bluuebunny/crossref_metadata_2025 huggingface dataset:
An optimized whole blood method for flow cytometric measurement of ZAP‐70 protein expression in chronic lymphocytic leukemia
Authors: Shankey T. Vincent , Forman Meryl , Scibelli Paul , Cobb Jeffrey , Smith Cecilia M. , Mills Rhonda , Holdaway Karen , Bernal‐Hoyos Elizabeth , Van Der Heiden Mafalda , Popma Jan , Keeney Mike
Published: August 2006

Background:

ZAP‐70 protein expression has been proposed as a marker for immunoglobulin heavy chain mutational status, which some studies have correlated with disease course in B‐cell chronic lymphocytic leukemia (CLL). Studies published to date measuring levels of expression of ZAP‐70 intracellular protein using flow cytometry have demonstrated poor performance, as defined by the difference in signal in known positive and negative lymphocyte populations.

Methods:

A recently published method (Chow S, Hedley DW, Grom P, Magari R, Jacobberger JW, Shankey TV, Cytometry A 2005;67:4–17) to measure intracellular phospho‐epitopes was optimized using a design of experiments (DOE) approach to provide the best separation of ZAP‐70 expression in positive T‐ or NK‐cells as compared to negative B‐cells in peripheral blood samples. A number of commercially available anti‐ZAP‐70 antibody‐conjugates were screened using this methodology, and the antibody‐conjugate showing the best performance was chosen to develop a four‐color, five antibody assays to measure ZAP‐70 levels in whole blood specimens.

Results:

Using the optimized fixation and permeabilization method, improvement in assay performance (signal‐to‐noise, S/N) was seen in most of the antibodies tested. The custom SBZAP conjugate gave the best S/N when used in conjunction with this optimized fixation /permeabilization method. In conjunction with carefully standardized instrument set‐up protocols, we obtained both intra‐ and interlaboratory reproducibility in the analysis of ZAP‐70 expression in whole blood samples from normal and CLL patients.

Conclusions:

The development of a sensitive, specific and highly reproducible ZAP‐70 assay represents only the first essential step for any clinical assay. The universal implementation of a validated data analysis method and the establishment of methodology‐based cutoff points for clinical outcomes must next be established before ZAP‐70 protein analysis can be routinely implemented in the clinical laboratory. © 2006 International Society for Analytical Cytology
Torque and suspension force in a bearingless switched reluctance motor
Authors: Takemoto Masatsugu , Chiba Akira , Akagi Hirofumi , Fukao Tadashi
Published: August 2006

Bearingless switched reluctance motors, which can control rotor radial positions with magnetic force, have been proposed. The bearingless switched reluctance motors are characterized by integration of switched reluctance motors and magnetic bearings. These motors have two kinds of stator windings composed of motor main windings and suspension windings in the same stator in order to produce suspension force that can realize rotor shaft suspension without mechanical contacts or lubrication. For successful stable operation, accurate theoretical formulas of instantaneous torque and suspension force are necessary to a rotational speed controller and a rotor radial position controller. This paper derives the theoretical formulas of the instantaneous torque and the suspension force from an assumption of simple permeance distribution. This derivation process makes an assumption that fringing fluxes are distributed on elliptical lines. It is shown with experimental results that the derived theoretical formulas are very accurate in terms of practical application. © 2006 Wiley Periodicals, Inc. Electr Eng Jpn, 157(2): 72–82, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20157
Order and parameter estimation of time‐varying system by subspace method
Authors: Tamaoki Morimichi , Akizuki Kageo , Oura Kunihiko
Published: August 2006

This paper proposes an identification algorithm for time‐varying systems. We apply subspace method for estimation, since it is known to be useful when the input–output (I/O) data are observed by multi‐input multi‐output (MIMO) systems. Among many proposed techniques of subspace methods, we use MOESP (MIMO Output‐Error State Space model identification) in this paper, which assures arithmetic stability by RQ factorization and singular value decomposition (SVD). Generally, subspace methods can be applied after I/O data collection, so that we introduce updated steps of matrices for PI‐MOESP, which uses past inputs for instrumental variables. We propose a recursive update algorithm of PI‐MOESP, including estimation step of the system order, and consider some parameters inherent to the algorithm, namely, initial number of data, estimation step of the order, and forgetting factor. A numerical example shows the usefulness of the proposed method. © 2006 Wiley Periodicals, Inc. Electr Eng Jpn, 157(2): 57–64, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20169
Formation control of multiple nonholonomic mobile robots
Authors: Ikeda Takashi , Jongusuk Jurachart , Ikeda Takayuki , Mita Tsutomu
Published: August 2006

Tracking control problem of multiple mobile robots is considered. Our system is composed of a reference and follower robots of unicycle type. The robots are assumed to satisfy pure rolling and nonslipping conditions, which lead to nonholonomic constraints. The purpose is to control the followers so that the reference is tracked with arbitrary desired clearance and also to avoid interrobot collisions. To accomplish this goal, we first introduced a virtual robot (VR) tracking control to establish and maintain the formation when no collision is detected. VR is an ideal robot fixed with each follower and helps in simplifying the control, as the tracking error becomes zero in the final stage. During the process, if the possibility of collision is detected, a collision avoidance technique (l−ψ or l−l control) will be applied to the lower priority robot. The result of this control gives a monotonic convergence in an internal shape of distance variables, which enables us to predict the movement of the robots during this control and leads to collision‐free movement. These processes are repeated until the desired motion is accomplished. Simulation results prove the efficiency of our control techniques. © 2006 Wiley Periodicals, Inc. Electr Eng Jpn, 157(3): 81–88, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20192 Copyright © 2006 Wiley Periodicals, Inc.
Thermal behavior of small lithium‐ion secondary battery during rapid charge and discharge cycles
Authors: Ohshima Takamasa , Nakayama Masato , Fukuda Kenichi , Araki Takuto , Onda Kazuo
Published: August 2006

