bluuebunny/crossref_metadata_2025 huggingface dataset:
Competing designs for phase I clinical trials: a review
Authors: Rosenberger William F. , Haines Linda M.
Published: October 2002

Phase I clinical trials are typically small, uncontrolled studies designed to determine a maximum tolerated dose of a drug which will be used in further testing. Two divergent schools have developed in designing phase I clinical trials. The first defines the maximum tolerated dose as a statistic computed from data, and hence it is identified, rather than estimated. The second defines the maximum tolerated dose as a parameter of a monotonic dose–response curve, and hence is estimated. We review techniques from both philosophies. The goal is to present these methods in a single package, to compare them from philosophical and statistical grounds, to hopefully clear up some common misconceptions, and to make a few recommendations. This paper is not a review of simulation studies of these designs, nor does it present any new simulations comparing these designs. Copyright © 2002 John Wiley & Sons, Ltd.
Performance‐steered design of software architectures for embedded multicore systems
Authors: Bechini Alessio , Prete Cosimo Antonio
Published: October 2002

Many software applications demanding a considerable computing power are moving towards the field of embedded systems (and, in particular, hand‐held devices). A possible way to increase the computing power of this kind of platform, so that both cost and power consumption are kept low, is the employment of multiple CPU cores on the same chipset. Consequently, it is essential to design applications that meet performance requirements leveraging the underlying parallel platform. As embedded applications are usually built using different components (whose source code is often not available) from different companies, the designer can mostly only operate at the architectural level. So far, methodologies for designing software architectures have mainly addressed general‐purpose systems, often relying on hardware platforms with a high degree of parallelism. In this paper, we present our experience in architectural design of parallel embedded applications; as a result, we propose a possible methodology for the application design at the architectural level, targeted to embedded systems built upon multicore chipsets with a low degree of parallelism. It makes use of performance predictions, obtained by simulations. Such a methodology can be employed both for retargeting existing sequential applications to parallel processing platforms and for designing complete applications from scratch. We show the application of the proposed methodology to an embedded digital cartographic system. Starting with a software description using UML diagrams, candidate software architectures (utilizing different parallel solutions) are first defined and then evaluated, to end with the selection of the one yielding the highest performance gain. Copyright © 2002 John Wiley & Sons, Ltd.
Specificity of synapse formation between Lymnaea heart motor neuron and muscle fiber is maintained in vitro in a soma–muscle configuration
Authors: Lee Thomas K.M. , Leung Alexander A.C. , Brezden Boris L. , Lukowiak Ken , Syed Naweed I.
Published: October 2002

Precise neuronal connectivity during development is subservient to all nervous system functions in adult animals. However, the cellular mechanisms that mastermind this neuronal connectivity remain largely unknown. This lack of fundamental knowledge regarding nervous system development is due in part to the immense complexity of mammalian brain, as cell–cell interactions between defined sets of pre‐ and postsynaptic partners are often difficult to investigate directly. In this study, we developed a novel model system which has allowed us to reconstruct synapses between identified motor neurons and their target heart muscle cell in a soma–muscle configuration. Utilizing this soma–myocardial cell synapse model, we demonstrate that synapses between somata and heart muscle cells can be reconstructed in cell culture. The soma‐myocardial cell synapses required 12–24 h to develop and thus differed temporally from conventional neuromuscular synapses (seconds to a few minutes). We also demonstrate that the synapses are target cell‐type‐specific and are most likely independent of transmitter phenotypic characteristics of presynaptic neurons. Synapse 46:66–71, 2002. © 2002 Wiley‐Liss, Inc.
Byssoloma Llimonae sp nov., from Continental Spain, Madeira and the Canary Islands
Authors: Sérusiaux E. , Gómez-Bolea A. , Longán A. , Lücking R.
Published: October 2002

Byssoloma llimonae, a new species described from NE Spain, Madeira and the Canary Islands (Gomera, La Palma and Tenerife), is a mostly corticolous species, closely related to the more widespread and usually foliicolous Bapalmuia kakouettae (=Byssoloma aptrootii). The generic position of this group of species within the Pilocarpaceae is still unclear. The new combination Byssoloma kakouettae (Sérus.) R. Lücking & Sérus. is introduced.
The minimal tRNA: unique structure of Ascaris suum mitochondrial tRNASerUCU having a short T arm and lacking the entire D arm
Authors: Ohtsuki Takashi , Kawai Gota , Watanabe Kimitsuna
Published: October 2002

The tertiary structure of Ascaris suum mitochondrial tRNASer
UCU was examined by nuclear magnetic resonance analysis using its transcript, since tRNASer
UCU, lacking the D arm and possessing a truncated T arm, is the shortest of all the known tRNAs. Most basepairs in the proposed secondary structure of tRNASer
UCU were shown to exist, but the connector region comprising the truncated D loop and the extra loop was flexible. This flexibility, would enable adjustment of the mutual distance between the 3′‐terminus and the anticodon consistent with that of usual tRNAs. Thus, tRNASerUCU appears to function in a similar way to that of usual tRNAs in the ribosome.
The sodium/substrate symporter family: structural and functional features
Authors: Jung Heinrich
Published: October 2002

