bluuebunny/crossref_metadata_2025 huggingface dataset:
Recession and Economic Revival in Britain: The Role of Policy in the 1930s and 1980s
Authors: Kitson Michael
Published: July 2002

During the 1980s economic policy in the UK increasingly embraced free-market economics. For many, this was a necessary shift which improved economic performance, whereas previous periods of increased intervention, such as the 1930s, had harmed the UK economy. This article takes an alternative perspective. It argues that economic revival in the 1930s was primarily policy-induced; whereas economic growth in the 1980s can be largely explained by the unintentional demand side-effects of policy, with many of the free-market policies having, at best, a neutral impact and, in some cases, harming the long-run growth potential of the economy.
Chronic pain in women: new perspectives on pathophysiology and management
Authors: Stones RW
Published: July 2002

Over the last fifty years the understanding of a number of symptomatic gynaecological conditions has crystallized to the point where a coherent framework of pathogenesis and a systematic approach to treatment can be discerned. Examples are endometriosis, menorrhagia, premenstrual syndrome and the symptoms associated with the climacteric. Chronic pelvic pain is only now reaching the stage of similar systematization, and it is interesting to speculate why this has taken so long. Two factors can perhaps be cited as relevant: in the conditions listed above, either reasonably plausible models for causation based on visible pathology have been available, as with endometriosis, or effective treatments have been readily available, for example hormone replacement therapy (HRT) for estrogen deficiency symptoms. In the case of pelvic pain, models of causation have often been speculative rather than based on research, and simple effective treatments have proved elusive. In this review current concepts of pain physiology and therapy are discussed with a view to placing in perspective the clinical problem of pelvic pain. The condition is best seen from a bio-psycho-social perspective but the main focus of the present review is the neurobiological aspect.
Lie-group methods
Authors: Iserles Arieh , Munthe-Kaas Hans Z. , Nørsett Syvert P. , Zanna Antonella
Published: July 2002

Many differential equations of practical interest evolve on Lie groups or on
manifolds acted upon by Lie groups. The retention of Lie-group structure
under discretization is often vital in the recovery of qualitatively correct geometry
and dynamics and in the minimization of numerical error. Having
introduced requisite elements of differential geometry, this paper surveys the
novel theory of numerical integrators that respect Lie-group structure, highlighting
theory, algorithmic issues and a number of applications.
The New Dutch Law on Legalizing Physician-Assisted Death
Authors: KIMSMA GERRIT , VAN LEEUWEN EVERT
Published: July 2002

On April 10, 2001, after extensive committee deliberations,
the Second Chamber of the Dutch Parliament passed a bill that
was introduced in August 1999 legalizing physician-assisted
death. The bill is officially called “The Evaluation of
Ending Life on Request and Assistance in Suicide and a Change
of the Penal Code and the Burial Act (Law Evaluating Ending
Life and Assistance with Suicide).” It was passed by a
majority vote in the Second Chamber of Parliament and was supported
by the majority parties constituting the present coalition
government (i.e., liberals and socialists). Opposition to the
law came mainly from a minority of Christian parties. In this
report we explore the meaning of this bill and describe some
of its problematic and paradoxical items.
The Minimum Size of Saturated Hypergraphs
Authors: PIKHURKO OLEG
Published: July 2002

Let [Fscr ] be a family of forbidden k-hypergraphs
(k-uniform set systems). An [Fscr ]-saturated
hypergraph is a maximal k-uniform set system not containing any member of
[Fscr ]. As the main result we prove that, for any finite family
[Fscr ], the minimum number of edges of an [Fscr ]-saturated hypergraph is
O(nk−1). In particular, this implies a conjecture
of Tuza. Some other related results are presented.
Complex answers: a case study using
a WWW question answering system
Authors: BUCHHOLZ S. , DAELEMANS W.
Published: July 2002

We investigate the problem of complex answers in question answering. Complex answers
consist of several simple answers. We describe the online question answering system SHAPAQA,
and using data from this system we show that the problem of complex answers is quite
common. We define nine types of complex questions, and suggest two approaches, based on
answer frequencies, that allow question answering systems to tackle the problem.
Transducer parsing of free and frozen sentences
Authors: ROCHE EMMANUEL
Published: July 2002

In language processing, finite state models are not a lesser evil
that bring simplicity and
efficiency at the cost of accuracy. On the contrary, they provide a very
natural framework
to describe complex linguistic phenomena. We present here one aspect
of parsing with finite
state transducers and show that this technique can be applied to
complex linguistic situations.
Using semantic lexicons for full text message
retrieval in a communication aid
Authors: LANGER STEFAN , HICKEY MARIANNE
Published: July 2002

