bluuebunny/crossref_metadata_2025 huggingface dataset:
Euclidean shape-encoded combinatorial chemical libraries
Authors: Vaino Andrew R. , Janda Kim D.
Published: July 2002

A method for the encoding of split/mix combinatorial chemical
libraries based on Euclidean shapes is described. The shapes are
fashioned from a polymeric matrix designed to swell in common organic
solvents while retaining their unique forms, and exhibit good
mechanical strength. The lightly crosslinked gel-type polymer was
processed into an array of Euclidean forms that serve as encoding
elements in the synthesis of combinatorial chemical libraries by using
the split/pool methodology. To assess the viability of this approach,
a library of compounds based on a urea scaffold was prepared. The
validity of this methodology was demonstrated through correct
deconvolution of the library mixture by shape discrimination.
Furthermore, because the shapes used have a large surface area to
volume ratio, each monolith can act as an independent chemical reactor.
This simplifies the analytical identification process because each
compound can be prepared in significant quantities and isolated as
single entities. Given the high loading capacity of the monoliths and
the conceptually simple encoding strategy, it is envisioned that these
Euclidean forms will find significant application in combinatorial and
high-throughput synthetic chemistry.
γ-Aminobutyric acid type B receptors are expressed and functional in mammalian cardiomyocytes
Authors: Lorente Paco , Lacampagne Alain , Pouzeratte Yvan , Richards Stephen , Malitschek Barbara , Kuhn Rainer , Bettler Bernhard , Vassort Guy
Published: July 2002

γ-Hydroxybutyrate (GHB), an anesthetic adjuvant analog of γ-aminobutyrate (GABA), depresses cell excitability in hippocampal neurons by inducing hyperpolarization through the activation of a prominent inwardly rectifying K
+
(Kir3) conductance. These GABA type B (GABA
B
)-like effects are clearly shown at high concentrations of GHB corresponding to blood levels usually reached during anesthesia and are mimicked by the GABA
B
agonist baclofen. Recent studies of native GABA
B
receptors (GABA
B
Rs) have favored the concept that GHB is also a selective agonist. Furthermore, cloning has demonstrated that GABA
B
Rs assemble heteromeric complexes from the GABA
B
R1 and GABA
B
R2 subtypes and that these assemblies are activated by GHB. The surprisingly high tissue content, together with anti-ischemic and protective effects of GHB in the heart, raises the question of a possible influence of GABA
B
agonists on excitable cardiac cells. In the present study, we provide electrophysiological evidence that GHB activates an inwardly rectifying K
+
current in rat ventricular myocytes. This effect is mimicked by baclofen, reversibly inhibited by GABA
B
antagonists, and prevented by pertussis toxin pretreatment. Both GABA
B
R1 and GABA
B
R2 are detected in cardiomyocytes by Western blotting and are shown to coimmunoprecipitate. Laser scanning confocal microscopy discloses an even distribution of the two receptors in the sarcolemma and along the transverse tubular system. Hence, we conclude that GABA
B
Rs are distributed not only in neuronal tissues but also in the heart, where they can be activated and induce electrophysiological alterations through G-protein-coupled inward rectifier potassium channels.
Genetics and the population history of Europe
Authors: Barbujani Guido , Bertorelle Giorgio
Published: July 2002

Analysis of genetic variation among modern individuals is
providing insight into prehistoric events. Comparisons of levels and
patterns of genetic diversity with the predictions of models based on
archeological evidence suggest that the spread of early farmers from
the Levant was probably the main episode in the European population
history, but that both older and more recent processes have left
recognizable traces in the current gene pool.
Double-level “orthogonal” dynamic combinatorial libraries on transition metal template
Authors: Goral Vasiliy , Nelen Marina I. , Eliseev Alexey V. , Lehn Jean-Marie
Published: July 2002

Dynamic combinatorial libraries are mixtures of compounds
that exist in a dynamic equilibrium and can be driven to compositional
self adaptation via selective binding of a specific assembly of certain
components to a molecular target. We present here an extension of this
initial concept to dynamic libraries that consists of two levels, the
first formed by the coordination of terpyridine-based ligands to the
transition metal template, and the second, by the imine formation with
the aldehyde substituents on the terpyridine moieties. Dialdehyde 7 has
been synthesized, converted into a variety of ligands, oxime ethers
L
11
–L
33
and acyl hydrazones
L
44
–L
77
, and subsequently into corresponding
cobalt complexes. A typical complex,
Co(L
22
)
2
2+
is shown to engage in rapid
exchange with a competing ligand L
11
and with another
complex, Co(L
22
)
2
2+
in 30%
acetonitrile/water at pH 7.0 and 25°C. The exchange in the
corresponding Co(III) complexes is shown to be much slower. Imine
exchange in the acyl hydrazone complexes
(L
44
–L
77
) is strongly controlled by pH and
temperature. The two types of exchange, ligand and imine, can thus be
used as independent equilibrium processes controlled by different types
of external intervention, i.e., via oxidation/reduction of the metal
template and/or change in the pH/temperature of the medium. The
resulting double-level dynamic libraries are therefore named
orthogonal, in similarity with the orthogonal protecting groups in
organic synthesis. Sample libraries of this type have been synthesized
and showed the complete expected set of components in electrospray
ionization MS.
Class analysis from a normative perspective*
Authors: Swift Adam
Published: July 2002

