bluuebunny/crossref_metadata_2025 huggingface dataset:
PTGF-β
, a type β transforming growth factor (TGF-β) superfamily member, is a p53 target gene that inhibits tumor cell growth via TGF-β signaling pathway
Authors: Tan Mingjia , Wang Yixin , Guan Kunliang , Sun Yi
Published: July 2002

Identification and characterization of p53 target genes would lead to a better understanding of p53 functions and p53-mediated signaling pathways. Two putative p53 binding sites were identified in the promoter of a gene encoding PTGF-β, a type β transforming growth factor (TGF-β) superfamily member. Gel shift assay showed that p53 bound to both sites. Luciferase-coupled transactivation assay revealed that the gene promoter was activated in a p53 dose- as well as p53 binding site-dependent manner by wild-type p53 but not by several p53 mutants. The p53 binding and transactivation of the
PTGF-β
promoter was enhanced by etoposide, a p53 activator, and was largely blocked by a dominant negative p53 mutant. Furthermore, expression of endogenous PTGF-β was remarkably induced by etoposide in p53-positive, but not in p53-negative, cell lines. Finally, the conditioned medium collected from PTGF-β-overexpressing cells, but not from the control cells, suppressed tumor cell growth. Growth suppression was not, however, seen in cells that lack functional TGF-β receptors or Smad4, suggesting that PTGF-β acts through the TGF-β signaling pathway. Thus, PTGF-β, a secretory protein, is a p53 target that could mediate p53-induced growth suppression in autocrinal as well as paracrinal fashions. The finding made a vertical connection between p53 and TGF-β signaling pathways in controlling cell growth and implied a potential important role of p53 in inflammation regulation via PTGF-β.
Scaffold proteins may biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties
Authors: Levchenko Andre , Bruck Jehoshua , Sternberg Paul W.
Published: July 2002

In addition to preventing crosstalk among related signaling pathways, scaffold proteins might facilitate signal transduction by preforming multimolecular complexes that can be rapidly activated by incoming signal. In many cases, such as mitogen-activated protein kinase (MAPK) cascades, scaffold proteins are necessary for full activation of a signaling pathway. To date, however, no detailed biochemical model of scaffold action has been suggested. Here we describe a quantitative computer model of MAPK cascade with a generic scaffold protein. Analysis of this model reveals that formation of scaffold–kinase complexes can be used effectively to regulate the specificity, efficiency, and amplitude of signal propagation. In particular, for any generic scaffold there exists a concentration value optimal for signal amplitude. The location of the optimum is determined by the concentrations of the kinases rather than their binding constants and in this way is scaffold independent. This effect and the alteration of threshold properties of the signal propagation at high scaffold concentrations might alter local signaling properties at different subcellular compartments. Different scaffold levels and types might then confer specialized properties to tune evolutionarily conserved signaling modules to specific cellular contexts.
A phylogenetically conserved NAD
+
-dependent protein deacetylase activity in the Sir2 protein family
Authors: Smith Jeffrey S. , Brachmann Carrie Baker , Celic Ivana , Kenna Margaret A. , Muhammad Shabazz , Starai Vincent J. , Avalos Jose L. , Escalante-Semerena Jorge C. , Grubmeyer Charles , Wolberger Cynthia , Boeke Jef D.
Published: July 2002

The yeast Sir2 protein, required for transcriptional silencing, has an NAD
+
-dependent histone deacetylase (HDA) activity. Yeast extracts contain a NAD
+
-dependent HDA activity that is eliminated in a yeast strain from which
SIR2
and its four homologs have been deleted. This HDA activity is also displayed by purified yeast Sir2p and homologous Archaeal, eubacterial, and human proteins, and depends completely on NAD
+
in all species tested. The yeast
NPT1
gene, encoding an important NAD
+
synthesis enzyme, is required for rDNA and telomeric silencing and contributes to silencing of the
HM
loci. Null mutants in this gene have significantly reduced intracellular NAD
+
concentrations and have phenotypes similar to
sir2
null mutants. Surprisingly, yeast from which all five
SIR2
homologs have been deleted have relatively normal bulk histone acetylation levels. The evolutionary conservation of this regulated activity suggests that the Sir2 protein family represents a set of effector proteins in an evolutionarily conserved signal transduction pathway that monitors cellular energy and redox states.
Erythropoietin crosses the blood–brain barrier to protect against experimental brain injury
Authors: Brines Michael L. , Ghezzi Pietro , Keenan Sonja , Agnello Davide , de Lanerolle Nihal C. , Cerami Carla , Itri Loretta M. , Cerami Anthony
Published: July 2002

