bluuebunny/crossref_metadata_2025 huggingface dataset:
Unequivocal assignment of the fullerene carbons of diethyl 1,2‐methano[60]fullerene 61,61‐dicarboxylate using 2D INADEQUATE NMR spectroscopy
Authors: Burley Glenn A. , Keller Paul A. , Pyne Stephen G. , Ball Graham E.
Published: September 2002

Assignment of all carbons of the [60]fullerene sphere of diethyl 1,2‐methnano[60]fullerene 61,61‐dicarboxylate using 2D INADEQUATE NMR spectroscopy is described. Acquiring the INADEQUATE data with small spectral widths and optional F1 folding with States‐TPPI phase implementation provides a convenient route to high‐resolution data. A description of the topology of the [60]fullerene sphere and its comparison with x‐ray crystallographic analysis is also presented. Copyright © 2001 John Wiley & Sons, Ltd.
Special reactions of α,β‐unsaturated ketones: Part II. Structure and stereochemistry of perhydro‐5a,11a‐epoxydibenz[b,f]oxepin‐4a‐ol, a bridged Diels–Alder dimer of 2‐methylenecyclohexanone
Authors: Gößnitzer Edith , Wendelin Winfried
Published: September 2002

The paper deals with the structure elucidation of (4aRS,5aRS,9aRS,11aRS)‐perhydro‐5a,11a‐epoxydibenz[b,f]oxepin‐4a‐ol (6), which is unexpectedly formed from 2‐dimethylaminomethylcyclohexanone hydrochloride (1·HCl) in the presence of phenylguanidine in boiling ethanol. In detail, two molecules of 2‐methylenecyclohexanone (generated from 1 by elimination of dimethylamine) afforded via Diels–Alder reaction, subsequent addition of water and ring closure a product C14H22O3, which finally proved to be the title compound. The structure of the tetracyclic hemiacetal 6 was deduced from one‐ and two‐dimensional NMR experiments (1D TOCSY, DEPT‐135, 1H,1H‐COSY, gs‐HSQC, gs‐HMBC, gs‐HSQC‐TOCSY). In particular, the one‐dimensional selective TOCSY and the gradient‐selected HSQC‐TOCSY, performed as a pseudo‐3D experiment without the evolution period in the TOCSY part, proved to be very helpful for the unambiguous assignment of signals in overcrowded regions. NOE data confirmed the stereochemistry of epoxydibenzoxepinol 6. Copyright © 2001 John Wiley & Sons, Ltd.
Ovarian expression of melatonin Mel1a receptor mRNA during mouse development
Authors: Lee Chang Joo , Do Byung Rok , Lee Yang Han , Park Jong Hyuk , Kim Sun Jong , Kim Jin Kyu , Roh Sung Il , Yoon Yong‐Dal , Yoon Hyun Soo
Published: September 2002

Melatonin, secreted by the pineal gland, is involved in the regulation of many physiological functions of various species of animals. In the present study, the expression of gene for melatonin Mel1a receptor (MelR) was evaluated in the ovary, hypothalamus, and pituitary according to the developmental stages in female mice. Semiquantitative reverse‐transcription polymerase chain reaction (RT‐PCR) and in situ PCR techniques were applied. According to the developmental stages, gene for MelR was differently expressed on ovary, hypothalamus, and pituitary. MelR gene was first expressed on pituitary prior to the expression in hypothalamus and ovary. Ovarian MelR gene started to express at birth. Unlike hypothalamic expression of MelR gene which was identified after birth, in pituitary, it was expressed at 16 days post coitum. In the ovary, the expression signal of MelR gene was identified on granulosa cells. However, the signal was not detected in the theca cells. It was weak in the primordial and atretic follicles. Taken together, it can be considered that melatonin has a pivotal role in the folliculogenesis. Mol. Reprod. Dev. 59:126–132, 2001. © 2001 Wiley‐Liss, Inc.
Development of a PEDRI free‐radical imager using a 0.38 T clinical MRI system
Authors: Lurie David J. , Li Haihong , Petryakov Sergey , Zweier Jay L.
Published: September 2002

Proton electron double resonance imaging (PEDRI) uses the Overhauser effect to image the distribution of free‐radicals in biological samples and animals. Standard MRI hardware and software is used, with the addition of hardware to irradiate the free‐radical‐of‐interest's EPR resonance. For in vivo applications it must be implemented at a sufficiently low magnetic field to result in an EPR irradiation frequency that will penetrate the sample but will not cause excessive nonresonant power deposition therein. Many clinical MRI systems use resistive magnets that are capable of operating at 10–20 mT, and which could thus be used as PEDRI imagers with the addition of a small amount of extra hardware. This article describes the conversion of a 0.38 T whole‐body MRI system for operation as a 20.1 mT small‐animal PEDRI imager. The magnet power supply control electronics required a small modification to operate at the lower field strength, but no permanent hardware changes to the MRI console were necessary, and no software modification was required. Frequency down‐ and up‐conversion was used on the NMR RF system, together with a new NMR/EPR dual‐resonance RF coil assembly. The system was tested on phantoms containing free‐radical solution, and was also used to image the distribution of a free‐radical contrast agent injected intravenously into anesthetized mice. Magn Reson Med 47:181–186, 2002. © 2002 Wiley‐Liss, Inc.
Multiple field of view MR fluoroscopy
Authors: Aksit Pelin , Derbyshire J. Andrew , Serfaty Jean‐Michel , Atalar Ergin
Published: September 2002

