bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of carbon codoping on lattice locations of erbium in silicon
Authors: Huang M. B. , Ren X. T.
Published: October 2002

The effects of carbon codoping on the lattice location of Er atoms in silicon have been investigated using ion beam channeling. A float-zone (FZ) Si (100) wafer was first amorphized to a depth of ∼0.3 μm by Si ion implantation at 77 K. The amorphous Si layer was then implanted with carbon ions, and recrystallized via solid phase epitaxial growth. Finally, Er ions were implanted into C-doped and C-free Si samples at 300 °C. Angular scans along three major crystalline directions, that is, 〈100〉, 〈110〉, and 〈111〉, were performed for Er-implanted Si with and without C codoping. In FZ-Si, in which the carbon concentration is very low (<1016 cm−3), a large fraction (∼50%) of implanted Er atoms are found to occupy the near-tetrahedral (T) interstitial site, while few Er atoms are on the hexagonal (H) interstitial site. It is evident that the incorporation of C into Si tends to decrease the fraction of T-site Er atoms and relocate them to the H site. We have also determined the effective number (∼1.5) of carbon atoms required for depopulating an Er atom from the T site to H site. Implications on the configuration of Er luminescence centers are discussed.
Control of the confining potential in ballistic constrictions using a persistent charging effect
Authors: Fischer S. F. , Apetrii G. , Skaberna S. , Kunze U. , Reuter D. , Wieck A. D.
Published: October 2002

GaAs/AlGaAs quantum point contacts are fabricated by atomic force microscope lithography and wet chemical etching. The lateral confinement potential of a given ballistic constriction is varied by persistent fractional charging of the donors in the supply layer. A forward bias voltage applied to the gate electrode during sample cooling shifts the conductance threshold at T=4.2 K towards higher gate voltage due to partial neutralization of the donors. Simultaneously, the width of the quantized conductance plateaus at multiples of 2e2/h decreases. Measurements under finite drain voltage reveal a reduction of the lowest subband separation from ΔE1,2=17.5±1 to 13±1 meV as the cooling bias voltage is raised from 0 to +0.6 V.
Tunable single-photon source using Korteweg–de Vries solitons
Authors: Matsuda Ken-ichi , Hatakenaka Noriyuki , Takayanagi Hideaki , Sakuma Tetsuro
Published: October 2002

We describe the quantum transport of electrons by solitary waves and use it as the basis for a scheme for generating a single photon with highly nonclassical nature. A concave soliton acting as an attractive potential can capture an electron in its only eigenstate and the captured electron can be transported by soliton propagation. A single photon is generated by a transition between eigenstates in the interacting soliton potential when a soliton with a captured electron interacts with an empty soliton with a lower eigenstate.
Quantum-cascade-laser structures as photodetectors
Authors: Hofstetter Daniel , Beck Mattias , Faist Jérôme
Published: October 2002

We evaluated two different quantum-cascade-laser structures as photodetectors. The first device was a 5.3 μm two-phonon-resonance structure, and the second one a 9.3 μm bound-to-continuum transition laser. The 5.3 μm structure had a peak responsivity of 120 μA/W at 2200 cm−1 and functioned up to 325 K. On the other hand, the 9.3 μm device also worked up to 297 K but had a lower responsivity of 50 μA/W at 1330 cm−1. Since the absorption peak of these devices can be shifted by applying an external bias, we envision interesting applications in free-space optical telecommunications.
Operation of individual integrally gated carbon nanotube field emitter cells
Authors: Guillorn M. A. , Hale M. D. , Merkulov V. I. , Simpson M. L. , Eres G. Y. , Cui H. , Puretzky A. A. , Geohegan D. B.
Published: October 2002

In this work, we examine the operation of individual field emitter cells contained in a field emitter array composed of integrally gated multiwalled carbon nanotube (MWNT)-based field emission cathodes. These devices were found to behave in a manner consistent with a multiple emission site model of Fowler–Nordheim field emission. These results show considerable variation in the operational characteristics of cells contained within the same array and indicate that data obtained from arrays of cells are not necessarily indicative of individual cell performance.
Effect of Si doping on the relaxation mechanism of InGaAs on GaAs
Authors: Parbrook P. J. , Tanner B. K. , Lunn B. , Hogg J. H. C. , Keir A. M. , Johnson A. D.
Published: October 2002

We report measurements on the initial stages of relaxation of Si-doped In0.04Ga0.96As epitaxial layers on (001) GaAs using in situ high-resolution double-crystal x-ray topography during molecular beam epitaxial growth. For Si concentrations up to 5×1018 cm−3, the critical thickness for formation of the first B(g) misfit dislocations is modeled accurately by the Matthews–Blakeslee model, extended to include a lattice friction force varying linearly with the dopant concentration. Below a Si concentration of 2×1018 cm−3, the model can be used to predict the critical thickness for generation of the orthogonal A(g) dislocation set, with the x-ray topographs showing that the B(g) misfit multiplication occurs at damaged edges of the wafer. However, above 2×1018 cm−3 Si concentration, the critical thickness for A(g) nucleation becomes almost independent of concentration and the x-ray topographs show that cross slip becomes important in the multiplication process. For most of the Si concentrations examined, the critical thickness for nucleation of the slow A(g) misfit dislocations corresponded to that of multiplication of the fast B(g) set.
Accidental conical intersections of three states of the same symmetry. I. Location and relevance
Authors: Matsika Spiridoula , Yarkony David R.
Published: October 2002