Distinguishing between an explanatory and a normative interest in social stratification, this paper considers the relation between class analysis and the value of equality. Starting from the familiar distinction between (in) equality of position and (in) equality of opportunity, and noting the extent to which mobility research focuses on the latter, it suggests that class positions can themselves be characterized in terms of the opportunities they yield to those occupying them. This enables the clear identification of the kinds of inequality that are and are not addressed by research findings presented in terms of class categories and odds ratios. The significance of those findings from a normative perspective is then discussed, and their limitations are emphasized – though the paper also explains in what ways they are indeed of normative relevance.
Towards the social analysis of twinship
Authors: Stewart Elizabeth A.
Published: July 2002

The article examines the proposition that twinship is an irreducibly social phenomenon. Gender, age, birth order, socio‐economic status and other variables are considered, along with the role of different patterns of socialization as these affect twinship. It is argued that, to a very large extent, from conception, through gestation, childbirth and subsequently childhood and adolescence, the social processing and regulation of social members take place in unitary terms and that therefore twins (and higher multiples) are an anomaly in relation to such processes. Twins' reactions to stigma, stereotyping and labelling are explored as an integral aspect of the social structuring of twinship. The role of the twin, as distinct from the role of the non‐twin, is examined in the context of cultural expectations of twinship regarding similarity of identity and similarity of behaviour. Subsequent or concurrent processes of differentiation between twins are also examined. The article concludes with suggestions for further analyses of twinship.
Generational differences in acculturation among Asian families in Canada: A comparison of Vietnamese, Korean, and East‐Indian groups
Authors: Kwak Kyunghwa , Berry John W.
Published: July 2002

By examining generational differences between adolescents and their parents, the present study attempts to establish which specific aspects of strong kinship are maintained among Asian groups undergoing acculturation. Vietnamese (adolescent N = 104; parent N = 70), Korean (N = 111; N = 83), and East‐Indian (N = 97; N = 84) families were compared for family relations and acculturation attitudes. As compared to the Anglo‐Celtic group (adolescent N = 151; parent N = 116), Asian adolescents maintained stronger responsibilities within the family while disagreeing more with parents about their independence and roles in decision making, and expressing different preferences about intercultural contacts. However, since both parents and adolescents from the three groups clearly differ from each other for both family relations and acculturation attitudes, it is argued that generational differences should be particularized by each group's selective emphasis upon different cultural issues.
Obstacles to Empowerment: Local Politics and Civil Society in Metropolitan Manila, the Philippines
Authors: Shatkin Gavin
Published: July 2002

In recent years, the Philippine government has undertaken a number of reforms for decentralising urban governance and increasing the role of community-based organisations (CBOs) and non-governmental organisations in urban policy and programme development and implementation. Popular interpretations see these changes as an outcome of the 'people's power' movement against centralisation and authoritarianism and stress the potential for increased civil society participation in government in the future. This paper critically examines these interpretations with reference to the situation of CBOs in informal settlements in Metropolitan Manila. Specifically, it argues that decentralisation reflects the interests of a variety of politically powerful social groups, including not only organisations of civil society, but also local political families and international and domestic business interests. In addition, a number of factors continue to inhibit meaningful civil society participation. These include the lack of local government capacity in many cities and municipalities and the existence of powerful economic interests at the local level that compete with civil society organisations for influence.
Why Not NIMBY? Reputation, Neighbourhood Organisations and Zoning Boards in a US Midwestern City
Authors: Matejczyk Anthony P.
Published: July 2002

In US municipalities, petitions for exception to the zoning code are thought to elicit 'not in my backyard' or 'nimby' responses from neighbourhood organisations concerned about potential negative externalities. This paper brings qualitative and quantitative data to bear on a theory arguing that municipal zoning boards provide incentives over time for neighbourhood organisations to come to consensus with developers. The findings suggest that neighbourhood organisations have greater success influencing zoning boards to deny zoning exception petitions after establishing reputations for coming to agreement with developers in the past. Further, neighbourhood groups that choose more oppositional strategies tend to face more noxious zoning petitions in the neighbourhood in the future.
Assessing the Option Value of a Publicly Provided Service: The Case of Local Transport
Authors: Roson Roberto
Published: July 2002

This paper presents a theoretical and empirical study of the problem of valuation of local public transport services. A contingent valuation exercise, considering two case studies in northern Italy, is illustrated. This serves as a basis for an econometric analysis aimed at highlighting the role of socioeconomic variables in the determination of the willingness to pay, through public funds, for the subsidisation of public transport services. It is argued that social preferences for the provision of a public transport service cannot be directly deducted from observable market behaviour and that the preferred supply level of transport capacity weakly depends on individual consumption levels, whereas the perception of mobility problems (possibly generated by experience) and the characteristics of social networks (especially the family) are likely to be much more important.
Large Metropolises in the Third World: An Explanation
Authors: Alonso-Villar Olga
Published: July 2002