Erythropoietin (EPO), recognized for its central role in erythropoiesis, also mediates neuroprotection when the recombinant form (r-Hu-EPO) is directly injected into ischemic rodent brain. We observed abundant expression of the EPO receptor at brain capillaries, which could provide a route for circulating EPO to enter the brain. In confirmation of this hypothesis, systemic administration of r-Hu-EPO before or up to 6 h after focal brain ischemia reduced injury by ≈50–75%. R-Hu-EPO also ameliorates the extent of concussive brain injury, the immune damage in experimental autoimmune encephalomyelitis, and the toxicity of kainate. Given r-Hu-EPO's excellent safety profile, clinical trials evaluating systemically administered r-Hu-EPO as a general neuroprotective treatment are warranted.
A distinctive clade B HIV type 1 is heterosexually transmitted in Trinidad and Tobago
Authors: Cleghorn F. R. , Jack N. , Carr J. K. , Edwards J. , Mahabir B. , Sill A. , McDanal C. B. , Connolly S. M. , Goodman D. , Bennetts R. Q. , O'Brien T. R. , Weinhold K. J. , Bartholomew C. , Blattner W. A. , Greenberg M. L.
Published: July 2002

HIV-1 transmission worldwide is predominantly associated with heterosexual activity, and non-clade B viruses account for the most spread. The HIV-1 epidemic in Trinidad/Tobago and the Caribbean shares many features with such heterosexual epidemics, including a prominent role for coincident sexually transmitted diseases. This study evaluates the molecular epidemiology of HIV-1 in Trinidad/Tobago during a period when abrupt transition from homosexual to heterosexual transmission occurred in the absence of injecting drug use, concomitant with a rapid rise in HIV-1 prevalence in the heterosexual population. Of 31 viral isolates studied during 1987–1995, all cluster with subtype B reference strains. In the analysis of full
env
genes from 22 early seroconverters, the Trinidad isolates constitute a significant subcluster within the B subtype. The Trinidad V3 consensus sequence differs by a single amino acid from the prototype B V3 consensus and demonstrates stability over the decade of this study. In the majority of isolates, the V3 loop of
env
contains a signature threonine deletion that marks the lineage of the Trinidad HIV-1 clade B epidemic from pre-1984. No phenotypic features, including syncitium induction, neutralization profiles, and chemokine receptor usage, distinguish this virus population from other subtype B viruses. Thus, although the subtype B HIV-1 viruses being transmitted in Trinidad are genetically distinguishable from other subtype B viruses, this is probably the result of a strong founder effect in a geographically circumscribed population rather than genetic selection for heterosexual transmission. These results demonstrate that canonical clade B HIV-1 can generate a typical heterosexual epidemic.
The operator algebra approach to quantum groups
Authors: Kustermans Johan , Vaes Stefaan
Published: July 2002

A relatively simple definition of a locally compact quantum group
in the C*-algebra setting will be explained as it was recently obtained
by the authors. At the same time, we put this definition in the
historical and mathematical context of locally compact groups, compact
quantum groups, Kac algebras, multiplicative unitaries, and duality
theory.
Acceleration of oligomerization, not fibrillization, is a shared property of both α-synuclein mutations linked to early-onset Parkinson's disease: Implications for pathogenesis and therapy
Authors: Conway Kelly A. , Lee Seung-Jae , Rochet Jean-Christophe , Ding Tomas T. , Williamson Robin E. , Lansbury Peter T.
Published: July 2002

The Parkinson's disease (PD) substantia nigra is characterized by
the presence of Lewy bodies containing fibrillar α-synuclein.
Early-onset PD has been linked to two point mutations in the gene that
encodes α-synuclein, suggesting that disease may arise from
accelerated fibrillization. However, the identity of the pathogenic
species and its relationship to the α-synuclein fibril has not been
elucidated. In this
in vitro
study, the rates of
disappearance of monomeric α-synuclein and appearance of fibrillar
α-synuclein were compared for the wild-type (WT) and two mutant
proteins, as well as equimolar mixtures that may model the heterozygous
PD patients. Whereas one of the mutant proteins (A53T) and an equimolar
mixture of A53T and WT fibrillized more rapidly than WT α-synuclein,
the other (A30P) and the corresponding equimolar mixture with WT
fibrillized more slowly. However, under conditions that ultimately
produced fibrils, the A30P monomer was consumed at a comparable rate or
slightly more rapidly than the WT monomer, whereas A53T was consumed
even more rapidly. The difference between these trends suggested the
existence of nonfibrillar α-synuclein oligomers, some of which were
separated from fibrillar and monomeric α-synuclein by sedimentation
followed by gel-filtration chromatography. Spheres (range of heights:
2–6 nm), chains of spheres (protofibrils), and rings resembling
circularized protofibrils (height:
ca.
4 nm) were
distinguished from fibrils (height:
ca.
8 nm) by atomic
force microscopy. Importantly, drug candidates that inhibit
α-synuclein fibrillization but do not block its oligomerization could
mimic the A30P mutation and thus may accelerate disease progression.
Selective CXCR4 antagonism by Tat: Implications forin vivoexpansion of coreceptor use by HIV-1
Authors: Xiao Hua , Neuveut Christine , Tiffany H. Lee , Benkirane Monsef , Rich Elizabeth A. , Murphy Philip M. , Jeang Kuan-Teh
Published: July 2002