This work describes a real‐time imaging and visualization technique that allows multiple field of view (FOV) imaging. A stream of images from a single receiver channel can be reconstructed at multiple FOVs within each image frame. Alternately, or in addition, when multiple receiver channels are available, image streams from each channel can be independently reconstructed at multiple FOVs. The implementation described here provides for real‐time visualization of the placement of guidewires and catheters on a dynamic roadmap during interventional procedures. The loopless catheter antenna, an electrically active intravascular probe, was used for MR signal reception. In 2D projection images, the catheter and surrounding structures within its diameter of sensitivity appear as bright signal. The simplicity of the resulting images allows very‐narrow‐FOV imaging to decrease imaging time. Very‐narrow‐FOV images are acquired on MR receiver channels that collect guidewire or catheter data. These very‐narrow‐FOV images provide very high frame rate continuous, real‐time imaging of the interventional devices (25 fps). Large‐FOV images are formed from receiver channels that collect anatomical data from standard imaging surface coils, and simultaneously provide a dynamic, frequently updated roadmap. These multiple‐FOV images are displayed together, improving visualization of interventional device placement. Magn Reson Med 47:53–60, 2002. © 2002 Wiley‐Liss, Inc.
High b‐value q‐space analyzed diffusion‐weighted MRI: Application to multiple sclerosis
Authors: Assaf Y. , Ben‐Bashat D. , Chapman J. , Peled S. , Biton I.E. , Kafri M. , Segev Y. , Hendler T. , Korczyn A.D. , Graif M. , Cohen Y.
Published: September 2002

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) which affects nearly one million people worldwide, leading to a progressive decline of motor and sensory functions, and permanent disability. High b‐value diffusion‐weighted MR images (b of up to 14000 s/mm2) were acquired from the brains of controls and MS patients. These diffusion MR images, in which signal decay is not monoexponential, were analyzed using the q‐space approach that emphasizes the diffusion characteristics of the slow‐diffusing component. From this analysis, displacement and probability maps were constructed. The computed q‐space analyzed MR images that were compared with conventional T1, T2 (fluid attenuated inversion recovery (FLAIR)), and diffusion tensor imaging (DTI) images were found to be sensitive to the pathophysiological state of white matter. The indices used to construct this q‐space analyzed MR maps, provided a pronounced differentiation between normal tissue and tissues classified as MS plaques by the FLAIR images. More importantly, a pronounced differentiation was also observed between tissues classified by the FLAIR MR images as normal‐appearing white matter (NAWM) in the MS brains, which are known to be abnormal, and the respective control tissues. The potential diagnostic capacity of high b‐value diffusion q‐space analyzed MR images is discussed, and experimental data that explains the consequences of using the q‐space approach once the short pulse gradient approximation is violated are presented. Magn Reson Med 47:115–126, 2002. © 2002 Wiley‐Liss, Inc.
Postacquisition suppression of large‐vessel BOLD signals in high‐resolution fMRI
Authors: Menon Ravi S.
Published: September 2002

Large‐vessel BOLD contamination is a serious impediment to localization of neural activity in high‐resolution fMRI studies. A new method is presented which estimates and removes the fraction of BOLD signal that arises from oriented vessels, such as cerebral and pial veins in a voxel, by measuring their influence on the phase angle of the complex valued fMRI time series. A maximum likelihood estimator based on a linear least‐squares fit of the BOLD signal phase to the BOLD signal magnitude in a voxel is shown to efficiently suppress the BOLD effect from these larger veins, whose activation is not well colocalized with the neural response. In high‐resolution in vivo fMRI data at 4 T, it is estimated that the method is sensitive to the phase changes in the cerebral, larger intracortical, and pial veins. The technique requires no special pulse sequence modifications or acquisition strategies, and is computationally fast and intrinsically robust. Magn Reson Med 47:1–9, 2002. © 2002 Wiley‐Liss, Inc.
Separation of intra‐ and extracellular lactate NMR signals using a lanthanide shift reagent
Authors: Aime Silvio , Botta Mauro , Mainero Valentina , Terreno Enzo
Published: September 2002

This work describes the use of [Pr‐DO3A] as a shift reagent for differentiating intra‐ and extracellular L‐lactate resonance in 1H‐ and 13C‐NMR spectra. DO3A acts as heptadentate ligand towards lanthanide(III) ions, leaving two coordination vacancies for the coordination of the L‐lactate ion. The exchange between free and [Pr‐DO3A]‐bound L‐lactate is fast on the NMR timescale, thus yielding a paramagnetically shifted L‐lactate signal for the substrate in the compartment containing the paramagnetic chelate. The evaluation of the method was carried out on a model system based on sealed ghosts from human red blood cells. Magn Reson Med 47:10–13, 2002. © 2002 Wiley‐Liss, Inc.
Estimation of relative cardiovascular pressures using time‐resolved three‐dimensional phase contrast MRI
Authors: Ebbers Tino , Wigström Lars , Bolger Ann F. , Engvall Jan , Karlsson Matts
Published: September 2002

Accurate, easy‐to‐use, noninvasive cardiovascular pressure registration would be an important addition to the diagnostic armamentarium for assessment of cardiac function. A novel noninvasive and three‐dimensional (3D) technique for estimation of relative cardiovascular pressures is presented. The relative pressure is calculated using the Navier‐Stokes equations along user‐defined lines placed within a time‐resolved 3D phase contrast MRI dataset. The lines may be either straight or curved to follow an actual streamline. The technique is validated in an in vitro model and tested on in vivo cases of normal and abnormal transmitral pressure differences and intraaortic flow. The method supplements an intuitive visualization technique for cardiovascular flow, 3D particle trace visualization, with a quantifiable diagnostic parameter estimated from the same dataset. Magn Reson Med 45:872–879, 2001. © 2001 Wiley‐Liss, Inc.
A specific force deficit exists in skeletal muscle after partial denervation
Authors: Kalliainen Loree K. , Jejurikar Sameer S. , Liang Lawrence W. , Urbanchek Melanie G. , Kuzon William M.
Published: September 2002