Members of the sodium/substrate symporter family (SSSF, TC 2.A.21) catalyze the uptake of a wide variety of solutes including sugars, proline, pantothenate, and iodide into cells of pro‐ and eukaryotic origin. Extensive analyses of the topology of different SSSF proteins suggest an arrangement of 13 transmembrane domains as a common topological motif. Regions involved in sodium and/or substrate binding were identified. Furthermore, protein chemical and spectroscopic studies reveal ligand‐induced structural alterations which are consistent with close interactions between the sites of sodium and substrate binding, thereby supporting an ordered binding mechanism for transport.
Do longevity assurance genes containing Hox domains regulate cell development via ceramide synthesis?
Authors: Venkataraman Krishnan , Futerman Anthony H.
Published: October 2002

A gene family containing a longevity assurance gene (Lag1p) motif is described. Database searches revealed >40 members of this family of transmembrane proteins, two of which have recently been shown to regulate the synthesis of ceramide, a lipid second messenger involved in a variety of cellular processes. We speculate that other family members, some of which contain a Hox domain, may also be involved in the synthesis of specific ceramide pools, perhaps explaining the role of longevity assurance genes in regulating development.
Glycogen synthase: towards a minimum catalytic unit?
Authors: Cid Emili , Geremia Roberto A , Guinovart Joan J , Ferrer Juan C
Published: October 2002

Classically, α‐1,4‐glucan synthases have been divided into two families, animal/fungal glycogen synthases (GS) and bacterial/plant starch synthases (G(S)S), according to differences in sequence, sugar donor specificity and regulatory mechanisms. Detailed sequence analysis, predicted secondary structure comparison and threading analysis show that these two families are structurally related and that some domains of GSs were acquired to meet regulatory requirements. Archaeal G(S)S present structural and functional features that are conserved in one, the other or both families. Therefore, they are the link between GS and G(S)S and harbor the minimal sequence and structural features that constitute the minimum catalytic unit of the α‐1,4‐glucan synthase superfamily.
Tamoxifen‐induced endometrial changes in postmenopausal women with breast carcinoma
Authors: Juneja M , Jose R , Kekre A.N , Viswanathan F , Seshadri L
Published: October 2002

Objectives: To assess the effects of tamoxifen (TAM) on the endometrium in postmenopausal women. Methods: A case control study of postmenopausal women with breast carcinoma, who were undergoing treatment in the Department of Radiotherapy and Surgery at the Christian Medical College Hospital, Vellore, India was done. Thirty‐five women who were on tamoxifen (20 mg/day) for a period of at least 6 months formed the study group. Thirty‐three women who were not receiving tamoxifen, formed the control group. Subjects in both groups had a pelvic examination and transvaginal sonogram followed by endometrial biopsy. Results: There was a statistically significant difference in the mean endometrial thickness between the study group and control group (7.8±6.4 mm vs. 4.0±2.0 mm, respectively) More women in the tamoxifen group had an endometrial thickness of >5 mm but the number of women with polyps or hyperplasia of the endometrium did not differ significantly between the two groups. There were no women with endometrial carcinoma in either group. Conclusion: All patients on tamoxifen need to be evaluated by clinical examination annually. A transvaginal sonogram and endometrial biopsy/hysteroscopy may be performed on patients with abnormal vaginal bleeding, bloody discharge, staining or spotting.
Deliveries at a district hospital in Rwanda, 1997–2000
Authors: Rahlenbeck S , Hakizimana C
Published: October 2002

Objectives: To obtain data on pregnancy outcomes and maternal mortality at a district hospital in Rwanda. Methods: All delivery records from January 1997 to December 2000 were reviewed. Results: Over the 4‐year period, 3408 women delivered a total of 3497 neonates, and 349 stillbirths (10%) occurred. The mean birthweight (twins excluded) was 3097 g and decreased significantly from 3160 g in 1997 to 3043 g in 2000. The prevalence of low birthweight was 12.5%. The mean age of women was 26.2 years. Cesarean section was done in 26% of deliveries at the hospital, equaling a cesarean section rate of 1.1% in the population. Nineteen maternal deaths occurred, yielding a (hospital) maternal mortality rate of 600 per 100 000 live births. Uterine rupture occurred in 52 women, of whom six died (11.5%). Conclusions: Efforts to educate women at risk to deliver at a health center, and early referral of women to the hospital should be reinforced. The reduction of mean birthweight is of concern and reasons for this need to be analyzed.
Endometriosis: current concepts and therapy
Authors: Valle R.F
Published: October 2002

Endometriosis is the growth of endometrial tissue in ectopic locations. The clinical picture is extremely pleiomorphic, which can make the diagnosis difficult. Despite 70 years of theories and experimentation, the cause is not clear, and it is likely that more than one mechanism is at work in most patients. Both medical and surgical treatments are available. In each case, the woman and her physician should formulate a comprehensive treatment plan that addresses the primary complaint as well as the patient's reproductive desires.
Why should marketing and manufacturing work together?
Authors: Hausman Warren H. , Montgomery David B. , Roth Aleda V.
Published: October 2002

This paper presents an exploratory investigation of the manufacturing/marketing (hereafter M/M) interface. Drawing on the literature and prior empirical work in M/M strategies, we propose a path model for assessing the mediating impact of the M/M interface harmony—the functions’ ability to work together—on M/M morale and business performance. Using two convenience samples of executives, we empirically test the direct and indirect influence of predisposing factors (antecedents) and performance outcomes (consequences) that are expected theoretically to influence or be influenced by M/M interface harmony.