Chemokines and chemokine receptors play important roles in HIV-1 infection and tropism. CCR5 is the major macrophage-tropic coreceptor for HIV-1 whereas CXC chemokine receptor 4 (CXCR4) serves the counterpart function for T cell-tropic viruses. An outstanding biological mystery is why only R5-HIV-1 is initially detected in new seroconvertors who are exposed to R5 and X4 viruses. Indeed, X4 virus emerges in a minority of patients and only in the late stage of disease, suggesting that early negative selection against HIV-1–CXCR4 interaction may exist. Here, we report that the HIV-1 Tat protein, which is secreted from virus-infected cells, is a CXCR4-specific antagonist. Soluble Tat selectively inhibited the entry and replication of X4, but not R5, virus in peripheral blood mononuclear cells (PBMCs). We propose that one functional consequence of secreted Tat is to select against X4 viruses, thereby influencing the earlyin vivocourse of HIV-1 disease.
The corticofugal system for hearing: Recent progress
Authors: Suga Nobuo , Gao Enquan , Zhang Yunfeng , Ma Xiaofeng , Olsen John F.
Published: July 2002

Peripheral auditory neurons are tuned to single frequencies of
sound. In the central auditory system, excitatory (or facilitatory) and
inhibitory neural interactions take place at multiple levels and
produce neurons with sharp level-tolerant frequency-tuning curves,
neurons tuned to parameters other than frequency, cochleotopic
(frequency) maps, which are different from the peripheral cochleotopic
map, and computational maps. The mechanisms to create the response
properties of these neurons have been considered to be solely caused by
divergent and convergent projections of neurons in the ascending
auditory system. The recent research on the corticofugal (descending)
auditory system, however, indicates that the corticofugal system
adjusts and improves auditory signal processing by modulating neural
responses and maps. The corticofugal function consists of at least the
following subfunctions. (
i
) Egocentric selection for
short-term modulation of auditory signal processing according to
auditory experience
.
Egocentric selection, based on
focused positive feedback associated with widespread lateral
inhibition, is mediated by the cortical neural net working together
with the corticofugal system. (
ii
) Reorganization for
long-term modulation of the processing of behaviorally relevant
auditory signals
.
Reorganization is based on egocentric
selection working together with nonauditory systems.
(
iii
) Gain control based on overall excitatory,
facilitatory, or inhibitory corticofugal modulation
.
Egocentric selection can be viewed as selective gain control.
(
iv
) Shaping (or even creation) of response properties
of neurons
.
Filter properties of neurons in the
frequency, amplitude, time, and spatial domains can be sharpened by the
corticofugal system. Sharpening of tuning is one of the functions of
egocentric selection.
On cortical coding of vocal communication sounds in primates
Authors: Wang Xiaoqin
Published: July 2002

Understanding how the brain processes vocal communication sounds is
one of the most challenging problems in neuroscience. Our understanding
of how the cortex accomplishes this unique task should greatly
facilitate our understanding of cortical mechanisms in general.
Perception of species-specific communication sounds is an important
aspect of the auditory behavior of many animal species and is crucial
for their social interactions, reproductive success, and survival. The
principles of neural representations of these behaviorally important
sounds in the cerebral cortex have direct implications for the neural
mechanisms underlying human speech perception. Our progress in this
area has been relatively slow, compared with our understanding of other
auditory functions such as echolocation and sound localization. This
article discusses previous and current studies in this field, with
emphasis on nonhuman primates, and proposes a conceptual platform to
further our exploration of this frontier. It is argued that the
prerequisite condition for understanding cortical mechanisms underlying
communication sound perception and production is an appropriate animal
model. Three issues are central to this work: (
i
)
neural encoding of statistical structure of communication sounds,
(
ii
) the role of behavioral relevance in shaping
cortical representations, and (
iii
) sensory–motor
interactions between vocal production and perception systems.
Optimization of the helper-dependent adenovirus system for production and potency
in
vivo
Authors: Sandig Volker , Youil Rima , Bett Andrew J. , Franlin Laura L. , Oshima Masanobu , Maione Domenico , Wang Fubao , Metzker Michael L. , Savino Rocco , Caskey C. Thomas
Published: July 2002

Helper-dependent (HD) adenoviral vectors devoid of all viral coding sequences provide for safe and highly efficient gene transfer with long-lasting transgene expression. High titer stocks of HD vectors can be generated by using the cre-recombinase system. However, we have encountered difficulties with this system, including rearranged HD vectors and variable efficiency of HD vector rescue. These problems represent a major hindrance, particularly with regard to large-scale production. To overcome these limitations, we have modified the system in two ways: We constructed a new helper virus with a modified packaging signal and enhanced growth characteristics. We also redesigned the vector backbones by including noncoding adenovirus sequences adjacent to the right inverted terminal repeat and by incorporated a number of different segments of noncoding DNA of human origin as “stuffer.” Comparison of these vectors showed that the nature of the stuffer sequence affects replication of the HD vector. Optimization of the system resulted in a more robust and consistent production of HD vectors with low helper contamination and high
in vivo
potency.
Auditory sensitivity provided by self-tuned critical oscillations of hair cells
Authors: Camalet Sébastien , Duke Thomas , Jülicher Frank , Prost Jacques
Published: July 2002