An efficient algorithm for locating conical intersections of three states of the same symmetry is presented. The algorithm, which derives its efficiency from the use of analytic gradient techniques, is used to locate a three state intersection for the excited 3p Rydberg states of the ethyl radical. The existence of a seam of three state conical intersections in a 3p Rydberg manifold is expected to be a general occurrence.
Local structure and luminescence of nanocrystalline Y2O3:Eu
Authors: Qi Zeming , Shi Chaoshu , Zhang Weiwei , Zhang Weiping , Hu Tiandou
Published: October 2002

Nanosized Y2O3:Eu was synthesized by using a solution–combustion method. The samples were characterized by x-ray diffraction, extended x-ray absorption fine structure (EXAFS), and photoluminescence spectroscopy. Our EXAFS result showed that the local environments surrounding both Y and Eu atoms had obviously changed when the particle size was smaller than 10 nm. The coordination number and the bond length of Y (Eu)–O shell increased and the disorder became larger. This change also produced an emission peak and the charge-transfer band showed an unusual redshift as the particle size decreased. The luminescence properties can be explained by use of the EXAFS results.
Polycentricity, Households and the Identity of Places
Authors: Musterd Sako , van Zelm Ingrid
Published: October 2002

Recently, the use of the term polycentric or polynuclear urban region has clearly increased greatly in the European urban (planning) literature and also in policy documents. Literally, polycentricity in urban form refers to nothing more than the existence of more than one centre in a city, region or other geographical unit. It is not surprising to find that many more specific elements have been added to this rather broad and empty definition. These additions are strongly contingent on the viewpoint of researchers, especially with respect to the geographical unit that is being referred to. In this contribution, the different concepts and definitions are discussed from the perspective of changing households and related changes in activity patterns and residential preferences. We argue that, from a household perspective, polycentric urban regions the size of the Randstad or Rhine-Ruhr area are too large to constitute relevant geographical units. However, at more local spatial level, the notion of polycentricity is relevant. Rather than focusing on the size of the urban region too much, we believe it makes sense to look at residential milieus. Over recent decades, households have diversified and have, on average, become more affluent and mobile, resulting in increased opportunities for choosing both a house and a residential environment. Simultaneously, polycentric milieus with different sub-milieus have emerged. In this contribution, it is argued that, together, these developments have made the functional uniqueness and complementarity of places more important. Therefore, the unique, spatially bounded qualities of places should play a more prominent part in the development of residential environments in polycentric urban areas than they do at present. Data from the Netherlands are applied to illustrate our viewpoint.
Contextualising Regional Identity and Imagination in the Construction of Polycentric Urban Regions: The Cases of the Ruhr Area and the Basque Country
Authors: van Houtum Henk , Lagendijk Arnoud
Published: October 2002

In this contribution, we aim at positioning and sharpening the concept of 'polycentric urban region' (PUR) by comparing it with preceding approaches to interurban interdependency and by discussing its potentials and pitfalls. The main outcome of the comparison is that the notion of a PUR constitutes a strategic rather than an analytical concept. To unravel the pros and cons of the concept of PUR, a link is made between the strategic interpretation of the PUR concept and the notion of regional identity. The argument put forward is that the strategic dimension of the PUR concept rests on, and mobilises, the identification of a region as an area with distinct morphological and functional characteristics, and a unique cultural identity. In practice, the way these strategic, functional and cultural dimensions interact varies between specific cases of PUR. Two examples are presented here. The Ruhr area in Germany shows how strategic action, supported by an existing functional integration and identity, is geared towards reshaping and mobilising the cultural identity. The Basque country reveals a reverse pattern, in which 'geo-strategic' considerations, fed by a strong cultural identity, shape and invoke functional images to support the concept of a 'Basque polynuclear system'. We end by discussing the possible success of PUR as a core concept in urban planning in western Europe.
Reducing Housing Subsidy: Swedish Housing Policy in an International Context
Authors: Turner Bengt , Whitehead Christine M. E.
Published: October 2002

Swedish housing policy was dramatically changed during the 1990s. A traditional formally tenure-neutral and generous subsidy system has been replaced by much lower levels of assistance, more directed at lower-income households and depressed areas. This paper sets the Swedish policy in an international context as part of a much more general pattern of reduced and rebalanced expenditures associated with liberalisation and the transfer of risk. The paper then addresses the direct and indirect impacts of the Swedish 'grand restructuring', concentrating on the extent of the cutbacks; rents and prices; levels of output; and the potential for increased segregation. The evidence suggests that the policy changes, together with their effect on expectations, significantly modified the housing system. They reduced demand for new building, particularly in less-pressured areas; increased vacancies, especially in the social sector; transferred risk to both the social and private sectors; and increased outcome differentials between the well-off and those with fewer resources—both in terms of individuals and areas. The analysis presented here provides evidence against which the Swedish policy can begin to be evaluated. It also suggests lessons for other industrialised economies that are addressing similar issues.
Trends in Dutch Housing Policy and the Shifting Position of the Social Rented Sector
Authors: Boelhouwer Peter
Published: October 2002