Skeletal muscle demonstrates a specific force deficit after repair of injured peripheral nerves, microneurovascular muscle transfer, and normal aging. Because atrophy cannot account for deficits in specific force, other, unknown, mechanisms are responsible for the resulting muscle contractile dysfunction under these circumstances. We tested the hypothesis that a subpopulation of denervated fibers is partially or completely responsible for the specific force deficit after partial denervation of the rat extensor digitorum longus muscle (EDL). Adult Fisher rats underwent either sham exposure or partial transection of 80% of the cross‐sectional area of the left deep peroneal nerve. After a 2‐week recovery period, maximum isometric force (F0) was measured in situ and maximum specific force (sF0) was calculated for EDL from both control (n = 8) and partial denervation (n = 7) groups. Innervated fiber cross‐sectional area (CSAinn) was measured directly from whole EDL cross sections after immunohistochemical labeling for neural cell adhesion molecule (NCAM), a marker of muscle fiber denervation. A corrected specific force value (sF0‐inn) was calculated by normalizing F0 to CSAinn. Partial skeletal muscle denervation resulted in significant reductions in muscle mass, F0, and sF0. The percentage of muscle fibers expressing NCAM in the extrajunctional sarcolemma increased from 1.0 ± 0.8% in control to 49 ± 15% in partially denervated EDL muscles. A 62.7% deficit in EDL specific force was observed after partial denervation. Denervated muscle fibers accounted for 59.3% of this deficit, but sF0‐inn still differed significantly between control and partially denervated muscles, with a 25.5% difference between groups. In partially denervated muscles, the specific force deficit is partially but not fully explained by a subpopulation of noncontractile, denervated fibers. © 2002 John Wiley & Sons, Inc. Muscle Nerve 25: 31–38 2002
Dipolar coupling and ordering effects observed in magnetic resonance spectra of skeletal muscle
Authors: Boesch Chris , Kreis Roland
Published: September 2002

Skeletal muscle is a biological structure with a high degree of organization at different spatial levels. This order influences magnetic resonance (MR) in vivo—in particular 1H‐spectra—by a series of effects that have very distinct physical sources and biomedical applications: (a) bulk fat (extramyocellular lipids, EMCL) along fasciae forms macroscopic plates, changing the susceptibility within these structures compared to the spherical droplets that contain intra‐myocellular lipids (IMCL); this effect leads to a separation of the signals from EMCL and IMCL; (b) dipolar coupling effects due to anisotropic motional averaging have been shown for 1H‐resonances of creatine, taurine, and lactate; (c) aromatic protons of carnosine show orientation‐dependent effects that can be explained by dipolar coupling, chemical shift anisotropy or by relaxation anisotropy; (d) limited rotational freedom and/or compartmentation may explain differences of 1H‐MR‐visibility of the creatine/phosphocreatine resonances; (e) lactate 1H‐MR resonances are reported to reveal information on tissue compartmentation; (f) transverse relaxation of water and metabolites show multiple components, indicative of intra‐, extracellular and/or macromolecular‐bound pools, and in addition dipolar or J‐coupling lead to a modulation of the signal decay, hindering straightforward interpretation; (g) diffusion weighted 31P‐MRS has shown restricted diffusion of phosphocreatine; (h) magnetization transfer (MT) indicates that there is a motionally restricted proton pool in spin‐exchange with free creatine; reduced availability or restricted motion of creatine is particularly important for an estimation of ADP from 31P‐MR spectra, and in addition MT effects may alter the signal intensity of creatine 1H‐resonances following water‐suppression pulses; (i) transcytolemmal water‐exchange can be studied in 1H‐MRS by contrast‐agents applied to the extracellular space; (k) transport of glucose across the cell membrane has been studied in diabetes patients using a combination of 13C‐ and 31P‐MRS; and (l) residual quadrupolar interaction in 23Na MR spectra from human skeletal muscle suggest that sodium ions are bound to ordered muscular structures. Copyright © 2001 John Wiley & Sons, Ltd.

Abbreviations used:

ADC

apparent diffusion coefficient

BMS

bulk magnetic susceptibility

CK

creatine kinase

Cr

creatine

Cr/PCr

creatine and/or phosphocreatine

CSA

chemical shift anisotropy

EMCL

extramyocellular lipids

IMCL

intramyocellular lipids

MQF

multi‐quantum‐filtering

MRI

Magnetic resonance imaging

MRS

magnetic resonance spectroscopy

MT

magnetization transfer

PCr

phosphocreatine.
Common processing of in vivo MR spectra
Authors: in 't Zandt HJA , van der Graaf M , Heerschap A
Published: September 2002

This introductory article addresses approaches currently in use to process in vivo spectra. First, a brief overview is given of the information content represented by the parameters of MR signals. Subsequently, common steps in the processing of MR spectra such as pre‐processing, normalisation and quantification and the use of prior knowledge are described. Finally, some prospects for more advanced processing are given. Copyright © 2001 John Wiley & Sons, Ltd.
Calcium imaging of epileptiform events with single‐cell resolution
Authors: Badea Tudor , Goldberg Jesse , Mao Buqing , Yuste Rafael
Published: September 2002

