FOR HARD-SPHERE AND LENNARD-JONES FLUIDS
Authors: KHASARE S. B.
Published: November 2008

In the present work, an extension of the scaled particle theory (ESPT) for fluid using computer algebra is developed to obtain an equation of state (EOS), for Lennard-Jones fluid. A suitable functional form for surface tension S(r,d,∊) is assumed with intermolecular separation r as a variable, given below: [Formula: see text] where m is arbitrary real number, and d and ∊ are related to physical property such as average or suitable molecular diameter and the binding energy of the molecule respectively. It is found that, for hard sphere fluid ∊ = 0, the above assumption when introduced in scaled particle theory (SPT) frame and choosing arbitrary real number, m = 1/3, the corresponding EOS is in good agreement with the computer simulation of molecular dynamics (MD) result. Furthermore, for the value of m = -1 it gives a Percus–Yevick (pressure), and for the value of m = 1, it corresponds Percus–Yevick (compressibility) EOS.
A FOUR-LEVEL ATOM INTERACTING WITH A SINGLE-MODE CAVITY FIELD: DOUBLE Ξ-CONFIGURATION
Authors: ABDEL-WAHAB N. H.
Published: November 2008

In this article, the problem of a double Ξ-type four-level atom interacting with a single-mode cavity field is considered. The considered model describes several distinct configurations of a four-level atom. Also, this model includes the detuning parameters of the atom-field system. We obtain the constants of motion and the wavefunction is derived when the atom is initially prepared in the upper state. We used this model for computing a number of the field aspects for the considered system. As an illustration, the model is used for studying the time evolution of the Mandel Q-parameter, amplitude-squared squeezing phenomenon and Q-function when the input field is considered in a coherent state. The results show that these phenomena are affected by the presence of detuning parameters.
THE IMPORTANCE OF Fe SURFACE STATES FOR MAGNETIC TUNNEL JUNCTION BASED SPINTRONIC DEVICES
Authors: CHANTIS ATHANASIOS N. , BELASHCHENKO KIRILL D. , TSYMBAL EVGENY Y. , SUS INNA V.
Published: November 2008

In this article we give a review of our recent theoretical studies of the influence of Fe (001) surface (interface) states on spin-polarized electron transport across magnetic tunnel junctions with Fe electrodes. We show that minority-spin surface (interface) states are responsible for at least two effects which are important for spin electronics. First, they can produce a sizable tunneling anisotropic magnetoresistance in magnetic tunnel junctions with a single Fe electrode. The effect is driven by a Rashba shift of the resonant surface band when the magnetization changes direction. This can introduce a new class of spintronic devices, namely, tunneling magnetoresistance junctions with a single ferromagnetic electrode. Second, in Fe/GaAs (001) magnetic tunnel junctions minority-spin interface states produce a strong dependence of the tunneling current spin polarization on applied electrical bias. A dramatic sign reversal within a voltage range of just a few tenths of an eV is predicted. This explains the observed sign reversal of spin polarization in recent experiments of electrical spin injection in Fe/GaAs (001) and related reversal of tunneling magnetoresistance through vertical Fe/GaAs/Fe trilayers.
ZINC OXIDE NANORODS PREPARED AT LOW TEMPERATURES WITHOUT CATALYST
Authors: SHAH M. A.
Published: November 2008

An easy and novel approach is described for the formation of zinc oxide nanorods by simple reaction of zinc metal with water in a very low temperature range of 25–75°C. It offers a facile and fast route for large scale production of zinc oxide nanorods without catalysts. The diameters of the nanorods range from 30–120 nm with several micrometers in length. The resulting nanorods have been comprehensively characterized by Field Emission Scanning Electron Microscopy (FESEM) coupled with Energy Dispersive Analysis (EDX). A plausible mechanism is proposed for the formation of these nanorods and it is expected that this synthetic technique can be extended to obtain other oxides. This will contribute to broadening the range of materials.
DYNAMIC PROPERTIES OF THE LARGE-DETUNING CAVITY QED SYSTEM IN THE PRESENCE OF CAVITY DECAY
Authors: GAO CHENG-YUAN , MA LEI , LIU JIN-MING
Published: November 2008