The secondary batteries for an electric vehicle (EV) generate much heat during rapid charge and discharge cycles above the rated condition, when the EV starts quickly consuming the battery power and stops suddenly recovering the inertia energy. During rapid charge and discharge cycles, the cell temperature rises significantly and may exceed the allowable temperature. We calculated the temperature rise of a small lithium‐ion secondary battery during rapid charge and discharge cycles using our battery thermal behavior model, and confirmed its validity during discharge cycle at current smaller than the discharge rate of 1C. The heat source factors were measured by the methods described in our previous study, because the present batteries have been improved in their performance and have low overpotential resistance. The battery heat capacity was measured by a twin‐type heat conduction calorimeter, and determined to be a linear function of temperature. Further, the heat transfer coefficient was measured again precisely by the method described in our previous study, and was arranged as a function of cell and ambient temperatures. The calculated temperature by our battery thermal behavior model using these measured data agrees well with the cell temperature measured by thermocouple. Therefore, we can confirm the validity of this model again during rapid charge and discharge cycles. © 2006 Wiley Periodicals, Inc. Electr Eng Jpn, 157(3): 17–25, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20249 Copyright © 2006 Wiley Periodicals, Inc.
Measurement of spinal cord evoked magnetic fields by vector SQUID biomagnetometer
Authors: Adachi Yoshiaki , Miyamoto Masakazu , Kawai Jun , Uehara Gen
Published: August 2006

Biomagnetometry is a powerful method for the investigation of neural activity. We developed a multichannel superconducting quantum interference device (SQUID) biomagnetometer system for measurement of the evoked magnetic field from stimulated spinal cords. The system is equipped with three dimensionally configured SQUID vector gradiometers, which can detect not only the radial components of the magnetic field applied to the subject but also the tangential components. With the system, we could successfully observe the distribution of the evoked magnetic field corresponding to neuronal signals propagating in the spinal cords of small animals in the form of momentarily changing vector maps. © 2006 Wiley Periodicals, Inc. Electr Eng Jpn, 157(2): 15–23, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20277
A current sensorless MPPT control method for a stand‐alone‐type PV generation system
Authors: Itako Kazutaka , Mori Takeaki
Published: August 2006

In this paper, a current sensorless MPPT control method for a stand‐alone‐type PV generation system is proposed. This control method offers advantages of the simplified hardware configuration and low cost by using only one sensor to measure the PV output voltage. When used as a stand‐alone‐type with a battery load, the experimental results show that the estimated values of PV output current are accurate, and the use of the proposed MPPT control increases the PV generated energy by 16.3% compared to the conventional system. Furthermore, the authors clarified that the proposed method has an extremely high UUF (useful utilization factor) of 98.7%. © 2006 Wiley Periodicals, Inc. Electr Eng Jpn, 157(2): 65– 71, 2006; Published online in Wiley InterScience (www.interscience. wiley.com). DOI 10.1002/eej.20424
Computation Revealed a Case where Kinetic Selectivity is Controlled by Dynamics: Isomerization of Benzylideneanilines
Authors: Cheettu Ammal Salai , Yamataka Hiroshi
Published: August 2006

The cis–trans isomerization of benzylideneaniline proceeds via a single transition state to afford two conformational isomers on the potential energy surface. Ab initio molecular dynamic simulations revealed that the observed kinetic selectivity of the two conformers for each of the cis and trans isomers is not governed by the relative stabilities of two independent transition states that would lead to the two conformers, respectively, but by the reaction dynamics. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Influence of ultrasonic disintegration on the dewaterability of waste activated sludge
Authors: Wang F. , Ji M. , Lu S.
Published: August 2006

Ultrasound can be used to disintegrate waste activated sludge (WAS), resulting in changes in sludge dewaterability. To observe and explain the change in sludge dewatering properties before and after ultrasonic disintegration, the specific resistance to filtration (SRF), capillary suction time (CST), content of biopolymers (proteins + polysaccharides), and free water in the sludge before and after disintegration were examined. Despite the degradation of extracellular polymeric substances (EPS), the sludge dewatering properties worsened after disintegration. This result is attributed to two changes in the sludge, one being the effect of the water retained by the biopolymers and the other being the adsorption effect of the fine sludge particles for free water. © 2006 American Institute of Chemical Engineers Environ Prog, 2006
The costs of wind's intermittency in Germany: application of a stochastic electricity market model
Authors: Swider Derk J. , Weber Christoph
Published: August 2006