Epileptic discharges propagate through apparently normal circuits, although it is still unclear how this recruitment takes place. To understand the role of different classes of neurons in neocortical epilepsy, we have developed a novel imaging assay that detects which neurons participate in epileptiform discharges. Using calcium imaging of neuronal populations during bicuculline‐induced spontaneous epileptiform events in slices from juvenile mouse somatosensory cortex, we find that fast calcium transients correlate with epileptiform field potentials and intracellular depolarizing shifts and can be used as an optical signature that a given neuron has participated in an epileptiform event. Our results demonstrate a novel method to characterize epileptiform events with single‐cell resolution. In addition, our data are consistent with an important role for layer 5 in generating neocortical seizures and indicate that subgroups of neurons are particularly prone to epileptiform recruitment. © 2001 John Wiley & Sons, Inc. J Neurobiol 48: 215–227, 2001
NADPH‐diaphorase activity in the frontal cortex of NBM‐lesioned rats treated with verapamil
Authors: Caballero‐Bleda María , Redondo‐Aniorte Francisco Javier , Aldeguer‐Montiel Antonio , Popović Natalija , Popović Miroljub , Puelles Luis
Published: September 2002

The effect of the calcium antagonist verapamil on NADPH‐diaphorase activity was studied in the frontal cortex of rats with lesioned nucleus basalis magnocellularis (NBM). Treatment with verapamil (5 mg/kg/12h ip) started 24 h after NBM lesions and lasted 8 days. Animals were sacrificed on day 21 after NBM‐lesions. There were no significant differences between control, saline‐ and verapamil‐treated NBM‐lesioned rats in the total number of neurons expressing NADPH‐diaphorase. However, the number of neurons which show loss of enzymatic reaction in their processes was significantly higher in saline‐treated NBM‐lesioned rats. This may relate to incipient neurodegeneration in these neurons. The obtained reactive decrease of NADPH‐diaphorase staining was abolished by verapamil treatment, which suggests a significant neuroprotective effect of this calcium antagonist.
Calcium channel blocker flunarizine suppresses epileptiform activity induced by penicillin in rats
Authors: Bağirici Faruk , Gökçe Fatih M. , Demi̇r Şerif , Marangoz Cafer
Published: September 2002

Epilepsy is a neurological disorder that affects approximately 1% of the world population. It is accepted that calcium influx into the cell is the first step of epileptic neuronal events. In the present study, the effects of flunarizine on epileptiform activity were investigated in an experimental epilepsy model induced by intracortical (i.c.) penicillin administration. The left cerebral cortex was exposed by craniotomy in anaesthetised rats. The epileptic focus was produced by injection of penicillin G potassium (500 units) into the somatomotor cortex. After epileptiform activity reached maximum frequency and amplitude, flunarizine was injected into the same area with a Hamilton microinjector. Before flunarizine administration, the average frequency of spikes was 18.7 ± 2.1/min and the average amplitude of the spikes was 1123 ± 85 μV. Microinjection of flunarizine (10, 100 μM) into the same area inhibited electrocorticogram epileptiform activity for 4‐5 minutes (p<0.001). Solvent alone did not affect epileptiform activity (p>0.05). The results of this study suggest that flunarizine may be an anticonvulsant agent for the treatment of epilepsy.
Dynamic optimization and Skiba sets in economic examples
Authors: Beyn Wolf‐Jürgen , Pampel Thorsten , Semmler Willi
Published: September 2002

We discuss two optimization problems from economics. The first is a model of optimal investment and the second is a model of resource management. In both cases the time horizon is infinite and the optimal control variables are continuous. Typically, in these optimal control problems multiple steady states and periodic orbits occur. This leads to multiple solutions of the state–costate system each of which relates to a locally optimal strategy but has its own limiting behaviour (stationary or periodic). Initial states that allow different optimal solutions with the same value of the objective function are called Skiba points. The set of Skiba points is of interest, because it provides thresholds for a global change of optimal strategies. We provide a systematic numerical method for calculating locally optimal solutions and Skiba points via boundary value problems. In parametric or higher dimensional systems Skiba curves (or manifolds) appear and we show how to follow them by a continuation process. We apply our method to the models above where Skiba sets consist of points or curves and where optimal solutions have different stationary or periodic asymptotic behaviour. Copyright © 2001 John Wiley & Sons, Ltd.
Challenges of managing local elections in transitional and developing countries: an illustrative essay
Authors: Hirschmann David
Published: September 2002

The purpose of this investigation into local elections in developing and transitional countries is to highlight typical challenges to the management of local elections, emphasizing the difficulties that appear to be peculiar to local as opposed to national elections; and help explain why they often turn out to be more difficult to manage than national elections, are of less interest to the public, and often less satisfactory in outcome. It gives attention first to differentiating between categories of subnational elections, and then deals with a number of problems faced in local elections. These are size, scale and complexity of managing such elections, lack of public interest, potential for local manipulation, challenges to fair or adequate media coverage and campaign finance arrangements. The article sets out to challenge simplification and optimism about local elections in developing and transitional societies. Copyright © 2001 John Wiley & Sons, Ltd.
African states, bureaucratic culture and computer fixes
Authors: Berman Bruce J. , Tettey Wisdom J.
Published: September 2002