In this paper, we present results of a project that investigated

the application of lexicon
based text retrieval techniques to Alternative and Augmentative Communication
(AAC). As
a practical outcome of this research, a communication aid based on message
retrieval by key
words was designed, implemented and evaluated. The message retrieval module
in the system
uses a large semantic lexicon, derived from the WordNet database, for query
expansion. Trials
have been carried out with the device to evaluate whether the approach
is suitable for AAC,
and to determine the semantic relations that lead to efficient
message retrieval. The first part
of this paper describes the background of the project and highlights the
retrieval requirements
for a communication aid, which differ considerably from the requirements
in standard text
retrieval. We then present the overall design of the WordKeys communication
aid and describe
the tasks of its sub-modules. We summarise trials that have been carried
out to determine the
effect of semantic query expansion on the success of message retrieval.
Evaluation results show
that information about word frequency can solve problems that occurred
in the semantic
query expansion because of taxonomies that have too many intermediate steps
between
closely related words. Finally, a user evaluation with the improved system
showed that full
text retrieval is an effective approach to message access in a communication
aid.
Validating the TEMAA LE evaluation
methodology: a case study on Danish spelling
checkers
Authors: PAGGIO PATRIZIA , UNDERWOOD NANCY L.
Published: July 2002

This paper describes the work carried out at the Center for
Sprogteknologi in Copenhagen to
validate the LE evaluation methodology developed by the LRE project TEMAA.
TEMAA has
developed a framework for the evaluation of LE products, implemented in
a Parameterisable
Testbed (PTB). The framework allows for a modular, formal and exible description
of user
requirements and objects of evaluation, it accommodates test methods of
various kind and
provides a methodology for assessing test results in the light of the requirements
expressed by
different user types. While the fundamentals of the TEMAA framework are
meant to apply to
adequacy evaluation of LE products in general, a detailed methodology has
been worked out
for the evaluation of spelling and grammar checkers, and applied to the
concrete evaluation
of Danish and Italian spelling checkers. The main focus of this paper is
on showing that
the general methodology provides a valid model for designing and carrying
out a concrete
evaluation, as in the case study on Danish spelling checkers.
Finding a domain-appropriate sense inventory
for semantically tagging a corpus
Authors: CUCCHIARELLI ALESSANDRO , VELARDI PAOLA
Published: July 2002

Semantically tagging a corpus is useful for many intermediate NLP tasks such as: acquisition
of word argument structures in sublanguages; acquisition of syntactic disambiguation cues;
terminology learning; etc. The general idea is that semantic tags allow the generalization of
observed word patterns, and facilitate the discovery of recurrent sublanguage phenomena and
selectional rules of various types. Yet, as opposed to POS tags in morphology, there is no
consensus in the literature about the type and granularity of the semantic tags to be used. In
this paper, we argue that an appropriate selection of semantic tags should be domain-dependent. We propose a method by which we select from WordNet an inventory of semantic
tags that are ‘optimal’ for a given corpus, according to a scoring
function defined as a linear
combination of general and corpus-dependent performance factors. We believe that an optimal
selection of a category inventory is a necessary premise for obtaining better results in all
lexically learning algorithms that are based on, or concerned with, semantic categorization of
words. Furthermore, an adequate inventory (one which intuitively ‘fits’ with the semantics of
a domain, e.g. phenomenon for Natural Science, or part, piece for a technical handbook) may
facilitate the manual annotation of large corpora.
Semantic tagging of unknown proper nouns
Authors: CUCCHIARELLI ALESSANDRO , LUZI DANILO , VELARDI PAOLA
Published: July 2002

In this paper, we describe a context-based method to semantically tag unknown proper
nouns (U-PNs) in corpora. Like many others, our system relies on a gazetteer and a set of
context-dependent heuristics to classify proper nouns. However, proper nouns are an open-end class: when parsing new fragments of a corpus, even in the same language domain, we
can expect that several proper nouns cannot be semantically tagged. The algorithm that we
propose assigns to an unknown PN an entity type based on the analysis of syntactically
and semantically similar contexts already seen in the application corpus. The performance of
the algorithm is evaluated not only in terms of precision, following the tradition of MUC
conferences, but also in terms of information gain, an information theoretic measure that
takes into account the complexity of the classification task.
GENDER DIFFERENCES IN ANXIETY: AN INVESTIGATION OF THE SYMPTOMS, COGNITIONS, AND SENSITIVITY TOWARDS ANXIETY IN A NONCLINICAL POPULATION
Authors: Armstrong Kerry A. , Khawaja Nigar G.
Published: July 2002

Past research has demonstrated that anxiety disorders represent a significant mental health concern. A review of the literature in the area indicates that there is limited information regarding gender differences on the basis of cognitions in clinical or nonclinical samples. The current investigation sought to determine whether any observable gender differences existed in the expression of symptoms, cognitions, and anxiety sensitivity for a nonclinical sample of 48 males and 49 females. Multivariate analyses of variance revealed support for gender differences in the expression of physiological hyperarousal, catastrophic cognitions and a general level of anxiety sensitivity in a nonclinical population. The strengths, limitations, and directions for future research are discussed.
In defense of the frontal lobe hypothesis of cognitive aging
Authors: WEST ROBERT
Published: July 2002

