bluuebunny/crossref_metadata_2025 huggingface dataset:
A Ypt/Rab effector complex containing the Sec1 homolog Vps33p is required for homotypic vacuole fusion
Authors: Seals Darren F. , Eitzen Gary , Margolis Nathan , Wickner William T. , Price Albert
Published: July 2002

Yeast vacuoles undergo priming, docking, and homotypic fusion, although little has been known of the connections between these reactions. Vacuole-associated Vam2p and Vam6p (Vam2/6p) are components of a 65S complex containing SNARE proteins. Upon priming by Sec18p/NSF and ATP, Vam2/6p is released as a 38S subcomplex that binds Ypt7p to initiate docking. We now report that the 38S complex consists of both Vam2/6p and the class C Vps proteins [Reider, S. E. and Emr, S. D. (1997)
Mol. Biol. Cell
8, 2307–2327]. This complex includes Vps33p, a member of the Sec1 family of proteins that bind t-SNAREs. We term this 38S complex HOPS, for
ho
motypic fusion and vacuole
p
rotein
s
orting. This unexpected finding explains how Vam2/6p associates with SNAREs and provides a mechanistic link of the class C Vps proteins to Ypt/Rab action. HOPS initially associates with vacuole SNAREs in “cis” and, after release by priming, hops to Ypt7p, activating this Ypt/Rab switch to initiate docking.
Functional evolution of the Ultrabithorax protein
Authors: Grenier Jennifer K. , Carroll Sean B.
Published: July 2002

The Hox genes have been implicated as central to the evolution of animal body plan diversity. Regulatory changes both in Hox expression domains and in Hox-regulated gene networks have arisen during the evolution of related taxa, but there is little knowledge of whether functional changes in Hox proteins have also contributed to morphological evolution. For example, the evolution of greater numbers of differentiated segments and body parts in insects, compared with the simpler body plans of arthropod ancestors, may have involved an increase in the spectrum of biochemical interactions of individual Hox proteins. Here, we compare thein vivofunctions of orthologous Ultrabithorax (Ubx) proteins from the insectDrosophila melanogasterand from an onychophoran, a member of a sister phylum with a more primitive and homonomous body plan. These Ubx proteins, which have been diverging in sequence for over 540 million years, can generate many of the same gain-of-function tissue transformations and can activate and repress many of the same target genes when expressed duringDrosophiladevelopment. However, the onychophora Ubx (OUbx) protein does not transform the segmental identity of the embryonic ectoderm or repress theDistal-lesstarget gene. This functional divergence is due to sequence changes outside the conserved homeodomain region. The inability of OUbx to function likeDrosophilaUbx (DUbx) in the embryonic ectoderm indicates that the Ubx protein may have acquired new cofactors or activity modifiers since the divergence of the onychophoran and insect lineages.
Cerebral protein synthesis in a genetic mouse model of phenylketonuria
Authors: Smith Carolyn Beebe , Kang Julia
Published: July 2002

Local rates of cerebral protein synthesis
(lCPS
leu
) were measured with the quantitative
autoradiographic [1-
14
C]leucine method in a genetic mouse
model (
Pah
enu2
) of phenylketonuria. As in
the human disease,
Pah
enu2
mice have a
mutation in the gene for phenylalanine hydroxylase. We compared adult
homozygous (HMZ) and heterozygous (HTZ)
Pah
enu2
mice with the background strain
(BTBR). Arterial plasma concentrations of phenylalanine (Phe) were
elevated in both HMZ and HTZ mutants by 21 times and 38%,
respectively. In the total acid-soluble pool in brain concentrations of
Phe were higher and other neutral amino acids lower in HMZ mice
compared with either HTZ or BTBR mice indicating a partial saturation
of the
l
-amino acid carrier at the blood brain barrier by
the elevated plasma Phe concentrations. In a series of steady-state
experiments, the contribution of leucine from the arterial plasma to
the tRNA-bound pool in brain was found to be statistically
significantly reduced in HMZ mice compared with the other groups,
indicating that a greater fraction of leucine in the precursor pool for
protein synthesis is derived from protein degradation. We found
reductions in lCPS
leu
of about 20% throughout the brain in
the HMZ mice compared with the other two groups, but no reductions in
brain concentrations of tRNA-bound neutral amino acids. Our results in
the mouse model suggest that in untreated phenylketonuria in adults,
the partial saturation of the
l
-amino acid transporter at
the blood–brain barrier may not underlie a reduction in cerebral
protein synthesis.
Genetics and visual attention: Selective deficits in healthy adult carriers of the ɛ4 allele of the apolipoprotein
E
gene
Authors: Greenwood Pamela M. , Sunderland Trey , Friz Judy L. , Parasuraman Raja
Published: July 2002