In this paper a stochastic fundamental electricity market model is applied to estimate the integration costs of wind due to changed system operation and investments in Germany. The model's principle is cost minimization by determining the system costs mainly as a function of available generation and transmission capacities, primary energy prices, plant characteristics, and electricity demand. To obtain appropriate estimates of the integration costs notably reduced efficiencies at part load and start‐up costs are taken into account. The intermittency of wind is covered by a stochastic recombining tree and the system is considered to adapt on increasing wind integration over time by endogenous modeling of reserve requirements and investments in thermal power plants. The results highlight the need for stochastic optimization models and the strong dependency on the actual system and its development over time to get sufficient estimates of the integration costs of wind's intermittency. Copyright © 2006 John Wiley & Sons, Ltd.
Central bank communications and equity ETFs
Authors: Wang Tao , Yang Jian , Wu Jingtao
Published: August 2006

This article examines effects of monetary policy surprises on returns, volatilities, trading volumes, and bid–ask spread of two equity ETFs, the S&P 500 SPY fund and the S&P 400 MDY fund. The policy surprises are measured by both surprises in the federal funds rate target changes and surprises in the future direction of the Federal Reserve monetary policy. The results show that there is an overreaction of the SPY to the federal funds rate target surprise in the first 5 minutes' trading and that both the SPY and the MDY returns, volatilities, trading volumes, and bid–ask spread react more strongly to surprise cuts than to surprise increases in the federal funds rate target. Quantitatively, after 45 minutes, an unanticipated 25‐basis‐point cut in the federal funds rate target is associated with an increase of 1.2 and 1.6% in the SPY and the MDY, respectively, while an unanticipated 25‐basis‐point decline (or rise) in the four‐quarter‐ahead eurodollar futures rate is associated with an increase (or decrease) of 0.71 and 0.40% in the SPY and the MDY, respectively. Further evidence also suggests that the market reacts more strongly to surprises in the future direction of monetary policy during the monetary tightening period and that the impact of monetary policy surprises depends on their sizes. © 2006 Wiley Periodicals, Inc. Jrl Fut Mark 26:959–995, 2006
The olfactory bulb and olfactory mucosa obtained from human cadaver donors as a source of olfactory ensheathing cells
Authors: Miedzybrodzki Ryszard , Tabakow Pawel , Fortuna Wojciech , Czapiga Bogdan , Jarmundowicz Wlodzimierz
Published: August 2006

During the last decade, olfactory ensheathing cells (OECs) have been successfully applied in multiple experimental approaches aimed to repair damaged mammalian spinal cord. Some of these experiments have consequently been translated into clinical trials. Finding a reliable source of human OECs that is easily accessible and can ensure a sufficient number of cells is a major prerequisite for conducting studies on OEC‐mediated spinal cord regeneration. Here, we present a procedure for obtaining olfactory bulbs (OBs) and olfactory mucosa (OM) simultaneously from adult cadaver heart‐beating donors for OEC isolation and analyze some of the factors that may condition successful OEC culture. We show that the results of OEC culture from OBs (10 cases) correlated significantly with warm ischemia time (WIT) as well as the initial viability of the isolated cells. Efficient OEC culture was possible when the WIT for the OB was up to 20 min. Brain damage, assessed by determination of S100B serum level, was not related to the success of OEC culture from the OB. Cadaver OM (7 cases) was shown to be a more reliable source of human OECs than the OB. In most of the examined cases the efficacy of culturing OECs from cadaver OM obtained even 180 min after cardiac arrest was comparable to that of living patients. The method of obtaining OBs and OM from cadavers enables the use of an alternative source of primary adult human OECs for further preclinical and clinical studies on their neurotrophic properties. © 2006 Wiley‐Liss, Inc.
The effects of concurrent cannabis use among ecstasy users: neuroprotective or neurotoxic?
Authors: Fisk John E. , Montgomery Catharine , Wareing Michelle , Murphy Philip N.
Published: August 2006

The research evidence regarding the potential effects of ecstasy suggests that it may be neurotoxic and that its use is associated with cognitive impairment. In recent years evidence has emerged suggesting that cannabinoids, the active ingredients in cannabis, can be neuroprotective under certain conditions. Given that many ecstasy users also consume cannabis at the same time, the possibility emerges that these individuals might be less susceptible to ecstasy‐related impairment. The present paper reanalyses the data from a number of previous studies, contrasting the performance of those individuals who generally consume cannabis and ecstasy at the same time with those who generally consume ecstasy on its own. The two ecstasy‐using groups are compared with non‐ecstasy users on a range of measures including processing speed, random letter generation, verbal and visuo‐spatial working memory span, reasoning and associative learning. The two ecstasy user groups did not differ significantly from each other on any of the measures. Both user groups were significantly worse than non‐ecstasy users on measures of associative learning, verbal and visuo‐spatial working memory and reasoning. The results suggest that consuming cannabis at the same time as ecstasy does not reduce the likelihood of cognitive impairment. Copyright © 2006 John Wiley & Sons, Ltd.
Electronic structure of CO—An exercise in modern chemical bonding theory
Authors: Frenking Gernot , Loschen Christoph , Krapp Andreas , Fau Stefan , Strauss Steven H.
Published: August 2006

This paper discusses recent progress that has been made in the understanding of the electronic structure and bonding situation of carbon monoxide which was analyzed using modern quantum chemical methods. The new results are compared with standard models of chemical bonding. The electronic charge distribution and the dipole moment, the nature of the HOMO and the bond dissociation energy are discussed in detail. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006
Dispersion and repulsion contributions to the solvation free energy: Comparison of quantum mechanical and classical approaches in the polarizable continuum model
Authors: Curutchet Carles , Orozco Modesto , Luque F. Javier , Mennucci Benedetta , Tomasi Jacopo
Published: August 2006