Over the past decade a number of reviewers have
argued that the pattern of spared and impaired cognitive
functions observed in the cognitive aging literature can
be understood within the context of a neuropsychologically
constrained model that proposes that the prefrontal cortex
is more vulnerable to the effects of normal aging than
other cortical regions (Dempster, 1992; Hartley, 1993;
Moscovitch & Winocur, 1992; West, 1996). While this
model has served as a valuable heuristic in my own thinking
about cognitive aging, the current review of Greenwood
and theoretical work emerging from other laboratories argues
that the “frontal lobe hypothesis” (FLH) no
longer provides a useful or accurate framework within which
to understand brain behavior relationships in cognitive
aging. While I agree with several of the ideas developed
in the review of Greenwood (this issue) I believe the continued
utility of the FLH can be demonstrated by considering two
questions: (1) What does the FLH predict about cognitive
aging and is there support for these predictions? and (2)
Has the time come to move beyond a general specification
of the FLH? In answering these questions I will provide
one or two findings from the empirical literature. These
are intended to be illustrative, not exhaustive.
Mesial temporal, diencephalic, and striatal contributions to deficits
in single word reading, word priming, and recognition memory
Authors: JERNIGAN TERRY L. , OSTERGAARD ARNE L. , FENNEMA-NOTESTINE CHRISTINE
Published: July 2002

Fifty-three volunteer participants were studied with
the fade-in task (Ostergaard, 1998) to measure naming
latency, word priming, and recognition-memory performance,
and with morphometric magnetic resonance imaging (MRI)
techniques to measure volumes of mesial temporal lobe,
diencephalic, striatal, and neocortical structures. The
relationship between measures of cerebral volume loss and
performance deficits was modeled using simultaneous regression
analyses in which the behavioral measures were dependent
variables. The results suggested that damage in both hippocampal
and amygdala/entorhinal areas as well as damage in the
diencephalon and the nucleus accumbens all contributed
independently to the severity of recognition-memory deficits.
Both caudate nucleus damage and hippocampal damage contributed
independently to increased naming latency (slowed single-word
reading). Finally, only damage in the hippocampus appeared
to result in decreased word priming. These results provide
further evidence against the assertion that word priming
represents a form of memory unaffected by damage to the
mesial temporal lobes. (JINS, 2001, 7,
63–78.)
Patterns of verbal learning and memory in traumatic brain injury
Authors: CURTISS GLENN , VANDERPLOEG RODNEY D. , SPENCER JAN , SALAZAR ANDRES M.
Published: July 2002

CVLT and WMS–R Digit Span variables were used to
calculate indexes of seven specific short- and long-term
memory processes: working memory span and central executive
functions, and long-term memory encoding, consolidation,
retention, retrieval, control abilities. Scores on these
indexes were then cluster-analyzed to determine whether
subtypes of memory performance exist that correspond to
deficits in these theoretical memory constructs. Parallel
analyses were conducted with two large samples (N
= 150 and N = 151) of individuals who had sustained
a traumatic brain injury (TBI). Findings showed that TBI
results in subgroups of memory disorders with specific
deficits in consolidation, retention, and retrieval processes.
Control problems (keeping track of list versus
non-list items) only appeared in conjunction with retrieval
deficits. Working memory span and central executive functioning
(i.e., the ability to manipulate information in working
memory) do not appear to be deficits characteristic of
TBI as no such clusters emerged in the analyses. By using
specific indexes of memory processes, and in contrast to
previous studies, patterns of memory dysfunction were found
that correspond to deficits in theoretically meaningful
memory constructs. (JINS, 2001, 7, 574–585.)
Clustering and switching on verbal fluency tests in Alzheimer's
and Parkinson's disease
Authors: Troyer Angela K. , Moscovitch Morris , Winocur Gordon , Leach Larry , Freedman and Morris
Published: July 2002

Two components of verbal fluency performance—clustering
(i.e., generating words within subcategories) and switching
(i.e., shifting between subcategories)—were examined
in patients with dementia of the Alzheimer type (DAT),
patients with dementia with Parkinson's disease (DPD),
nondemented patients with Parkinson's disease (NPD),
and demographically matched controls. The DAT and DPD groups
were impaired in the number of words generated on both
phonemic and semantic fluency. The DAT group produced smaller
clusters on both tasks and switched less often on semantic
fluency than controls. The DPD group switched less often
on both tasks and produced smaller clusters on phonemic
fluency than controls. The NPD group was not impaired on
any fluency variable. Thus, the total number of words generated
on phonemic and semantic fluency did not discriminate the
dementia groups from their respective control groups, but
measures of clustering and switching did. This differential
pattern of performance provides evidence for the potential
usefulness of measures of switching and clustering in the
assessment of dementia. (JINS, 1998, 4,
137–143.)
The effects of age, education, and ethnicity on verbal fluency
Authors: KEMPLER DANIEL , TENG EVELYN L. , DICK MALCOLM , TAUSSIG I. MARIBEL , DAVIS DEBORAH S.
Published: July 2002

A group of 317 healthy participants between 54
and 99 years of age performed a verbal fluency task. The
participants included Chinese, Hispanic, and Vietnamese
immigrants, as well as White and African American English
speakers. They were given 1 min to name as many animals
as possible in their native language. The results showed
that more animal names were produced by younger people
and those with more education. Language background was
also an important factor: The Vietnamese produced the most
animal names and the Spanish speakers produced the fewest.
The exaggerated difference between these two groups is
attributed to the fact that Vietnamese animal names are
short (predominantly 1 syllable) while the Spanish animal
names are longer than any other language in this study
(2 and 3 syllables per word). Finally, although the ethnic
groups named different animals, and appeared to vary in
the variety of animal names they used, these factors did
not affect overall verbal fluency performance. (JINS,
1998, 4, 531–538.)
Rehabilitation of a case of pure alexia: Exploiting residual
abilities
Authors: MAHER LYNN M. , CLAYTON M. CATHERINE , BARRETT ANNA M. , SCHOBER-PETERSON DEBRA , ROTHI LESLIE J. GONZALEZ
Published: July 2002