In this paper, we have developed a model that sets out to explain the existence of megacities in developing countries, in the context of a Krugman-type core-periphery model. The paper also suggests that agglomeration can be fostered by manufacturers mainly serving the domestic market. However, the analysis goes further by emphasising that megacities are not only the result of protective trade policies, but also the consequence of the relative position of a country, in terms of industrialisation, with respect to the rest of the world.
Perceptions of Place and Health in Socially Contrasting Neighbourhoods
Authors: Ellaway Anne , Macintyre Sally , Kearns Ade
Published: July 2002

This paper describes an analysis of perceptions of the local residential environment and self-reported health in four socially contrasting neighbourhoods in Glasgow in the late 1990s. After adjusting for individual characteristics such as age, sex and social class, neighbourhood of residence predicted perceptions of problems and neighbourhood cohesion in the area: and self-assessed health, mental health and recent symptoms were associated with perceived local problems and neighbourhood cohesion. Housing tenure and employment status also predicted perceptions of the neighbourhood. These results support the importance of tackling anti-social problems in worst-off areas and of neighbourhood management across a range of areas.
Neighbourhood Effects and Cultural Exclusion
Authors: Bauder Harald
Published: July 2002

The idea of neighbourhood effects implies that the demographic context of poor neighbourhoods instills 'dysfunctional' norms, values and behaviours into youths, triggering a cycle of social pathology. It is argued that neighbourhood effects are part of a wider discourse of inner-city marginality that stereotypes inner-city neighbourhoods. Reflecting upon arguments made in the existing literature, the ideological underpinnings of the idea of neighbourhood effects are revealed. Essentialist conceptions of neighbourhood culture among employers, educators and institutional staff contribute to the neighbourhood effects phenomenon. It is also suggested that researchers and policy-makers must recognise wider forces of cultural differentiation and exclusion.
Manufacturing Services and Servicing Manufacturing: Knowledge-based Cities and Changing Forms of Production
Authors: Daniels P.W. , Bryson J.R.
Published: July 2002

There is an important shift away from production that is dependent upon material resources to production that utilises knowledge as the key source of competitiveness and innovation. Urban areas are key locations for a process that is also changing the way in which goods and services are consumed. The decade of the 1990s was a period of innovation and revitalisation in economic geography; it was also a time when economic geographers began again to explore old concepts in different ways-for example, new industrial spaces-intent on explaining the changing economic landscapes of capitalism. There is a real danger, however, that for economic geography the first decade of the 21st century will be a period of repetition and extension rather than one of development. This paper reviews aspects of the debate about the distinction between service and manufacturing activities and suggests that it needs to be reconsidered in relation to on-going and important changes in the production process that are as important for cities as they are for the economy as a whole.
Making Connections with IT
Authors: Conan Michel
Published: July 2002

The rapid development of new information technologies has to date received scant attention from the housing research community. This paper attempts to redress this shortfall through outlining a brief history of IT in French housing and providing a critique of current housing research on IT. Finally, drawing upon current theoretical debates within the social sciences, the paper takes some tentative steps towards identifying an agenda for future research.
Further Evidence on the Accuracy of Residential Vacancy Chain Models
Authors: Emmi Philip C. , Magnusson Lena
Published: July 2002

Residential vacancy chain models simulate the transfer of vacant housing opportunities among sectors of an urban housing market. The Markov model simulates forward-reaching chains in response to vacancy initiations. The Leontief model simulates backward-reaching chains in response to vacancy absorptions. Each simulates residential mobility among housing sectors as a by-product. The accuracy of these models was assessed in earlier work by the authors, using 1975-80 data from Gävle, Jonkoping and Vasteras, Sweden, to project intra-urban residential mobility in each town during the 1980-85 period. Using log-linear analysis to compare projected moves with observed moves, they found projection errors ranging from 3-12 per cent. In this paper, data from the 1985-90 period are used first to repeat these assessments over the subsequent time-period and then to extend the projection period from 5 to 10 years. Projection errors range from 5-11 per cent for the 5-year period and from 8-18 per cent for the 10-year period. Both the Markov and the Leontief models perform equally well. Models with more homogeneous housing sector definitions produce more consistent results.
Housing Density: A Neglected Dimension of Fiscal Impact Analysis
Authors: Dekel Gabriel P.
Published: July 2002

Conventional fiscal impact analysis has failed to address adequately the spatial dimensions of development alternatives, notably the costs associated with housing density. This paper proposes a method that can correct this methodological shortcoming as well as determine, in budgetary terms, the optimal levels of housing density for various neighbourhoods. These optimal densities reflect the balance between the costs of land-related municipal services and the total property tax revenues in each neighbourhood. The enforcement of such optimal densities can help to eliminate the gap between taxation levels, which can recover land-related service costs, and the actual tax revenues in each neighbourhood. By linking planning to the budgetary process, planners can play a leading role in local decision-making. Local governments, for their part, can better comply with the need for budget restraint.
Stochastic Housing Model with Random Constructions
Authors: Srinivasa Rao K. , Vijaya Kumar C.V.R.S.
Published: July 2002