We consider a physical process of two Λ-type three-level atoms interacting with a bimodal cavity including the influence of the cavity decay. We analyze the influence of cavity decay on several physical quantities of the process, such as atomic population probability, residual entanglement, concurrence of two atoms, average population inversion, average photon number, the fidelity for quantum phase gate, and the fidelity of generating atomic EPR state. It is found that all of these physical quantities decrease with the increase of cavity decay when the other relevant parameters are fixed.
PERIODIC COMPONENTS AND CHARACTERISTIC TIME SCALES IN THE FINANCIAL MARKET
Authors: YANG CHUNXIA , WU HONGFA , ZHANG YINGCHAO
Published: November 2008

Based on six large empirical data sets, the financial data sequences are decomposed by Empirical Mode Decomposition (EMD) into various quasi-periodic fluctuation modes, including weekly, half-month, seasonal, about-four-years and so on, which may indicate some abnormal return oscillation patterns. The corresponding average periods are calculated by Fast Fourier Transform Algorithm (FFT), about 6 days for the weekly, about 10 days for the half-month, about 60 days for the seasonal and 1020 days or so for the about-four-years. These obtained results show that the mode periods may be universal for different markets.
Erythropoietin in Cancer Patients
Authors: Glaspy John A.
Published: November 2008

Therapy with erythropoiesis-stimulating agents (ESAs) is associated with well-documented benefits to anemic cancer patients undergoing chemotherapy, most importantly a reduction in the likelihood of needing red cell transfusions. One challenge in supportive cancer care is a relative resistance to ESAs, requiring high doses with a significant rate of nonresponse. Recent advances in our understanding of iron metabolism in patients with chronic illness and the results of clinical trials indicate that parenteral iron improves ESA response in this setting. Another issue is the safety of ESA treatment in cancer patients. There is an increased risk of venous thrombosis that must be considered in clinical decision making. There are also recent data raising concerns that ESAs may enhance tumor progression or decrease patient survival. Although the preponderance of the data suggests that ESAs do not alter survival when used to treat chemotherapy-induced anemia, large well-controlled trials addressing this issue are needed.
Gene by Environment Interaction in Asthma
Authors: London Stephanie J. , Romieu Isabelle
Published: November 2008

Marked international differences in rates of asthma and allergies and the importance of family history highlight the primacy of interactions between genetic variation and the environment in asthma etiology. Environmental tobacco smoke (or secondhand smoke), ambient air pollutants, and endotoxin and/or other pathogen-associated molecular patterns are the ambient exposures studied most frequently for interactions with genetic polymorphisms in asthma. To date, results from the literature remain inconclusive. Most published studies are underpowered to study interactions between genetic polymorphisms and ambient exposures, each with weak effects. Strategies to increase power include cooperation across studies to increase sample sizes and improve measures of both exposure and asthma phenotypes. Genome-wide association studies hold promise for identifying unexpected gene environment interactions, but given the statistical power issues, candidate gene association studies will remain important. New tools are enabling the study of epigenetic mechanisms for environmental interactions.
Klotho ablation converts the biochemical and skeletal alterations in FGF23 (R176Q) transgenic mice to a Klotho-deficient phenotype
Authors: Bai Xiuying , Dinghong Qiu , Miao Dengshun , Goltzman David , Karaplis Andrew C.
Published: November 2008