Our central argument in this article is that the introduction of computers in African states fails to produce the intended results. This is precisely because the trajectory of development of bureaucratic institutions in Africa has resulted in internal and external contexts that differ fundamentally from those of the Western states within which computing and information technology has been developed. This article explores the context in which computers were developed in Western industrialized societies to understand the circumstances that the technologies were designed to respond to and the bureaucratic culture that helped produce desired results. We then proceed to analyse the truncated nature of institution building in the colonial state, and how it structured the peculiar setting of the post‐colonial African state and dynamics surrounding the integration of the new information and communication technologies. We argue that the colonial state bequeathed to its post‐colonial successor three crucial characteristics that are of central importance to understanding why the introduction of computers does not produce anticipated improvements in public administration. These are the very limited technical capabilities of the bureaucracy; authoritarian decision‐making processes under the control of generalist administrators; and the predominance of patron–client relationships. Copyright © 2001 John Wiley & Sons. Ltd.
Local Government Restructuring: Privatization and Its Alternatives
Authors: Warner Mildred , Hebdon Robert
Published: September 2002

Local government restructuring should no longer be viewed as a simple dichotomy between private and public provision. A 1997 survey of chief elected township and county officials in New York shows that local governments use both private and public sector mechanisms to structure the market, create competition, and attain economies of scale. In addition to privatization and inter‐municipal cooperation, two alternative forms of service delivery not previously researched—reverse privatization and governmental entrepreneurship—are analyzed here. Logistic regression on the 201 responding governments differentiates the decision to restructure from the level and complexity of restructuring. Results confirm that local governments are guided primarily by pragmatic concerns with information, monitoring, and service quality. Political factors are not significant in the restructuring process and unionization is only significant in cases of simple restructuring (privatization or cooperation used alone). Fiscal stress is not a primary motivator, but debt limits are associated with more complex forms of restructuring. Restructuring service delivery requires capacity to take risks and is more common among experienced local officials in larger, higher‐income communities. Restructuring should be viewed as a complex, pragmatic process where governments combine public and private provision with an active role as service provider and market player. © 2001 by the Association for Public Policy Analysis and Management.
Novel point charge models: reliable instruments for­molecular electrostatic
Authors: Oliferenko Alexander A. , Palyulin Vladimir A. , Pisarev Sergei A. , Neiman Alexei V. , Zefirov Nikolai S.
Published: September 2002

A novel method to compute atomic charge distribution is proposed. The starting data for the computation are the topology of a molecule and electronegativities of either constituent atoms or atomic orbitals. The topology of a molecule is represented by a molecular graph or, in a more advanced model, by an orbital graph that reflects an orbital constitution of atoms. The distinctive feature of the method is that the starting atomic (orbital) electronegativities equilibrate in the same fashion that electrical potentials do in the nodes of a closed electrical network. Thus, the well‐developed formalism of the theory of electrical circuits was applied for computation of partial atomic charges. In addition, the problem of parametrization of halogens was solved using a specially developed procedures. Comparison of the obtained charges with those produced by means of various computational schemes [Partial Equalization of Orbital Electronegativities (PEOE), Mulliken population analysis, natural population analysis, Bader's AIM, method of generalized atomic polar tensors (GAPT) and an electrostatic potential‐based method, CHELPG] and with some molecular spectral characteristics proves that both models, but especially the orbital graph charge model, provide fast, convenient and reliable methods to calculate theoretically justifiable atomic charges for a variety of chemical species. The developed charge models are well suited for application in many areas of molecular modeling and QSAR/QSPR studies. Copyright © 2001 John Wiley & Sons, Ltd.
Prophylactic oophorectomy versus screening: psychosocial outcomes in women at increased risk of ovarian cancer
Authors: Fry Alison , Busby‐Earle Camille , Rush Robert , Cull Ann
Published: September 2002

This study investigated the psychosocial outcome of prophylactic oophorectomy versus regular screening in women at increased risk of ovarian cancer. Women who had undergone prophylactic oophorectomy (n=29) were compared with women who remained on the ovarian screening programme (n=28). Assessments were made retrospectively by postal questionnaire. The surgical group showed significantly poorer functioning on two sub‐scales of the Short Form (SF)‐36 Health Status Questionnaire (role‐emotional (p=0.04) and social functioning (p=0.01)), and there was a trend (p=0.06) for them to report more menopausal symptoms. General Health Questionnaire (GHQ) scores were significantly higher (p=0.03) in the surgical group. There were no significant differences between the groups for cancer worry or sexual functioning. Experience of the operation was better (p=0.01) and incidence of self‐reported post‐operative problems was lower (p=0.02) for women who had undergone the ‘keyhole’ rather than an ‘open’ procedure. Being pre‐menopausal at the time of surgery predicted higher GHQ (p=0.04) and longer subjective recovery time (p=0.04). Women who have undergone prophylactic oophorectomy may have more physical and emotional symptoms than women who remain on an ovarian cancer screening programme, and may report equivalent levels of cancer worry. Those who are pre‐menopausal at the time of the operation may be particularly vulnerable to psychological distress and take longer to recover post‐operatively. A larger prospective study is needed to evaluate the casual versus causal role of oophorectomy in these findings, and the extent to which it allays patients' fear of cancer. Copyright © 2001 John Wiley & Sons, Ltd.
Combined modality radioimmunotherapy for human prostate cancer xenografts with taxanes and 90yttrium‐DOTA‐peptide‐ChL6
Authors: O'Donnell Robert T. , DeNardo Sally J. , Miers Laird A. , Lamborn Kathleen R. , Kukis David L. , DeNardo Gerald L. , Meyers Frederick J.
Published: September 2002

BACKGROUND

Therapy for prostate cancer in the PC3 tumor‐nude mouse model with 90yttrium‐(90Y)‐DOTA‐peptide‐ChL6 (5.55 MBq;150 μCi) has resulted in durable responses. To make radioimmunotherapy (RIT) more effective, the radiation‐enhancing drugs Taxol (paclitaxel) and Taxotere (docetaxel) were tested for synergy with 90Y‐DOTA‐peptide‐ChL6.