We find that 11 of the 13 hypothesized direct effects are significant at the 0.012 level or below; and attesting to the mediating influence of the M/M ability to work together, 11 of the 12 indirect effects were significant at the 0.02 level or below. Increasing the emphasis on the importance of marketing or manufacturing, or both, improves the ability of both functions to work harmoniously, which in turn impacts M/M morale. Interfunctional harmony appears to have a stronger influence on each function’s morale than the importance attached to that function, ceteris paribus. Contrary to conventional wisdom, the study provides insight on the distinctive roles whereby marketing and manufacturing functions influence performance. Marketing acts to improve competitive position and profitability through the mediating influence of M/M interface harmony and improved marketing morale. However, manufacturing morale was not shown to be a significant factor impacting performance. Rather, emphasis on manufacturing impacts competitive position directly, as indicated by the resource‐based view of manufacturing strategy. This exploratory study provides new empirical evidence that the M/M interface harmony, as expressed by the functions’ ability to work together, matters significantly to business outcomes directly and indirectly.
Asymptotic behavior of ground states of quasilinear elliptic problems with two vanishing parameters
Authors: Gazzola Filippo , Serrin James
Published: October 2002

We study the asymptotic behavior of the radially symmetric ground state solution of a quasilinear elliptic equation involving the

m

-Laplacian. The case of two vanishing parameters is considered: we show that these two parameters have opposite effects on the asymptotic behavior. Moreover the results highlight a suprising phenomenon: different asymptotic are obtained according to whether

n>m^2

or

n⩽m^2

, where

n

is the dimension of the underlying space.

Nous étudions le comportement asymptotique de l'état fondamental à symétrie radiale d'une équation elliptique quasilinéaire contenant le

m

-Laplacien. Le cas de deux paramètres tendant vers 0 est considéré : nous montrons que ces deux paramètres sont en compétition. Les résultats obtenus découvrent un nouveau surprenant phénomène : deux comportements asymptotiques complètement différents sont obtenus suivant une relation entre le paramètre

m

et la dimension

n

de l'espace.
GH‐independent cardiotropic activities of hexarelin in patients with severe left ventricular dysfunction due to dilated and ischemic cardiomyopathy
Authors: Imazio M. , Bobbio M. , Broglio F. , Benso A. , Podio V. , Valetto M.R. , Bisi G. , Ghigo E. , Trevi G.P.
Published: October 2002

Aim:

To investigate acute cardiotropic activities of hexarelin in patients with severe left ventricular dysfunction due to ischemic (iCMP) and dilated cardiomyopathy (dCMP).

Methods and results:

We studied the effect of intravenous hexarelin administration on growth hormone (GH) levels and left ventricular ejection fraction (LVEF) evaluated by radionuclide angiography in eight patients with dCMP (age 53.0±2.8, LVEF 16.7±2.1%) and five patients with iCMP (age 52.0±2.8 years, LVEF 22.6±2.1). Results were compared with a group of seven normal subjects (age 37.4±3.4 years, LVEF 64.0±1.5%) and seven patients with severe growth‐hormone deficiency (GHD; age 42.0±4.4 years, LVEF 50.0±1.9%) previously studied with the same methodology. In dCMP and iCMP patients hexarelin induced a similar significant (P<0.05) increase in GH levels. In iCMP patients hexarelin induced a LVEF increase (peak LVEF 26.2±2.5%, P<0.05) as observed in normals and GHD, while in dCMP LVEF was unchanged (peak LVEF 17.7±1.7, P ‐ NS). In all groups other hemodynamic parameters were unchanged.

Conclusions:

Acute hexarelin administration increases LVEF in iCMP patients (as in normals and GHD) but not in dCMP patients in spite of a similar GH releasing effect and basal LVEF. A possible explanation of the positive inotropic effect of hexarelin in iCMP could be a direct stimulation on viable myocardium or myocardial contractile reserve.
Devolution, Sustainability and Local Economic Development: Impacts on Local Autonomy, Policymaking and Economic Development Outcomes
Authors: Benneworth Paul , Roberts Peter
Published: October 2002

In this paper, we examine how devolution has affected local sustainable development. We focus on attempting to gauge how devolution will affect the promotion of sustainable development in the English regions through an analysis of the changes to date in Scotland, Wales and London. This evaluation is made more difficult because of the range of changes which devolution involves - political, institutional, organizational and cultural, and it is hard to ascribe particular outcomes to particular changes. The focus of the paper is examining how local sustainability regimes have been affected by devolution in the three case study regions. We then conclude that devolution can only add value to existing arrangements if it creates an additional level of legitimacy which supports local coalitions deepening their commitment to the principles of local sustainable development.
A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion Formation
Authors: Massberg Steffen , Brand Korbinian , Grüner Sabine , Page Sharon , Müller Elke , Müller Iris , Bergmeier Wolfgang , Richter Thomas , Lorenz Michael , Konrad Ildiko , Nieswandt Bernhard , Gawaz Meinrad
Published: October 2002

The contribution of platelets to the process of atherosclerosis remains unclear. Here, we show in vivo that platelets adhere to the vascular endothelium of the carotid artery in ApoE−/− mice before the development of manifest atherosclerotic lesions. Platelet–endothelial cell interaction involved both platelet glycoprotein (GP)Ibα and GPIIb-IIIa. Platelet adhesion to the endothelium coincides with inflammatory gene expression and preceded atherosclerotic plaque invasion by leukocytes. Prolonged blockade of platelet adhesion in ApoE−/− mice profoundly reduced leukocyte accumulation in the arterial intima and attenuated atherosclerotic lesion formation in the carotid artery bifurcation, the aortic sinus, and the coronary arteries. These findings establish the platelet as a major player in initiation of the atherogenetic process.
The D0 Domain of KIR3D Acts as a Major Histocompatibility Complex Class I Binding Enhancer
Authors: Khakoo Salim I. , Geller Ron , Shin Sunny , Jenkins Jomaquai A. , Parham Peter
Published: October 2002

