bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Structures and Information Extraction from Biological
Texts: The PASTA System
Authors: Gaizauskas R. , Demetriou G. , Artymiuk P. J. , Willett P.
Published: December 2002

Motivation: The rapid increase in volume of protein structure literature means useful information may be hidden or lost in the published literature and the process of finding relevant material, sometimes the rate-determining factor in new research, may be arduous and slow.

Results: We describe the Protein Active Site Template Acquisition (PASTA) system, which addresses these problems by performing automatic extraction of information relating to the roles of specific amino acid residues in protein molecules from online scientific articles and abstracts. Both the terminology recognition and extraction capabilities of the system have been extensively evaluated against manually annotated data and the results compare favourably with state-of-the-art results obtained in less challenging domains. PASTA is the first information extraction (IE) system developed for the protein structure domain and one of the most thoroughly evaluated IE system operating on biological scientific text to date.

Availability: PASTA makes its extraction results available via a browser-based front end: http://www.dcs.shef.ac.uk/nlp/pasta/. The evaluation resources (manually annotated corpora) are also available through the website: http://www.dcs.shef.ac.uk/nlp/pasta/results.html.

Contact: r.gaizauskas@dcs.shef.ac.ukg.demetriou@dcs.shef.ac.ukp.artymiuk@shef.ac.ukp.willett@shef.ac.uk

* To whom correspondence should be addressed.
Genetic Power Calculator: design of linkage and
association genetic mapping studies of complex traits
Authors: Purcell S. , Cherny S. S. , Sham P. C.
Published: December 2002

Summary: A website for performing power calculations for the design of linkage and association genetic mapping studies of complex traits.

Availability: The package is made available athttp://statgen.iop.kcl.ac.uk/gpc/

Contact: s.purcell@iop.kcl.ac.uk

* To whom correspondence should be addressed.
Diary Methods: Capturing Life as it is Lived
Authors: Bolger Niall , Davis Angelina , Rafaeli Eshkol
Published: December 2002

In diary studies, people provide frequent reports on the events and experiences of their daily lives. These reports capture the particulars of experience in a way that is not possible using traditional designs. We review the types of research questions that diary methods are best equipped to answer, the main designs that can be used, current technology for obtaining diary reports, and appropriate data analysis strategies. Major recent developments include the use of electronic forms of data collection and multilevel models in data analysis. We identify several areas of research opportunities: 1. in technology, combining electronic diary reports with collateral measures such as ambulatory heart rate; 2. in measurement, switching from measures based on between-person differences to those based on within-person changes; and 3. in research questions, using diaries to (a) explain why people differ in variability rather than mean level, (b) study change processes during major events and transitions, and (c) study interpersonal processes using dyadic and group diary methods.
Qualitative and Quantitative Analyses of Historical Data
Authors: Simonton Dean Keith
Published: December 2002

Although the typical study in psychology involves the quantitative analysis of contemporary research participants, occasionally psychologists will study historical persons or events. Moreover, these historical data may be analyzed using either qualitative or quantitative techniques. After giving examples from the subdisciplines of cognitive, developmental, differential, abnormal, and social psychology, the distinctive methodological features of this approach are outlined. These include both data collection (sampling, unit definition, etc.) and data analysis (both qualitative and quantitative). The discussion then turns to the advantages and disadvantages of this research method. The article closes by presenting the reasons why (a) psychologists will probably continue to use historical data and (b) quantitative analyses may eventually replace qualitative analyses in such applications.
Disappointment aversion equilibrium in a futures market
Authors: Lien Donald , Wang Yaqin
Published: December 2002

This article examines the effect of disappointment aversion on the equilibrium in a commodity futures market.
Consider a commodity market with a producer and a speculator. We show that the equilibrium price is positively
related to either agent's risk or disappointment aversion, and to the market volatility. The market trading
volume is positively related to the producer's risk or disappointment aversion, but negatively related to
the speculator's risk or disappointment aversion. The producer lowers his or her reference point in
response to an increase in the risk aversion or disappointment aversion of either agent, and to an increase in
spot price volatility. The speculator raises his or her reference point when the producer becomes more risk
averse or disappointment averse, or when the spot price becomes more volatile. A more
disappointment‐averse speculator will lower his or her reference point. However, a more
risk‐averse speculator raises (lowers) the reference point if he or she is less
(more) risk averse than the producer. Numerical examples are provided to further support the above
analytical results. © 2003 Wiley Periodicals, Inc. Jrl Fut Mark 23:135–150, 2003
Permanence and global attractivity for facultative mutualism system with delay
Authors: Mukherjee Debasis
Published: December 2002