The ɛ4 allele of the apolipoprotein
E
(APOE) gene is
associated with altered brain physiology in healthy adults before old
age, but concomitant deficits in cognition on standardized tests of
cognitive function have not been consistently demonstrated. We
hypothesized that sensitive and specific assessment of basic
attentional functions that underlie complex cognition would reveal
evidence of impairment in otherwise asymptomatic individuals. We found
that as early as middle age, nondemented carriers of the ɛ4 allele of
the APOE gene showed deficits when visual attention was spatially
directed by cues in tasks of visual discrimination and visual search,
in comparison to those without the ɛ4 allele (ɛ2 and ɛ3
carriers). Two component attentional operations were selectively
affected: (
i
) shifting spatial attention following
invalid location cues, and (
ii
) adjusting the spatial
scale of attention during visual search. These changes occurred only in
the presence of the ɛ4 allele and without decline in other aspects of
attention (vigilance), memory, or general cognition. The results show
that specific components of visual attention are affected by APOE
genotype and that the course of cognitive aging is subject to selective
alteration by a genetic trait.
A census of glutamine/asparagine-rich regions: Implications for their conserved function and the prediction of novel prions
Authors: Michelitsch Melissa D. , Weissman Jonathan S.
Published: July 2002

Glutamine/asparagine (Q/N)-rich domains have a high propensity
to form self-propagating amyloid fibrils. This phenomenon underlies
both prion-based inheritance in yeast and aggregation of a number of
proteins involved in human neurodegenerative diseases. To examine the
prevalence of this phenomenon, complete proteomic sequences of 31
organisms and several incomplete proteomic sequences were examined for
Q/N-rich regions. We found that Q/N-rich regions are essentially
absent from the thermophilic bacterial and archaeal proteomes.
Moreover, the average Q/N content of the proteins in these organisms
is markedly lower than in mesophilic bacteria and eukaryotes.
Mesophilic bacterial proteomes contain a small number (0–4) of
proteins with Q/N-rich regions. Remarkably, Q/N-rich domains are
found in a much larger number of eukaryotic proteins (107–472 per
proteome) with diverse biochemical functions. Analyses of these regions
argue they have been evolutionarily selected perhaps as modular
“polar zipper” protein–protein interaction domains. These data
also provide a large pool of potential novel prion-forming proteins,
two of which have recently been shown to behave as prions in yeast,
thus suggesting that aggregation or prion-like regulation of protein
function may be a normal regulatory process for many eukaryotic
proteins with a wide variety of functions.
A stable complex of a novel transcription factor IIB- related factor, human TFIIIB50, and associated proteins mediate selective transcription by RNA polymerase III of genes with upstream promoter elements
Authors: Teichmann Martin , Wang Zhengxin , Roeder Robert G.
Published: July 2002

Transcription factor IIIB (TFIIIB) is directly involved in
transcription initiation by RNA polymerase III in eukaryotes. Yeast
contain a single TFIIIB activity that is comprised of the TATA-binding
protein (TBP), TFIIB-related factor 1 (BRF1), and TFIIIB′′, whereas two
distinct TFIIIB activities, TFIIIB-α and TFIIIB-β, have been
described in human cells. Human TFIIIB-β is required for
transcription of genes with internal promoter elements, and contains
TBP, a TFIIIB′′ homologue (TFIIIB150), and a BRF1 homologue (TFIIIB90),
whereas TFIIIB-α is required for transcription of genes with promoter
elements upstream of the initiation site. Here we describe the
identification, cloning, and characterization of TFIIIB50, a novel
homologue of TFIIB and TFIIIB90. TFIIIB50 and tightly associated
factors, along with TBP and TFIIIB150, reconstitute human TFIIIB-α
activity. Thus, higher eukaryotes, in contrast to the yeast
Saccharomyces cerevisiae
, have evolved two distinct
TFIIB-related factors that mediate promoter selectivity by RNA
polymerase III.
Carbon monoxide and nitric oxide as coneurotransmitters in the enteric nervous system: Evidence from genomic deletion of biosynthetic enzymes
Authors: Xue L. , Farrugia G. , Miller S. M. , Ferris C. D. , Snyder S. H. , Szurszewski J. H.
Published: July 2002

Nitric oxide (NO) and carbon monoxide (CO) seem to be neurotransmitters in the brain. The colocalization of their respective biosynthetic enzymes, neuronal NO synthase (nNOS) and heme oxygenase-2 (HO2), in enteric neurons and altered intestinal function in mice with genomic deletion of the enzymes (
nNOS
Δ/Δ
and
HO2
Δ/Δ
) suggest neurotransmitter roles for NO and CO in the enteric nervous system. We now establish that NO and CO are both neurotransmitters that interact as cotransmitters. Small intestinal smooth muscle cells from
nNOS
Δ/Δ
and
HO2
Δ/Δ
mice are depolarized, with apparent additive effects in the double knockouts (
HO2
Δ/Δ
/
nNOS
Δ/Δ
). Muscle relaxation and inhibitory neurotransmission are reduced in the mutant mice. In
HO2
Δ/Δ
preparations, responses to electrical field stimulation are nearly abolished despite persistent nNOS expression, whereas exogenous CO restores normal responses, indicating that the NO system does not function in the absence of CO generation.
Yeast ribonucleotide reductase has a heterodimeric iron-radical-containing subunit
Authors: Chabes Andrei , Domkin Vladimir , Larsson Göran , Liu Aimin , Gräslund Astrid , Wijmenga Sybren , Thelander Lars
Published: July 2002