In contrast to the KIR2D:HLA-C interaction, little is known of KIR3DL1's interaction with HLA-B or the role of D0, the domain not present in KIR2D. Differences in the strength and specificity for major histocompatibility complex class I of KIR3DL1 and its common chimpanzee homologue Pt-KIR3DL1/2 were exploited to address these questions. Domain-swap, deletion, and site-directed mutants of KIR3DL1 were analyzed for HLA-B binding using a novel, positively signaling cell–cell binding assay. Natural ‘deletion’ of residues 50 and 51 from its D0 domain causes Pt-KIR3DL1/2 to bind Bw4+ HLA-B allotypes more avidly than does KIR3DL1. Deletion of these residues from KIR3DL1, or their substitution for alanine, enhanced binding of Bw4+ HLA-B. None of 15 different point mutations in D0 abrogated KIR3DL1 binding to Bw4+ HLA-B. In contrast point mutations in the D1 and D2 domains of KIR3DL1, made from knowledge of KIR2D:HLA-C interactions, disrupted binding to Bw4+ HLA-B. The results are consistent with a model in which D1 and D2 make the principal contacts between KIR3DL1 and HLA-B while D0 acts through a different mechanism to enhance the interaction. This modulatory role for D0 is compatible with natural loss of expression of the D0 domain, a repeated event in the evolution of functional KIR genes.
E‐commerce: the challenge for UK SMEs in the twenty‐first century
Authors: Quayle Michael
Published: October 2002

This article explores the awareness and level of implementation of e‐commerce in UK small and medium‐sized enterprises (SMEs). Results of a survey of 298 small firms suggest that issues of leadership and waste management are of greater importance to SMEs than development of e‐commerce capability. Those SMEs which have developed e‐commerce capability have not done so strategically and have yet to enjoy significant cost and time savings. The survey also identifies the challenges faced by SMEs. Finally, paths are suggested, which might be followed by such firms in seeking to enhance their performance in e‐commerce.
QCD VACUUM AND AXIONS: WHAT'S HAPPENING?
Authors: GABADADZE GREGORY , SHIFMAN M.
Published: October 2002

A deeper understanding of the vacuum structure in QCD invites one to rethink certain aspects of axion physics. The recent advances are mostly due to developments in super-symmetric gauge theories and the brane theory, in which QCD can be embedded. They include, but are not limited to, the studies of metastable vacua in multicolor gluo-dynamics, and the domain walls. We briefly review basics of axion physics and then present a modern perspective on a rich interplay between the QCD vacuum structure and axion physics.
STOCHASTIC DYNAMICS OF A COUPLED ATMOSPHERE–OCEAN MODEL
Authors: DUAN JINQIAO , GAO HONGJUNG , SCHMALFUß BJÖRN
Published: October 2002

The investigation of the coupled atmosphere-ocean system is not only scientifically challenging but also practically important.

We consider a coupled atmosphere-ocean model, which involves hydrodynamics, thermodynamics, and random atmospheric dynamics due to short time influences at the air–sea interface. We reformulate this model as a random dynamical system. First, we have shown that the asymptotic dynamics of the coupled atmosphere-ocean model is described by a random climatic attractor. Second, we have estimated the atmospheric temperature evolution under oceanic feedback, in terms of the freshwater flux, heat flux and the external fluctuation at the air–sea interface, as well as the earth's longwave radiation coefficient and the shortwave solar radiation profile. Third, we have demonstrated that this system has finite degree of freedom by presenting a finite set of determining functionals in probability. Finally, we have proved that the coupled atmosphere-ocean model is ergodic under suitable conditions for physical parameters and randomness, and thus for any observable of the coupled atmosphere-ocean flows, its time average approximates the statistical ensemble average, as long as the time interval is sufficiently long.
Significant Effect of Carbonate Ions on the Photooxidation of Water on Mesoporous TiO2 Film Electrodes
Authors: Sayama Kazuhiro , Augustynski Jan , Arakawa Hironori
Published: October 2002

Carbonate ions cause a net increase of the saturation photocurrent as well as the occurrence of a stepwise photocurrent/potential (I/V) characteristic for the photooxidation of water at a nanocrystalline TiO2 photoanode deposited on the conducting glass.
Exploring white matter tracts in band heterotopia using diffusion tractography
Authors: Eriksson Sofia H. , Symms Mark R. , Rugg‐Gunn Fergus J. , Boulby Philip A , Wheeler‐Kingshott Claudia A. M. , Barker Gareth J. , Duncan John S. , Parker Geoffrey J. M.
Published: October 2002