In this paper, we consider a facultative mutualism system with different delays. Sufficient criteria for permanence and global attractivity for the system are established. Ultimate uniform boundedness of the solutions ensures permanence. For the global attractivity of the system, magnitude of the delays plays a major role. Copyright © 2003 John Wiley & Sons, Ltd.
Description of the metal–ligand bonding in f‐element complexes: A DFT study including scalar relativistic effects
Authors: Vetere Valentina , Maldivi Pascale , Adamo Carlo
Published: December 2002

A comparative density functional study on metal–ligand (M–L) interaction has been performed on X3–M–L (X = F, I; M = U, La, Nd: L = NH3, NCCH3, CO) and X3–M–(CO)2species including scalar relativistic effects by means of the zero‐order regular approximation (ZORA) hamiltonian. The role of the halogen atoms in modeling the M–L interactions is discussed for π‐acceptor ligands CO and NCCH3and for the σ‐donor NH3. The fluoride counterions, compared with previous calculations on the iodide complexes, stabilize more tedraedral structure with longer M–L distances. Finally, the addition of a second ligand to the previous species has permitted a more complete discussion on the backbonding effects on the uranium complexes. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
How to Simplify the Co-Ordination of Social Security
Authors: Eichenhofer Eberhard
Published: December 2002

The key piece of EU-legislation on social security deals with co-ordination. The provisions on co-ordination are very complicated and, at the Edinburgh Summit in 1992, the Council mandated the Commission to simplify them. The paper presents and assesses three approaches to reform them and outlines an alternative approach for simplifying the provisions on co-ordination.
Social Regulation and the Social Dimension in Europe: The Example of Insurance
Authors: Mabbett Deborah
Published: December 2002

This paper examines three aspects of the development of the Single European Market in insurance. First, it looks at the interplay between harmonisation and mutual recognition in the formulation of the directives creating a single market in insurance. Second, it examines the scope for exclusion of ‘insurance forming part of a statutory system of social security‘, which is intended to preserve member states' capacity to undertake their own social policies. Third, it discusses the impact of recent efforts to promote a ‘social dimension’ in European integration. The main findings are that the exemption of social insurance from the directives does protect member states' ability to conduct budgetary social policy, but that the single market curtails their social-regulatory powers, and that the ‘social dimension’ partly revives national capacities for social regulation.
The Future of Community Coalition Building
Authors: Wolff Thomas
Published: December 2002

The future holds great promise for community coalitions as powerful interventions for community change. Community change is envisioned as: working with whole communities; increasing grassroots and civic engagement; promoting diversity, collaboration and, advocacy; increasing roles for professional technical assistance and evaluation; future changes in the role of government; and the building of healthy communities. Examples of these dimensions follow, as contributed by activists from a wide range of fields.
Functional Domains within Fusion Proteins: Prospectives for Development of Peptide Inhibitors of Viral Cell Fusion
Authors: Shai Yechiel
Published: December 2002

The entry of enveloped viruses into host cells is accomplished by fusion ofthe viral envelope and target plasma membrane and is mediated by fusionproteins. Recently, several functional domains within fusion proteins fromdifferent viral families were identified. Some are directly involved inconformational changes after receptor binding, as suggested by the recentrelease of crystallographically determined structures of a highly stablecore structure of the fusion proteins in the absence of membranes. However, in the presence of membranes, this core binds strongly to the membrane's surface and dissociates therein. Other regions, besides the N-terminal fusionpeptide, which include the core region and an internal fusion peptide inparamyxoviruses, are directly involved in the actual membrane fusion event, suggesting an “umbrella” like model for the membrane inducedconformational change of fusion proteins. Peptides resembling these regionshave been shown to have specific antiviral activity, presumably because theyinterfere with the corresponding domains within the viruses. Overall, thesestudies shed light into the molecular mechanism of membrane fusion induced byenvelope glycoproteins and suggest that fusion proteins from different viralfamilies share common structural and functional motifs.
Perceptions of Parenting: Individual Differences and the Effect of Community
Authors: Caughy Margaret O'Brien , Brodsky Anne E. , O'Campo Patricia J. , Aronson Robert
Published: December 2002