We present a case study of a 43-year-old woman
with chronic and stable pure alexia. Using a multiple baseline
design we report the results of two different interventions
to improve reading. First, a restitutive treatment
approach using an implicit semantic access strategy was
attempted. This approach was designed to exploit privileged
access to lexical–semantic representations and met
with little success. Treatment was then switched to a substitutive
treatment strategy, which involved using the patient's
finger to pretend to copy the letters in words and sentences.
Reading using this motor cross-cuing strategy
was 100% accurate and doubled in speed after 4 weeks of
intervention. We propose that this patient's inability
to benefit from the implicit semantic access treatment
approach may be in part related to her inability to suppress
the segmental letter identification process of word recognition.
(JINS, 1998, 4, 636–647.)
Explaining the environmental Kuznets curve: structural change and international agreements in reducing sulphur emissions
Authors: DE BRUYN SANDER M.
Published: July 2002

Environmental Kuznets curves have been estimated using a simple reduced-form model that gives no information on the mechanisms underlying the estimated inverted U-shaped relationship between some pollutants and income. Various intuitive appealing explanations for the observed patterns have been offered, such as structural changes and environmental policy, but these have rarely been empirically investigated. Expanding the reduced-form model with explanatory variables may introduce serious multicollinearity problems, a reason why decomposition analysis is a preferable alternative for investigating the origins of change in emissions. Applying decomposition analysis fails to find evidence for structural changes as an important determinant of the impressive reductions in SO2 emissions of developed economies during the 1980s. Environmental policy, fostered by international agreements, gives a better explanation why pollution curbs downward at high income levels. Besides the level of income, the present state of the environment seems an important, but often neglected, variable that explains the ambition of environmental policy.
Ideas on quantification of resilience-based management
Authors: BROCK WILLIAM ALLEN
Published: July 2002

Levin et al. give us a sweeping vision of the notion of resilience and the response of management. In these comments I wish to discuss the daunting task of quantification of the resilience-based management issues raised by Levin et al. I also wish to suggest directions of future research.
HERD BEHAVIOR AND AGGREGATE FLUCTUATIONS IN FINANCIAL MARKETS
Authors: Cont Rama , Bouchaud Jean-Philipe
Published: July 2002

We present a simple model of a stock market where a random communication structure between agents generically gives rise to heavy tails in the distribution of stock price variations in the form of an exponentially truncated power law, similar to distributions observed in recent empirical studies of high-frequency market data. Our model provides a link between two well-known market phenomena: the heavy tails observed in the distribution of stock market returns on one hand and herding behavior in financial markets on the other hand. In particular, our study suggests a relation between the excess kurtosis observed in asset returns, the market order flow, and the tendency of market participants to imitate each other.
Is lexical selection in bilingual speech production language-specific? Further evidence from Spanish–English and English–Spanish bilinguals
Authors: Costa Albert , Caramazza Alfonso
Published: July 2002

In this study we address the question of how lexical selection is achieved by bilingual speakers during speech production. Specifically, we test whether there is competition between the two lexicons of a bilingual during lexical access. In two picture–word interference experiments we explore the performance of two groups of bilinguals, English–Spanish and Spanish–English proficient bilinguals while naming pictures either in their L1 (Spanish) or in their L2 (Spanish). Picture naming was facilitated when the name of the picture and the distracter word were the “same”, regardless of the language in which the distracter was printed: same-language (e.g., mesa–mesa [table in Spanish]) or different-language pairs (e.g., mesa–table). The magnitude of this facilitatory effect was similar when naming in L1 (Experiment 1) and in L2 (Experiment 2). We also found that naming latencies were slower when the distracter word was semantically related to the picture's name (e.g., mesa–chair), regardless of the language in which the distracter was printed. The results suggest that there is no competition between the two lexicons of a bilingual during lexical access for production. This interpretation favors a model of lexical access in which lexical selection is language-specific both when speaking in L1 and in L2.
A review of reproductive strategies in cephalopods
Authors: ROCHA FRANCISCO , GUERRA ÁNGEL , GONZÁLEZ ÁNGEL F.
Published: July 2002

Cephalopod reproductive strategies are reviewed in order to clarify their current, confusing status. Based on the type of ovulation, spawning pattern and growth between egg batches or spawning periods, five comprehensive and flexible cephalopod reproductive strategies are defined. Accordingly, with these three factors the following classification is proposed. (a) Spawning once (formerly semelparity) consisting of simultaneous terminal spawning, with synchronous ovulation, monocyclic spawning and absence of growth between egg batches. (b) Spawning more than once (formerly iteroparity) including: (i) polycyclic spawning with egg‐laying occurring in separate batches during the spawning season and growth occurring between production of egg batches and spawning seasons; (ii) multiple spawning, with group‐synchronous ovulation, monocyclic spawning and growth between egg batches; (iii) intermittent terminal spawning, with group‐synchronous ovulation, monocyclic spawning and no growth between egg batches; (iv) continuous spawning, with asynchronous ovulation, monocyclic spawning and growth between egg batches. Examples of species exhibiting each of these reproductive strategies are given. The large amount of inter‐species variation in several life‐history traits related to reproductive events is discussed.
Time Travel to a Possible Self: Searching for the Alternative Cosmopolitanism of Cochin
Authors: Nandy Ashis
Published: July 2002