Band heterotopia is a malformation of cortical development characterized by bands of gray matter in the white matter parallel to the surface of the neocortex. Histopathological studies have suggested that small white matter tracts pass through the heterotopia, and functional magnetic resonance imaging studies have shown activation in the malformation. We used diffusion tractography to explore the anatomical connectivity of band heterotopia and, in particular, whether in vivo white matter tracts traverse the heterotopic gray matter. Five patients with band heterotopia and five control subjects were scanned with whole brain diffusion tensor imaging. Anisotropy maps were calculated. Using fast marching tractography, we produced maps of connectivity and tract traces from two seed points, in the splenium of the corpus callosum and the right parietal lobe. Eigenvectors were found to pass through the band heterotopia in an aligned fashion. Patterns for maps of connectivity were similar in patients and control subjects. Areas of high connectivity were found in the band heterotopia and in cortical areas on the far side of the malformation from the seed point. The tracts hence appeared to traverse or end within the band heterotopia. The results are in agreement with previous histopathological studies and indicate the structural basis of the functional connectivity and absence of focal deficits in these patients.
Fracture characteristics of vinylester resin under impact fatigue
Authors: Ray Dipa , Sarkar B. K. , Bose N. R.
Published: October 2002

The impact fatigue behavior of a vinylester resin was studied with a pendulum‐type repeated‐impact tester especially designed and fabricated for the determination of single‐impact and repeated‐impact strengths. A well‐defined energy–endurance impact fatigue curve was obtained with a progressive endurance at values of the impact energy below the critical value, with the endurance limit set at an energy level of 31 N mm, 17.4% of the single‐impact energy. The nature of the crack propagation was investigated for a single impact as well as high, medium, and low impact energy levels with progressively longer endurance. The fracture characteristics varied with the impact energy imparted and the number of cycles endured. The rate of lip growth was high at the higher impact energy levels with a lower number of endurance cycles and low at the lower impact energy levels with longer endurance; the repeated impacts created large and small compressive zones through the bending of specimens with the development of long and short lips, respectively. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1995–2001, 2002
Recycling of dry and wet polyamide 6
Authors: La Mantia F. P. , Curto D. , Scaffaro R.
Published: October 2002

Recycling of polycondensation polymers can give rise to secondary materials with good mechanical properties only if a careful drying is carried out before the melt reprocessing operations. The presence of humidity provokes the hydrolytic chain scission of the macromolecules and the consequent decrease of molecular weight and properties. In this work, the drying step was substituted by the addition of an antioxidant that is able to protect the macromolecules because it is the autioxidant is more prone to hydrolysis, thus removing the water from the melt. The mechanical properties of polyamide 6 reprocessed more times in wet conditions and in the presence of this stabilizer are even better than those obtained reprocessing the dry polyamide. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1899–1903, 2002
Carbon black containing IPNs based on unsaturated polyester/epoxy. I. Dynamic mechanical properties, thermal analysis, and morphology
Authors: Shih Yeng‐Fong , Jeng Ru‐Jong
Published: October 2002

A series of carbon black containing interpenetrating polymer networks (IPNs) based on unsaturated polyester/epoxy (weight ratios 10/90, 20/80, 30/70) were developed. Scanning electronic microscopy exhibits that the compatibility was decreased and the morphology seemed to become less rigid as the content of unsaturated polyester increased in IPNs. The results also indicate that flame retardants were uniformly distributed in the IPN matrices. It is found that the heat resistance, damping, and mechanical properties were all improved simultaneously by adding the plate‐shaped carbon black flame retardants to the unsaturated polyester/epoxy IPNs. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1904–1910, 2002
Synthesis, properties, and comparative analyses on the chain flexibility of an ultrastable vinyl polyperoxide
Authors: Nanda A. K. , Kishore K.
Published: October 2002

The most stable vinyl polyperoxide, namely, poly(indene peroxide) (PINDP), an alternating copolymer of indene and oxygen, was synthesized by the oxidative polymerization of indene. It was characterized by 1H‐NMR and 13C‐NMR, Fourier transform infrared, differential scanning calorimetry, direct pyrolysis mass spectrometry, and gas chromatography mass spectrometry studies. The overall activation energy for the degradation and the glass‐transition temperature of PINDP were 47 kcal/mol and 327 K respectively, which were very high compared to those of other vinyl polyperoxides. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2108–2114, 2002
Age‐based warranty data analysis without date‐specific sales information
Authors: Wang Lianhua , Suzuki Kazuyuki , Yamamoto Wataru
Published: October 2002

Age‐based analysis of warranty claim data forms the basis for the estimation, prediction, and comparison of claims across different product groups or across time. The age of a product means the elapsed calendar time since the product was sold or entered service. In this article, we develop a method to deal with situations when the information on date‐specific sales amounts is not available but the total sales quantity can be determined from other sources. Date‐specific sales amounts, i.e. the number of products sold on different dates, are difficult to determine for many products from many wholesalers and retailers around the world. We consider the problem of maximum likelihood estimation of the expected number of claims for repairable items based on a non‐homogeneous Poisson process model, and of the probability of a claim for non‐repairable items based on a multinomial model. These estimators derived for the above two cases are in a closed‐form expression and are the same. We carry out numerical simulation to evaluate the effectiveness of these proposed estimators by comparing them with those obtained under the assumption that date‐specific sales amounts are available. Copyright © 2002 John Wiley & Sons, Ltd.
Effectiveness of neural networks to regression with structural changes
Authors: Asano Miyoko , Tsubaki Hiroe , Yoshizawa Tadashi
Published: October 2002

This paper reports simple numerical experiments of the application of multi‐layered and feed‐forward neural networks to regression with change points to clarify one of the effectiveness of the neural network model compared with non‐parametric regression methods based on scatter plot smoothing. We also show an illustrative example, which successfully draws too rapid growth of GDP in Japan at the bubble economy around 1990 by interpreting decomposition of regression function suggested by the optimal neural networks fitting. Copyright © 2002 John Wiley & Sons, Ltd.
Peripheral blood stem cell support reduces the toxicity of intensive chemotherapy for children and adolescents with metastatic sarcomas
Authors: Hawkins Douglas S. , Felgenhauer Judy , Park Julie , Kreissman Susan , Thomson Blythe , Douglas James , Rowley Scott D. , Gooley Ted , Sanders Jean E. , Pendergrass Thomas W.
Published: October 2002

BACKGROUND

To increase the dose intensity (DI) of chemotherapy for pediatric patients with metastatic sarcomas, including the Ewing sarcoma family of tumors (ESFT) and rhabdomyosarcoma (RMS), the authors tested the feasibility of an intensive regimen supported by granulocyte‐colony stimulating factor (G‐CSF) and peripheral blood stem cells (PBSC).