Ribonucleotide reductase (RNR) catalyzes the
de novo
synthesis of deoxyribonucleotides. Eukaryotes have an α
2
β
2
form of RNR consisting of two homodimeric subunits, proteins R1 (α
2
) and R2 (β
2
). The R1 protein is the business end of the enzyme containing the active site and the binding sites for allosteric effectors. The R2 protein is a radical storage device containing an iron center-generated tyrosyl free radical. Previous work has identified an RNR protein in yeast, Rnr4p, which is homologous to other R2 proteins but lacks a number of conserved amino acid residues involved in iron binding. Using highly purified recombinant yeast RNR proteins, we demonstrate that the crucial role of Rnr4p (β′) is to fold correctly and stabilize the radical-storing Rnr2p by forming a stable 1:1 Rnr2p/Rnr4p complex. This complex sediments at 5.6 S as a ββ′ heterodimer in a sucrose gradient. In the presence of Rnr1p, both polypeptides of the Rnr2p/Rnr4p heterodimer cosediment at 9.7 S as expected for an α
2
ββ′ heterotetramer, where Rnr4p plays an important role in the interaction between the α
2
and the ββ ′ subunits. The specific activity of the Rnr2p complexed with Rnr4p is 2,250 nmol deoxycytidine 5′-diphosphate formed per min per mg, whereas the homodimer of Rnr2p shows no activity. This difference in activity may be a consequence of the different conformations of the inactive homodimeric Rnr2p and the active Rnr4p-bound form, as shown by CD spectroscopy. Taken together, our results show that the Rnr2p/Rnr4p heterodimer is the active form of the yeast RNR small subunit.
BH4 domain of antiapoptotic Bcl-2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondrial changes and cell death
Authors: Shimizu Shigeomi , Konishi Akimitsu , Kodama Takashi , Tsujimoto Yoshihide
Published: July 2002

A change of mitochondrial membrane permeability is essential for
apoptosis, leading to translocation of apoptogenic cytochrome
c
and apoptosis-inducing factor into the
cytoplasm. We recently showed that the Bcl-2 family of proteins
regulate cytochrome
c
release and the mitochondrial
membrane potential (Δψ) by directly modulating the activity of the
voltage-dependent anion channel (VDAC) through binding. Here we
investigated the biochemical role of the conserved N-terminal homology
domain (BH4) of Bcl-x
L
, which has been shown to be
essential for inhibition of apoptosis, with respect to the
regulation of mitochondrial membrane permeability and found that BH4
was required for Bcl-x
L
to prevent cytochrome
c
release and Δψ loss. A study using VDAC liposomes
revealed that Bcl-x
L
, but not Bcl-x
L
lacking
the BH4 domain, inhibited VDAC activity. Furthermore, BH4 oligopeptides
of Bcl-2 and Bcl-x
L
, but not mutant peptides, were able to
inhibit both VDAC activity on liposomes even in the presence of Bax and
apoptotic Δψ loss in isolated mitochondria. It was also
shown that the BH4 domain, fused to the protein transduction domain of
HIV TAT protein (TAT-BH4), efficiently prevented apoptotic cell
death. These results indicate that the BH4 of
Bcl-2/Bcl-x
L
is essential and sufficient for inhibiting
VDAC activity, which in turn prevents apoptotic mitochondrial
changes, and for preventing apoptotic cell death. Finally, the
data suggest that the TAT-BH4 peptide is potentially useful as a
therapeutic agent for diseases caused by accelerated apoptosis.
The murine homolog of human Nectin1δ serves as a species nonspecific mediator for entry of human and animal αherpesviruses in a pathway independent of a detectable binding to gD
Authors: Menotti Laura , Lopez Marc , Avitabile Elisa , Stefan Alessandra , Cocchi Francesca , Adelaide Jose , Lecocq Eric , Dubreuil Patrice , Campadelli-Fiume Gabriella
Published: July 2002

The full-length cDNA of the murine homolog of human nectin1δ (mNectin1δ), also known as human poliovirus receptor related 1 (PRR1) or herpesvirus entry mediator C, was cloned and showed a >90% identity with its human counterpart. mNectin1δ is expressed in some murine cell lines, exemplified by NIH 3T3 and L cells, and in murine tissues. It mediates entry of an extended range of herpes simplex virus (HSV) strains, porcine pseudorabies virus (PrV), and bovine herpesvirus 1. A soluble form of the mediator blocked infectivity in mNectin1δ and human nectin1δ (hNectin1δ)-expressing cells, suggesting a physical interaction of the mediator with virions. The higher concentrations of soluble mNectin1 required to block infectivity relative to soluble hNectin1 suggest that the target of the two molecules is not identical. Entry of HSV, but not PrV, was blocked by soluble mNectin1δ in NIH 3T3 and L cells. Two features were unexpected. First, soluble mNectin1δ failed to physically interact with HSV glycoprotein D (gD) at a detectable level, although it interacted physically with virions. Second, coexpression of mNectin1δ and HSV gD did not restrict HSV or PrV infection, whereas coexpression of hNectin and gD did restrict infection, suggesting that mNectin1δ fails to be sequestered by HSV gD. We conclude that mNectin1δ serves as a species-nonspecific mediator for entry of the human and animal αherpesviruses. This activity, at least for HSV, is independent of a detectable binding to gD.
A fibronectin fragment inhibits tumor growth, angiogenesis, and metastasis
Authors: Yi Ming , Ruoslahti Erkki
Published: July 2002