In this article, a stochastic housing model of a city having various grades of houses and a random number of new constructions at each discrete time-interval is developed. Using the multi-type Galton-Watson process, a method for computing the means and variances of the number of houses in various grades of the city at discrete points of time is given. An application of this model is also demonstrated through real data.
The Political Economy of Urban Land Reform in Hawaii
Authors: La Croix Sumner J. , Mak James , Rose Louis A.
Published: July 2002

In the mid 1960s there were about 22 000 single-family leasehold homes in Honolulu. Dissatisfaction with leasehold led to reform legislation in 1967, allowing lessees to buy leased land. By 1991 less than 5000 lessees remained. This paper examines why landowners elected to lease rather than sell land and attributes the rise of leasehold to legal constraints on land sales by large estates, duties of estate trustees and the federal tax code. Ideological forces initiated land reform in 1967, but rent-seeking forces captured the process in the mid 1970s. It is concluded that Hawaii's experiment with leasehold was a failure due to the difficulties associated with specifying and enforcing long-term contracts in residential land.
French Towns, Higher Urban Functions and Strategic Employment
Authors: Julien Philippe
Published: July 2002

Owing to the over-simplified nature of a sectoral analysis of employment, a functional approach is advocated. It focuses on 12 'higher urban' functions and the employment relating to these, which is called 'strategic employment'. This is evaluated for the 51 French towns with more than 50 000 jobs. The possible opportunities following from this approach are discussed in the final section.
Male Sub-metropolitan Black-White Wage Gaps: New Evidence for the 1980s
Authors: Rodgers William M.
Published: July 2002

This study analyses trends in US male black-white earnings gaps by sub-metropolitan residence. Large suburban earnings gaps existed in 1979; however, central city gaps exhibited the largest increases during the 1980s. The increases are decomposed into changes in measurable characteristics, changes in the prices of measurable characteristics, changes in discrimination and/or unobservable skills, and changes in white earnings inequality. Changes in measured characteristics and their prices, and changes in inequality account for little of the increases in central city gaps. Either labour market discrimination worsened or racial differences in unobservable skills widened. A review of the literature suggests that this paper's evidence is more consistent with a worsening in discrimination.
The Effect of Environmental Assessment on UK Local Planning Authority Decisions
Authors: Wood Christopher , Jones Carys E.
Published: July 2002

Environmental assessment (EA) is intended to ensure that environmental considerations are properly weighed in the decisions made by local planning authorities on planning applications. This paper analyses whether, to what extent, and how, EA has influenced LPA decisions. Forty case studies were analysed by examining relevant documentation and conducting interviews with participants in the EA process. EA appears to have had a gradual rather than a revolutionary effect on decision-making. Its main benefits have been the enhanced provision of environmental information and, to a lesser extent, assistance in setting conditions and in modifying proposals. However, these benefits are not occurring in all cases, and changes are needed if the expected advantages of EA—better integration of environmental considerations into project planning and decision-making-are to be fully realised in the UK.
Economic Theory and the Spatial Mismatch Hypothesis
Authors: Arnott Richard
Published: July 2002

The spatial mismatch hypothesis is that "Serious limitations on black residential choice, combined with the steady dispersal of jobs from central cities, are responsible for the low rates of employment and low earnings of Afro-American workers" (Kain, 1994, p. 371). Despite a wealth of related empirical studies, there has been little work formalising the hypothesis. This paper presents a trade-theoretic model, with three regions (downtown, suburbia and the rest of the world), four goods (a tradable home good, untraded services, a tradable foreign good and land), and two factors (skilled and unskilled workers). Blacks are constrained to live downtown but by incurring commuting costs can work in suburbia. Several exogenous changes are considered (for example a fall in transport costs between suburbia and the rest of the world) which may lead simultaneously to a fall in the downtown unskilled wage and to job suburbanisation, and which therefore provide a theoretical basis for the hypothesis.
Evaluating the Influence of Amenities on the Location of Manufacturing Establishments in Urban Areas
Authors: Granger Maury D. , Blomquist Glenn C.
Published: July 2002

Public and private planners concerned with economic growth and development are increasingly marketing intangible characteristics. This paper investigates the notion that amenities influence manufacturers' location choices in urban areas. If amenities affect wages, land values and other costs, then amenities will influence location decisions. Using urban, county-level, Census data, regression models were estimated for the location of small and medium-sized manufacturing establishments. Holding constant scale and agglomeration economies, amenities, measured by a quality-of-life index, are found to influence manufacturers' location with the effects varying by industry. Labour-intensive industries are more strongly attracted to high-amenity urban locations.
Lowering the Drawbridge: A Case Study of Analogy and Metaphor in the Social Construction of Home-ownership
Authors: Gurney Craig M.
Published: July 2002