METHODS

Twenty‐three children and adolescents with metastatic sarcomas received vincristine, doxorubicin, cyclophosphamide, ifosfamide, sodium mercaptoethanesulfonate (mensa), and etoposide (VACIME) chemotherapy, consisting of 8 courses of vincristine 2 mg/m2 on Day 0, doxorubicin 37.5 mg/m2 per day on Days 0–1, cyclophosphamide 360 mg/m2 per day on Days 0–4, ifosfamide 1800 mg/m2 per day on Days 0–4, mesna 2400 mg/m2 per day, and etoposide 100 mg/m2 per day on Days 0–4. Doxorubicin was omitted in Courses 7 and 8. G‐CSF was given after each course of therapy. Courses of therapy were repeated every 21 days or as soon as hematopoietic recovery permitted. PBSC were collected twice: first, after Course 2 (infused after Courses 3 and 4) and, second, after Course 4 (infused after Courses 5 and 6). Surgical resection followed Course 6, and radiotherapy followed Course 8.

RESULTS

PBSC collections were adequate in 91% of all harvests. The mean DI was 82% (standard deviation, 14%) of the intended DI, which was greater than historic data without PBSC support. Seventeen patients (74%) achieved a complete response (CR), 12 patients with chemotherapy alone and 5 more patients after undergoing surgical resection. Fifteen patients developed progressive disease, with a 2‐year event free survival (EFS) rate of 39% (95% confidence interval, 19–59%). Hematopoietic toxicity was severe and cumulative, although it was less than that seen previously without PBSC support.

CONCLUSIONS

PBSC‐supported multicycle chemotherapy is a feasible method to increase chemotherapy DI for pediatric patients with metastatic sarcomas. Although the CR rate compared favorably with previously reported response rates, the 2‐year EFS rate was similar to that achieved with other intensive regimens. Cancer 2002;95:1354–65. © 2002 American Cancer Society.

DOI 10.1002/cncr.10801
Expression of EphB receptors and EphrinB ligands in the developing chick auditory brainstem
Authors: Cramer Karina S. , Karam Sana D. , Bothwell Mark , Cerretti Douglas Pat , Pasquale Elena B. , Rubel Edwin W
Published: October 2002

Nucleus magnocellularis (NM) in the avian auditory brainstem receives auditory input from nerve the VIIIth and projects bilaterally to nucleus laminaris (NL). This projection preserves binaural segregation in that ipsilateral NM projects to dorsal dendrites of NL and contralateral NM projects to ventral dendrites of NL. We have begun to examine the molecular signals that influence segregation of inputs onto discrete regions of NL cells. We previously showed that the Eph receptor, EphA4, is expressed selectively in the dorsal NL neuropil from embryonic day (E) 9 to E11, when NM axons grow into the NL neuropil. This asymmetric distribution suggests that EphA4 acts as a guidance molecule during binaural segregation. We report here on the developmental changes in the expression of two other Eph receptors, EphB2 and EphB5, and two ligands, ephrin‐B1 and ephrin‐B2, in the chick auditory brainstem. These proteins are expressed in the auditory nuclei during the maturation of the NM–NL projection. EphB2, EphB5, and ephrin‐B1 are expressed in dorsal and ventral NL neuropil and at the midline of the brainstem at E10–E12. At this age, ephrin‐B2, a ligand for EphB receptors and for EphA4, is expressed in NL cell bodies and NM–NL axons. The expression of these proteins diminishs in the posthatch ages examined. These results suggest that several members of the Eph family are involved in maturation of the nuclei and their projections. Moreover, ephrin‐B2 in growing axons may interact with the asymmetrically expressed EphA4 during the establishment of binaural segregation. J. Comp. Neurol. 452:51–64, 2002. © 2002 Wiley‐Liss, Inc.
Therapeutic strategies of Alzheimer's disease through manipulation of Aβ metabolism: a focus on Aβ‐degrading peptidase, neprilysin
Authors: Fukami Shinjiro , Iwata Nobuhisa , Saido Takaomi C.
Published: October 2002