We report a systematic comparison of the dispersion and repulsion contributions to the free energy of solvation determined using quantum mechanical self‐consistent reaction field (QM‐SCRF) and classical methods. In particular, QM‐SCRF computations have been performed using the dispersion and repulsion expressions developed in the framework of the integral equation formalism of the polarizable continuum model, whereas classical methods involve both empirical pairwise potential and surface‐dependent approaches. Calculations have been performed for a series of aliphatic and aromatic compounds containing prototypical functional groups in four solvents: water, octanol, chloroform, and carbon tetrachloride. The analysis is focused on the dependence of the dispersion and repulsion components on the level of theory used in QM‐SCRF computations, the contribution of those terms in different solvents, and the magnitude of the coupling between electrostatic and dispersion–repulsion components. Finally, comparison is made between the dispersion–repulsion contributions obtained from QM‐SCRF calculations and the results determined from classical approaches. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006
Software news and updates carma: A molecular dynamics analysis program
Authors: Glykos Nicholas M.
Published: August 2006

A computer program has been developed to aid the analysis of molecular dynamics trajectories. The program is tuned for macromolecular large‐scale problems and supports features such as removal of global translations‐rotations of the solute, calculation of average distance maps and their corresponding standard deviations, calculation of the variance‐covariance and cross‐correlation matrices, and principal component analysis of trajectories with the added ability to create artificial trajectories based on selected eigenvectors. Limited graphics (trajectory viewing) capabilities are also available. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006
Photochemistry of CH3Mn(CO)5: A multiconfigurational ab initio study
Authors: González Leticia , Daniel Chantal
Published: August 2006

The electronic spectroscopy of CH3Mn(CO)5 has been investigated by means of ab initio multiconfigurational MS‐CASPT2/CASSCF calculations. The absorption spectrum is characterized by a series of Metal‐Centered (MC) excited states in the UV energy domain (below 290 nm) that could be responsible for the observed photoreactivity starting at 308 nm. The upper part of the spectrum is overcrowded between 264 and 206 nm and dominated by a high density of Metal‐to‐Ligand‐Charge‐Transfer (MLCT) states corresponding mainly to 3dMn → π*CO excitations. A non‐negligible contribution of Metal‐to‐σ‐Bond‐Charge‐Transfer (MSBCT) states corresponding to 3dMn → σ*Mn‐CH3 excitations is also present in the theoretical spectrum of CH3Mn(CO)5. However, in contrast to other transition metal hydrides and methyl substituted (HMn(CO)5, HCo(CO)4, and CH3Co(CO)4) these MSBCT transitions do not participate to the lowest bands of the spectrum as main contributions. The photochemistry of CH3Mn(CO)5, namely the loss of a CO ligand vs. the metal‐methyl bond homolysis, is investigated by means of MS‐CASPT2 states correlation diagrams. This study illustrates the complexity of the photodissociation mechanism of this class of molecules, which involves a large number of nearly degenerate electronic states with several channels for fragmentation. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006
Theoretical mechanistic study on the radical–molecule reactions of cyanomethylidyne with PH3, H2S, and HCl
Authors: Wang Jian , Ding Yi‐Hong , Sun Chia‐Chung
Published: August 2006

The cyanomethylidyne (CCN) has been the long‐standing subject of extensive theoretical and experimental studies on its structures and spectroscopies. However, there are few investigations on its reactivity. Our very recent theoretical work indicated that even with the simplest methane, the CCN reaction faces almost zero barriers following the carbyne mechanism as CH does. This was suggestive of the powerfulness of the nonatomic and nonhydrogenated CCN radical in depleting old molecules and synthesizing new cyanogen‐containing molecules in either combustion or interstellar processes. In this paper, a detailed mechanistic study at the CCSD(T)/6‐311+G(2df,p)//B3LYP/6‐311g(d,p) and G2M(CC1)//B3LYP/6‐311G(d,p) computational levels is reported for the reactions of CCN with a series of σ‐bonded molecules of the second row HnX (X,n) = (P,3), (S,2), and (Cl,1). The carbenoid insertion is confirmed as the most favored entrance channel, forming Hn−1XC(H)CN. Subsequently, Hn−1XC(H)CN will predominantly lead to product Hn−2XC(H)CN+H via the H‐extrusion processes (except X = Cl). Yet, the CCN+HX (X = Cl) reaction is the exception because XC(H)CN intrinsically has no H‐atoms at X for extrusion or migration. At G2M(CC1)//B3LYP/6‐311G(d,p) computational level, ClC(H)CN can only dissociate back to the reactant or be stabilized with its isomers upon sufficient collisions or radiation. The carbyne character confirmed in this paper provides a useful base for future experimental and theoretical study on the chemistry of this nonatomic and nonhydrogenated reactive radical. In addition, interestingly, the complexes HnX‐CCN (X,n) = (P,3) and (S,2) formed in the reactions are found not to be the simple (loosely bound) donor–accepter complexes as those formed in the CCN insertions into other hydrides (NH3, H2O, HF, HCl).On the basis of the comparison with the qualitative features of typical ylides, H3PCCN and H2SCCN are considered to be similar to the ylides in nature, being “ylide‐like radicals.” They might be observed in some experiments, since they are in deep potential wells on the energy surface. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006
Explicit factorization of external coordinates in constrained statistical mechanics models
Authors: Echenique Pablo , Calvo Iván
Published: August 2006