Cochin or Kochi is one of the few cities in India where the precolonial traditions of cultural pluralism refuse to die. It is one of the largest natural harbours in India and has also become, during the last fifty years, a major centre of the Indian Navy. With the growing security consciousness in official India, it has recently become less accessible to non-Indians, particularly if they happen to be from one of the countries with which India''s relationship is tense. Few mind that, for the city no longer means much to the outside world. To Indians, too, except probably for the more historically conscious Malayalis, Cochin is no longer the ‘epitome of adventure’ it was to Mohandas Karamchand Gandhi or a crucible of cultures, as it is to its former mayor, K. J. Sohan. For most, it is now one of those regional cities not quite up to the standard of India's major metropolitan centres.
Constraint Logic Programming with Hereditary Harrop formulas
Authors: LEACH JAVIER , NIEVA SUSANA , RODRÍGUEZ-ARTALEJO MARIO
Published: July 2002

Constraint Logic Programming (CLP) and Hereditary Harrop formulas (HH) are two well
known ways to enhance the expressivity of Horn clauses. In this paper, we present a novel
combination of these two approaches. We show how to enrich the syntax and proof theory of
HH with the help of a given constraint system, in such a way that the key property of HH as
a logic programming language (namely, the existence of uniform proofs) is preserved. We also
present a procedure for goal solving, showing its soundness and completeness for computing
answer constraints. As a consequence of this result, we obtain a new strong completeness
theorem for CLP that avoids the need to build disjunctions of computed answers, as well as
a more abstract formulation of a known completeness theorem for HH.
Ataxia telangiectasia mutated is essential during adult neurogenesis
Authors: Allen Duane M. , van Praag Henriette , Ray Jasodhara , Weaver Zoë , Winrow Christopher J. , Carter Todd A. , Braquet Ray , Harrington Elizabeth , Ried Thomas , Brown Kevin D. , Gage Fred H. , Barlow Carrolee
Published: July 2002

Ataxia telangiectasia (A-T) is an autosomal recessive disease characterized by normal brain development followed by progressive neurodegeneration. The gene mutated in A-T (ATM) is a serine protein kinase implicated in cell cycle regulation and DNA repair. The role of ATM in the brain and the consequences of its loss on neuronal survival remain unclear. We studied the role of ATM in adult neural progenitor cells in vivo and in vitro to define the role of ATM in dividing and postmitotic neural cells from Atm-deficient (Atm−/−) mice in a physiologic context. We demonstrate that ATM is an abundant protein in dividing neural progenitor cells but is markedly down-regulated as cells differentiate. In the absence of ATM, neural progenitor cells of the dentate gyrus show abnormally high rates of proliferation and genomic instability.Atm−/− cells in vivo, and in cell culture, show a blunted response to environmental stimuli that promote neural progenitor cell proliferation, survival, and differentiation along a neuronal lineage. This study defines a role for ATM during the process of neurogenesis, demonstrates that ATM is required for normal cell fate determination and neuronal survival both in vitro and in vivo, and points to a mechanism for neuronal cell loss in progressive neurodegenerative diseases.
Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1
Authors: Tao Weikang , Pennica Diane , Xu Lifeng , Kalejta Robert F. , Levine Arnold J.
Published: July 2002

We report the isolation and cloning of the Wrch-1 (Wnt-1 responsive Cdc42 homolog) cDNA. Wrch-1 is a novel gene whose mRNA level increases in response to Wnt-1 signaling in Wnt-1 transformed cells, Wnt-1 transgene induced mouse mammary tumors, and Wnt-1 retrovirus infected cells. Wrch-1 encodes a homolog of the Rho family of GTPases. It shares 57% amino acid sequence identity with Cdc42, but possesses a unique N-terminal domain that contains several putative PXXP SH3-binding motifs. Like Cdc42, Wrch-1 can activate PAK-1 and JNK-1, and induce filopodium formation and stress fiber dissolution. Active Wrch-1 stimulates quiescent cells to reenter the cell cycle. Moreover, overexpression of Wrch-1 phenocopies Wnt-1 in morphological transformation of mouse mammary epithelial cells. Taken together, Wrch-1 could mediate the effects of Wnt-1 signaling in the regulation of cell morphology, cytoskeletal organization, and cell proliferation.
Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 gene
Authors: Chen William S. , Xu Pei-Zhang , Gottlob Kathrin , Chen Mei-Ling , Sokol Karen , Shiyanova Tanya , Roninson Igor , Weng Wei , Suzuki Ryo , Tobe Kazuyuki , Kadowaki Takashi , Hay Nissim
Published: July 2002