Transgenic mice overexpressing fibroblast growth factor (FGF23) (R176Q) ( F Tg) exhibit biochemical {hypophosphatemia, phosphaturia, abnormal 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] metabolism} and skeletal (rickets and osteomalacia) abnormalities attributable to FGF23 action. In vitro studies now implicate the aging-related factor Klotho in the signaling mechanism of FGF23. In this study, we used a mouse genetic approach to validate in vivo the pivotal role of Klotho in the metabolic and skeletal derangements associated with FGF23 (R176Q) overexpression. To this end, we crossed mice heterozygous for the hypomorphic Klotho allele ( Kl+/−) to F Tg mice and obtained F Tg transgenic mice homozygous for the Kl-hypomorphic allele ( F Tg/ Kl−/−). Mice were killed on postnatal day 50, and serum and tissues were procured for analysis and comparison with F Tg, wild-type, and Kl−/− controls. From 4 wk onward, F Tg/ Kl−/− mice were clearly distinguishable from F Tg mice and exhibited a striking phenotypic resemblance to the Kl−/− controls. Serum analysis for calcium, phosphorus, parathyroid hormone, 1,25(OH)2D3, and alkaline phosphatase activity confirmed the biochemical similarity between the F Tg/ Kl−/− and Kl−/− mice and their distinctness from the F Tg controls. The characteristic skeletal changes associated with FGF23 (R176Q) overexpression were also dramatically reversed by the absence of Klotho. Hence the wide, unmineralized growth plates and the osteomalacic abnormalities apparent in trabecular and cortical bone were completely reversed in the F Tg/ Kl−/− mice. Nevertheless, independent actions of Klotho on bone were suggested as manifested by alterations in mineralized bone, and in cortical bone volume which were observed in both the Kl−/− and F Tr/ Kl−/− mutants. In summary, our findings substantiate in vivo the essential role of Klotho in the mechanism of action of FGF23 in view of the fact that Klotho ablation converts the biochemical and skeletal manifestations resulting from FGF23 overexpression to a phenotype consistent with Klotho deficiency.
Inhibition of Invasion and Metastasis of Hepatocellular Carcinoma Cells via Targeting RhoC In vitro and In vivo
Authors: Wang Wei , Wu Fan , Fang Feng , Tao Yiming , Yang Lianyue
Published: November 2008

Purpose: Hepatocellular carcinoma (HCC) is one of the most deadly human cancers because of its high incidence of metastasis. Our previous work identified a strong correlation between increased expression of RhoC and HCC metastasis. Here, we investigate to define the role of RhoC in HCC metastasis. Furthermore, we sought to determine whether inhibition of the expression of RhoC might block the metastasis of HCC in vivo.

Experimental Design: A stable retroviral small interfering RNA approach was employed to selectively knockdown the expression of RhoC in vitro and in vivo. Invasion and migration assay, MTT and fluorescence-activated cell sorting analysis, Rho activity assay, and immunofluorescence staining were carried out to characterize RhoC in vitro. An anti-RhoC retroviral gene delivery BALB/c nude mice model was established to investigate whether knockdown of the expression of RhoC might inhibit the metastasis of HCC in vivo.

Results: We confirmed the correlation of RhoC expression and metastatic potentials of HCC cell lines. We also showed that suppression of RhoC expression resulted in inhibition of invasion and migration without an apparent effect on cell survival and proliferation in HCCLM3 cells. Furthermore, a similar effect of RhoC on autotaxin-induced invasion of HCCLM3 cells was also observed. Significantly, we successfully adopted an HCC metastatic mouse model that allowed us to show that knockdown of the RhoC expression resulted in inhibition of metastasis of HCC in vivo for the first time.

Conclusions: Our results show a critical role of RhoC in metastasis of HCC, implicating RhoC as a potential therapeutic target to block HCC metastasis.
The Interleukin-8 Pathway in Cancer
Authors: Waugh David J.J. , Wilson Catherine
Published: November 2008

Interleukin-8 (IL-8) is a proinflammatory CXC chemokine associated with the promotion of neutrophil chemotaxis and degranulation. This chemokine activates multiple intracellular signaling pathways downstream of two cell-surface, G protein–coupled receptors (CXCR1 and CXCR2). Increased expression of IL-8 and/or its receptors has been characterized in cancer cells, endothelial cells, infiltrating neutrophils, and tumor-associated macrophages, suggesting that IL-8 may function as a significant regulatory factor within the tumor microenvironment. The induction of IL-8 signaling activates multiple upstream signaling pathways that (a) impinge on gene expression via regulation of numerous transcription factor activities, (b) modulate the cellular proteome at the level of translation, and/or (c) effect the organization of the cell cytoskeleton through posttranslational regulation of regulatory proteins. As a consequence of the diversity of effectors and downstream targets, IL-8 signaling promotes angiogenic responses in endothelial cells, increases proliferation and survival of endothelial and cancer cells, and potentiates the migration of cancer cells, endothelial cells, and infiltrating neutrophils at the tumor site. Accordingly, IL-8 expression correlates with the angiogenesis, tumorigenicity, and metastasis of tumors in numerous xenograft and orthotopic in vivo models. Recently, IL-8 signaling has been implicated in regulating the transcriptional activity of the androgen receptor, underpinning the transition to an androgen-independent proliferation of prostate cancer cells. In addition, stress and drug-induced IL-8 signaling has been shown to confer chemotherapeutic resistance in cancer cells. Therefore, inhibiting the effects of IL-8 signaling may be a significant therapeutic intervention in targeting the tumor microenvironment.
Interleukin-6 and Soluble Interleukin-6 Receptor Levels as Markers of Disease Extent and Prognosis in Neuroblastoma
Authors: Egler Rachel A. , Burlingame Susan M. , Nuchtern Jed G. , Russell Heidi V.
Published: November 2008