If a macromolecule is described by curvilinear coordinates or rigid constraints are imposed, the equilibrium probability density that must be sampled in Monte Carlo simulations includes the determinants of different mass‐metric tensors. In this work, the authors explicitly write the determinant of the mass‐metric tensor G and of the reduced mass‐metric tensor g, for any molecule, general internal coordinates and arbitrary constraints, as a product of two functions; one depending only on the external coordinates that describe the overall translation and rotation of the system, and the other only on the internal coordinates. This work extends previous results in the literature, proving with full generality that one may integrate out the external coordinates and perform Monte Carlo simulations in the internal conformational space of macromolecules. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006
Electrophysiological abnormalities precede apparent histological demyelination in the central nervous system of mice overexpressing proteolipid protein
Authors: Tanaka Hisataka , Ikenaka Kazuhiro , Isa Tadashi
Published: August 2006

Myelin proteolipid protein (plp), a major myelin protein in the CNS, has been proposed to function in myelin assembly. Transgenic mice overexpressing the plp gene by introduction of two extra wild‐type (Wt) mouse plp genes (plptg/–) exhibit normal myelination and ion channel clustering at the age of 2 months. However, at the age of 5 months, demyelination becomes observable, accompanied by a reduction in the number of K+ channel clusters at Ranvier's node and a progressive increase in motor deficit. To clarify how these age‐dependent changes are related to nerve conduction in the CNS, we analyzed the conduction velocity (CV) and relative refractory period (RRP) of identified spinal ascending or descending tracts, such as the dorsal column pathway, the vestibulospinal and reticulospinal tracts, and the pyramidal tract, in plptg/– mice 2, 5, and 8 months of age. We found that CVs decreased as age increased. Importantly, CVs were significantly reduced and prolonged RRPs were observed in 2‐month‐old (2M) plptg/– mice that had no apparent demyelination. Immunohistological examination revealed that densities of Na+ and K+ channel clusters decreased as plptg/– and Wt mice aged. However, a clear correlation was not observed between CVs and mean channel cluster densities or between mean channel cluster densities and progress of demyelination. Performance in the rotarod test was normal in 2M plptg/– mice but deteriorated in mice older than age 5 months. These results suggest that electrophysiological analysis can detect the abnormalities of the plptg/– mice earlier than histological or behavioral measures. © 2006 Wiley‐Liss, Inc.
D‐β‐hydroxybutyrate protects dopaminergic SH‐SY5Y cells in a rotenone model of Parkinson's disease
Authors: Imamura Keiko , Takeshima Takao , Kashiwaya Yoshihiro , Nakaso Kazuhiro , Nakashima Kenji
Published: August 2006

It has been postulated that the pathogenesis of Parkinson's disease (PD) is associated with mitochondrial dysfunction. Rotenone, an inhibitor of mitochondrial complex I, provides models of PD both in vivo and in vitro. We investigated the neuroprotective effect of D‐β‐hydroxybutyrate (bHB), a ketone body, against rotenone toxicity by using SH‐SY5Y dopaminergic neuroblastoma cells. SH‐SY5Y cells, differentiated by all‐trans‐retinoic acid, were exposed to rotenone at concentrations ranging from 0 to 1,000 nM. We evaluated cellular oxidation reduction by the alamarBlue assay, viability by lactate dehydrogenase (LDH) assay, and survival/death ratio by live/dead assays. Exposure to rotenone for 48 hr oxidized cells and decreased their viability and survival rate in a concentration‐dependent manner. Pretreatment of cells with 8 mM bHB provided significant protection to SH‐SY5Y cells. Whereas rotenone caused the loss of mitochondrial membrane potential, released cytochrome c into the cytosol, and reduced cytochrome c content in mitochondria, addition of bHB blocked this toxic effect. bHB also attenuated the rotenone‐induced activation of caspase‐9 and caspase‐3. Administration of 0–10 mM 3‐nitropropionic acid, a complex II inhibitor, also decreased the reducing power of SH‐SY5Y cells measured by alamarBlue assay. Pretreatment with 8 mM bHB attenuated the decrease of alamarBlue fluorescence. These data demonstrated that bHB had a neuroprotective effect that supported the mitochondrial respiration system by reversing the inhibition of complex I or II. Ketone bodies, the alternative energy source in the mammalian brain, appear to have therapeutic potential in PD. © 2006 Wiley‐Liss, Inc.
Restoration of growth plate function following radiotherapy is driven by increased proliferative and synthetic activity of expansions of chondrocytic clones
Authors: Horton Jason A. , Margulies Bryan S. , Strauss Judith A. , Bariteau Jason T. , Damron Timothy A. , Spadaro Joseph A. , Farnum Cornelia E.
Published: August 2006