We have shown previously that a polymeric form of fibronectin is
strongly antimetastatic when administered systemically to tumor-bearing
mice. The polymeric fibronectin, sFN, is formed
in vitro
by treating soluble fibronectin with a 76-aa peptide, III1-C, which is
derived from the first type III repeat in fibronectin. Here we show
that the III1-C peptide and sFN also reduce tumor growth in mice, and
that this effect correlates with a low density of blood vessels in the
tumors of the treated mice. III1-C also polymerized fibrinogen, and the
fibrinogen polymer, sFBG, had antitumor and antiangiogenic effects
similar to those of sFN. Mice that had been injected s.c. with three
different types of human tumor cells and treated with biweekly i.p.
injections of III1-C, sFN, or sFBG over a 5-week period had tumors that
were 50–90% smaller than those of control mice. Blood vessel density
in the tumors of the treated mice was reduced by 60–80% at the end of
the experiment. Xenograft tumors from a human breast carcinoma line
(MDA-MB-435) were particularly susceptible to these treatments.
Metastasis into the lungs from the primary s.c. tumors also was
inhibited in the mice treated with III1-C and the two polymers. The
III1-C peptide is an antiangiogenic and antimetastatic agent. Because
of its ability to suppress tumor growth, angiogenesis, and metastasis,
we have named the III1-C peptide anastellin [from
anastello
(Greek), inhibit, force a retreat].
Molecular cloning of a cytochrome P450 taxane 10β-hydroxylase cDNA fromTaxusand functional expression in yeast
Authors: Schoendorf Anne , Rithner Christopher D. , Williams Robert M. , Croteau Rodney B.
Published: July 2002

The early steps in the biosynthesis of Taxol involve the cyclization of geranylgeranyl diphosphate to taxa-4(5),11(12)-diene followed by cytochrome P450-mediated hydroxylation at C5, acetylation of this intermediate, and a second cytochrome P450-dependent hydroxylation at C10 to yield taxadien-5α-acetoxy-10β-ol. Subsequent steps of the pathway involve additional cytochrome P450 catalyzed oxygenations and CoA-dependent acylations. The limited feasibility of reverse genetic cloning of cytochrome P450 oxygenases led to the use ofTaxuscell cultures induced for Taxol production and the development of an approach based on differential display of mRNA-reverse transcription-PCR, which ultimately provided full-length forms of 13 unique but closely related cytochrome P450 sequences. Functional expression of these enzymes in yeast was monitored byin situspectrophotometry coupled toin vivoscreening of oxygenase activity by feeding taxoid substrates. This strategy yielded a family of taxoid-metabolizing enzymes and revealed the taxane 10β-hydroxylase as a 1494-bp cDNA that encodes a 498-residue cytochrome P450 capable of transforming taxadienyl acetate to the 10β-hydroxy derivative; the identity of this latter pathway intermediate was confirmed by chromatographic and spectrometric means. The 10β-hydroxylase represents the initial cytochrome P450 gene of Taxol biosynthesis to be isolated by an approach that should provide access to the remaining oxygenases of the pathway.
Women and class structure in contemporary Japan1
Authors: Shirahase Sawako
Published: July 2002

The main purpose of this study is to examine how to determine the class position of women, especially married women, in Japan. This study examines three different approaches to conceptualizing women's position in the class structure: the conventional approach, the individual approach, and the dominance approach. Since 1975, the overall rate of female labour force participation in Japan has increased, and given this growth, particularly of employees working outside home, I discuss whether the increased entry of women, particularly married women, into the labour market challenges the conventional way of assigning class positions to women by simply deriving them from their husband's class positions. The data set used in this study is derived from the 1995 Japanese Social Stratification and Mobility Survey.

An examination of class distributions suggests that the pictures of macro‐class structure provided by the conventional approach and the dominance approach show very little difference. Married women who belong to the female‐dominant family still form a very small minority of all married women in the society. Furthermore, the male‐dominant family shows the greatest stability over the life course whereas the female‐dominant family, where the wife experiences with‐drawal from the labour market, is least stable. The increasing number of married women in the labour market, thus, has not yet become a major threat to the conventional way of assigning women to a class position in contemporary Japan. Women, even among those working on a full‐time basis, perceive their position in the stratification system using not only their own work, but also their husband's. In contrast, men's perception is determined by their own education and employment, not by their wives'. This asymmetry in the effect of the husband's class and of the wife's class on class identification is related not only to gender inequality within the labour market but also to the division of labour by gender within the household.
The Neighbourhood Contact Hypothesis: Evidence from the Multicity Study of Urban Inequality
Authors: Ihlanfeldt Keith R. , Scafidi Benjamin P.
Published: July 2002

The paper provides evidence on the neighbourhood contact hypothesis, which states that interracial neighbourhood contact acts to break down prejudice. Contact, therefore, may result in stable racially integrated neighbourhoods. By exploiting unique features of new data from the Multicity Study of Urban Inequality, our estimates are the first to account directly for the endogeneity of contact. Results indicate that neighbourhood contact affects Whites' attitudes towards Black neighbours only if this contact is with Blacks of the same or higher social status. Blacks' attitudes towards White neighbours, on the other hand, are affected by neighbourhood contact regardless of the relative social status of participating Whites, although the effect is twice as strong if the contact is with Whites of equal or higher status.
Residential Amenities, Firm Location and Economic Development
Authors: Gottlieb Paul D.
Published: July 2002