This paper makes contributions to long-established debates about the meaning of home-ownership and to the growing interest in discourse and language in urban and housing research. It outlines a theoretical framework in which analogy and metaphor are crucial devices in the social construction of home-ownership knowledge. The paper draws upon some results from qualitative fieldwork undertaken amongst a small group of home-owner households in Bristol, UK, to illustrate metaphorically structured, common-sense aphorisms as rhetorical techniques in the mobilisation of tenure prejudice. The paper concludes by outlining new directions for research exploring the cultural significance of housing tenure, and makes some more general observations regarding the significance of analogy and metaphor in urban studies.
Modelling the Residential Sub-market: Breaking the Monocentric Mould
Authors: Bailey Timothy J.
Published: July 2002

This paper evaluates the performance of a land-rent model which predicts the residential location pattern in a metropolitan centre when suburban land constraints and a polycentric form are incorporated in the household location decision. The model is based on the variables of residential space, accessibility and income and tests different measures for each. Based on different combinations of measures, iterations of the model predict theoretical incomes. These values are compared to actual data over the full study area and by socioeconomic sector. The goodness of fit and the applicability of the measures are assessed using weighted least-squares multiple regression and cluster analysis. Overall, the model performs quite strongly.
An Emerging Logic of Urban Water Management, Cochabamba, Bolivia
Authors: Marvin Simon , Laurie Nina
Published: July 2002

This paper examines the emergence of a new logic of water management in developing cities. We argue that water provision is characterised by two largely disconnected circuits of water supply. Formally organised distribution networks provide a publicly subsidised service to higher-income users, while an informal system of water vendors provides a more expensive supply to marginalised communities. A new style of water management is now challenging the productionist logic that has created and maintained these dual networks. The case study of water privatisation in the city of Cochabamba, Bolivia, illustrates how this emerging logic is reconfiguring the management of urban water networks with a shift from large supply options towards greater consideration of user needs and extension of the network to unconnected communities. The productionist logic is in a period of profound transition as efforts are being made to mesh together more effectively the formal and informal networks. While this process is highly contested, many of the central assumptions of the productionist logic are challenged and new opportunities for a more socially inclusionary and environmentally sensitive style of water management are emerging.
Maternal Sensitivity and Infant Attachment Security in Japan: A Longitudinal Study
Authors: Vereijken Carolus M.J.L. , Riksen-Walraven J. Marianne , Kondo-Ikemura Kiyomi
Published: July 2002

In this study we examined the relation between maternal sensitivity and child attachment security, one of the core propositions of attachment theory, in a Japanese sample. Attachment security was assessed with the Attachment Q-Sort at the ages of 14 and 24 months. At the same ages, ratings were obtained for the mothers’ sensitivity in interactions with their children. The expected significant relationship between maternal sensitivity and child security was found both at 14 and 24 months. Maternal sensitivity showed moderate stability between the two ages. LISREL analysis showed that the correlation between maternal sensitivity and infant security at 24 months is not fully explained by the correlation between sensitivity and security 10 months earlier. This indicates that maternal sensitivity continues to play a significant role in the development of a secure attachment relationship in the second year of life.
Ionizing radiation enhances IL‐6 and IL‐8 production by human endothelial cells
Authors: Meeren A. Van Der , Bertho J.-M. , Vandamme M. , Gaugler M.-H.
Published: July 2002

Irradiation exposure is known to induce an inflammatory reaction. Endothelial cells play a crucial role both in the inflammatory process and in radiation damage. Therefore, supernatants and cell lysates of 60Co‐irradiated human umbilical vein endothelial cells (HUVEC) have been assessed for the presence of pro‐inflammatory cytokines. After gamma irradiation, interleukin (IL)‐1α, IL‐1β and tumor necrosis factor (TNF)‐α remained undetectable in both cell supernatants and cell lysates. However, a dose‐dependent increase in the production of IL‐6 and IL‐8 has been demonstrated up to 6 days after exposure. These data indicate that the pro‐inflammatory cytokines IL‐6 and IL‐8 may be involved in the inflammatory response of vascular endothelium induced by exposure to ionizing radiation.
Treatment of Acute Opioid Withdrawal with Ibogaine
Authors: Alper Kenneth R. , Lotsof Howard S. , Frenken Geerte M. N. , Luciano Daniel J. , Bastiaans Jan
Published: July 2002

Ibogaine is an alkaloid with putative effect in acute opioid withdrawal. Thirty‐three cases of treatments for the indication of opioid detoxification performed in non‐medical settings under open label conditions are summarized involving an average daily use of heroin of .64 ± .50 grams, primarily by the intravenous route. Resolution of the signs of opioid withdrawal without further drug seeking behavior was observed within 24 hours in 25 patients and was sustained throughout the 72‐hour period of posttreat‐ment observation. Other outcomes included drug seeking behavior without withdrawal signs (4 patients), drug abstinence with attenuated withdrawal signs (2 patients), drug seeking behavior with continued withdrawal signs (1 patient), and one fatality possibly involving surreptitious heroin use. The reported effectiveness of ibogaine in this series suggests the need for systematic investigation in a conventional clinical research setting.
Cadmium, Copper, Lead, and Zinc in Five Toothed Whale Species of the Mediterranean Sea
Authors: Frodello J. P. , Marchand B.
Published: July 2002