The housing system of the Netherlands has acquired an international reputation because of its special nature and the way it has evolved. In this contribution, we explain how the Dutch social rented sector came to have this specific character. We establish that the position of the social rented sector is strongly influenced by developments in society at large. In particular, its specific position may be explained with reference to the emergence and transformation of the Dutch welfare state. In the Netherlands, the development of the social rented sector coincided with the vigorous build-up of the welfare state. That sector continued to grow in the Netherlands for a longer period than in most other west European countries. Ultimately, the share of the Dutch social rented sector reached its highest point—41 per cent of the stock—at the beginning of the 1990s. The current position of the social rented sector in the Netherlands is determined not only by the structure of the Dutch welfare state and the country's distinct housing policy. It is also the result of the shifting balance of supply and demand in the national housing market. Compared with other countries, the particular historical development of the Dutch social rented sector makes the adjustment of the housing system to a more market-orientated policy—in which more attention is devoted to the freedom of choice of the housing consumer—an unprecedented activity to say the least. This process will require the present housing associations to show a large measure of creativity and flexibility.
Social Housing Policy in a Conservative Welfare State: Austria as an Example
Authors: Matznetter Walter
Published: October 2002

Taking Austria as an example, the article sets out to explore the relationship between a particular type of welfare regime and the kind of social housing policy developed within such an environment. Austria has repeatedly and consistently been classified as the ideal type of a conservative and familialistic welfare regime and as a paradigm case of corporatism. Particular attributes of such a regime (fragmentation, corporatism, familialism, immobilism) do have their repercussions within Austrian housing and may be detected within Austrian housing policy.
Social Rented Housing in Western Europe: Developments and Expectations
Authors: van der Heijden Harry
Published: October 2002

What lies ahead for the social rented sector in western Europe? Do countries differ merely in degree, or do differences between countries offer grounds on which to sketch divergent scenarios for the future? This paper treats these questions in light of the work of Harloe and Kemeny. Based on the development of the policy context and the size and the character of the social rented sector in six west European countries, three plausible scenarios will be presented. The first (residual dual market) scenario is comparable to Harloe's residual model and Kemeny's dual market model. The second (residual unitary market) scenario starts with Kemeny's unitary market model but develops in the direction of the first (residual dual market) scenario. The third (unitary rental market) scenario combines social responsibilities with a market approach to housing provision.
The Future of European Union Social Policy and its Implications for Housing
Authors: Kleinman Mark
Published: October 2002

European economic integration raises important questions about the role of social policy in an economic and monetary union. In the past, it was often argued that there would be upward convergence in the social policies of member-states. More recently, fears have been expressed about downward convergence, partly as a result of globalisation pressures. These fears are shown to be largely unfounded, although there have been trends towards greater similarity in social policy across countries. In the future, it is very unlikely that an extensive welfare state at the European level will develop. However, further European action in 'peripheral' parts of the social policy agenda is more likely. This includes actions in relation to housing, which lies at the intersection of economic policy and social policy.
Testing Governance: Partnerships, Planning and Conflict in Waterfront Regeneration
Authors: Bassett Keith , Griffiths Ron , Smith Ian
Published: October 2002

This paper explores issues of urban governance through a case study of a major, waterfront regeneration project in an English city (Bristol). The first part of the paper sets the development of this project within the broader theoretical context of urban regime theory and changing structures of governance in the city. The paper then outlines the attempts to build a city-wide consensus in Bristol around a viable development project in a situation marked by strongly conflicting views and contrasting visions of urban space. Political and planning processes are explored in some detail to identify the strengths and weaknesses of local governance structures. The paper concludes with some comments on the relevance of the case study for debates on urban regime theory.
'Food Deserts' in British Cities: Policy Context and Research Priorities
Authors: Wrigley Neil
Published: October 2002

This paper provides an introduction to the 'food deserts' theme by outlining how the problem of access to food, particularly foods integral to a healthy diet, for low-income households in poor neighbourhoods in British cities, became an increasingly important issue in the social exclusion and health inequalities debates, during the late 1990s. It documents the emergence of a policy response by UK government to this issue and the way in which policy development ran somewhat ahead of systematic research on key facets of the problem. The paper outlines the research priorities which became apparent by the end of the 1990s and some of the projects which have been funded by the UK research councils and by government departments and agencies to meet this need for fundamental research.
Deriving Indicators of Access to Food Retail Provision in British Cities: Studies of Cardiff, Leeds and Bradford
Authors: Clarke Graham , Eyre Heather , Guy Cliff
Published: October 2002