Neighborhood norms are an important determinant of beliefs and attitudes about parenting, and measuring changes in community norms is an important component of evaluating community‐based programs for improving child outcomes. The purpose of this study was to determine whether or not a survey of community residents' perceptions of parenting could be used to measure community parenting norms and whether these perceptions differed by individual or community characteristics. Two community surveys with 870 and 914 respondents, respectively, were conducted in 3 low‐income neighborhoods. Results indicated that perceptions of parenting could be measured reliably at the community level although it is important to consider the presence of multiple norms when using such measures. Furthermore, differences in perceptions of parenting associated with individual characteristics were markedly decreased when neighborhood characteristics were considered, suggesting that the association of individual characteristics with perceptions of parenting is confounded by neighborhood characteristics.
Virus Membrane Fusion Proteins: Biological Machines that Undergo a Metamorphosis
Authors: Ellis Dutch Rebecca , Jardetzky Theodore S. , Lamb Robert A.
Published: December 2002

Fusion proteins from a group of widely disparate viruses, including the paramyxovirus F protein, the HIV and SIV gp160 proteins, the retroviral Env protein, the Ebola virus Gp, and the influenza virus haemagglutinin, share a number of common features. All contain multiple glycosylation sites, and must be trimeric and undergo proteolytic cleavage to be fusogenically active. Subsequent to proteolytic cleavage, the subunit containing the transmembrane domain in each case has an extremely hydrophobic region, termed the fusion peptide, or at near its newly generated N-terminus. In addition, all of these viral fusion proteins have 4–3 heptad repeat sequences near both the fusion peptide and the transmembrane domain. These regions have been demonstrated from a tight complex, in which the N-terminal heptad repeat forms a trimeric-coiled coil, with the C-terminal heptad repeat forming helical regions that buttress the coiled-coil in an anti-parallel manner. The significance of each of these structuralelements in the processing and function of these viral fusion proteins is discussed.
Oxidation of galactose by galactose‐1‐phosphate uridyltransferase‐deficient lymphoblasts
Authors: Yager C. , Gibson J. , States B. , Elsas L. J. , Segal S.
Published: December 2002

The ability of EB virus‐transformed lymphoblasts with undetectable galactose‐1‐phosphate uridyltransferase (GALT) from 15 galactosaemic patients to oxidize [1‐14C]galactose to 14CO2 was compared to that of cells from 7 normal subjects. The oxidation of galactose but not of glucose was markedly diminished by cells from Q188R homozygous galactosaemic patients but was not absent. After 2.5 h these cells liberated 14CO2 at nearly 3% and at 5 h up to 9% of normal. Cells from patients homozygous for the S135L mutation produced much larger amounts of 14CO2 (15–17% of normal) and were distinguishable from the Q188R homozygous cells. A cell line with a homozygous deletion of the GALT gene oxidized galactose at 7% of the normal rate, suggesting that pathways(s) other than GALT exist in these cells as well as Q188R homozygous cells for oxidation of galactose to CO2. Concentration dependence studies are consistent with the presence of a pathway that is unsaturable or has a very high Km. The ability of 107 lymphoblasts with the S135L genotype to oxidize more than 7% of the sugar to 14CO2 in 5 h suggests the presence of residual GALT despite the inability to detect the activity by enzymatic analysis.
A splice mutation in the GTP cyclohydrolase I gene causes dopa‐responsive dystonia by exon skipping
Authors: Skrygan M. , Bartholomé B. , Bonafé L. , Blau N. , Bartholomé K.
Published: December 2002