Deposition of amyloid‐β peptide (Aβ), a pathological hallmark of Alzheimer's disease (AD), locates upstream of the AD cascade. Aβ is constantly anabolized and catabolized in the brain, and the steady‐state Aβ level is physiologically determined by the metabolic balance between the anabolic and catabolic activities. Even subtle alterations in this metabolic balance over a long period of time could turn Aβ into a pathogenic agent that influences both the pathological progression and incidence of the disease. Therefore, AD may be a consequence of proteolytic disorder. In order to overcome AD, lowering the Aβ levels in the brain is necessary. There are many strategies to address this, such as β‐, γ‐secretase inhibitors or Aβ vaccination. Recently, we demonstrated that neprilysin is the most potent Aβ‐degrading enzyme in vivo and hypothesized that neprilysin deficiency would influence the steady‐state Aβ levels in the brain by alternating the Aβ metabolism. Therefore, to maintain or upregulate neprilysin activity in the brain will be a relevant strategy for prevention and therapy of AD through reduction of the Aβ levels. In this review, we describe several therapeutic strategies for manipulating the Aβ level and our current understanding of Aβ metabolism, focusing on the Aβ‐degrading enzyme, neprilysin. Drug Dev. Res. 56:171–183, 2002. © 2002 Wiley‐Liss, Inc.
Development and evaluation of a health‐related quality of life questionnaire for the elderly with dementia in Japan
Authors: Terada Seishi , Ishizu Hideki , Fujisawa Yoshikatsu , Fujita Daisuke , Yokota Osamu , Nakashima Hanae , Haraguchi Takashi , Ishihara Takeshi , Yamamoto Shin , Sasaki Ken , Nakashima Yoshihiko , Kuroda Shigetoshi
Published: October 2002

Objectives

The purpose of this study was the development of the quality of life (QOL) questionnaire for dementia (QOL‐D) in Japan.

Methods

We performed a questionnaire survey of QOL assessment in elderly patients with dementia in Japan, and developed QOL‐D.

Results

The final version consists of only 31 items grouped into six response sets, each with its own scale. Reliability is good to excellent, and validity is, to some extent, established. The six domains of health‐related QOL are divided into two groups. One is the positive and the other is the negative aspects of health‐related QOL. The positive aspects have been shown to correlate positively with cognitive function and activities of daily living (ADL) score, whereas the negative aspects have not. The concept of QOL for elderly patients with dementia in Japan is similar to that in Western countries.

Conclusion

We demonstrated that QOL‐D is a reliable and valid instrument for QOL assessment in elderly patients with dementia in Japan. Copyright © 2002 John Wiley & Sons, Ltd.
New truths and old verities
Authors: Ramaley Judith A.
Published: October 2002

An environment for learning should be established that reflects an informed awareness of how people learn, one that prepares all students for life and work in a society dominated by science and technology and is based on the expectation that all students can learn science and mathematics.
Building natural science communities
Authors: Brady Thomas E.
Published: October 2002

By giving concerted attention to each of the junctures at which students were being lost to the study of science and mathematics, a community of K–16 educators realizes greater success and persistence for its students.
In vitro evaluation of phosphonylated low‐density polyethylene for vascular applications
Authors: Caldwell Rebecca A. , Woodell Jennifer E. , Ho Sunita Pullela , Shalaby Shalaby W. , Boland Thomas , Langan Eugene M. , Laberge Martine
Published: October 2002

The use of catheters for vascular applications is often complicated by the development of friction between the catheter material and the vessel wall, which leads to endothelial cell removal and intimal lesions. Phosphonylation, a chemical surface treatment, has been proposed as a means of increasing the hydrophilicity of low‐density polyethylene (LDPE), a commonly used catheter material, in efforts to impart lubricity to the material and reduce vascular tissue damage. In an in vitro tribological study, phosphonylated LDPE produced a lower coefficient of friction and allowed greater retention of endothelial cells on vessels as compared to untreated LDPE when the materials were reciprocated against normal porcine aorta. Chemical characterizations of the LDPE before and after friction testing involving Fourier transform infrared and energy‐dispersive X‐ray (EDX) confirmed the phosphorus content on phosphonylated LDPE. Election spectroscopy for chemical analysis (ESCA) and atomic force micrscope (AFM) analyses verified that proteins initially adsorb to both the phosphonylated and untreated LDPE surfaces and that the proteins interfere with water to lubricate the surfaces. However, with repeated friction, proteins are removed from the surface and hydrophilicity, as imparted by phosphonylation, becomes a principal factor in the lubrication process. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 514–524, 2002
Intracellular signaling involved in macrophage adhesion and FBGC formation as mediated by ligand–substrate interaction
Authors: Kao Weiyuan John , Liu Yiping
Published: October 2002

Fibronectin and RGD‐ and/or PHSRN‐containing oligopeptides were preadsorbed onto physicochemically distinct substrata: polyethyleneglycol‐based networks or tissue culture polystyrene (TCPS). The role of selected signaling kinases (namely protein tyrosine kinases, protein serine/threonine kinases, PI3‐kinase, Src, and MAPK) in the adhesion of human primary blood‐derived macrophages and the formation of foreign‐body giant cells (FBGC) on these modified substrata was investigated. The involvement of individual intracellular signaling molecules in mediating macrophage adhesion dynamically varied with the culture time, substrate, and ligand. For example, fibronectin on TCPS or networks involved similar signaling events for macrophage adhesion; however, fibronectin and G3RGDG6PHSRNG, but not peptides with other RGD and/or PHSRN orientations, mediated similar signaling events for macrophage adhesion on TCPS but mediated different signaling events on networks. Depending on the substrate, a specific molecule (i.e., Src, protein kinase C) within the protein tyrosine kinase or protein serine/threonine kinase family was either an antagonist or agonist in mediating FBGC formation. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 478–487, 2002
Genetic training of network using chaos concept: Application to QSAR studies of vibration modes of tetrahedral halides
Authors: Lu Qingzhang , Shen Guoli , Yu Ruqin
Published: October 2002