This paper attempts to quantify patterns of access to food retailing in two urban areas (Leeds/Bradford and Cardiff). We introduce, first, a locally based mapping approach and, secondly, a systematic city-wide modelling approach. This quantifies provision levels in terms of modelling shopping flows, in order to identify areas of poor access to food retailing. The paper then compares these contrasting methods of identifying 'food deserts', using the study areas of Leeds/Bradford and Cardiff. Two 'what if' type analyses are also undertaken (one in Leeds, one in Cardiff) to investigate the impact on 'food deserts' of opening new food retailing stores.
Assessing the Impact of Improved Retail Access on Diet in a 'Food Desert': A Preliminary Report
Authors: Wrigley Neil , Warm Daniel , Margetts Barrie , Whelan Amanda
Published: October 2002

If poor food retail access in deprived areas of British cities is linked, as suggested in many of the policy debates of the late 1990s, via compromised diets/undernutrition to poor health and widening health inequalities, what is the impact of a sudden and significant improvement in food retail access likely to be on the food consumption patterns of residents? In this paper, we describe and provide preliminary results from the first-ever UK study of a major retail provision on diet in a 'food desert'—a 'before/after' study of food consumption patterns in the highly deprived, previously poor food retail access area of Seacroft, Leeds, experiencing a sudden and significant change in its food retail access as a result of the opening of a large superstore by the UK's leading food retailer. We suggest that this study has the potential to provide some of the missing links between poor food retail access, compromised diets/undernutrition, poor health and compound social exclusion that characterised statements on the topic of 'food deserts' in the health inequalities and social exclusion debates of the late 1990s, and that its findings may have significant implications for policy debate.
Urban Regeneration, Social Inclusion and Large Store Development: The Seacroft Development in Context
Authors: Wrigley Neil , Guy Cliff , Lowe Michelle
Published: October 2002

Of central importance to the policy debate which emerged during the late 1990s in the UK on the topic of 'food deserts' were the causes of the perceived worsening access to food retail provision in certain poor neighbourhoods of British cities. The 1980s/early 1990s era of intense food superstore development on edge-of-city sites was seen as having unevenly stripped food retailing out of parts of those cities, or having repositioned that provision downwards in range and quality terms. By the late 1990s, however, tightened land-use planning regulation had begun significantly to impact the development programmes of the major food retailers and those retailers increasingly came to adopt an urban regeneration agenda to drive forwards the new store development vital to their corporate growth. Simultaneously, issues of social exclusion rose to prominence on the political agenda and 'tackling social exclusion' began to be promoted as a possible new criterion for retail planning policy in the UK. In this paper, we explore this nexus of interest in urban regeneration and social inclusion. Using the example of a major retail development in the deprived area of Seacroft, Leeds, we outline the characteristics of the increasingly important regeneration partnerships involving retailers, local authorities, government agencies and community groups. We ask to what extent such partnerships can be dismissed merely as 'clever devices to get stores built and passed by planners' and discuss the implications for retail planning policy of attempts to address both the social exclusion and public health agendas of deprived and poorly served areas of British cities.
China's Changing Urban Governance in the Transition Towards a More Market-oriented Economy
Authors: Wu Fulong
Published: October 2002

China's changing urban development processes and urban landscapes in the transition towards a more market-oriented economy have received extensive research attention in recent years. Relatively, the governing of Chinese cities is still underresearched. This article aims to analyse the forces released both inside and outside the formal socialist state system and the impacts on phenomenal restructuring of urban governance, especially at local levels. Marketisation has created new elements beyond the reach of state work-units that represent the state's 'hierarchical' control. The pillars of the socialist governing structure-the party-state, the work-units system and household registration-are shaken by these forces. The changes in the organisation of people, capital, production materials, infrastructure and space fundamentally demand new urban governance. Territorial organisations such as the municipality, urban districts, Street Office and Residents' Committees are reinvented and consolidated to restore a governable society. The devolution towards the base level and the reinvention of local communities reflect the state's attempt to reconsolidate its power to create a governable society as well as to cope with practical pressures such as the provision of social assistance to poor and aged residents, re-employment of laid-off workers and the management of 'floating' immigrants. The combination of new market elements and decentralised state apparatus has given rise to the entrepreneurial endeavour of China's governance. This research highlights the micro-foundation of the new urban governance in addition to the `globalisation-capital mobility—city competitiveness' thesis.
Sectoral Shares, Specialisation and Metropolitan Wages in the United States, 1969-96
Authors: Drennan Matthew , Larsen Shannon , Lobo Jose , Strumsky Deborah , Utomo Wahyu
Published: October 2002

We investigate the effect of specialisation upon the level of metropolitan wage per worker. Specialisation is measured by the share of metropolitan earnings in each of five traded goods and services sectors. Sectoral specialisations are assumed to be determinants of location-specific productivity, which in turn is treated as a term in a metropolitan production function. Panel data are used for estimating that production function for 313 metropolitan areas in the US, over the long period 1969-96 and two shorter periods. We find that some specialisations raise average metropolitan wages, some lower it and some have no effect, and that the effects of specialisation differ by time-period.
Competitive Dynamics of Southern California's Clothing Industry: The Widening Global Connection and its Local Ramifications
Authors: Scott Allen J.
Published: October 2002