The cadmium, lead, copper, and zinc levels were measured in six organs (lung, liver, kidney, skin, muscle, and bone) from 18 specimens of toothed whales, belonging to five species, found stranded along the Corsican coast between November 1993 and December 1998. The five species examined were the bottlenose dolphin Tursiops truncatus, the common dolphin Delphinus delphis, the striped dolphin Stenella coeruleoalba, the pilot whale Globicephala melas, and the Risso's dolphin Grampus griseus. The values obtained demonstrate that there is a great variability in the accumulation of toxic metals. A comparison of the values with those obtained in other geographical regions also demonstrates an extensive variability in metal levels. The presence of metals in the stomach contents of three of the individuals studied shows that the food source is responsible for a significant input of pollutants to the whales. Measured pollutant levels in whales are thus the result of an accumulation occurring throughout the animal's life.
Developmental Toxicity Study of Pentachlorophenol in the Rabbit
Authors: Bernard Bruce K. , Ranpuria Anish K. , Hoberman Alan M.
Published: July 2002

The potential for developmental toxicity of pentachlorophenol (penta) was studied in New Zealand white rabbits at doses of 0 (corn oil), 7.5, 15, and 30 mg/kg/day administered by gavage on days 6 to 18 of gestation. The rabbits were sacrificed on day 29 of presumed gestation and necropsied. Measurements included number of corpora lutea, pregnancy, number and distribution of implantations, early and late resorptions, live and dead fetuses, fetal weight, gender, and gross external, soft tissue, and skeletal alterations. The mid and high doses reduced maternal body weight gain; the high dose caused transient weight loss and reduced feed consumption. There were no effects on embryofetal development at any of the doses evaluated. Based on these data, the maternal no-observable-adverse-effect level (NOAEL) is 7.5 mg/kg/day, while the developmental NOAEL is 30 mg/kg/day. Penta is not a developmental toxicant in a nonrodent animal model.
Developmental Toxicity of Cumene Vapor in Cd Rats and New Zealand White Rabbits
Authors: Darmer Kenneth I. , Neeper-Bradley Teresa L. , Cushman Janette R. , Morris Carl R. , Francis Barbara O.
Published: July 2002

The potential developmental toxicity of cumene vapor (99.9% pure) was assessed in pregnant CD (Sprague-Dawley) rats and New Zealand White rabbits exposed for 6 h per day by inhalation, the most relevant route of potential human exposure. Groups of 25 rats were exposed on gestational days (GD) 6–15 to concentrations of 0 (filtered air), 100, 500, or 1200 ppm, and groups of 15 rabbits were exposed on GD 6–18 to 0, 500, 1200, and 2300 ppm cumene vapor. In rats, reduced maternal body weight gain and increased relative liver weight was observed at 1200 ppm cumene. In rats and rabbits, reduced food consumption was observed at concentrations of 500 and 1200 ppm. A t 2300 ppm, 2 rabbits died, body weight gain and food consumption were reduced during the exposure period, and relative liver weights were increased. None of the gestational parameters, including numbers of viable implantations per litter, sex ratio, and fetal body weights, were affected at any exposure level in rats or rabbits. There were no treatment-related increases in incidences of external, visceral, or skeletal malformations or in the incidences of variations at any level. Thus, in rats, the no observable adverse effect level (NO A EL) for maternal toxicity was 100 ppm and the NO A EL for developmental toxicity was 1200 ppm, the highest concentration of cumene vapor tested. In rabbits, there was no NO A EL for maternal toxicity, but the NO A EL for developmental toxicity was 2300 ppm for cumene, the highest concentration tested. Therefore, even at exposure levels associated with maternal toxicity, cumene was not a developmental toxicant by inhalation exposure in either rats or rabbits.
Lack of Neuronal Vacuolation and Necrosis in Monkeys Treated with Selfotel (CGS 19755), A Competitive N-methyl-D-aspartate Receptor Antagonist
Authors: Huber Kirk R. , Sahota Pritam S. , Kapeghian John , Hsu Helen Han , Amemiya Kenjie , Arthur Alan T. , Tripp Spencer L. , Traina Vincent M.
Published: July 2002

Several N-methyl-D-aspartate (N M D A) receptor antagonists are being developed to reduce overstimulation of N M D A receptors by excessive glutamate, released as a consequence of acute cerebral hypoxial ischemia after stroke or head trauma. N M D A receptor antagonists, including Selfotel (C G S 19755), have been demonstrated to cause neuronal vacuolation and neuronal necrosis in the retrosplenial and / or posterior cingulate cerebral cortices of rats; however, little in formation is available on their effects on the cerebral cortices of primates. Cynomolgus monkeys were treated with single parenteral doses of N M D A antagonists (Selfotel or M K-801). Monkeys were administered intravenous doses of Selfotel at 2 or 20 mg/kg and were necropsied 4, 24, or 72 h postdose. Additional monkeys, administered M K-801 subcutaneously at 0.25 mg/kg, were necropsied 4 or 72 h postdose. Overt, centrally mediated clinical signs occurred in both Selfote l- and M K-801–treated monkeys (e.g., at axia, hypoactivity, salivation, convulsions, disorientation, dyspnea, apnea, recumbency, and cyanosis). Brains were perfusion-fixed in situ with 1% paraformaldehyde and 1.5% glutaraldehyde in pyrophosphate buffer. Brain sections from the animals necropsied 4 and 24 h postdose we reembedded in plastics (Durcupan) and paraffin, cut at 1 or 2 μm thickness, and stained with Richardson's stain. Brains from the animals necropsie d 72 h postdose were embedded in paraffin, cut at 4 μm, and stained with hematoxylin and eosin. Microscopic examination of posterior cingulate and/or retrosplenial cerebral cortices from monkey streated with Selfotel or M K-801 did not reveal any neuronal vacuolation or necrosis.
In vivo and in vitro potency studies of 6ß‐naltrexol, the major human metabolite of naltrexone
Authors: PORTER SUSAN J. , SOMOGYI ANDREW A. , WHITE JASON M.
Published: July 2002