Radiation therapy encompassing an active epiphysis can negatively impact the potential for bone growth by disrupting cell‐cycle progression and accelerating apoptosis and terminal differentiation in physeal chondrocytes. Despite functional derangement following radiation exposure, the irradiated growth plate retains a capacity for regeneration and recovery of growth. The purpose of this study was to characterize the initial sequence of events leading to functional growth recovery in irradiated weanling rat growth plates. We hypothesized that growth in an irradiated epiphysis would be partially restored due to the expansion of chondrocytic clones. Stereological histomorphometry was used to compare chondrocytic cell and matrix turnover between the first and second week following irradiation, and to determine the relative contribution of each of the cellular and extracellular matrix (ECM) compartments to growth. We found that restoration of growth in the irradiated limb was strongly associated with the proliferative activity and production of ECM by these chondrocytic clones, as they expand in average volume, but not in numerical density. We conclude that chondrocytes forming expansive clones and exhibiting increased mitotic and matrix synthesis activity initiate the early restoration of function in the irradiated growth plate, and would be a logical target for strategies to restore full growth potential. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1945–1956, 2006
The role of surgery in treatment of stage IV melanoma
Authors: Young Shawn E. , Martinez Steve R. , Essner Richard
Published: August 2006

The prognosis for patients with melanoma has not improved over the last 30 years. So far, almost without exception, clinical trials conducted with single or multiple agent chemotherapy, biological therapy (interferon‐alpha, interleukin‐2), and biochemotherapy have failed to demonstrate consistent survival benefit. Without effective alternate treatments, surgery must be considered the primary treatment of melanoma, independent of disease stage. Although surgery is clearly favored as the treatment of localized melanoma, consensus opinion and clinician preference become divided once melanoma progresses beyond its primary site. Many physicians will adopt an attitude of resignation and hesitancy when treating metastatic melanoma. As a result, patients with advanced disease are often treated with medications that produce little survival or palliative benefit at the expense of significant toxicity. Numerous studies have demonstrated clear and durable survival advantages for patients undergoing complete resection of metastatic melanoma. Further, surgical resection can produce an immediate decrease in tumor burden with minimal morbidity and mortality at a reasonable cost. J. Surg. Oncol. 2006;94:344–351. © 2006 Wiley‐Liss, Inc.
Mohs micrographic surgery in the treatment of lentigo maligna and melanoma
Authors: Temple Claire L.F. , Arlette John P.
Published: August 2006

Background and Objectives

The treatment of lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging due to lesion location, size, patient age, and potential for recurrence and spread. The largest studies to date confirm that for melanocytic tumours, MMS provides high local control rates while minimizing tissue loss. Herein we report our local control rate for melanoma treated by MMS over a decade.

Methods

Charts were reviewed on all patients with melanocytic tumors treated by a single physician (JPA) using MMS over the time period of 1993–2002. Demographic, surgical and pathological details were recorded. Patients were followed for local, regional and distant recurrences.

Results

The patient population was comprised of 199 patients with 202 melanomas. There were 69 invasive lesions, with a mean Breslow depth of 0.92 mm (0.2–3.6 mm). The mean number of levels required to clear the lesions was 2.7 (1–7), resulting in a mean defect size of 11.8 cm2 (0.9–70.7 cm2). Patients with LMM were significantly older (73.2 vs. 66.5 yrs, p = 0.012) and had larger defects after MMS (16.74 cm2 vs. 10.27 cm2) than patients with LM. At a mean follow‐up of 29.8 months, there were no local recurrences, four regional recurrences, and two distant recurrences.

Conclusion

MMS is an effective modality for the clearance of melanocytic tumors. J. Surg. Oncol. 2006;94:287–292. © 2006 Wiley‐Liss, Inc.
Expression of DPC4/Smad4 gene in stone‐containing intrahepatic bile duct
Authors: Lee King‐Teh , Chang Wen‐Tsan , Wang Shen‐Nien , Chuang Shih‐Chang , Chai Chee‐Yin , Hu Shih‐Wen
Published: August 2006

Background and Objectives

Hepatolithiasis is etiologically related to cholangiocarcinoma. We underwent this study with an attempt to examine the expression of DPC4/Smad4 gene in stone‐containing intrahepatic bile ducts (IHD) and intrahepatic cholangiocarcinoma (ICC).

Patients and Methods

The immunohistochemical method and RT‐PCR analysis were used to study the expression of DPC4/Smad4 gene in normal IHD, stone‐containing IHD, and ICC. All the specimens were from hepatic resection.

Results

The immunohistochemical study showed that all specimens from 24 normal IHD had marked expression of DPC4/Smad4 gene, while there was 4.4% (2/46) and 33.3% (3/9) loss of DPC4/Smad4 expression in stone‐containing IHD and ICC, respectively. Among the specimens of stone‐containing IHD, all the hyperplastic epithelial cells showed normal expression of DPC4/Smad4 gene while dysplastic epithelial cells showed 20% (2/10) loss expression of DPC4/Smad4. The RT‐PCR analysis showed that the normal IHD had the highest content of DPC4/Smad4 mRNA, which was threefold and sixfold higher than that of stone‐containing IHD and ICC, respectively.

Conclusion

Loss expression of DPC4/Smad4 gene was found both in stone‐containing IHD and ICC. Dysplastic epithelium of stone‐containing IHD had higher potential for malignant transformation. J. Surg. Oncol. 2006;94:338–343. © 2006 Wiley‐Liss, Inc.
Number of lymph node metastases and its prognostic significance in early gastric cancer: A multicenter italian study
Authors: Roviello Franco , Rossi Simone , Marrelli Daniele , Pedrazzani Corrado , Corso Giovanni , Vindigni Carla , Morgagni Paolo , Saragoni Luca , de Manzoni Giovanni , Tomezzoli Anna
Published: August 2006

Background and Objectives

This study was aimed at evaluating the prognostic significance of the number of metastatic nodes in early gastric cancer (EGC).