The serine/threonine kinase Akt has been implicated in the control of cell survival and metabolism. Here we report the disruption of the most ubiquitously expressed member of theakt family of genes, akt1, in the mouse. Akt1−/− mice are viable but smaller when compared to wild-type littermates. In addition, the life span of Akt1−/− mice, upon exposure to genotoxic stress, is shorter. However, Akt1−/− mice do not display a diabetic phenotype. Increased spontaneous apoptosis in testes, and attenuation of spermatogenesis is observed in Akt1−/− male mice. Increased spontaneous apoptosis is also observed in the thymi of Akt1−/− mice, and Akt1−/− thymocytes are more sensitive to apoptosis induced by γ-irradiation and dexamethasone. Finally, Akt1−/− mouse embryo fibroblasts (MEFs) are more susceptible to apoptosis induced by TNF, anti-Fas, UV irradiation, and serum withdrawal.
Tandem Clusters of Membrane Proteins in Complete Genome Sequences
Authors: Kihara Daisuke , Kanehisa Minoru
Published: July 2002

The distribution of genes coding for membrane proteins was investigated in 16 complete genomes: 4 archaea, 11 bacteria, and 1 eukaryote. Membrane proteins were identified by our new method of predicting transmembrane segments (Kihara et al. 1998) after the removal of amino-terminal signal peptides. Interestingly, about half of the membrane protein genes in each genome were found to be located next to another, forming tandem clusters. Roughly 10%–30% of the tandem clusters were conserved among organisms, and most of the conserved tandem clusters belonged to one of the three functional groups, namely, transporters, the electron transport system, and cell motility. A tandem cluster sometimes contained paralogous membrane proteins, in which case the cluster size and the number of transmembrane segments could be related to a functional category, especially to transporters. In addition to the clustering of membrane proteins, the clustering of membrane proteins and ATP-binding proteins in the complete genomes was also analyzed. Although this clustering was not statistically significant, it was useful to identify candidate membrane protein partners of isolated ATP-binding protein components in the ABC transporters. Possible implications of tandem cluster organization of membrane protein genes are discussed including the complex formation and other functional coupling of protein products and the mechanism of protein translocation to the cell membrane.
Comparative Genome Sequence Analysis of the Bpa/Str Region in Mouse and Man
Authors: Mallon A.-M. , Platzer M. , Bate R. , Gloeckner G. , Botcherby M.R.M. , Nordsiek G. , Strivens M.A. , Kioschis P. , Dangel A. , Cunningham D. , Straw R.N.A. , Weston P. , Gilbert M. , Fernando S. , Goodall K. , Hunter G. , Greystrong J.S. , Clarke D. , Kimberley C. , Goerdes M. , Blechschmidt K. , Rump A. , Hinzmann B. , Mundy C.R. , Miller W. , Poustka A. , Herman G.E. , Rhodes M. , Denny P. , Rosenthal A. , Brown S.D.M.
Published: July 2002

The progress of human and mouse genome sequencing programs presages the possibility of systematic cross-species comparison of the two genomes as a powerful tool for gene and regulatory element identification. As the opportunities to perform comparative sequence analysis emerge, it is important to develop parameters for such analyses and to examine the outcomes of cross-species comparison. Our analysis used gene prediction and a database search of 430 kb of genomic sequence covering the Bpa/Str region of the mouse X chromosome, and 745 kb of genomic sequence from the homologous human X chromosome region. We identified 11 genes in mouse and 13 genes and two pseudogenes in human. In addition, we compared the mouse and human sequences using pairwise alignment and searches for evolutionary conserved regions (ECRs) exceeding a defined threshold of sequence identity. This approach aided the identification of at least four further putative conserved genes in the region. Comparative sequencing revealed that this region is a mosaic in evolutionary terms, with considerably more rearrangement between the two species than realized previously from comparative mapping studies. Surprisingly, this region showed an extremely high LINE and low SINE content, low G+C content, and yet a relatively high gene density, in contrast to the low gene density usually associated with such regions.

[The sequence data described in this paper have been submitted to EMBL under the following accession nos.: Mouse Genomic Sequence: Mouse contig A (AL021127), Mouse contig B (AL049866), BAC41M10 (AL136328), PAC303O11(AL136329). Human Genomic Sequence: Human contig 1 (U82671, U82670), Human contig 2 (U82695).]
Microsatellites in Different Eukaryotic Genomes: Survey and Analysis
Authors: Tóth Gábor , Gáspári Zoltán , Jurka Jerzy
Published: July 2002

We examined the abundance of microsatellites with repeated unit lengths of 1–6 base pairs in several eukaryotic taxonomic groups: primates, rodents, other mammals, nonmammalian vertebrates, arthropods,Caenorhabditis elegans, plants, yeast, and other fungi. Distribution of simple sequence repeats was compared between exons, introns, and intergenic regions. Tri- and hexanucleotide repeats prevail in protein-coding exons of all taxa, whereas the dependence of repeat abundance on the length of the repeated unit shows a very different pattern as well as taxon-specific variation in intergenic regions and introns. Although it is known that coding and noncoding regions differ significantly in their microsatellite distribution, in addition we could demonstrate characteristic differences between intergenic regions and introns. We observed striking relative abundance of (CCG)n•(CGG)n trinucleotide repeats in intergenic regions of all vertebrates, in contrast to the almost complete lack of this motif from introns. Taxon-specific variation could also be detected in the frequency distributions of simple sequence motifs. Our results suggest that strand-slippage theories alone are insufficient to explain microsatellite distribution in the genome as a whole. Other possible factors contributing to the observed divergence are discussed.
GBuilder—An Application for the Visualization and Integration of EST Cluster Data
Authors: Muilu Juha , Rodriguez-Tomé Patricia , Robinson Alan
Published: July 2002