We introduce the concept of self-tuned criticality as a general mechanism for signal detection in sensory systems. In the case of hearing, we argue that active amplification of faint sounds is provided by a dynamical system that is maintained at the threshold of an oscillatory instability. This concept can account for the exquisite sensitivity of the auditory system and its wide dynamic range as well as its capacity to respond selectively to different frequencies. A specific model of sound detection by the hair cells of the inner ear is discussed. We show that a collection of motor proteins within a hair bundle can generate oscillations at a frequency that depends on the elastic properties of the bundle. Simple variation of bundle geometry gives rise to hair cells with characteristic frequencies that span the range of audibility. Tension-gated transduction channels, which primarily serve to detect the motion of a hair bundle, also tune each cell by admitting ions that regulate the motor protein activity. By controlling the bundle's propensity to oscillate, this feedback automatically maintains the system in the operating regime where it is most sensitive to sinusoidal stimuli. The model explains how hair cells can detect sounds that carry less energy than the background noise.
Evolution of the chordate body plan: New insights from phylogenetic analyses of deuterostome phyla
Authors: Cameron Chris B. , Garey James R. , Swalla Billie J.
Published: July 2002

The deuterostome phyla include Echinodermata, Hemichordata, and Chordata. Chordata is composed of three subphyla, Vertebrata, Cephalochordata (Branchiostoma), and Urochordata (Tunicata). Careful analysis of a new 18S rDNA data set indicates that deuterostomes are composed of two major clades: chordates and echinoderms + hemichordates. This analysis strongly supports the monophyly of each of the four major deuterostome taxa: Vertebrata + Cephalochordata, Urochordata, Hemichordata, and Echinodermata. Hemichordates include two distinct classes, the enteropneust worms and the colonial pterobranchs. Most previous hypotheses of deuterostome origins have assumed that the morphology of extant colonial pterobranchs resembles the ancestral deuterostome. We present a molecular phylogenetic analysis of hemichordates that challenges this long-held view. We used 18S rRNA to infer evolutionary relationships of the hemichordate classes Pterobranchia and Enteropneusta. Our data show that pterobranchs may be derived within enteropneust worms rather than being a sister clade to the enteropneusts. The nesting of the pterobranchs within the enteropneusts dramatically alters our view of the evolution of the chordate body plan and suggests that the ancestral deuterostome more closely resembled a mobile worm-like enteropneust than a sessile colonial pterobranch.
Abnormal spermatogenesis and reduced fertility in transition nuclear protein 1-deficient mice
Authors: Yu Y. Eugene , Zhang Yun , Unni Emmanual , Shirley Cynthia R. , Deng Jian M. , Russell Lonnie D. , Weil Michael M. , Behringer Richard R. , Meistrich Marvin L.
Published: July 2002

Transition nuclear proteins (TPs), the major proteins found in chromatin of condensing spermatids, are believed to be important for histone displacement and chromatin condensation during mammalian spermatogenesis. We generated mice lacking the major TP, TP1, by targeted deletion of theTnp1gene in mouse embryonic stem cells. Surprisingly, testis weights and sperm production were normal in the mutant mice, and only subtle abnormalities were observed in sperm morphology. Electron microscopy revealed large rod-like structures in the chromatin of mutant step 13 spermatids, in contrast to the fine chromatin fibrils observed in wild type. Steps 12–13 spermatid nuclei from the testis ofTnp1-null mice contained, in place of TP1, elevated levels of TP2 and some protamine 2 (P2) precursor. Most of the precursor was processed to mature P2, but high levels of incompletely processed forms remained in epididymal spermatozoa. Sperm motility was reduced severely, and ≈60% ofTnp1-null males were infertile. We concluded that TP1 is not essential for histone displacement or chromatin condensation. The absence of TP1 may partially be compensated for by TP2 and P2 precursor, but this dysregulation of nucleoprotein replacement results in an abnormal pattern of chromatin condensation and in reduced fertility.
A molecular logic gate
Authors: Kompa K. L. , Levine R. D.
Published: July 2002

We propose a scheme for molecule-based information processing by
combining well-studied spectroscopic techniques and recent results from
chemical dynamics. Specifically it is discussed how optical transitions
in single molecules can be used to rapidly perform classical (Boolean)
logical operations. In the proposed way, a restricted number of states
in a single molecule can act as a logical gate equivalent to at least
two switches. It is argued that the four-level scheme can also be used
to produce gain, because it allows an inversion, and not only a
switching ability. The proposed scheme is quantum mechanical in that it
takes advantage of the discrete nature of the energy levels but, we
here discuss the temporal evolution, with the use of the populations
only. On a longer time range we suggest that the same scheme could be
extended to perform quantum logic, and a tentative suggestion, based on
an available experiment, is discussed. We believe that the pumping can
provide a partial proof of principle, although this and similar
experiments were not interpreted thus far in our terms.
Psychological, sociocultural, and marital adaptation of Turkish immigrant couples in Canada
Authors: Ataca Bilge , Berry John W.
Published: July 2002