A general outline of the functional and spatial characteristics of the clothing industry in Southern California is sketched out. Two important trends are noted: the increasing design- and knowledge-intensive structure of the industry; and, the marked increase in off-shore sub-contracting by local manufacturers that has occurred in recent years. The predicaments and promises of this situation are explored. Will the industry simply continue to lose its employment base in the region? Will it succeed in making the transition to the status of a major world centre of fashion? It is argued that the southern California clothing industry is potentially capable of rising to the latter challenge, although it remains strongly overshadowed by the New York industry in terms of both fashion significance and commercial reach, and it also retains strong elements of its traditional underbelly of sweatshops. It is further argued that considerable effort needs to be invested in building social infrastructures to reinforce current positive trends in the industry. Given the right kinds of private and public response, it is submitted that Southern California is capable of becoming an international fashion centre on a par with New York, Paris, London or Milan.
Local Government and the Decentralisation of Urban Regeneration Policies in The Netherlands
Authors: Korthals Altes Willem K.
Published: October 2002

In The Netherlands, national urban regeneration policies are undergoing a radical process of decentralisation. Many major national funds are concentrated in an Investment Budget for Urban Regeneration (IUR) and are decentralised to 30 major cities and the 12 provinces for the smaller municipalities. Establishing the IUR is seen as an important precondition for regeneration policies in the Dutch context. The paper discusses the capacity of local government to be the central government agent for the urban regeneration policies being promoted by the IUR. Decentralising urban regeneration policies involves more than decentralising the budget. The domain of local government must have sufficient capacity to engage in the policies decentralised by national government.
Kampung Rules: Landscape and the Contested Government of Urban(e) Malayness
Authors: Bunnell Tim
Published: October 2002

Kampung ('village') habits and traits have been widely invoked in 'explanations' of inappropriate urban conduct among Malays in Malaysia. State-sponsored rural-urban migration for Malays from the 1970s was bound up with a conception of urbanisation as a remedy for the supposedly socioeconomically debilitating effects of kampung life. Yet many such migrants, especially in the national capital, Kuala Lumpur, came to live in squatter kampungs. A dominant Malay nationalist rationality of government has long understood squatter settlements as a failure of attempts to urbanise the Malay. Even when squatters are relocated to public flats, 'kampung values' have been invoked to account for inappropriate social conduct. However, kampung norms and forms are increasingly drawn upon in authoritative conceptions of Malay and even Malaysian urbanity. 'Kampung rules' for Kuala Lumpur's physical and moral landscape are shown to emerge from the contested government of urban(e) Malayness.
Oral (Drinking Water) Two-Generation Reproductive Toxicity Study of Dibromoacetic Acid (DBA) in Rats
Authors: Christian M. S. , York R. G. , Hoberman A. M. , Frazee J. , Fisher L. C. , Brown W. R. , Creasy D. M.
Published: October 2002

In a two-generation study of dibromoacetic acid (DBA), Crl SD rats (30 rats/sex/group/generation) were provided DBA in drinking water at 0 (reverse osmosis-deionized water), 50,250, and 650 ppm (0,4.4 to 11.6,22.4 to 55.6, and 52.4 to 132.0 mg/kg/day, respectively; human intake approximates 0.1 μg/kg/day [0.0001 mg/kg/day]). Observations included viability, clinical signs, water and feed consumption, body and organ weights, histopathology, and reproductive parameters (mating, fertility, abortions, premature deliveries, durations of gestation, litter sizes, sex ratios and viabilities, maternal behaviors, reproductive organ weights, sperm parameters and implantation sites, sexual maturation). Histopathological evaluations were performed on at least 10 P and F1 rats/sex at 0 and 650 ppm (gross lesions, testes, intact epididymis; 10 F1 dams at 0, 250, and 650 ppm for primordial follicles). Developmental observations included implantations, pup numbers, sexes, viabilities, body weights, morphology, and reproductive performance. At 50 ppm and higher, both sexes and generations had increased absolute and relative liver and kidneys weights, and female rats in both generations had reduced absolute and relative adrenal weights; adrenal changes were probably associated with physiological changes in water balance. The livers and kidneys (10/sex/group/generation) had no histopathological changes. Other minimal effects at 50 ppm were reduced water consumption and a transient reduction in body weight. At 250 and 650 ppm, DBA reduced parental water consumption, body weight gains, body weights, feed consumption, and pup body weights. P and F1 generation male rats at 250 and 650 ppm had altered sperm production (retained step 19 spermatids in stages IX and X tubules sometimes associated with residual bodies) and some epididymal tubule changes (increased amounts of exfoliated spermatogenic cells/residual bodies in epididymal tubules, atrophy, and hypospermia), although inconsistently and at much lower incidences. Unilateral abnormalities of the epididymis (small or absent epididymis) at 650 ppm in four F1 generation male rats were considered reproductive tract malformations. The no-observable-adverse-effect level (NOAEL) and reproductive and developmental NOAELs for DBA were at least 50 ppm (4.5 to 11.6 mg/kg/day), 45,000 to 116,000 times the human adult exposure level. Reproductive and developmental effects did not occur in female rats exposed to DBA concentrations as high as 650 ppm. Based on the high multiples of human exposure required to produce effects in male rats, DBA should not be identified as a human reproductive or developmental risk.
Genotoxicity and Carcinogenicity Studies of Soy Isoflavones
Authors: Misra R. R. , Hursting S. D. , Perkins S. N. , Sathyamoorthy N. , Mirsalis J. C. , Riccio E. S. , Crowell J. A.
Published: October 2002