This paper presents a network-centric DNA sequence visualization and analysis tool called GBuilder. The tool is an easy-to-use Java application that can be used to analyze DNA sequence clusters and assemblies. The emphasis is on the analysis of EST data, where these highly redundant collections of low-quality and often alternatively spliced or chimeric sequence data are difficult to explore. The tool has the capacity to visualize similarities or dissimilarities between sequences at the level of the nucleotide base or annotation in many ways. Sequences may also be edited manually. The novel feature of GBuilder is its ability to access different data sources and analysis applications available on the Internet and to integrate these results and functionality back into itself. External resources such as EST cluster databases and conventional command-line analysis applications are integrated and accessed using CORBA (Common Object Request Broker Architecture), which provides a standard implementation independent protocol for integration. New CORBA services can be integrated immediately if they use a known interface described using the Interface Definition Language.
Zebrafish Comparative Genomics and the Origins of Vertebrate Chromosomes
Authors: Postlethwait John H. , Woods Ian G. , Ngo-Hazelett Phuong , Yan Yi-Lin , Kelly Peter D. , Chu Felicia , Huang Hui , Hill-Force Alicia , Talbot William S.
Published: July 2002

To help understand mechanisms of vertebrate genome evolution, we have compared zebrafish and tetrapod gene maps. It has been suggested that translocations are fixed more frequently than inversions in mammals. Gene maps showed that blocks of conserved syntenies between zebrafish and humans were large, but gene orders were frequently inverted and transposed. This shows that intrachromosomal rearrangements have been fixed more frequently than translocations. Duplicated chromosome segments suggest that a genome duplication occurred in ray-fin phylogeny, and comparative studies suggest that this event happened deep in the ancestry of teleost fish. Consideration of duplicate chromosome segments shows that at least 20% of duplicated gene pairs may be retained from this event. Despite genome duplication, zebrafish and humans have about the same number of chromosomes, and zebrafish chromosomes are mosaically orthologous to several human chromosomes. Is this because of an excess of chromosome fissions in the human lineage or an excess of chromosome fusions in the zebrafish lineage? Comparative analysis suggests that an excess of chromosome fissions in the tetrapod lineage may account for chromosome numbers and provides histories for several human chromosomes.
The Complete Human Olfactory Subgenome
Authors: Glusman Gustavo , Yanai Itai , Rubin Irit , Lancet Doron
Published: July 2002

Olfactory receptors likely constitute the largest gene superfamily in the vertebrate genome. Here we present the nearly complete human olfactory subgenome elucidated by mining the genome draft with gene discovery algorithms. Over 900 olfactory receptor genes and pseudogenes (ORs) were identified, two-thirds of which were not annotated previously. The number of extrapolated ORs is in good agreement with previous theoretical predictions. The sequence of at least 63% of the ORs is disrupted by what appears to be a random process of pseudogene formation. ORs constitute 17 gene families, 4 of which contain more than 100 members each. “Fish-like” Class I ORs, previously considered a relic in higher tetrapods, constitute as much as 10% of the human repertoire, all in one large cluster on chromosome 11. Their lower pseudogene fraction suggests a functional significance. ORs are disposed on all human chromosomes except 20 and Y, and nearly 80% are found in clusters of 6–138 genes. A novel comparative cluster analysis was used to trace the evolutionary path that may have led to OR proliferation and diversification throughout the genome. The results of this analysis suggest the following genome expansion history: first, the generation of a “tetrapod-specific” Class II OR cluster on chromosome 11 by local duplication, then a single-step duplication of this cluster to chromosome 1, and finally an avalanche of duplication events out of chromosome 1 to most other chromosomes. The results of the data mining and characterization of ORs can be accessed at the Human Olfactory Receptor Data Exploratorium Web site (http://bioinfo.weizmann.ac.il/HORDE).
Creating the Gene Ontology Resource: Design and Implementation
Authors: Consortium The Gene Ontology
Published: July 2002

The exponential growth in the volume of accessible biological information has generated a confusion of voices surrounding the annotation of molecular information about genes and their products. The Gene Ontology (GO) project seeks to provide a set of structured vocabularies for specific biological domains that can be used to describe gene products in any organism. This work includes building three extensive ontologies to describe molecular function, biological process, and cellular component, and providing a community database resource that supports the use of these ontologies. The GO Consortium was initiated by scientists associated with three model organism databases: SGD, the Saccharomyces Genome database; FlyBase, the Drosophila genome database; and MGD/GXD, the Mouse Genome Informatics databases. Additional model organism database groups are joining the project. Each of these model organism information systems is annotating genes and gene products using GO vocabulary terms and incorporating these annotations into their respective model organism databases. Each database contributes its annotation files to a shared GO data resource accessible to the public athttp://www.geneontology.org/. The GO site can be used by the community both to recover the GO vocabularies and to access the annotated gene product data sets from the model organism databases. The GO Consortium supports the development of the GO database resource and provides tools enabling curators and researchers to query and manipulate the vocabularies. We believe that the shared development of this molecular annotation resource will contribute to the unification of biological information.
Mapping of Quantitative Trait Loci with Knockout/Congenic Strains
Authors: Bolivar Valerie J. , Cook Melloni N. , Flaherty Lorraine
Published: July 2002