Amenities are regarded as increasingly important to the location decisions of certain types of firm. Yet they are often ignored in economic development research because of the assumption that they attract only workers, and that this workforce, in turn, attracts firms. This paper argues for a reduced form model of the impact of amenities on corporate location. When testing such a model at the intra-metropolitan scale, it will be necessary to measure amenities not only at the potential worksite, but also where employees are likely to live. This paper tests such a firm location model using a sample of municipalities in northern New Jersey. Results support the hypothesis that firms evaluate certain amenities with respect to the likely residential locations of their employees.
The Settlement Patterns of Developed World Migrants in London
Authors: White Paul
Published: July 2002

Contemporary international migration flows into European cities are now more diverse than used to be the case. The movement of less-skilled labour migrants has been replaced by the circulation of high-skill executives and specialist personnel involved in transnational corporations and in the financial services and other sectors affected by economic globalisation. To these are added other new service migrants and increased flows of students and independent young people. As a result, world cities are now witnessing the emergence of important categories of non-racialised international migrant groups. This paper considers whether such groups form distinctive residential concentrations in Greater London and uses the limited aggregate data available from the census to establish a general view of the geography of developed world migrants. There are important implications for urban theory and for discussions of urban ethnicity.
Land Conversion at the Urban Fringe: A Comparative Study of Japan, Britain and the Netherlands
Authors: Mori Hiroshi
Published: July 2002

In the 1980s, the multiplier between land values for agricultural and urban uses was found to run at 50-200 (times) or even higher in the areas surrounding expanding cities in Japan and Britain, compared to 2-3 in the Netherlands (no servicing costs considered). The Japanese experience suggests that this socially inexcusably large gap may result mainly from the speculative motives of landowners rather than from alleged excessive public regulations of development. A more desirable policy orientation is proposed, whereby landowners, either sellers or buyers of greenfields, should bear more explicitly the social costs of land-use conversion rather than merely relying on the loosening of development regulations to remedy problems.
The LDLP Faction in the Lithuanian Seimas, 1992–1996*
Authors: Clark Terry D. , Holscher Stacy J. , Hyland Lisa A.
Published: July 2002

In the 1992 elections to the national legislature, Lithuania became the first country in Eastern Europe to return its former communist party to power. Headed by Algirdas Brazauskas, the former First Secretary who had led the party in its split from the Communist Party of the Soviet Union (CPSU) in December 1990, the party had rejected the Soviet past and renamed itself the Lithuanian Democratic Labor Party (LDLP). Declaring itself a social-democratic party, the LDLP supported democracy and a free market “with a human face.” In the 1992 elections the LDLP campaigned as a party of experienced, competent administrators capable of managing the reforms in such a way as to lessen their social impact. As a result the party won a resounding victory in the elections of that year to the national legislature, winning 73 of the 141 seats in the Seimas.
The Meaning of Action in Learning and Teaching
Authors: Franks Anton , Jewitt Carey
Published: July 2002

Abstract Action is a highly theorised aspect of social life. Nonetheless, it remains a relatively neglected source of data within educational research. This article attempts to highlight the significance of the analysis of organised action within educational research. It describes and demonstrates an analytical approach to action applicable to the classroom developed from approaches to the analysis of bodily communication and action in drama education and from new approaches to rhetoric. These approaches draw on social semiotic theories of making meaning in order to describe the complex relationship between the semiotics of social action and the situated experience of learning in the classroom. This article describes how action realises meanings and shapes classroom interaction through the application of the schema to video data from a science lesson on energy with Year 9 pupils (14 years old). Finally, it draws attention to the research and pedagogical implications of a focus on action in the science classroom and in education more generally.
Action regulation in old age: Time samples from everyday contexts
Authors: Klumb Petra L.
Published: July 2002

The operation of self-efficacy beliefs was investigated in a group of 81 participants between 73 and 97 years of age with intensive time samples including activities carried out at the moment a signal was received, their subjective difficulty, and concurrent mood in everyday life. In a two-level approach, occasion-level and person-level effects could be modelled simultaneously. Within individuals, productive activities were perceived more difficult, on average, than nonproductive ones. Furthermore, perceived difficulty was lower the more positive concurrent mood was rated. Variance in these intra-individual slopes was partially explained by inter-individual differences in self-belief of efficacy regarding everyday activities.
Balancing Closeness and Individuality in Adolescent Close Relationships
Authors: Shulman Shmuel , Knafo Danielle
Published: July 2002

A systemic perspective is adapted in this account of close friendships and romantic relationships in adolescence. Data from a series of studies conducted on dyads of close friends and romantic partners illustrate how, in each relationship, partners simultaneously negotiate closeness and the expression of individual needs. Two relational types—interdependent and disengaged—were consistently found across all adolescent age groups. Interdependent partners were clearly capable of co-operation. Disengaged partners, although they identified each other as closest friends, appeared incapable of restraining competition to act co-operatively. Differences between the two friendship types were evident at each developmental stage. A three-stage developmental model of adolescent friendship is proposed based on age-related issues as reflected in the two relational types.
The Development of Productive Goal Setting with 2- to 4-Year-old Children
Authors: Lysyuk Lidija G.
Published: July 2002