Abstract Naltrexone, a mu opioid receptor antagonist, is used in the treatment of opioid and alcohol dependence. Naltrexone's longer duration of action compared to naloxone has been considered to be due partly to its major human metabolite, 6 β ‐naltrexol. To date, no studies have examined the in vitro or in vivo potency of 6 β ‐naltrexol compared to naltrexone and naloxone. In the electrically‐stimulated guinea pig ileum, 6 β ‐naltrexol was more potent (K i = 94 ± 25 pM), than naloxone (420 ± 150 pM), and naltrexone (265 ± 101 pM). In vivo comparative potencies were assessed using the mouse hotplate test and morphine (agonist), with doses of the antagonists from 0.001 to 30 mg/kg. The order of potency was naltrexone (ID 50 7 μ g/kg), naloxone (ID 50 16 μ g/kg) and 6 β ‐naltrexol (ID 50 1300 μ g/kg). Antagonist ID 50 doses were then administered at 45, 90, 120, 180 and 1080 minutes prior to morphine administration. The duration of antagonist activity to decrease by 50% was 80, 125 and 340 minutes for naltrexone, naloxone and 6 β ‐naltrexol, respectively. 6 β ‐naltrexol is highly potent in the guinea pig ileum, but much less so in vivo after an acute dose. However, the potency of 6 β ‐naltrexol in vivo is time‐dependent, and it has a longer duration of action than naloxone and naltrexone, consistent with a pharmacokinetic longer terminal half‐life. Therefore, 6 β ‐naltrexol is likely to contribute to the efficacy of naltrexone in humans.
Catalase and the production of brain acetaldehyde: a possible mediator of the psychopharmacological effects of ethanol
Authors: SMITH BRIAN R. , ARAGON CARLOS M. G. , AMIT ZALMAN
Published: July 2002

This review represents an attempt to assess the available data on the role of catalase in the mediation of the behavioral actions of ethanol and the regulation of voluntary ethanol consumption. It is argued that acetaldehyde may be formed in brain through the peroxidatic activity of catalase. Furthermore, acetaldehyde formed centrally through the activity of this enzyme, may be responsible, at least in part, for some of the motivational, behavioral and neurotoxic effects of ethanol.
A longitudinal group study of speech development in Danish children born with and without cleft lip and palate
Authors: Hutters Birgit , Bau Anja , Brøndsted Kirsten
Published: July 2002

The present study focuses on contoid vocalization by Danish 1‐year‐old unrepaired toddlers born with cleft lip and palate, and how they differ from their non‐cleft peers. Furthermore, we focus on how the same children master Danish consonants at 3 years of age compared with their non‐cleft peers in terms of their ability to produce consonants in accordance with adult target. Also, with the 3 year olds, we look at cleft speech characteristics as well as developmental speech characteristics found in both groups of children. Based on phonetic transcripion, it was found that Danish unoperated cleft palate children at 1 year of age produced few types of contoids and preferably contoids that did not require closure of the velopharyngeal port in their prespeech. In addition, the data suggest that consonants produced by cleft children who are treated with one‐stage surgery after speech onset, at 3 years of age differ from speech produced by non‐cleft children, not only as regards cleft speech characteristics, but also as regards developmental speech characteristics.
CDK1 Inactivation Regulates Anaphase Spindle Dynamics and Cytokinesis In Vivo
Authors: Wheatley Sally P. , Hinchcliffe Edward H. , Glotzer Michael , Hyman Anthony A. , Sluder Greenfield , Wang Yu-li
Published: July 2002

Through association with CDK1, cyclin B accumulation and destruction govern the G2/M/G1 transitions in eukaryotic cells. To identify CDK1 inactivation-dependent events during late mitosis, we expressed a nondestructible form of cyclin B (cyclin BΔ90) by microinjecting its mRNA into prometaphase normal rat kidney cells. The injection inhibited chromosome decondensation and nuclear envelope formation. Chromosome disjunction occurred normally, but anaphase-like movement persisted until the chromosomes reached the cell periphery, whereupon they often somersaulted and returned to the cell center. Injection of rhodamine-tubulin showed that this movement occurred in the absence of a central anaphase spindle. In 82% of cells cytokinesis was inhibited; the remainder split themselves into two parts in a process reminiscent of Dictyostelium cytofission. In all cells injected, F-actin and myosin II were diffusely localized with no detectable organization at the equator. Our results suggest that a primary effect of CDK1 inactivation is on spindle dynamics that regulate chromosome movement and cytokinesis. Prolonged CDK1 activity may prevent cytokinesis through inhibiting midzone microtubule formation, the behavior of proteins such as TD60, or through the phosphorylation of myosin II regulatory light chain.
Glypican and Biglycan in the Nuclei of Neurons and Glioma Cells: Presence of Functional Nuclear Localization Signals and Dynamic Changes in Glypican During the Cell Cycle
Authors: Liang Yu , Häring Monika , Roughley Peter J. , Margolis Renée K. , Margolis Richard U.
Published: July 2002