METHODS

Nude mice bearing human prostate cancer PC3 xenografts were treated with 90Y‐DOTA‐peptide‐ChL6 (2.78 MBq; 75 μCi) and after 24 hr, paclitaxel (300 or 600 μg), or docetaxel (300 μg). Tumor size, survival, blood counts, and pharmacokinetics were monitored to assess efficacy and toxicity.

RESULTS

Docetaxel plus RIT had a 67% cure rate, whereas no mice were cured among the RIT alone, chemotherapy alone, or untreated controls. Paclitaxel (600 μg) plus RIT produced a 100% response rate with 20% cures. Average tumor volume was reduced to a greater degree in the combined modality radioimmunotherapy (CMRIT) groups compared to controls and the anti‐tumor response was durable. Myelotoxicity in the combined modality groups (RIT plus paclitaxel or RIT plus docetaxel) were similar to groups receiving the same dose of RIT alone.

CONCLUSION

In the PC3‐tumor nude mouse model, addition of paclitaxel or docetaxel to 90Y‐DOTA‐peptide‐ChL6, in doses clinically achievable in humans, provided therapeutic synergy without increased or excessive toxicity. Prostate 50: 27–37, 2002. © 2002 Wiley‐Liss, Inc.
Evidence for stem cells in cultures of mouse prostate epithelial cells
Authors: Sawicki Janet A. , Rothman Craig J.
Published: September 2002

BACKGROUND

Primary cultures of mouse prostatic epithelial cells were studied to identify cells having stem cell characteristics.

METHODS

Culture conditions supporting the growth of mouse prostatic epithelial cells were identified. Immunostaining identified cells expressing cytokeratin 5 (K5), cytokeratin 8 (K8), and bcl‐2. Cells with clonogenic capacity were identified by replating dissociated cells from primary colonies.

RESULTS

Only 2–4% of prostatic epithelial cells that were plated formed colonies. Most cells cultured for 2–4 days expressed bcl‐2, K5, and K8. After 6 days in culture, colonies had two distinct phenotypes, star‐ or disc‐shaped. In colonies of both phenotypes, only a few cells expressed K5 and bcl‐2, while all cells expressed K8. Upon replating, two‐thirds of star‐shaped colonies gave rise to a single colony; of 29 disc‐shaped colonies, none gave rise to new colonies.

CONCLUSIONS

Colonies deriving from putative prostatic epithelial stem cells are identified. These cells express K5 and bcl‐2 and are clonogenic. Prostate 50: 46–53, 2002. © 2002 Wiley‐Liss, Inc.
Seismic retrofitting of structures with fibre‐reinforced polymers
Authors: Triantafillou T C
Published: September 2002

Externally bonded (eb) fibre‐reinforced polymers (FRPs) have been employed extensively throughout the world in numerous rehabilitation applications of reinforced concrete or masonry structures. This paper focuses on the seismic retrofitting (removal of seismic deficiency) of RC elements (mainly columns, but also walls and beam–column joints) and masonry walls by means of FRPs. Basic retrofit issues, namely shear strengthening and increase of confinement at plastic hinge or lap splice regions, are summarized first and a summary of application techniques is given. Some key behaviour and design aspects for shear‐strengthened or FRP‐confined members are provided and a brief description of some recent developments related to the seismic strengthening of beam–column joints is presented. Finally, key issues on the seismic retrofitting of masonry walls for in‐plane or out‐of‐plane action are discussed.
Correlation of peel and burst tests for pouches
Authors: Feliú‐Báez Rosamari , Lockhart Hugh E. , Burgess Gary
Published: September 2002

Theoretical equations based on force diagrams were developed in order to explain pouch behaviour during a restrained burst test. According to the resulting equation, P = 2 S/D, the burst pressure (P) increases directly with seal strength (S) and inversely with the distance between the restraining plates (D). After performing a restrained burst test and a peel test on Tyvek/plastic pouches, it was found that the theoretical development did not exactly explain burst test results
in terms of peel test values. The test results demonstrate that even though the peeling times for the peel and burst tests were controlled to be the same, the theoretical formula (P = 2 S/D) tends to overestimate the burst pressure. The overestimation increases at smaller gaps. These results are an indication that the formula is not universal and they suggest that it is an oversimplification. It might work for some materials at a particular set of testing conditions but not for others. Copyright © 2001 John Wiley & Sons, Ltd.
Non‐born–oppenheimer density functional theory for excited states by using green's function techniques
Authors: Yoshimoto T. , Ohta Y. , Maki J. , Shigeta Y. , Nagao H. , Nishikawa K.
Published: September 2002

We have proposed a numerical scheme for the non‐Born–Oppenheimer density functional calculation based upon the Green function techniques within the GW approximation for evaluating quasiparticle excitations of the electronic and nuclear motion in the full quantum mechanical treatment. We calculate the excitation energy and the orbital energy of a hydrogen molecule, a muon molecule, and a positronium–hydrogen complex within the treatment of the dynamical screening. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem 84: 354–362, 2001
Recent progress in the accurate and rapid evaluation of all Coulomb integrals over slater‐type orbitals
Authors: Safouhi Hassan , Hoggan Philip
Published: September 2002