The study examined the acculturation and adaptation of 200 married Turkish immigrants in Toronto, Canada, using self‐report questionnaires. As an extension of research from sojourners to immigrants, and from individuals to married couples, marital adaptation was introduced and three facets of adaptation were differentiated: psychological, sociocultural, and marital. The findings support the contention that adaptation is multifaceted. Consistent with stress and coping models, psychological adaptation of married couples was associated with the personality variable of hardiness, social support, acculturation attitudes, and discrimination. On the other hand, in line with social learning perspectives, sociocultural adaptation was mostly related to the variables instrumental in acquiring social skills in the new culture, namely, language proficiency and contact with members of the dominant group. Marital adaptation was mostly associated with marital stressors and marital support. The lack of research on gender differences in the differentiation of adaptation was addressed. This differentiation was clearer in men than in women; there were also different variables associated with the facets of men's and women's adaptation. The effects of socioeconomic status and gender have also been examined. The findings made it evident that Turkish immigrants did not acculturate uniformly. Two groups of Turkish immigrants, working class and professionals were clearly distinguished in their acculturation experiences and adaptation. Gender differences were most apparent in the low socioeconomic status group. Women in general were psychologically more vulnerable than men; the group that faced more risk factors were those women of low socioeconomic status. In terms of acculturation attitudes, Turkish immigrant couples strongly endorsed separation; however, those of high socioeconomic status preferred integration and assimilation to a greater, and separation to a lesser extent than those of low socioeconomic status.
Power Function Forgetting Curves as an Emergent Property of Biologically Plausible Neural Network Models
Authors: Sikström Sverker
Published: July 2002

Empirical forgetting curve data have been shown to follow a power function. In contrast, many connectionist models predict either an exponential decay or flat forgetting curves. This paper simulates power function forgetting curves in a Hopfield network modified to incorporate the more biologically realistic assumptions of bounded weights and a distribution of learning rates. The modified model produces power function forgetting curves. The bounded weights introduce exponential decay for individual weights, and a power function forgetting curve when summing exponential decays with different learning rates. Because these assumptions are biologically reasonable, power function forgetting curves may be an emergent property of biological networks. The results fit empirical data and indicate that forgetting curves restrict possible implementation of models of memory.
Street Scenes: Practices of Public and Private Space in Urban Vietnam
Authors: Drummond Lisa B. W.
Published: July 2002

This paper contributes an initial venture into thinking about the uses of the terms 'public' and `private' space in the context of Vietnamese urban life. It is argued that these terms, while they are critiqued and debated in Western academia, still retain substantial descriptive power at an everyday level. In non-Western societies, however, these terms may be more difficult to apply and the paper provides an empirical section which argues that the boundaries between public and private spaces are fluid and routinely transgressed, as in Western societies, but for reasons and in ways which are distinctive to the Vietnamese situation. The paper concludes by noting that Vietnam is experiencing both a divergence from the Anglo-American urban experience, in that Vietnam displays a resurgence rather than a death of streetlife and a convergence with it in the construction of 'pseudo-public' leisure spaces. Local specificities must therefore be acknowledged when using these otherwise useful Western terms in non-Western contexts.
Excess Commuting and the Modifiable Areal Unit Problem
Authors: Horner Mark W. , Murray Alan T.
Published: July 2002

Excess commuting has emerged during the past two decades as an important construct for evaluating the spatial relationships between employment and residential locations. During this time-period, there has been an on-going debate regarding how one should measure excess commuting in urban regions. This paper contributes to the debate by focusing on the spatial issues inherent in excess commuting evaluation. We demonstrate how scale and unit definition (the modifiable areal unit problem) are manifested in the assessment of excess commuting, both in theoretical and empirical terms. To this end, a geographical information systems-based analysis is presented which explores spatial sensitivities in the excess commuting measure. Our results show that aggregation and spatial unit definition may have profound impacts on the estimation of excess commuting. This work provides a formal resolution to much of the recent debate regarding estimates of excess commuting in urban regions.
Changes in the Structure of Public Housing Provision in Urban China
Authors: Wu Fulong
Published: July 2002

Housing provision in a socialist country is generally characterised by the dominance of public housing. However, provision of public housing is a complicated process, which involves various social agencies. In the case of China, the simple notion of 'state provision' covers huge differences between municipally-managed and work-unit housing. The lack of understanding in the structure of public housing provision has led to unsuccessful efforts in promoting the 'commercialisation' of housing in recent years. This paper, adopting a perspective of structure of housing provision (SHP), attempts to examine the changes in public-sector housing in China and to reveal the critical role of state work-units in the SHP. Housing reform has led to some significant changes in the SHP. The transformation, however, is far from a process of commercialisation or privatisation of public housing stock. On the production side, work-units do withdraw themselves from direct involvement in housing construction. However, on the consumption side, the low incomes of state workers, due to the political economy, have forced the work-unit system to remain as an indispensable part of the SHP. The increasing role played by state work-units shows the contradiction embedded in a socialist market economy—i.e. the reproduction of labour through market mechanisms and the persistence of public ownership of production. The changes certainly have profound implications for the nation's urban development and urban spatial structure.
Affordability, Housing Demand and Housing Policy in Urban India
Authors: Tiwari Piyush , Parikh Jyoti
Published: July 2002