We have investigated the expression patterns and subcellular localization in nervous tissue of glypican, a major glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan that is predominantly synthesized by neurons, and of biglycan, a small, leucine-rich chondroitin sulfate proteoglycan. By laser scanning confocal microscopy of rat central nervous tissue and C6 glioma cells, we found that a significant portion of the glypican and biglycan immunoreactivity colocalized with nuclear staining by propidium iodide and was also seen in isolated nuclei. In certain regions, staining was selective, insofar as glypican and biglycan immunoreactivity in the nucleus was seen predominantly in a subpopulation of large spinal cord neurons. The amino acid sequences of both proteoglycans contain potential nuclear localization signals, and these were demonstrated to be functional based on their ability to target β-galactosidase fusion proteins to the nuclei of transfected 293 cells. Nuclear localization of glypican β-galactosidase or Fc fusion proteins in transfected 293 cells and C6 glioma cells was greatly reduced or abolished after mutation of the basic amino acids or deletion of the sequence containing the nuclear localization signal, and no nuclear staining was seen in the case of heparan sulfate and chondroitin sulfate proteoglycans that do not possess a nuclear localization signal, such as syndecan-3 or decorin (which is closely related in structure to biglycan). Transfection of COS-1 cells with an epitope-tagged glypican cDNA demonstrated transport of the full-length proteoglycan to the nucleus, and there are also dynamic changes in the pattern of glypican immunoreactivity in the nucleus of C6 cells both during cell division and correlated with different phases of the cell cycle. Our data therefore suggest that in certain cells and central nervous system regions, glypican and biglycan may be involved in the regulation of cell division and survival by directly participating in nuclear processes.
A Gamete-specific, Sex-limited Homeodomain Protein in Chlamydomonas
Authors: Kurvari Venkatesh , Grishin Nick V. , Snell William J.
Published: July 2002

During fertilization in Chlamydomonas, gametes of opposite mating types interact with each other through sex-specific adhesion molecules on their flagellar surfaces. Flagellar adhesion brings the cell bodies of the gametes into close contact and initiates a signal transduction pathway in preparation for cell–cell fusion. We have identified a cDNA, gsp1, whose transcript levels are upregulated during flagellar adhesion. The GSP1 polypeptide is a novel, gamete-specific homeodomain protein, the first to be identified in an alga. Its homeodomain shows significant identity with several higher plant homeodomain proteins. Although encoded by a single copy gene present in cells of both mating types, immunoblot analysis showed that GSP1 was expressed in mating type (mt)+ gametes, but was not detectable in mt− gametes or in vegetative cells of either mating type. Moreover, GSP1 appeared late during gametogenesis, suggesting that it may function during adhesion with mt− gametes or after zygote formation. GSP1 is expressed in imp11, mt− mutant gametes, which have a lesion in the mid gene involved in sex determination and exhibit many phenotypic characteristics of mt+ gametes. Thus, gsp1 is negatively regulated by mid and is the first molecule to be identified in Chlamydomonas that shows sex-limited expression.
LYVE-1, a New Homologue of the CD44 Glycoprotein, Is a Lymph-specific Receptor for Hyaluronan
Authors: Banerji Suneale , Ni Jian , Wang Shu-Xia , Clasper Steven , Su Jeffrey , Tammi Raija , Jones Margaret , Jackson David G.
Published: July 2002

The extracellular matrix glycosaminoglycan hyaluronan (HA) is an abundant component of skin and mesenchymal tissues where it facilitates cell migration during wound healing, inflammation, and em- bryonic morphogenesis. Both during normal tissue homeostasis and particularly after tissue injury, HA is mobilized from these sites through lymphatic vessels to the lymph nodes where it is degraded before entering the circulation for rapid uptake by the liver. Currently, however, the identities of HA binding molecules which control this pathway are unknown. Here we describe the first such molecule, LYVE-1, which we have identified as a major receptor for HA on the lymph vessel wall. The deduced amino acid sequence of LYVE-1 predicts a 322-residue type I integral membrane polypeptide 41% similar to the CD44 HA receptor with a 212-residue extracellular domain containing a single Link module the prototypic HA binding domain of the Link protein superfamily. Like CD44, the LYVE-1 molecule binds both soluble and immobilized HA. However, unlike CD44, the LYVE-1 molecule colocalizes with HA on the luminal face of the lymph vessel wall and is completely absent from blood vessels. Hence, LYVE-1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.