Based on the assumption that human behaviour is goal directed and that goals regulate activities, the purpose of the present study was to explore the development of productive goal setting with preschool children. Productive goals refer to children’s ideas about what they want to achieve as a result of concrete or imaginary transformations of the environment. For this purpose, 166 children (age range: 2-4 years) were invited to play with a set of different play materials (e.g. clay, colour pencils and paper, wooden building blocks, and three dolls). Their play activities were recorded as well as verbal statements about their activities. Indices for goal-directed behaviour were children’s spontaneous statements about the purpose of their activities. Comments at moments of completion of activities or concerning the results of activities were indices for productive outcome attainment. The data indicate that at the age of 3 years half the children were able to perform activities that were directly related to attaining the desired outcomes (i.e. fully manipulative activities). From the age of 3.6 years, the abilities to formulate productive goals and attain productive outcomes stabilise. The findings are discussed in terms of developmental prerequisites for the emergence of goal-directed behaviour.
Developmental Sensitivity to Temporal Grouping Effects in Short-term Memory
Authors: Towse John N. , Hitch Graham J. , Skeates Steven
Published: July 2002

Four experiments investigate developmental changes in the effect of providing time-based cues to lists for immediate recall. Data both provide a context for adult research and have implications for children’s memory processes. Sets of letters (Experiments 1-3) or numbers (Experiment 4) were presented to children with either regular inter-item temporal intervals (ungrouped lists) or pauses to segment sets (grouped lists). Experiment 1 indicated a developmental shift between 4 and 8 years of age, with an increasing recall bene”t from temporal group structure for visually presented ”xed-length lists. Experiment 2 confirmed the developmental shift with visual presentation using a span procedure, with sensitivity to temporal grouping becoming apparent by the age of 8 years. Experiments 3 and 4 revealed a similar developmental pattern with a span procedure using auditory stimuli. In summary, children capitalise on pauses in visual and auditory material at approximately the same age. There was no evidence that auditory presentation induces a fundamentally different grouping process or precocious strategy use, contrary to some previous accounts. Data are most consistent with the argument that grouping is a relatively late-developing, strategic process.
The London Development Agency and Local Regeneration Issues: an Overview of Urban Regeneration Management
Authors: Mutale Emmanuel , Edwards Michael
Published: July 2002

The London Development Agency (LDA) was established in July 2000 as part of the new Greater London Authority (GLA). It has a remit to work in partnership with local authorities, businesses, voluntary groups, regeneration partnerships and training institution s. This paper is a broad overview of selected issues related to regeneration management in London . The opening section provides a brief policy con text leading to the formation of the LDA an d its strategic agenda. Secondly, we argue for a local role in regeneration management. Third, we examine the creation of the LDA, its approach and offer a tentative assessment of the democratic principles leading to its formation and the content of its strategy. Fourth, we sketch local regeneration dynamics from three localities, before concluding with possible outcomes as the new institution al structure takes effect an d also offer some suggestions on the linking up an d democratization of local and regional processes.
The Rural-Urban 'Digital Divide' in New Zealand: Fact or Fable?
Authors: Howell Bronwyn
Published: July 2002

Much electronic commerce literature addresses the potential existence of digital divides between different classes of users. While many studies document users reported perceptions of disadvantage or cite infrastructure availability benchmarks, few studies quantify the extent of such divides in actual uptake and usage of electronic communications tools. This study seeks to quantify the extent of perceived rural-urban digital divides among businesses in New Zealand. Yellow Pages business register data are analysed to determine business uptake of e-mail and websites by location. The results challenge conventional perceptions of disadvantage on the basis of geography alone. Indeed, some provincial areas demonstrate higher uptake of business e-mail than their urban counterparts. Smaller and more remote provincial centre businesses are more likely to be using e-mail than their counterparts closer to the metropolitan centres. Those centres most remote from New Zealand's traditional commercial centre demonstrate higher uptake than those closer. Explanations based upon disadvantages such as poor telephony infrastructure appear inadequate in accounting for these observations. Rather, we contend that while infrastructure may play some part in the explanation for low rural hinterland uptake, the results of this study are consistent with economic determinations of the optimal time to invest in new technologies. Specifically, higher provincial and rural communication costs are a significant factor in encouraging higher and earlier levels of provincial and rural e-mail adoption, and the optimal time to invest in website adoption depends more upon firm size, local economic conditions and product than infrastructure quality and business location.
Service expectations, self‐reported educational and resource needs of general practitioners in managing patients with hepatitis C
Authors: GUPTA LEENA , PUECH MCHELE C. , WARD JEANETTE E.
Published: July 2002