Designing housing policies and programmes requires a careful estimation of household affordability and demand for housing. The efficiency of housing subsidies would depend on price elasticities of housing demand. Different households have different perceptions of housing demand based on their economic and demographic factors. We estimate the demand function of housing for urban India using step econometric analysis. The first step estimates the hedonic price index for states and in the second step the demand for housing is estimated as a function of economic and household characteristics. The problem of multicollinearity is observed with the data. Ridge regressions are used to correct for multicollinearity and to obtain efficient estimates. The results indicate that the housing demand is inelastic with respect to income and price. The income elasticity is 0.75 while price elasticity is slightly less than — 1. A further analysis to estimate income and price elasticities for different income classes as well as states has also been carried out. We comment on the efficiency of housing subsidies based on our results. The paper concludes with some policy questions.
Job Access, Commute and Travel Burden among Welfare Recipients
Authors: Ong Paul , Blumenberg Evelyn
Published: July 2002

Welfare recipients face a number of obstacles to making the transition from welfare to work. One is their geographical separation from employment opportunities: many welfare recipients live in 'job-poor' neighbourhoods far from employment for which they are qualified. Combining administrative data on welfare recipients and employment in Los Angeles with data from the 1990 decennial census, we show that greater access to local jobs in low-wage firms increases the likelihood that welfare recipients find employment in neighbourhood jobs. Moreover, welfare recipients who have long commutes earn less than those who find work closer to home, contrary to the pattern for most workers. These findings demonstrate that proximity to low-wage jobs benefits welfare recipients through reduced commuting expenses and increased earnings.
Re-establishing the Rent Gap: An Alternative View of Capitalised Land Rent
Authors: Hammel Daniel J.
Published: July 2002

The debate between the proponents of the rent gap hypothesis and Steven Bourassa concerning its internal consistency centres on the role of land use in capitalised land rent. Bourassa argues that capitalised land rent is nonsensical because it is determined in part by land use which is in conflict with land rent theory. The paper explores the determinants of capitalised land rent by reviewing the rent gap hypothesis and related research, and argues that the issue of scale is implicit in the rent gap. Land rent can be determined at a minimum of two scales resulting in at least two different land rents. This argument rectifies Bourassa's contentions, and is consistent with the theoretical foundations of the rent gap.
Volunteer Support in the Primary Classroom: The long‐term impact of one initiative upon children's reading performance
Authors: Elliott Julian , Arthurs Jane , Williams Robert
Published: July 2002

This article reports an evaluation of the effectiveness of a volunteer tutor reading intervention. Volunteers were provided with instruction and supervision in order that they might assist class teachers in the teaching of reading. A strong emphasis upon phonological awareness and storytelling underpinned the programme. Intervention took place in reception classes in three socially disadvantaged schools that could provide parallel classes to serve as controls. Assessment immediately after the intervention, and 3 years later, indicated that children receiving the volunteer intervention failed to make greater progress than same‐school controls. The article considers a number of possible reasons for the apparent failure of the intervention and concludes by cautioning against simplistic expectations that additional adult support should necessarily lead to gains in children's learning.
‘It's Taking Me a Long Time but I'll Get There in the End’: Mature students on access courses and higher education choice
Authors: Reay Diane , Ball Stephen , David Miriam
Published: July 2002

Abstract The UK policy rhetoric of commitment to widening access to higher education has identified mature students as playing a pivotal role in the expansion and reform of higher education. The article draws on the experiences of 23 mature access students in an inner London further education college in order to explore the range of opportunities and constraints mature students confront in their efforts to make the transition to higher education. In particular, the article focuses on the narratives of the seven students who failed to complete the access course. It is argued that complexities of ethnicity, gender and marital status intersect with, and compound, the consequences of class, making the transition process particularly difficult for working‐class, lone mothers. The article concludes that if the Government's ’New Learning Age' is not to reproduce past educational inequalities, then the rhetoric on widening participation needs to move beyond rhetoric into policies which provide possibilities for realisation.
Consequences of early parental loss and separation for health and well-being in midlife
Authors: Maier E. Hailey , Lachman Margie E.
Published: July 2002

We examined the impact of parental death and divorce prior to age 17 on physical and mental wellbeing in a national probability sample of middle-aged adults. The results suggest that, for men, parental divorce was associated with less positive relations with others, less self-acceptance, lower environmental mastery, and greater depression. Parental divorce predicted higher levels of physical health problems for both men and women. This relationship was mediated by income, education, drug use, and family support and was greater for men than women. Parental death predicted more autonomy for men and a higher likelihood of depression for women. The results contribute to understanding the developmental pathways involved in linking early life experiences to adulthood outcomes.
Children’s emotional development: Challenges in their relationships to parents, peers, and friends
Authors: von Salisch Maria
Published: July 2002