Four different mutations in the GTP cyclohydrolase I gene were found (P199L, M211V, IVS5+1G>A, G203R) in 6 out of 33 families with dopa‐responsive dystonia. A splice mutation (IVS5+1G>A) located at the border of exon 5 to intron 5 was found in one of these families. Three members of the family carry the IVS5+1G>A mutation on one allele, inherited from the father to the daughter and son. Examination of the mRNA showed an exon 5 skipping that results in a reduction of enzyme activity in cultured fibroblasts to 4–17% compared to controls. The father and daughter never had clinical symptoms of dopa‐responsive dystonia. The son was symptomatic at the age of 3 years and was treated successfully with L‐dopa/carbidopa. After 20 years this therapy was terminated and for the next 6 years he was free of symptoms. With increased motoric activity, symptoms reappeared and the therapy was reintroduced.
Congenital disorders of glycosylation type Ia and IIa are associated with different primary haemostatic complications
Authors: Van Geet C. , Jaeken J. , Freson K. , Lenaerts T. , Arnout J. , Vermylen J. , Hoylaerts M. F.
Published: December 2002

Congenital disorders of glycosylation (CDG) type I are mostly due to a deficient phosphomannomutase activity, called CDG Ia. CDG IIa (mutations in the MGAT2 gene) results from a deficient activity of the Golgi enzyme N‐acetylglucosaminyltransferase II. CDG Ia patients predominantly have a thrombotic tendency, whereas our CDG IIa patient has an increased bleeding tendency, despite similar coagulation factor abnormalities in both types. We have investigated whether abnormally glycosylated platelet membrane glycoproteins are involved in the haemostatic complications of both CDG groups. In flow cytometry, the binding of Ricinus communis lectin (reactive with β‐galactose primarily) to control platelets increased after neuraminidase treatment: this increase was smaller (p < 0.01) in CDG Ia patients (3.1 ± 0.08 times) than in control platelets (8.5 ± 1.8 times) and did not occur in the CDG IIa patient. Platelet‐rich plasma from CDG Ia patients, but not a CDG IIa patient, aggregated spontaneously and gel‐filtered platelets from CDG Ia patients agglutinated at very low concentrations of ristocetin, independently of von Willebrand factor (vWF). Accordingly, in stirred whole blood, the rate of single platelet disappearance of CDG Ia patients was twice that of control platelets. In contrast, perfusion of whole anticoagulated blood of the CDG IIa patient over collagen yielded markedly decreased platelet adherence to collagen at shear rates involving glycoprotein (GP) Ib–vWF interactions. Thus, abnormal glycosylation of platelet glycoproteins in CDG Ia enhances nonspecific platelet interactions, in agreement with a thrombotic tendency. The reduced GP Ib‐mediated platelet reactivity with vessel wall components in the CDG IIa patient under flow conditions provides a basis for his bleeding tendency.
The effect of relocation after a natural disaster
Authors: Najarian Louis M. , Goenjian Armen K. , Pelcovitz David , Mandel Francine , Najarian Berj
Published: December 2002

Twenty‐five women remaining in a city devastated by an earthquake were compared with 24 relocated survivors and 25 comparison women. The women were administered a structured PTSD interview, the Hamilton Depression Scale, and SCL‐90‐R. The women in both exposed groups showed significantly more symptoms of avoidance, arousal, and total PTSD than the comparison group. The women in the relocated city had significantly higher depression scores than the women in the earthquake city. On the SCL‐90‐R, relocated women were most symptomatic and comparison group women were least symptomatic. Relocation after a disaster appears to be associated more with risk for depression than with PTSD in situations where recovery is delayed following the trauma.
Open trial of nefazodone for combat veterans with posttraumatic stress disorder
Authors: Garfield David A. S. , Fichtner Christopher G. , Leveroni Catherine , Mahableshwarkar Atul
Published: December 2002