One of the main objectives in ab initio Slater research is rapid and accurate evaluation of the two‐, three‐, and four‐center Coulomb integrals. General expressions for these integrals were obtained and evaluated for the first time using the single center strategy and requisite orbital translations. The alternative strategy using the Fourier transform of the B functions basis has been thoroughly explored by the Steinborn group. The analytical expressions of these integrals have been shown to be adapted to the use of nonlinear transformations to accelerate their convergence. A complete study of D‐ (due to Levin and Sidi) and \documentclass{article}\pagestyle{empty}\begin{document}$\bar{D}$\end{document}‐transformations (due to Sidi) for all these integrals has led to the improved HD and \documentclass{article}\pagestyle{empty}\begin{document}$H\bar{D}$\end{document} methods, which greatly simplified the application of the above nonlinear transformations. The results presented show that the \documentclass{article}\pagestyle{empty}\begin{document}$H\bar{D}$\end{document} method gives unprecedented accuracy with speedup by a factor of 5 over the \documentclass{article}\pagestyle{empty}\begin{document}$\bar{D}$\end{document} approach and over 70 over the initial STOP method for four center terms. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001
A strategy for quantitative bioanalysis of non‐polar neutral compounds by liquid chromatography/electrospray ionization tandem mass spectrometry: determination of TS‐962, a novel acyl‐CoA:cholesterol acyltransferase inhibitor, in rabbit aorta and liver tissues
Authors: Yamaguchi Jun‐ichi , Matsuno Yumiko , Hachiuma Kenji , Ogawa Naoyoshi , Higuchi Shohei
Published: September 2002

A strategy for the sensitive and reliable quantitative determination of non‐polar neutral compounds in biological matrices by liquid chromatography/electrospray ionization tandem mass spectrometry is described in the context of assay development for TS‐962, a novel acyl‐CoA:cholesterol acyltransferase (ACAT) inhibitor, in rabbit aorta and liver tissues. The electrospray ionization (ESI) mass spectrum of this compound with a mobile phase of water/acetonitrile did not give abundant [M + H]+ ions, but did give alkali metal cation adducts such as [M + Na]+, [M + CH3CN + Na]+ and [M + K]+ ions. The cationized species are acknowledged as unsuitable precursor ions for selected reaction monitoring (SRM) for various reasons, such as difficulty in obtaining characteristic product ions in low‐energy collision‐induced dissociation, and irreproducibility of the adduct‐ion intensities. To overcome this problem, a solution of 3.4 mM trifluoroacetic acid in 2‐propanol was added to the mobile phase as a postcolumn additive, resulting in a decrease of the undesirable adduct formation and significant enhancement of [M + H]+ ion intensity. An attempt was then made to prevent the matrix effect by employing a column‐switching system, which allowed direct injection of a large volume of 2‐propanolic tissue homogenate (950 µL) followed by sufficient clean‐up, separation, and ESI‐SRM on‐line. This enabled development of a sensitive and reliable assay method for TS‐962 in rabbit aorta and liver tissues in the concentration range of 5–500 ng/g wet tissue using a 25‐mg aliquot of tissue sample. Application of this method to the determination of aortic TS‐962 levels at 24 h after repeated oral administration of this compound (3 mg/kg) once a day for 12 weeks to 1% cholesterol‐fed rabbits is also presented. Results showed that TS‐962 is well distributed to both the thoracic and abdominal aorta tissues, at levels higher than the 50% inhibitory concentration value of this compound for microsomal ACAT activity from rabbit aorta. Copyright © 2001 John Wiley & Sons, Ltd.
Proton mobility in protonated glycylglycine and N‐formylglycylglycinamide: a combined quantum chemical and RKKM study
Authors: Paizs Béla , Csonka István Pál , Lendvay György , Suhai Sándor
Published: September 2002

Theoretical model calculations were performed to investigate the degree of validity of the mobile proton model of protonated peptides. The structures and energies of the most important minima corresponding to different structural isomers of protonated diglycine and their conformers, as well as the barriers separating them, were determined by DFT calculations. The rate coefficients of the proton transfer reactions between the isomers were calculated using the RRKM method in order to obtain a quantitative measure of the time scale of these processes. The proton transfer reactions were found to be very fast already at and above the threshold to the lowest energy decomposition pathway. Two possible mechanisms of b2+‐ion formation via water loss from the dipeptide are also discussed. The rate‐determining step of the proton migration along a peptide chain is also investigated using the model compound N‐formylglycylglycinamide. The investigations revealed that this process very possibly occurs via the protonation of the carbonyl oxygens of the amide bonds, and its rate‐determining step is an internal rotation‐type transition of the protonated C=O‐H group between two adjacent C=O‐H…O=C bridges. Copyright © 2001 John Wiley & Sons, Ltd.
Evaluation of axial DC offsets during scanning of a quadrupole ion trap for sensitivity improvements
Authors: Vaden Timothy , Ardhal Ben , Lynn Bert C.
Published: September 2002

In the normal operation of quadrupole ion trap mass spectrometers, approximately half of the trapped ions are ejected through the source endcap during a mass‐selective instability scan. This reduces the sensitivity of the instrument by ∼50%. In this preliminary study, a circuit was constructed that produced a dipolar DC offset on the axial modulation waveform to recover this lost ion current. A variable (0 to 10 V DC), positive and negative offset was applied to the source and detector endcap, respectively. This DC offset axially displaced the ion cloud toward the detector endcap increasing the probability of detection. Several compounds, including 11 pesticides, were evaluated. Sensitivity enhancements ranged from 13 to 97% (theoretical 100%). No spectral resolution problems were observed; however, a compound‐dependent mass discrimination was observed in several cases. This mass discrimination problem is currently under investigation. Copyright © 2001 John Wiley & Sons, Ltd.
Stable isotopes and the international system of units
Authors: Slater Christine , Preston Tom , Weaver Lawrence T.
Published: September 2002