This literature review outlines the challenges and constraints which relationships to parents, peers, and friends offer for children’s emotional development, including the development of appraisal, experience, expression, and regulation of emotion. Parents are important for their children’s emotional development not only because they are attachment figures but also because of their cognitive and emotional expertise who instruct their offspring on the use of emotion labels, appraisals, expressions, and regulation strategies. In addition, parents introduce their children to cultural and subcultural rules on emotions. Yet parents’ understanding of their children’s emotions may be constrained by their social role as parents. Converging evidence suggests that display rules among peers promote the dampening of many emotions in many situations, especially those of vulnerability and anger. School-age children’s increasing use of distancing strategies may help them achieve this “cool” public self-presentation. Intimate friendship’s which permit (and may even require) the disclosure of private emotional experiences challenge preadolescents to learn how to be supportive to the friend in need and how to manage anger and contempt in these close relationships. Handling issues of trust and exposure, jealousy, and envy are related challenges for friendships.
Strategic Importance of Research Support through Pathology
Authors: Cockerell Gary L. , Mckim James M. , Vonderfecht Steven L.
Published: July 2002

The pace at which new drug candidates are being identified by Discovery Research demands that they be screened for preclinical attributes rapidly and efficiently. The early identification and elimination of compounds with toxic liabilities will produce safer drugs in a shorter time period, and with an increased rate of success. Most major pharmaceutical companies now recognize the strategic role of pathology support for research and have developed specific units to effect this outcome. The early interaction of these pathologists with drug discovery teams to identify compounds with toxic liabilities is critical. Approache s being used include high throughput in vitro screens to predict the relative toxicity of discovery compounds and to provide early indications of underlying mechanisms, target profiling to predict consequences of receptor-ligand interactions at other-than-indicated target sites, and acute in vivo studies to establish tolerability limits and target organs of toxicity. These approaches include the application of contemporary tools such as genomics, proteomics, metabonomics, and genetically engineered animal models. To maximize the benefit of discovery pathology, it is critical that pharmaceutical companies also actively participate in non-proprietary knowledge sharing and the education of pathologists and toxicologists to lead these efforts in the future.
Recovery of Injured Adrenal Medulla by Differentiation of Pre-Existing Undifferentiated Chromaffi n Cells
Authors: Chen-Pan Cleo , In Jen Pan  , Yamamoto Yuzuru , Hans Hc Chen  , Hayashi Yoshiro
Published: July 2002

We described previous that the adrenal medulla recovers rapidly from the injuries due to salinomycin. In the present study we found the recovery to be apparently due to differentiation of pre-existing, primitive undifferentiated, chromaffi n cells, rather than mitosis, as evidenced by lack of incorporation of 5-bromo-2-deoxyuridin e in the differentiating and/or differentiated chromaffi n cells. Electron-dense, striated fi brils observed within the necrotic cells and in the extracellular space were presumed to be intermediate degradation products. Schwann cells actively functioned as phagocytes in this study, and seemed to indirectly stimulate the differentiation of undifferentiated chromaffi n cells.
Peer‐delivered hepatitis C testing and counselling: a means of improving the health of injecting drug users
Authors: AITKEN CAMPBELL K. , KERGER MICHAEL , CROFTS NICK
Published: July 2002

We hypothesized that providing injecting drug users (IDUs) with free hepatitis C testing and counselling at a needle and syringe programme (NSP) would be an effective model. Between August 1999 and January 2000, our peer outreach worker offered these services from a busy NSP in western Melbourne. Over 300 counselling episodes were provided, and 47 IDUs who were not tested in the previous 12 months were given tests and full pre‐ and post‐test counselling, and were interviewed about reasons for not being tested, their knowledge of hepatitis C, and their risk behaviour. Twenty‐eight IDUs (59.6%) tested antibody‐positive, demonstrating the need to improve testing coverage and compliance with counselling requirements. Most were not tested because they did not think they were at risk, but their reported behaviour and antibody test results showed otherwise. Twenty people returned for a second interview, and improvements in their risk behaviour and knowledge of hepatitis C were detected. Our experience suggests that demand exists for hepatitis C testing and counselling of IDUs in Melbourne's western suburbs, that testing and counselling improve IDUs' ability to avoid harm, and that delivery of these services by a trained and experienced peer located at an NSP is an appropriate and effective model.
Measuring women's alcohol consumption in an Australian inner‐urban community using the AUDIT
Authors: BANWELL CATHY , O'BRIEN MARY , HAMILTON MARGARET , ATTEWELL ROBYN
Published: July 2002