Fourteen combat veterans completed a 9‐week open trial of nefazodone for treatment of posttraumatic stress disorder (PTSD). Overall PTSD symptoms as measured by the Clinician‐Administered PTSD Scale (CAPS) showed a modest but statistically significant decrease with nefazodone treatment. Decreases in CAPS reexperiencing and avoidance, but not hyperarousal symptoms, approached statistical significance. Anxiety decreased significantly, and there were trends toward decreased depression and anger on structured assessments. This study adds to the clinical evidence that nefazodone may be helpful for the management of PTSD symptoms.
On Classification of Quantum Channels
Authors: Iriyama Satoshi , Watanabe Noboru
Published: December 2002

Quantum mutual entropy and quantum capacity are rigorously defined by Ohya, and they are quite useful in the study of quantum communication processes [4, 7, 8, 9,10]. Mathematical models of optical communication processes are described by a quantum channel and optical states, and quantum capacity is one of the most important criteria to measure the efficiency of information transmission [4,7,8]. In actual optical communication, a laser beam is used for a signal, and it is denoted mathematically by a coherent state. Further, optical communication using a squeezed state, which is expected to be more efficient than that using a coherent state is proposed. In this paper, we define several quantum channels, that is, a squeezed channel and a coherent channel and so on. We compare them by calculating quantum capacity.
Swedish Disability Policy: From Universal Welfare to Civil Rights?
Authors: Lindqvist Rafael
Published: December 2002

During the 1990s, important shifts took place in Swedish welfare policies. Universal benefits and services still constitute basic form of social protection, but significant retrenchments have occurred in the universal part of the Swedish system. Compensation levels in social security benefits have been lowered and entitlement criteria have been tightened. Such developments have been paralleled by an emphasis on activation measures in social policies. In this respect, Swedish disability policies reflect a shift towards a stronger ‘deservingness ethic’. Another tendency has been the introduction of more selective social and civil rights, especially in disability policies. Relevant examples are the introduction of the Disability Reform in 1994 which was aimed at people with large and persistent difficulties in managing their daily lives, the Disability Ombudsman, and anti-discrimination legislation which aimed to protect disabled job-seekers and employees. The major changes in social security, social assistance and health services in the 1990s, as well as developments in disability services, are described in historical perspective. Statutory services which target those among the disabled who are most ‘deserving’ have enhanced the substantive rights of this group. However, changes in the universal welfare system towards greater selectivism indicate that new barriers have been raised for disabled people.
The Battle against Numbers: Disability Policies in the Netherlands
Authors: van Oorschot Wim , Boos Kees
Published: December 2002

Over the last twenty years, there has been a vigorous and ongoing disability debate in Dutch social policy over ways of controlling and reducing the number of people claiming disability insurance benefits. Many measures have been taken in this time. A first strategy was to reduce the inflow of claimants, but when this proved unsuccessful, a second strategy to promote outflow by promoting activation of claimants was emphasised. This article presents a review of the measures taken and critically discusses their effects. In addition, it briefly summarises developments in the provision of services, the promotion of equal treatment, and the relationship between national and EU level disability policies. Many new proposals for reducing the number of disability claimants have recently been put forward, but most of these can be described as ‘more of the same’, and their effectiveness is doubtful.
The Changing Face of Disability Legislation, Policy and Practice in Ireland
Authors: Lundström Francesca , McAnaney Donal , Webster Beverley
Published: December 2002

In the early 1990s, disability legislation, policy and provision in Ireland experienced seismic changes. These were brought about by international influences and by a concerted effort on the part of the centre-left government in office at that time. A ‘bottom-up’ approach was applied in order to uncover the experiences and identify the needs of people with disabilities throughout the country. Emanating from this, a Report published by the Commission on the Status of People with Disabilities in 1995 made 402 recommendations in 22 target areas based on the UN Standard Rules. An evaluation of the impact of this report in 1999 revealed that almost 75 per cent of the recommendations have been or are in the process of being implemented.