Hepatitis C infection is prevalent among injecting drug users in Australia. In an inner city area of Sydney, w undertook a survey of local general practitioners (GPs) in December 1996‐February 1997 to ascertain GPs self‐reported educational and resource needs and their approach to the management of asymptomatic patients with hepatitis C. A self‐administered questionnaire was developed to elicit GPs' ratings of the usefulness of 12 educational strategies, services and resources in managing patients with hepatitis C infection. GPs were also asked how they would manage clinically ‘uncomplicated’ patients. Demographic characteristics of respondent GPs were also obtained. Of the 108 GPs who agreed to be forwarded a questionnaire, 81 GPs returned it (75% response rate). GPs most frequently responded that information regarding interpretation of positive tests (69%), information about prevention of transmission (69%) and NHMRC guidelines on diagnosis and management (68%) would be of use in managing patients with hepatitis C infection. Thirty‐one percent of respondents thought that a shared care programme with GPs for patients undergoing interferon treatment or more counselling services (33%), would be ‘very useful’. When asked about their practice in relation to asymptomatic patients who would be unlikely to require referral to a specialist, GPs most frequently reported that they would test for blood‐borne viruses (86%). However, 50 (62%) indicated that they would refer the patient to a specialist. These findings provide important baseline information in a local population prior to commencement of local interventions to modify aspects of service provision. Availability of baseline data about service expectations and resource needs provided from our study has also provided a potential sentinel site to assess the impact of national guidelines for the management of people with hepatitis C.
Importance of Identifying Cocaine and Alcohol Dependent Methadone Clients
Authors: Rowan‐Szal Grace A. , Chatham Lois R. , Simpson D. Dwayne
Published: July 2002

Clients in outpatient methadone treatment (OMT) who abuse cocaine or alcohol are difficult to engage and retain in treatment. The impact a triple addiction to these drugs has on treatment was the focus of this study (N = 127). Admission characteristics, treatment response, and retention were compared among clients dependent on opiates only (O), opiates and alcohol (OA), opiates and cocaine (OC), or all three drugs (OAC). Findings indicate these groups differ in admission needs assessment, session attendance, issues discussed during treatment, and development of counselor rapport, with the OAC group being significantly more difficult to engage and retain in treatment.
Psychiatric Disorders Among Drug Dependent Subjects: Are They Primary or Secondary?
Authors: Compton Wilson M. , Cottler Linda B. , Phelps Deborah L. , Ben Abdallah Arbi , Spitznagel Edward L.
Published: July 2002

The relationship between substance use disorders and comorbid psychiatric conditions was investigated among 425 persons in drug treatment who met DSM‐III‐R criteria for drug dependence. Using the NIMH Diagnostic Interview Schedule to ascertain DSM‐III‐R psychiatric disorders among these drug dependent subjects, lifetime prevalence rates were 64% for alcohol abuse/dependence, 44% for antisocial personality disorder, 39% for phobic disorders, 24% for major depression, 12% for dysthymia, and 10% for generalized anxiety disorder. We found that antisocial personality disorder and phobias generally had onsets prior to the onset of drug dependence (that is, they were primary disorders). The majority of drug dependent persons with generalized anxiety disorder reported an onset after the onset of drug dependence (that is, they had secondary generalized anxiety). Alcohol dependence, depression, and dysthymia were divided nearly evenly between earlier (primary disorder) and later (secondary disorder). These results are consistent with the body of literature indicating the importance of antisocial syndromes in the etiology of substance abuse and the literature indicating the complex, varying nature of the relationship of psychiatric disorders to substance dependence. Finally, a precise nomenclature for “age of onset,” “primary,” and “secondary” was developed for this study that is critical to understanding these issues and is recommended for other studies.
Gender Differences in Treatment‐Seeking Cocaine Abusers—Implications for Treatment and Prognosis
Authors: McCance‐Katz Elinore F. , Carroll Kathleen M. , Rounsaville Bruce J.
Published: July 2002

This study examined gender differences in demographics, psychosocial functioning, substance abuse severity, psychopathology, and 1‐year outcome in cocaine‐dependent patients with the goal of identifying factors important to improving treatment and identifying prognostic indicators. The sample included 298 cocaine‐dependent adults (92 women). Ninety‐four patients (29 women) provided 1‐year follow‐up assessments. Compared to men, women consumed similar quantities of cocaine by more addictive routes and experienced more rapid progression of drug dependence, thus highlighting the need to facilitate treatment entry. The substantial rates of positive treatment outcomes emphasizes the effectiveness of treatment for cocaine‐dependent individuals.
Psychotherapies for Adolescent Substance Abusers: 15‐Month Follow‐up of a Pilot Study
Authors: Kaminer Yifrah , Burleson Joseph A.
Published: July 2002

In order to test the hypothesis that adolescent substance abusers could be matched to effective treatments on the basis of their co‐morbid psychopathology, 32 dually diagnosed adolescents were randomized into two short‐term outpatient group psychotherapies: cognitive‐behavioral treatment (CBT), and interactional treatment (IT). Two follow‐up assessments were conducted at 3 and 15 months after planned treatment completion. As reported recently, at the three‐month follow‐up, no patient‐treatment matching effects were identified. However, adolescents assigned to CBT demonstrated a significant reduction in severity of substance abuse compared to those assigned to IT. At 15‐month follow‐up, there were no differential improvements as a function of therapy type. However, subjects in general maintained significant treatment gains on the substance abuse, family function, and psychiatric status domains of the Teen‐Addiction Severity Index (T‐ASI), and both CBT and IT were associated with similar long‐term gains. Large scale, randomized, controlled treatment studies are further recommended to examine the findings of this small‐scale pilot study.
The Relationship of Axis II Personality Disorders to Other Known Predictors of Addiction Treatment Outcome
Authors: Pettinati Helen M. , Pierce John D. , Belden Portia P. , Meyers Kathleen
Published: July 2002