The potential cancer preventive efficacy of soy isoflavones is being investigated in preclinical and phase 1 clinical studies sponsored by the U.S. National Cancer Institute. Although 90-day oral toxicity studies with PTI G-2535 (an investigational soy isoflavone drug product) in rats and dogs, as well as teratology studies, indicated no signs of toxicity, there remains a mechanistic concern associated with the ability of isoflavones (i.e., genistein) to inhibit topoisomerase, possibly leading to DNA strand breaks. The present report describes results from two in vitro genotoxicity studies, one in vivo genotoxicity study, and a single carcinogenicity study conducted in p53 knockout mice. Bacterial mutagenesis experiments using six tester strains without metabolic activation revealed no evidence that PTI G-2535 was mutagenic. In similar experiments with exogenous metabolic activation there were statistically significant increases in revertants, but less than twofold, in a single (Salmonella typhimurium TA100) tester strain. Mouse lymphoma cell mutagenesis experiments conducted with and without metabolic activation revealed statistically significant increases in mutation frequency at PTI G-2535 concentrations ≥ 0.8 and 12 μg/ml, respectively; such increases were dose related and increases in the frequency of both small and large colonies were observed. A statistically significant increase in the frequency of micronucleated polychromatic erythrocytes was also seen 24 hours after treatment in male, but not female, mice who received 500 and 1000 mg/kg body weight PTI G-2535; however, such increases were small, were not dose related, and were not observed 48 hours after treatment. In contrast, dietary genistein had no effect on survival, weight gain, or the incidence or types of tumors that developed in cancer-prone rodents lacking the p53 tumor suppressor gene, p53 knockout mice. The apparent risk/benefit of isoflavone ingestion may ultimately depend on the dose and developmental timing of exposure.
Cardiorespiratory Effects Following Acute Exposure to Pyridostigmine Bromide and/or N,N-Diethyl-m-toluamide (DEET) in Rats
Authors: Chaney Leslie A. , Rockhold Robin W. , Hume Arthur S.
Published: October 2002

The acute lethal interaction that occurs in rodents when high doses of a peripherally restricted cholinesterase inhibitor, pyridostigmine bromide (PB), and the insect repellent N,N-diethyl-m-toluamide (DEET) are combined was first described during studies of chemical mixtures that were targeted as potential causative agents of Gulf War illnesses. This study was intended to provide insight into possible mechanisms of that lethal interaction. Following a single intraperitoneal injection of PB (2 mg/kg) and/or DEET (300 or 500 mg/kg), respiratory activity was measured in conscious freely moving rats using whole-body plethysmography. Cardiovascular function was also monitored simultaneously through an arterial catheter. PB (2 mg/kg) given alone stimulated respiration and increased blood pressure. Arterial pH levels were decreased, whereas pO2 and pCO2 remained at control levels. Administration of DEET (300 mg/kg) alone increased tidal volume and decreased blood pressure. Blood gases and pH levels were unaltered. A higher dose of DEET (500 mg/kg) also decreased respiratory and heart rate. Coadministration of PB (2 mg/kg) and DEET (300 mg/kg) increased tidal volume, decreased arterial pH, and elevated pCO2. Heart rate and blood pressure declined progressively after drug coadministration. Pretreatment with atropine methyl nitrate (AMN), a peripherally selective competitive antagonist at nicotinic and muscarinic receptor sites, reduced the individual effects of PB or DEET, and significantly increased survival after co-exposure to these agents. Although changes in respiratory function may have contributed to the lethal interaction, it was concluded that the primary cause of death was circulatory failure.
Oral (Gavage) Two-Generation (One Litter Per Generation) Reproduction Study of Pentachlorophenol (Penta) in Rats
Authors: Bernard Bruce K. , Hoberman Alan M. , Brown W. Ray , Ranpuria Anish K. , Christian Mildred S.
Published: October 2002