The chaotic dynamical system is introduced ingenetic algorithm to train ANN to formulate the CGANN algorithm. Logistic mapping as one of the most important chaotic dynamic mappings provides each new generation a high chance to hold GA's population diversity. This enhances the ability to overcome overfitting in training an ANN. The proposed CGANN has been used for QSAR studies to predict the tetrahedral modes (ν1(A1) and ν2(E)) of halides [MX4]ε. The frequencies predicted by QSAR were compared with those calculated by quantum chemistry methods including PM3, AM1, and MNDO/d. The possibility of improving the predictive ability of QSAR by including quantum chemistry parameters as feature variables has been investigated using tetrahedral tetrahalide examples. © 2002 Wiley Periodicals, Inc. J Comput Chem 14: 1357–1365, 2002
Lipopolysaccharide administration increases acid and alkaline phosphatase reactivity in the cardiac muscle
Authors: Okada Teruhiko , Zinchuk Vadim S. , Seguchi Harumichi
Published: October 2002

The effect of lipopolysaccharide (LPS) administration on the in situ distribution of the reaction product of acid phosphatase (AcPase) and alkaline phosphatase (AlPase) activity was examined in the rat cardiac muscle using catalytical cytochemistry. Tissues of the heart were fixed and then incubated in reaction media for detection of AcPase and AlPase reactivity. In normal hearts, reaction product of AcPase activity was observed in lysosomes. AlPase reactivity was detected at the extracellular surface of the capillary endothelilal cells and in their caveolae. Following LPS administration, the number and the size of lysosomes possessing AcPase reactivity as well as their electron density significantly increased. Furthermore, they tended to form groups consisting of three to five lysosomes. Cytochemical reaction 2 and 24 hours after injection was similar. One week later, the reaction returned to its normal pattern. As in the case with AcPase, the first changes of the distribution of the reaction product of AlPase activity were detected 2 hours after injection. The changes included a remarkable increase of the number of enzymatically positive capillaries, intensified cytochemical reaction in endothelial cells, and an increased number of caveolae. Again, no noticeable differences in reactivity were observed 2 and 24 hours after injection and the reaction returned to normal one week later. Collectively, our data indicate that both cardiac AcPase and AlPase are affected early after injection of LPS. Although the pattern of cytochemical reaction of both phosphatases was restored one week later, it is believed that the altered distribution of their reactivity in early periods after LPS administration may be a factor contributing to the development of pathological changes in this organ at a later stage. Microsc. Res. Tech. 58:421–426, 2002. © 2002 Wiley‐Liss, Inc.
Detection of human papillomavirus in esophageal carcinoma
Authors: Shen Zhong‐Ying , Hu Sheng‐Ping , Lu Li‐Chun , Tang Chun‐Zhi , Kuang Zhong‐Sheng , Zhong Shu‐Ping , Zeng Yi
Published: October 2002

The aim of the study was to assess the prevalence of human papillomavirus (HPV) in the esophagus in the coastal region of Eastern Guangdong, Southern China, an area with a high incidence of esophageal carcinoma. Fresh surgical resection esophageal specimens were obtained from 176 esophageal carcinoma patients admitted to the Tumor Hospital of Shantou University Medical College. The samples were subjected to polymerase chain reaction (PCR) to detect HPV infection using consensus and type‐specific primers for HPV type 6, 11, 16, and 18. The incidence rate was 65.5%, 69.1%, and 60% in tissues of cancerous, paracancerous and normal mucosa, respectively. Further analysis of the distribution of HPV types in the three sections of tissues showed that the high‐risk HPV types 16 and 18 were found mainly in the cancer cells (43.2%), whereas the low‐risk HPV types 6 and 11 were seen mainly in the normal mucosa (52.3%). The total infection rate of the high‐risk HPV types 16 and HPV 18 was the highest in cancerous tissues (54.5%), followed by paracancerous tissues (19.5%), and the lowest in normal mucosa (11.7%). There was high incidence of HPV infection in the esophageal epithelium in Eastern Guangdong, Southern China, where esophageal carcinoma is prevalent. HPV was seen in the normal, paracancerous and cancerous tissues, with the high‐risk HPV type 16 and 18 more common in cancerous tissues. The results indicate that the high incidence of esophageal carcinoma in this area is associated with HPV infection. J. Med. Virol. 68:412–416, 2002. © 2002 Wiley‐Liss, Inc.
Airflow through the auxiliary line of the laser fiber prevents ignition of intra‐airway fire during endoscopic laser surgery
Authors: Takanashi Shingo , Hasegawa Yukihiro , Ito Akihiko , Sato Masami , Kaji Kunihide , Okumura Ken
Published: October 2002

Background and Objectives

Ignition accidents during bronchoscopic laser irradiation have occasionally been reported, but the mechanisms responsible for the ignition accidents are not fully understood. We examined causative factors including ignition site, oxygen concentration, and role of airflow through the laser fiber.

Study Design/Materials and Methods

Porcine muscle tissue was placed in a bottle and irradiated by laser under various conditions. Also, a piece of porcine muscle was wedged in a main bronchus of the isolated porcine lungs and irradiated by laser in the same way.

Results

Flashing occurred on the tissue exposed to the laser, and this flashing reached the ignition when the oxygen concentration was above 30%. Increasing airflow through the laser fiber prevented the ignition even at an oxygen concentration at 100%.

Conclusions

In laser irradiation, the tissue exposed to the laser can be the ignition site of fire. Increasing airflow through the laser fiber was an effective technique to prevent airway fire. Lasers Surg. Med. 31:211–215, 2002. © 2002 Wiley‐Liss, Inc.