This study evaluated the prevalence of Axis II disorders in substance abuse patients and the relationship between Axis II psychopathology and two other known predictors of adverse addiction treatment outcomes, i.e., Axis I psychiatric comorbidity and illegal drug use, specifically cocaine. 232 patients with cocaine and/or alcohol dependence were admitted to either inpatient or outpatient addiction recovery programs at Carrier Foundation, a nonprofit, private‐pay hospital in New Jersey. Axis II disorders were more prevalent in cocaine than alcohol dependence and inpatients with Axis I psychiatric comorbidity. When all three predictors were evaluated in one prediction model, the combination of Axis I and II psychopathology was the best predictor of a return to substance use at one year post‐treatment, compared to the three factors alone. These findings highlighted the importance of the interrelationship of the relative prognostic value of three known predictors of addiction treatment.
A Study of the Developmental Toxicity Potential of Pentachlorophenol in the Rat
Authors: Bernard Bruce K. , Hoberman Alan M.
Published: July 2002

Pentachlorophenol (penta, CAS #87–86–5) is primarily used as a wood preservative. As part of the USEPA pesticide reregistration process, the developmental toxicity (embryo-fetal toxicity and teratogenic potential) of commercially available penta was studied following oral gavage to presumed pregnant female Sprague-Dawley rats (Crl:CD BR VAF/Plus Subdivision F, 83–3). Both study design and penta purity met the requirements of the USEPA. Doses of 0 (corn oil), 10, 30, and 80 mg/kg/day were administered to the rats at concentrations of 0, 2, 6, and 16 mg/ml, respectively from day 6 to day 15 of presumed gestation. The dosage volume was 5 ml/kg, adjusted on each day of dosage based on individual body weights recorded immediately before intubation. The rats were sacrificed on day 20 of presumed gestation and necropsied. The number of corpora lutea in each ovary was recorded. The uterus was examined for pregnancy, number and distribution of implantations, early and late resorptions and live and dead fetuses. Each fetus was weighed, sexed, and examined for gross external, soft tissue and skeletal alterations. The no-observable-adverse-effect-level (NOAEL) for maternal toxicity in rats was determined to be 30 mg/kg/day of penta. The developmental NOAEL for penta in rats was also found to be 30 mg/kg/day. The lowest-observable-adverse-effect-level (LOAEL) for penta developmental toxicity (80 mg/kg/day) was associated with increased resorptions, reduced live litter size and fetal body weights, and caused increased malformations and variations. These NOAELs, derived using USEPA approved study designs, are higher than those previously reported using penta that is no longer commercially available in studies with non-approved experimental designs. Penta should not be identified as a selective developmental toxicant in the rat because adverse effects on development of rat conceptuses occurred only at maternally toxic dosages.
Chronic (60-Week) Toxicity Study of DUROS Leuprolide Implants in Dogs
Authors: Cukierski Matthew J. , Johnson Paul A. , Beck James C.
Published: July 2002

The toxicity and pharmacodynamics of leuprolide acetate delivered from subcutaneously implanted DUROS leuprolide implants were examined in sexually mature male beagle dogs. The DUROS leuprolide implant is a sterile, nonpyrogenic, nonerodible, single-use, implantable, osmotically driven, drug delivery system for the palliative treatment of advanced prostate cancer. It contains 65 mg of leuprolide and is designed to deliver leuprolide continuously at a nominal rate of 120 μg per day for at least 12 months. Serum drug and testosterone concentrations were compared to values from dogs receiving monthly intramuscular injections of Lupron Depot 3.75 mg or no treatment (sham-operated). The local tissue response induced by subcutaneously implanted DUROS leuprolide implants was also evaluated. Beagles were implanted with a DUROS leuprolide implant for 52 weeks followed by removal and implantation of a new DUROS leuprolide implant for an additional 8 weeks. No mortality or morbidity occurred in this study. No treatment-related changes occurred in mean body weights, blood chemistry, or hematology during the study. Treatment-related atrophy of the testes, epididymides, and prostate gland, consistent with the known pharmacological effects of the drug, was observed in all dogs receiving the DUROS leuprolide implant or the Lupron Depot. Histological examination of these organs showed no distinguishable difference between dogs treated with the DUROS leuprolide implant or Lupron Depot. Weekly serum samples from dogs with DUROS leuprolide implants indicated continuous leuprolide delivery over 60 weeks, while some samples from the Lupron Depot group fell below measurable concentrations. Analysis of serum samples collected every 28 days just before Lupron Depot injection showed that 80 % of these samples had leuprolide concentrations below the limit of quantitation (0.1 ng/ml). Serum testosterone concentrations were below castrate levels (< 50 ng/dl) by 4 weeks after implantation of DUROS leuprolide implant and remained so for the duration of the study. Lupron Depot 3.75 mg also effectively lowered serum testosterone concentrations, but required reinjection every 28 days. All local tissue reactions to the DUROS leuprolide implant at implant sites were classified as mild following macroscopic examination. Microscopic site scores were mild to moderate. The DUROS leuprolide implant was shown to be safe, to provide continuous leuprolide delivery, and to effectively lower serum testosterone concentrations below castrate levels.