Methods

In this multicenter retrospective study 652 cases of resected EGC were analyzed. We searched for lymph node metastases‐associated risk factors and to identify subsets of patients with different prognosis according to the number of involved nodes.

Results

Nodal involvement was observed in 14.1%. A significant correlation was found between the presence of node metastases and tumor size (RR 1.34, P = 0.001), submucosal invasion (RR: 3.14, P = 0.007), Lauren diffuse/mixed type (RR: 4.88, P < 0.001) and Kodama Pen A type (RR: 4.59, P < 0.001). The 10‐year survival rate was 92% for N0 cases, 82% and 73% for tumors with one to three and four to six positive nodes while it dropped to 27% with more than six metastatic nodes. Interestingly enough, the 10‐year risk of recurrence diminished with the increasing number of retrieved nodes (>15) even in N0 patients.

Conclusions

Nodal involvement confirmed to be a significant prognostic factor. In view of the trend to a lower risk of recurrence when more than 15 nodes were retrieved and the better staging achieved we consider D2 lymphadenectomy the treatment of choice. J. Surg. Oncol. 2006;94:275–280. © 2006 Wiley‐Liss, Inc.
Lymphatic spread and microinvolvement in adenocarcinoma of the esophago‐gastric junction
Authors: Schurr Paulus G. , Yekebas Emre F. , Kaifi Jussuf T. , Lasch Steffi , Strate Tim , Kutup Asad , Cataldegirmen Guel , Bubenheim Michael , Pantel Klaus , Izbicki Jakob R.
Published: August 2006

Background

Adenocarcinoma of the esophago‐gastric junction (EGJ) potentially spreads to abdominal and mediastinal lymph nodes.

Methods

Eighty‐five patients with type I and II EGJ cancer underwent curative esophagectomy or esophago‐gastrectomy and radical abdominal and mediastinal lymphadenectomy. Microinvolvement was detected with the mAb Ber‐Ep4 in all histopathologically free lymph nodes.

Results

In type I tumors (n = 40), lower mediastinal lymph nodes were positive in 24% and among type II tumors (n = 45) in 10% of patients. Ber‐Ep4+ cells in apparently free lymph nodes were found in 49% of patients. On inclusion of Ber‐Ep4+ nodes, positive mediastinal lymph node staging was rising to 40 and 33% in type I and II patients, respectively. After a median observation time of 27.1 months, 37 of 85 patients (43.5%) had died of tumor disease. Kaplan–Meier analysis revealed a significant impact of nodal microinvolvement on disease‐specific survival for type I and type II tumors (P = 0.016 and P < 0.001, respectively). Cox regression analysis revealed a 2.77 higher independent risk (P = 0.002) for nodal microinvolvement.

Conclusions

Lymphatic microinvolvement shows a high incidence in curatively resected EGJ cancer. Spread to mediastinal lymph nodes seems to necessitate lymphadenectomy of the thoracic cavity in either type. J. Surg. Oncol. 2006;94:307–315. © 2006 Wiley‐Liss, Inc.
Clinical significance of extrahepatic bile duct resection for advanced gallbladder cancer
Authors: Sakamoto Yoshihiro , Kosuge Tomoo , Shimada Kazuaki , Sano Tsuyoshi , Hibi Taizo , Yamamoto Junji , Takayama Tadatoshi , Makuuchi Masatoshi
Published: August 2006

Background and Objectives

The aim of this study was to determine the clinical significance of extrahepatic bile duct (EHBD) resection during surgery for advanced gallbladder cancer.

Methods

Among 110 patients with pT2 or higher grade gallbladder cancer, 58 patients without microscopic invasion to the EHBD were reviewed. Prognostic factors of the 58 patients were evaluated by multivariate analysis. The impact of EHBD resection on survival was assessed in relation to two prognostic determinants: (i) lymph node metastasis: positive (n = 23) and negative (n = 35); (ii) perineural invasion: positive (n = 25) and negative (n = 33).

Results

Hepatic metastasis and perineural invasion were found to be independently significant prognostic factors. (i) No survival benefit of additional EHBD resection could be confirmed in each group of patients with or without nodal metastasis. (ii) In 25 patients with perineural invasion, 14 patients who underwent EHBD resection showed better survival as compared to the 11 patients who did not undergo EHBD resection (5‐year survival rate, 46% vs. 0%,P = 0.009). In the remaining 33 patients without perineural invasion, the additional EHBD resection did not yield significant improvement of survival (P = 0.28).

Conclusions

Resection of EHBD may offer prognostic advantage when perineural invasion exists, even in the absence of biliary infiltration. J. Surg. Oncol. 2006;94:298–306. © 2006 Wiley‐Liss, Inc.
Radical surgery‐peritonectomy and intraoperative intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis in recurrent or primary ovarian cancer
Authors: Rufián Sebastián , Muñoz‐Casares Francisco C. , Briceño Javier , Díaz Carlos J. , Rubio María J. , Ortega Rosa , Ciria Rubén , Morillo Manuel , Aranda Enrique , Muntané Jordi , Pera Carlos
Published: August 2006

Background and Objectives

Advanced ovarian cancer typically spreads in a diffuse intra‐abdominal fashion. This characteristic suggests that combined radical surgery and intraperitoneal chemotherapy may be a useful treatment procedure. The purpose of this study was to review patients submitted to surgical debulking and hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) and to evaluate the potential prognostic survival factors for advanced epithelial ovarian cancer in our center.