Purpose: To explore the relationships between interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) levels and disease extent and clinical outcome in childhood neuroblastoma.

Experimental Design: Pretreatment peripheral blood (PB; n = 53) and bone marrow (n = 18) samples from patients with neuroblastoma were assayed by ELISA for IL-6 and sIL-6R. PB values were compared with healthy pediatric controls (n = 28).

Results: PB IL-6 levels were significantly elevated in patients with high-risk disease compared with those with low and intermediate risk disease (23.9 versus 4.3 pg/mL; P < 0.001) and the normal control group (23.9 versus 3.3 pg/mL; P < 0.001). Similarly, bone marrow IL-6 levels were higher in high-risk patients when compared with low- and intermediate-risk patients (15 versus 0 pg/mL; P < 0.02). Other factors correlated with higher IL-6 levels were age of >18 months, bony metastases, and unfavorable histology. sIL-6R levels were not significantly correlated with disease stage. Patients with detectable PB IL-6 at diagnosis had significantly lower event-free survival rates (P < 0.008). sIL-6R levels <2.5 × 104 pg/mL were also associated with a significantly worse event-free survival (P = 0.016).

Conclusion: Elevated PB IL-6 levels correlated with features of high-risk neuroblastoma and poor prognosis in this population. Decreased PB sIL-6R levels correlated with the presence of metastatic disease. Further study of these markers in children with neuroblastoma seems warranted.
Cell Proliferation, Cell Cycle Abnormalities, and Cancer Outcome in Patients with Barrett's Esophagus: A Long-term Prospective Study
Authors: Chao Dennis L. , Sanchez Carissa A. , Galipeau Patricia C. , Blount Patricia L. , Paulson Thomas G. , Cowan David S. , Ayub Kamran , Odze Robert D. , Rabinovitch Peter S. , Reid Brian J.
Published: November 2008

Purpose: Elevated cellular proliferation and cell cycle abnormalities, which have been associated with premalignant lesions, may be caused by inactivation of tumor suppressor genes. We measured proliferative and cell cycle fractions of biopsies from a cohort of patients with Barrett's esophagus to better understand the role of proliferation in early neoplastic progression and the association between cell cycle dysregulation and tumor suppressor gene inactivation.

Experimental Design: Cell proliferative fractions (determined by Ki67/DNA multiparameter flow cytometry) and cell cycle fractions (DNA content flow cytometry) were measured in 853 diploid biopsies from 362 patients with Barrett's esophagus. The inactivation status of CDKN2A and TP53 was assessed in a subset of these biopsies in a cross-sectional study. A prospective study followed 276 of the patients without detectable aneuploidy for an average of 6.3 years with esophageal adenocarcinoma as an end point.

Results: Diploid S and 4N (G2/tetraploid) fractions were significantly higher in biopsies with TP53 mutation and loss of heterozygosity. CDKN2A inactivation was not associated with higher Ki67-positive, diploid S, G1, or 4N fractions. High Ki67-positive and G1-phase fractions were not associated with the future development of esophageal adenocarcinoma (P = 0.13 and P = 0.15, respectively), whereas high diploid S-phase and 4N fractions were (P = 0.03 and P < 0.0001, respectively).