The potential for pentachlorophenol (penta) to induce general and reproductive/developmental toxicity was evaluated in Crl Sprague-Dawley rats, employing a two-generation reproduction toxicity study. Penta was administered by gavage at doses of 0, 10, 30, and 60 mg/kg/day. In both generations, the parental animals (30/sex/group) were intubated daily for 10 weeks before cohabitation and continuing through cohabitation, gestation, and lactation periods. Intubation of the F1 generation was begun 28 days postpartum. Animals were evaluated daily for mortality and general toxicity (clinical observations, body weights and gains, feed consumption). Organ weights were recorded and histopathological evaluations were made. Specific indices of reproductive function evaluated included estrous cycles, mating and fertility, parturition, lactation, viability, and growth and development of offspring, including sexual maturation, sperm parameters, and numbers of ovarian primordial follicles. All deaths in the parental rats were unrelated to penta. Expected metabolic effects of penta, sporadic increased liver weights associated with hepatocellular centrilob-ular hypertrophy and vacuolation and lipofuscin pigmentation, were evident in the 10-, 30-, and 60-mg/kg/day dose group P1 and F1 animals. Toxicity, in the form of liver pathology (single cell necrosis), reduced body weights and associated reductions in organ weights, and reduced feed consumption were noted in both generations at the 30- and 60-mg/kg/day doses. Developmental toxicity associated with these doses included reduced pup weights and viability. The 60-mg/kg/day dose also resulted in delayed sexual maturation, decreased spermatid counts, small prostates and testes, decreased implantations, reduced fertility, and increased resorptions of embryos. Based on these results, it was concluded that 30 mg/kg/day is the lowest-observable-adverse-effect level (LOAEL) and 10 mg/kg/day is the no-observable-adverse-effect level (NOAEL) for both reproductive and general toxicity. These findings are consistent with results from previously conducted studies wherein reproductive/developmental toxicity was observed only at doses that also induced general toxicity. It differs from previous findings in that the NOAEL for general toxicity is two to three times higher for the more pure product than for products produced and tested previously. In addition, the results did not indicate bioaccu-mulation of penta. Thus, penta did not selectively affect reproduction or development of the offspring of rats at a dose of 10 mg/kg/day, a dose that is 7000 to 20,000 times higher than human exposure.
Dichlorvosand Mononuclear Cell Leukemia in Fischer 344 Rats: Lack of Effect of Chronic Administration on Progression of the Disease
Authors: Manley Ann , Brown W. Ray , Mennear John
Published: October 2002

The National Toxicology Program reported that the daily administration of dichlorvos, in the form of a corn oil gay age, was associated with an increased incidence of mononuclear cell leukemia (MCL) in male but not female Fischer 344 rats. Because of the high degree of variability with which this neoplasm appears in groups of control laboratory rats, supportive evidence is frequently sought to facilitate interpretation of increased incidences of the disease in chronic toxicity and carcinogenesis studies. In the National Toxicology Program study MCL was increased in only one sex of rats (m ales), did not occur earlier in DDVP-dosed than in control animals, and there was no evidence of a dose-response relationship. The U.S. Office of Science Technology Policy has recommended that the presence or absence of treatment-associated changes in tumor progression be employed as an adjunct in the interpretation of common tumors in rodents. The present study employed evaluative criteria described by the National Toxicology Program to determine the effects of DDVP on the progression of MCL in affected male rats. The results revealed that DDVP had no effect on either the severity or progression of MCL in male rats. Since there is no corroborative evidence supporting the interpretation of the increased incidence of MCL in male rats, this isolated DDVP-associated finding in a single sex of rats should not be considered to be evidence of a carcinogenic effect.
Efficacies of Atropine/2-PAM and Atropine/HI-6 in Treating Monkeys Intoxicated with Organophosphonate Nerve Agents
Authors: Olson C. T. , Menton R. G. , Riser R. C. , Matthews M. C. , Stotts R. R. , Romano J. R. , Koplovitz I. , Hackley B. E. , Johnson J. B.
Published: October 2002

The efficacies of atropine (ATR)/ 2-PAM and ATRl HI-6 in treating male rhesus monkeys injected with the neurotoxic organophosphonate (OP) agents GA, GB, GD, GF, or VX were compared. Experiments were conducted using no more than 8 monkeys per OP and treatment regimen. Doses were selected using a modified up-and-down experimental design, challenging one monkey per day per OP and treatment. Results were used to approximate the median lethal dose (MLD) for groups of treated monkeys or monkeys given only a vehicle following challenge with an OP. Mortality and signs of intoxication with each treatment were statistically compared. Doses of 2-PAM (25.7 mgl kg) or HI-6 (50 mgl kg) and atropine (0.4 mg free base! kg) were given in a single intramuscular (IM) injection 1 min following challenge with an OP. Strong and well-defined relationships between agent dose and 10-h lethality were observed in untreated animals. The 10-h IM OP MLDs for untreated monkeys were estimated to be 80, 43, 8.0, 22, and 7.4 μg/kg for GA, GB, GD, GF, and VX, respectively. No statistical differences w ere found between AT Rl 2-PAM and AT Rl HI-6 treatment efficacies in preventing lethality for any of the OPs. Both oxime combinations appear to provide protection against a 2 × 10-h MLD of GA, GF, or VX; only
Carcinogenicity of Monochloro-1,2-Propanediol (α-Chlorohydrin, 3-MCPD)
Authors: Lynch Barry S. , Bryant Douglas W. , Hook Graham J. , Nestmann Earle R. , Munro Ian C.
Published: October 2002