Methods

A series of patients (N = 33) diagnosed of peritoneal carcinomatosis for epithelial ovarian cancer (stage III) from January 1997 to December 2004 submitted to radical surgery‐peritonectomy and HIIC with paclitaxel was included in this study; 19 primary ovarian cancer and 14 recurrent ovarian cancer.

Results

Cytoreduction R0 (P = 0.018) and negative lymph nodes (P = 0.005) were covariables for major prognostic survival. Patients with optimal cytoreduction R0 obtained survival rates of 63% at 5 years in recurrent ovarian cancer and 60% in primary ovarian cancer, 71% and 63%, respectively with associated subtotal infra‐abdominal peritonectomy, and even better results if negative lymph nodes.

Conclusions

Radical surgery‐peritonectomy with HIIQ has been shown to be a surgical procedure with high tolerability, low morbimortality, enhanced survival, and prolonged disease‐free interval in patients with peritoneal carcinomatosis so much for recurrent or primary ovarian cancer. J. Surg. Oncol. 2006;94:316–324. © 2006 Wiley‐Liss, Inc.
The sacralised landscapes of Glencoe: from massacre to mass tourism, and back again
Authors: Knox Dan
Published: August 2006

History is said to hang heavily over the dramatic mountain landscapes of Glencoe. More precisely, multiple memories of the Massacre of Glencoe dominate heritage visions and interpretations of this valley in Argyll, Scotland. This paper makes use of the example of Glencoe to illustrate the processes through which performative acts and utterances make and remake the sacralised landscapes of what some have termed ‘dark’ tourism. Through the repeated telling or citation of stories about the massacre, and about the associated Highland War, Glencoe is repeatedly fixed and figured into discourses relating to fear, terror and bloodshed. What I am keen to demonstrate is the ways in which the effects of performative utterances and acts become concretised as they are made into the stuff of history and heritage tourism. Glencoe is repeatedly figured as, fixed into and haunted by the seventeenth century through the continued operation of ideologies rooted in the Enlightenment and related to a hegemonic Highland and martial vision of Scotland. The rhetoric surrounding Glencoe today, as both a site and as a tourist product, and through which the collective remembering of the events of 1692 is enacted, is overwhelmingly related to one historic incident and the relation of that incident to a particular vision of the Scottish nation. Visitors frequently report finding the glen a haunting, frightening and menacing place: popular photography depicts dark and shaded mountainsides, abandoned settlements and memorials that evoke similar feelings. By conducting a tracing out of connections between the material landscapes of Glencoe, historical and contemporary representations of the glen, and tourist representational practices, this paper sheds some light on the performative power of language and practice through, in and over history, heritage, tourism and landscape. Copyright © 2006 John Wiley & Sons, Ltd.
Tourism development in Iraq: the need for support from international academia
Authors: McGahey Stan
Published: August 2006

Iraq is an ancient land of historical and religious sights that possesses a vibrant culture and numerous natural attractions. The northern region of Kurdistan is home to the Erbil Citadel, one of the world's oldest continuously inhabited sites (8000 years), as well as to snowcapped mountains, waterfalls and deep canyons set amidst alpine meadows and pastoral villages. This autonomous region of Iraq already receives domestic tourists from the hotter, arid regions to the south, and it hopes to soon begin attracting international tourists. As a result of its geo‐political situation and the breakdown of Iraq's tourism industry for many years, Kurdistan is in the process of developing much of its tourism industry from the beginning stages. Its development will, in turn, exert a profound influence on Iraq's overall tourism industry and the appeal of its tourism products in the international marketplace. Although professional tourism training and education are priorities, Kurdish and other Iraqi tourism academicians are likewise completely detached from their international counterparts. International tourism scholars and researchers are thus presented with a unique opportunity to provide collegial assistance in the form of teaching materials, updated curriculums, research partners and publication connections. Copyright © 2006 John Wiley & Sons, Ltd.
Antioxidants in thermally treated buckwheat groats
Authors: Zieliński Henryk , Michalska Anna , Piskuła Mariusz K. , Kozłowska Halina
Published: August 2006

The seeds of buckwheat (Fagopyrum esculentum Moench L.) were dehulled and then, following milling, extruded on a counter rotating, twin‐screw extruder with the different barrel temperature profiles: 120, 160, and 200°C. After extrusion cooking process, the following compounds were analyzed: free and conjugated phenolic acids, total polyphenols (TPC), tocopherols (T) and tocotrienols (T3), inositol phosphates (IP), reduced glutathione (GSH), and melatonin (MLT). The antioxidant capacity and superoxide dismutase‐like activity (SOD‐like activity) were determined in the groats and extrudates. Extrusion caused a significant decrease in all the compounds tested, except for phenolic acids. The content of IP decreased by 13%, that of GSH by 42%, and that of T + T3 by 62%. A three‐fold lower level of MLT and TPC was noted whereas the SOD‐like activity disappeared when compared to the nonextruded material. A two‐fold higher content of phenolic acids (free and released from ester bonds) was observed. In spite of the clear decrease in the investigated antioxidants, the extruded dehulled buckwheat seeds contained still significant content of bioactive compounds, which resulted in as little as an average 10% decrease of the antioxidant capacity.