Conclusions: High Ki67-positive proliferative fractions were not associated with inactivation of CDKN2A and TP53 or future development of cancer in our cohort of patients with Barrett's esophagus. Biallelic inactivation of TP53 was associated with elevated 4N fractions, which have been associated with the future development of esophageal adenocarcinoma.
BRCA1 5083del19 Mutant Allele Selectively Up-Regulates Periostin Expression In vitro and In vivo
Authors: Quaresima Barbara , Romeo Francesco , Faniello Maria C. , Di Sanzo Maddalena , Liu Chang-Gong , Lavecchia Annamaria , Taccioli Cristian , Gaudio Eugenio , Baudi Francesco , Trapasso Francesco , Croce Carlo M. , Cuda Giovanni , Costanzo Francesco
Published: November 2008

Purpose: The aim of this study was to explore the gene expression pattern produced by the cancer-associated BRCA1 5083del19 founder mutation by using a microarray analysis. Such a mutation, identified in a subset of familial breast cancer patients, involves a deletion at the 3′ end of the BRCA1 messenger leading, in the mature protein, to the ablation of the BRCT tandem domain.

Experimental Design: We generated HeLa cells stably expressing both exogenous wild-type (HeLa/wtBRCA1), used as a control, and 5083del19 BRCA1 (HeLa/5083del19BRCA1) alleles; gene chips were then used to investigate any changes in the transcription profile induced by the 5083del19 BRCA1 mutant compared with controls.

Results: Among the genes showing perturbation of their expression, periostin was found to be up-regulated in HeLa/5083del19BRCA1 cells to an extent of 72-fold versus HeLa/pcDNA3.1/empty and 76-fold versus HeLa/wtBRCA1 cells. This finding was validated both in vitro in breast cancer cell lines harboring mutations of BRCA1 and in vivo by immunohistochemistry of breast cancer specimens bearing the 5083del19 BRCA1 mutation as well as by Western blot analysis of sera obtained from patients and healthy carriers of the same mutation.

Conclusions: Our results suggest that periostin overexpression, whose product is released from cells in the extracellular fluids, might be a potential marker for early cancer detection in a specific subset of hereditary breast carcinomas triggered by cancer-associated BRCA1 mutations that affect the BRCT tandem domain.
Circulating Tumor Cell Detection Predicts Early Metastatic Relapse After Neoadjuvant Chemotherapy in Large Operable and Locally Advanced Breast Cancer in a Phase II Randomized Trial
Authors: Pierga Jean-Yves , Bidard François-Clément , Mathiot Claire , Brain Etienne , Delaloge Suzette , Giachetti Sylvie , de Cremoux Patricia , Salmon Rémy , Vincent-Salomon Anne , Marty Michel
Published: November 2008

Purpose: Circulating tumor cells in blood from metastatic breast cancer patients have been reported as a surrogate marker for tumor response and shorter survival. The aim of this study was to determine whether circulating tumor cells are present in the blood of patients with large operable or locally advanced breast cancer before neoadjuvant chemotherapy and after neoadjuvant chemotherapy before surgery.

Experimental Design: Blood samples of 7.5 mL were obtained on CellSave tubes from patients included in a phase II trial (REMAGUS 02). Circulating tumor cells were immunomagnetically separated and fluorescently stained by the CellSearch system. Blood from 20 metastatic breast cancer patients was used as a positive control.

Results: From October 2004 to July 2006, preneoadjuvant chemotherapy and/or postneoadjuvant chemotherapy blood samples were obtained from 118 patients. At least 1 circulating tumor cell was detected in 22 of 97 patients with preneoadjuvant chemotherapy samples (23%; 95% confidence interval, 15-31%; median, 2 cells; range, 1-17 cells). Circulating tumor cell positivity rates were 17% in 86 postneoadjuvant chemotherapy samples and 27% in all 118 patients. Persistence of circulating tumor cells at the end of neoadjuvant chemotherapy was not correlated with treatment response. After a short median follow-up of 18 months, the presence of circulating tumor cells (P = 0.017), hormone receptor negativity, and large tumor size were independent prognostic factors for shorter distant metastasis–free survival.

Conclusion: Circulating tumor cells can be detected by the CellSearch system at a low cutoff of 1 cell in 27% of patients receiving neoadjuvant chemotherapy. Circulating tumor cell detection was not correlated to the primary tumor response but is an independent prognostic factor for early relapse.