The alcohol consumption of a systematically sampled population of women from an Australian inner‐urban community was measured using the AUDIT (Alcohol Use Disorders Identification Test) in three different ways to produce varying estimations of hazardous and harmful drinking. The study was located in an area in which there is a high density of licensed premises and its female population contains large numbers of women who are young, students and professionals and thus considered to be potentially risky drinkers. Five hundred and twenty‐five women returned completed questionnaires giving a response rate of 74%. Using an AUDIT score of eight as the cut‐off point, 21% of women were classified as being at risk of having problems associated with their alcohol consumption. These women were more likely than women who scored less than eight to be beer drinkers, to drink at licensed premises and drink with male and female friends. An association between higher AUDIT scores and being unmarried was found. This paper argues that investigating the social and contextual factors associated with women's potentially problematic drinking can promote more effective community‐based interventions. [Banwell C, O'Brien M, Hamilton H, Attewell R. Measuring women's alcohol consumption in an Australian inner‐urban community using the AUDIT. Drug Alcohol Rev 1999:18:379–388]
Heroin Chasers and Heroin Injectors: Differences Observed in a Community Sample in London, UK
Authors: Strang John , Grifiths Paul , Powis Beverly , Gossop Michael
Published: July 2002

“Chasing the dragon” has spread rapidly as a method of use of heroin in many countries over the last quarter of a century, and is now the most widely used method of heroin use worldwide. However, little examination has been made of the differences in characteristics and drug‐taking patterns between heroin chasers and injectors. In this study, a comparison is made of the personal, social and drug‐taking characteristics of heroin users in a community sample (i.e., not drawn from treatment services, contacted through a range of non‐treatment access routes), according to whether the heroin user was currently a heroin chaser or injector, and according to whether or not they had ever injected. Data were examined on 400 heroin users contacted and interviewed in South London by privileged access interviewers using a structured interview schedule. Severity of dependence was measured using the Severity of Dependence Scale (SDS). Heroin chasing and injecting were almost equally prevalent among this community sample. Of the 400 heroin users, 1 78 (44.5%) identified “chasing the dragon” as their current route of heroin use, and 222 (55.5%) injecting. Heroin chasers were younger, though they had first used at an older age, had a larger proportion of non‐using friends, and contained larger proportions of women and people of Afro‐Caribbean origin. Injectors were using higher daily doses and were signifi‐cantly more likely to be using on a daily basis. Those who had never injected were more likely to be women and to have friends who did not use drugs. Severity of Dependence (SDS) scores were greater amongst injectors, with scores for injectors almost all being above the informal clinical threshold of greater than 5; while one third of the chasers had SDS scores below this level. Heroin chasing had been a longstanding pattern of behavior for a large proportion of the study sample. Chasers were generally less deeply involved in a heroin‐using culture and were less likely to be using heroin daily. Almost all low scores for severity of dependence were seen among the chasers, though a significant number of chasers had dependence scores at the most extreme. Heroin chasers display distinctly different personal and drug‐taking characteristics and will need to be the subject of separate research studies and clinical programs.
Gender-Based Differences in Pharmacokinetics in Laboratory Animal Models
Authors: Czerniak Richard
Published: July 2002

The study of gender-based differences in the pharmacokinetics (PK) of compounds tested in animal models has received greater attention in recent years. As early as 1932, the pharmacological action of barbiturates was recognized as gender dependent—female rats required half the dose needed by male rats to induce sleep. Later, it was shown that gender differences in hepatic metabolism were responsible for this gender-related pharmacodynamic response. Today, it is well known that gender-dependent metabolism in rats often results from differences in expression of hepatic enzymes. The sex-specific cyctochrome P450s CYP2C11, CYP2C13, and CYP3A2 are expressed in males whereas CYP2C12 is expressed in females. Most of the known gender-related differences in toxicity of compounds in rats are due to gender-related hepatic metabolism differences. It is clear that compounds may undergo gender-dependent metabolism; it is also true that the fundamental PK parameters of clearance (CL) and volume (V) can demonstrate a gender dependence in a wide variety of animal species: rats, mice, rabbits, hamsters, dwarf goats, cattle, and rainbow trout. To appreciate how gender-related differences affect PK parameters, it is necessary to have a basic understanding of the factors that control the PK of compounds. Changes in these factors will be related to the primary PK parameters of CL and V. A review of the literature provides examples of gender-based differences in these factors and examples of the observed differences in the PK profile of the administered compound. Examples of gender-based differences in the PK of compounds leading to gender differences in the toxicity in nonclinical test species are also discussed.
Requirement for cGMP in Nerve Cell Death Caused by Glutathione Depletion
Authors: Li Yonghong , Maher Pamela , Schubert David
Published: July 2002

Glutathione depletion occurs in several forms of apoptosis and is associated with Parkinson's disease and HIV toxicity. The neurotransmitter glutamate kills immature cortical neurons and a hippocampal nerve cell line via an oxidative pathway associated with glutathione depletion. It is shown here that soluble guanylyl cyclase (sGC) activity is required for nerve cell death caused by glutathione depletion. Inhibitors of sGC block glutamate toxicity and a cGMP analogue potentiates cell death. Glutamate also induces an elevation of cGMP that occurs late in the cell death pathway. The resultant cGMP modulates the increase in intracellular calcium that precedes cell death because sGC inhibitors prevent calcium elevation and the cGMP analogue potentiates the increase in intracellular calcium. These results suggest that the final pathway of glutamate induced nerve cell death is through a cGMP-modulated calcium channel.