It is now over 60 years since Nier built the first isotope ratio mass spectrometer. The introduction of continuous‐flow techniques heralded a huge expansion in the use of stable isotopes in biomedical and environmental sciences, yet there is no consensus on the appropriate units, especially in the biomedical field. Most isotope ratio mass spectrometry (IRMS) instruments calculate isotopic abundance in terms of delta notation (δ, ‰, per mil), which is a convention determined by geochemistry, because most of the original IRMS instruments were developed in isotope geochemistry laboratories to measure natural abundance variations. Delta units are not SI units. This paper considers the appropriate units for studies using stable isotopes based on the International System of Units (SI). The SI base unit for concentration is the mol, from which atom fraction and mol fraction are derived. The units of stable isotope abundance, atom % and mol %, are the atom and mol fractions expressed as percentages. Atom % excess and mol % excess are the SI units of enrichment and are to be recommended for use in tracer studies. Copyright © 2001 John Wiley & Sons, Ltd.
Rapid quality control analysis of 13C‐enriched substrate synthesis by isotope ratio mass spectrometry
Authors: Morrison Douglas J. , Dodson Brian , Preston Tom , Weaver Lawrence T.
Published: September 2002

There is a growing interest in the use of 13C‐enriched substrates to investigate metabolic processes in humans. The non‐invasive nature of 13C breath tests makes them attractive to clinicians, particularly because they can be safely used in children. The availability of suitable 13C‐enriched substrates can limit the application of this biotechnology. We have used isotope ratio mass spectrometry to assay the chemical purity and isotopic enrichment of substrates that were synthesised to study gut transit and colonic fermentation. Lactose ureide and lactose [13C]ureide were synthesised by acid‐catalysed condensation of lactose and urea or 13C urea, respectively. Glucose ureide and glucose [13C]ureide were synthesised by similar methods but required an additional purification step to remove urea of crystallisation. Substrates were analysed by standard analytical techniques and combustion isotope ratio mass spectrometry for carbon and nitrogen content and 13C‐enrichment. Monitoring the C/N ratio proved to be a sensitive assay of chemical purity. Analysis of the percentage composition of C and N (and hence O + H) suggested that lactose ureide crystallises as the dihydrate. It was synthesised with ∼99% chemical purity and with the theoretical enrichment. Glucose ureide was synthesised with ∼98% chemical purity but with lower than theoretical enrichment. Copyright © 2001 John Wiley & Sons, Ltd.
The search for charge‐remote reactions of even‐electron anions derived from 1,3‐disubstituted adamantanes in the gas phase. Retro Diels‐Alder and Norrish II processes
Authors: Dua Suresh , Bowie John H.
Published: September 2002

The collision induced decompositions of 3‐substituted adamantane carboxylate anions have been studied with a view to uncovering charge‐remote fragmentations of the 3‐substituent. The 3‐substituent is chosen so that it cannot approach the anion site, and so any fragmentations of that substituent should proceed independently of the charged centre, viz. charge‐remote reactions. The following systems have been studied (i) the 3‐cyclohexenyl system shows no charge‐remote retro Diels‐Alder fragmentation (ΔH = +157 kJ mol−1), instead, charge‐remote loss of the cyclohexenyl radical is noted, (ii) the 3‐isobutyl ketone system shows no Norrish II cleavage (loss of C3H6, ΔH = +18 kJ mol−1), instead, the competitive losses of CO2 from the charged carboxyl centre, together with charge‐remote radical loss of the 3‐substituent are observed, and (iii) the corresponding 3‐isopropyl ester does show the ‘Norrish II’ loss of C3H6, together with competitive losses of CO2 and the 3‐substituent. It is concluded for cases (ii) and (iii), that an adamantane carboxylate anion system with a carbonyl group directly attached at the 3‐position is not a suitable model system for studying charge‐remote reactions. Copyright © 2001 John Wiley & Sons, Ltd.
Application of the combination of isotope ratio monitoring with isotope dilution mass spectrometry to the determination of glucose in serum
Authors: Dube Gunther , Henrion André , Ohlendorf Rüdiger , Vidal Christian
Published: September 2002

Isotope ratio monitoring combined with n(13C)/n(12C) isotope dilution mass spectrometry (IRM/IDMS) provides results of low uncertainty of the order of 0.1% if it is applied to the analysis of simple mixtures as found in organic chemistry, even if only low 13C spike additives to the sample are used. If the method is applied to the analysis of systems that require large‐scale sample preparation prior to the measurement, such as the determination of glucose in serum, the results obtained exhibit a higher uncertainty that is comparable to that of the conventional gas chromatography/isotope dilution mass spectrometry (GC/IDMS) method. The reason for this observation is that the small contribution that the IRM/IDMS method makes to the uncertainty budget of the result is superimposed on a large contribution due to the sample preparation. It appears therefore that the IRM/IDMS method has no advantage over the conventional GC/IDMS method. However, if a series of measurements is carried out, and if a suitable experimental design is chosen, the IRM/IDMS method can provide valuable additional information. The influence of sample preparation on each individual result can be quantified as its deviation from the average value of all results of the series. From these data conclusions can be drawn for an improvement in sample preparation. Copyright ©2001 John Wiley & Sons, Ltd.