Recently we have explored the use of knockout/congenic mouse strains for isolating and mapping quantitative trait loci (QTLs). Because most knockout strains have been bred to be B6.129 congenic strains, they can be used to test for QTLs in the targeted chromosomal area as long as there is a genetic difference between B6 and 129. Thus, we have tested a number of knockout/congenic strains in a series of behavioral tests in which mouse performance has a significant genetic component. We have also developed a breeding scheme for distinguishing the effects of background flanking genes from the targeted ablation. In screening several knockout/congenics, we have found at least one that harbors a behavioral QTL in the 129 chromosomal segment. The position of this QTL was confirmed subsequently by several F1 crosses.
Race, Ethnicity, and Genomics: Social Classifications as Proxies of Biological Heterogeneity
Authors: Foster Morris W. , Sharp Richard R.
Published: July 2002

Over the past century, genetics has experienced a tension between the view that racial and ethnic categories are biologically meaningful and the view that these social classifications have little or no biological significance. That tension continues to inform genomics and is evident in the assembly of biological collections and sequence databases that seek to approximate the genetic variation found in human populations. Although social identities can be useful and convenient proxies of some biological features, for example, in ensuring that genomic resources capture a range of genetic variants found in most human populations, the ways in which geneticists conceptualize the relationship between racial and ethnic identities and genetic variation can be problematic. Inclusion of racial and ethnic identifiers in genomic resources can create risks for all members of those identified populations and influence lay perceptions of the nature of racial and ethnic groups. Thus, the burden of showing the scientific utility of racial and ethic identities in the construction and analysis of genomic resources falls on researchers. This requires that genetic researchers pay as much attention to the social constitution of human populations as presently is paid to their genetic composition.
Further Evidence for a Dissociation Between Different Forms of Mnemonic Expressions in a Mouse Model of Age-related Cognitive Decline: Effects of Tacrine and S 17092, a Novel Prolyl Endopeptidase Inhibitor
Authors: Marighetto Aline , Touzani Khalid , Etchamendy Nicole , Torrea Cedric Cortes , De Nanteuil Guillaume , Guez David , Jaffard Robert , Morain Philippe
Published: July 2002

It has been demonstrated previously on the radial maze that the emergence of an age-related mnemonic impairment is critically dependent on the form which the discrimination problems took. Hence, when the arms were presented one by one (i.e., successive go-no-go discrimination), both adult and aged mice learned to distinguish between positive (baited) and negative (unbaited) arms readily, as evidenced by their increased readiness to enter positive relative to negative arms (i.e., by a differential in arm-entry latencies). A selective impairment in the aged mice was seen when these arms were presented subsequently as pairs, such that the mice were confronted with an explicit choice (i.e., simultaneous 2-choice discrimination). When discriminative performance was measured by the differential run speed between positive and negative arms, aged mice were also impaired. This was particularly pronounced in the 2-choice discrimination condition. We examined the effects of tacrine (3mg/kg, subcutaneously) or S 17092 (10mg/kg, orally) in aged mice on the three behavioral indices of this 2-stage spatial discrimination paradigm. The results indicated that: (1) Tacrine, but not S 17092, enhanced the acquisition of go-no-go discrimination as reflected in arm-entry latencies; (2) both drugs improved choice accuracy in simultaneous discrimination, although the effect of tacrine was less striking and, in particular, far from statistical significance in the very first 2-choice responses; and (3) neither drugs significantly affected run-speed performance. We conclude further that the specific patterns of drug effects on the three indices of discriminative performance might suggest that each index is associated with a distinct form of mnemonic expression relying on separate neural systems.
A Small GTP-Binding Host Protein Is Required for Entry of Powdery Mildew Fungus into Epidermal Cells of Barley
Authors: Schultheiss Holger , Dechert Cornelia , Kogel Karl-Heinz , Hückelhoven Ralph
Published: July 2002

Small GTP-binding proteins such as those from the RAC family are cytosolic signal transduction proteins that often are involved in processing of extracellular stimuli. Plant RAC proteins are implicated in regulation of plant cell architecture, secondary wall formation, meristem signaling, and defense against pathogens. We isolated aRacB homolog from barley (Hordeum vulgare) to study its role in resistance to the barley powdery mildew fungus (Blumeria graminis f.sp.hordei). RacB was constitutively expressed in the barley epidermis and its expression level was not strongly influenced by inoculation with B. graminis.However, after biolistic bombardment of barley leaf segments withRacB-double-stranded RNA, sequence-specific RNA interference with RacB function inhibited fungal haustorium establishment in a cell-autonomous and genotype-specific manner. Mutants compromised in function of the Mlowild-type gene and the Ror1 gene (genotype mlo5 ror1) that are moderately susceptible to B. graminis showed no alteration in powdery mildew resistance uponRacB-specific RNA interference. Thus, the phenotype, induced by RacB-specific RNA interference, was apparently dependent on the same processes asmlo5-mediated broad resistance, which is suppressed byror1. We conclude that an RAC small GTP-binding protein is required for successful fungal haustorium establishment and that this function may be linked to MLO-associated functions.