3-Monochloro-1,2-propanediol (3-MCPD) is a by-product found in trace amounts, generally less than 1 mg/kg (<1 ppm), in hydrolyzed vegetable protein produced through acid hydrolysis. In a chronic study with F344 rats, high doses of 3-MCPD produced benign renal tumors in both sexes and Leydig-cell and mammary tumors in males. 3-MCPD is genotoxic in vitro, but there is no evidence of genotoxicity in vivo. There is some question about the mechanism responsible for the carcinogenicity of 3-MCPD in certain species. Here we present a critical review of the toxicological, metabolic, and mechanistic data on 3-MCPD. On the basis of this review, the tumors reported in F344 rats are concluded to have developed as a result of nongenotoxic mechanisms and are considered not to be relevant to humans exposed to trace amounts of 3-MCPD. This conclusion was based on the lack of carcinogenicity of 3-MCPD in mice or Sprague-Dawley rats; the benign nature of the tumors involved; the dependence of the Leydig-cell and mammary tumors on species-and strain-dependent mechanisms involving chronic changes in hormone balance; the association of the renal tumors with chronic nephropathy and nephrotoxicity; and differences between bacterial and mammalian systems in the metabolism of 3-MCPD that likely account for its genotoxic activity in certain in vitro test systems. At trace levels in foods, 3 MCPD is considered not to pose a carcinogenic risk to humans.
Similar rewarding effects of testosterone in mice rated as short and long attack latency individuals
Authors: Arnedo M. Teresa , Salvador Alicia , Martínez‐Sanchís Sonia , Pellicer Olga
Published: October 2002

An attempt was made to confirm and extend the findings of an earlier study on the rewarding properties of testosterone in male mice using conditioned place preference (CPP). Previous results had only partially demonstrated such an effect because the reinforcement depended on environmental cues such as the colour of the compartment. High individual variability was evident, suggesting that basal levels of aggressiveness may modulate such effects. Animals were pre‐screened for aggressive behaviour and allocated to short and long attack latency (SAL and LAL) categories. Five days later the CPP procedure started. This involved pre‐conditioning tests, conditioning and post‐conditioning tests. SAL and LAL animals were treated with vehicle, 1 or 2 mg/kg of testosterone. During conditioning (on alternate days), a distinctive floor was paired four times with testosterone. On the intervening days animals were paired with a different floor with vehicle. CPP was clearly observed after testosterone treatment when the colour of the compartment was controlled in both SAL and LAL animals. These results provide additional support for the idea that testosterone and its derivatives have rewarding properties, which could explain processes of dependence.
Correlations between orbitofrontal dysfunction and tobacco smoking
Authors: Spinella Marcello
Published: October 2002

Orbitofrontal cortex is involved in various reward and reinforcement processes in the human brain. There is both anatomical and functional evidence for a dysfunction of orbitofrontal cortex in substance abusers, and nicotine has been shown to activate reward‐related structures in the brain similarly to other abused drugs. This study shows positive correlations between smoking parameters (smoking status and packs smoked per day) and impairment on putative measures of orbitofrontal dysfunction (go/no‐go, antisaccades, delayed alternation and impulsivity ratings). While causality could not be determined, other research suggests that an orbitofrontal dysfunction predisposes one toward tobacco abuse.
Obesity as a cause of “false‐positive” alcohol misuse laboratory investigations
Authors: Peters T. J. , Cook C. C. H.
Published: October 2002

Three patients are reported with a prior history of alcohol misuse accompanied by abnormal liver toxicity tests and other indices of alcohol misuse. A decreased but persistently raised serum γ ‐glutamyl transferase activity during subsequent abstinence or controlled drinking was interpreted incorrectly as due to continued alcohol misuse whereas obesity‐related fatty liver was the probable cause. The value of serum carbohydrate deficient transferrin assays in the differential diagnosis of abnormal liver toxicity tests is emphasized.
Processes and Outcomes of Care for Soft Tissue Sarcoma of theExtremities
Authors: Paszat Lawrence , O′Sullivan Brian , Bell Robert , Bramwell Vivien , Groome Patti , Mackillop William , Bartfay Emma , Holowaty Eric
Published: October 2002

Purpose: A population‐based cohort study of soft tissue sarcoma of the extremities (STSE) in Ontario, Canada was conducted
using linked administrative databases.

Methods and materials: Electronic administrative databases were linked from the Ontario Cancer Registry, the Canadian
Institute for Health Information, and Radiation Oncology Research Unit database of radiation therapy (RT) records.

Results: The definitive surgery was amputation for 6.0%, resection for 60.9%, biopsy for 7.5%; the remainder had no surgical
record. Adjuvant RT was administered to 40.2% of cases. Among cases initially treated by surgical resection, 2.0% later
underwent amputation and 9.5% underwent further resection during follow‐up. The adjusted odds ratio (OR) for amputation
as definitive surgery was 2.3 (1.19, 4.45) in eastern Ontario relative to Toronto. The likelihood of adjuvant RT among
those not registered at a cancer centre within 3 months of diagnosis was decreased (OR = 0.20 (95% CI (0.13, 0.30)) relative
to those registered. The adjusted relative risk of amputation at any time following diagnosis was 3.48 (95% CI (1.63, 7.46))
among cases not attending a cancer centre. The adjusted relative risk of death was 1.4; 95% CI (1.1, 1.7) among those not
attending a cancer centre.

Conclusions: Cases not seen at a multidisciplinary cancer centre within 3 months following diagnosis of STSE have an
increased relative risk for amputation at any time, and for death due to any cause. Many hypotheses for further study are
suggested by the results of this analysis.