However, these changes have as yet all taken place at the macro level, and their impact at the micro level – on the lives of people with disabilities – particularly relative to employment has so far been negligible. It may be that the changes made at the macro level are only aspirational, and that more intervention is required to make a difference at the micro level. Alternatively, it may simply be that more time is needed for the changes to filter down to the micro level. Only time will tell.
Survivors' Pension Rights in Occupational and Social Insurance: The Swedish Experience
Authors: Selén Jan , Ståhlberg Ann-Charlotte
Published: December 2002

Since the early 1990s, there has been no widow's pension in Swedish social insurance. This is consistent with the aim of implementing an individual model, in pursuit of the goal of economic independence for all adults. However, both a widow's and a widower's pension are included in occupational insurance schemes. In Sweden, these are based on collective labour market agreements and cover almost all employees. The survivors' pension can be seen as an annual non-wage benefit. As such, it should be taken into account when remuneration from work between different socio-economic groups is compared. However, we cannot directly observe the individual value of mandatory collective insurance. This article is an original attempt to determine the individual value of certain occupational and social insurance rights. A money value for earnings-related survivors' pension rights is estimated and added to the money wage to create an extended wage measure. We use Swedish microdata to analyze what the inclusion of different insurance rights might mean for wage differentials and wage dispersion. The study indicates that wage inequality is understated when non-wage benefits in the form of survivors' pension rights are excluded from the compensation measure and that a more complete picture of wage differentials is obtained when these rights are accounted for. If we were able to consider differences in survivors' pension rights between countries, this would be a step towards more complete wage comparisons between the different EU-countries.
Examination of predictors of severe violence in combat‐exposed Vietnam veterans
Authors: Nock Matthew K. , Kaufman Joan , Rosenheck Robert A.
Published: December 2002

This study examined several proposed predictors of severe wartime violence in a randomly selected, nationally representative sample of 1,125 Vietnam veterans. Participation in severe acts of violence during wartime was reported by 7.6% of the sample. Disruptive behavior before the age of 15 and increased combat exposure were both significant predictors of severe wartime violence. Childhood contextual factors were indirectly related to severe wartime violence via prewar disruptive behavior. The classification rate of perpetrators of severe violence was comparable to rates from studies of less severe forms of violence. The implications of these results and suggestions for future research in this area are discussed.
Ionic Charge, Hydrophobicity and Tryptophan Fluorescence of the Folate Binding Protein Isolated from Cow's Milk
Authors: Holm Jan , Hansen Steen Ingemann , Høier-Madsen Mimi
Published: December 2002

A high-affinity folate binding protein was isolated and purified from cow's milk by a combination of cation exchange chromatography and methotrexate affinity chromatography. Chromatofocusing studies revealed that the protein possessed isoelectric points in the pH-interval 8–7. Polymers of the protein prevailing at pH values close to the isoelectric points seemed to be more hydrophobic than monomers present at pH 5.0 as evidenced by hydrophobic interaction chromatography and turbidity (absorbance at 340 nm) in aqueous buffer solutions (pH 5–8). Ligand binding seemed to induce a conformation change that decreased the hydrophobicity of the protein. In addition, Ligand binding quenched the tryptophan fluorescence of folate binding protein suggesting that tryptophan is present at the binding site and/or ligand binding induces a conformation change that affects tryptophan environment in the protein. There was a noticeable discordance between the ability of individual folate analogues to compete with folate for binding and the quenching effect.
Antimalarial Drugs Exacerbate Rat Liver Microsomal Lipid Peroxidation in the Presence of Oxidants
Authors: Farombi E. Olatunde , Adoro Stanley , Uhunmwangho Samuel
Published: December 2002

The study was undertaken to evaluate the effect of prior treatment of rats with the antimalarial drugs amodiaquine (AQ) mefloquine (MQ) and halofantrine (HF) on rat liver microsomal lipid peroxidation in the presence of 1 mM FeSO4, 1 mM ascorbate and 0.2 mM H2O2 (oxidants). Ingestion of α-tocopheral, a radical chain-breaking antioxidant was also included to assess the role of antioxidants in the drug treatment. In the presence of oxidants AQ, MQ and HF elicited 288%, 175% and 225% increases in malondialdehyde (MDA) formation while the drugs induced 125%, 63% and 31% increases in the absence of oxidants respectively. Similarly, AQ, MQ and HF induced lipid hydroperoxide formation by 380%, 256%, 360% respectively in the presence of oxidants and 172%, 136% and 92% in the absence of exogenously added oxidants respectively. α-tocopherol reduced AQ, MQ and HF-induced MDA formation by 40%, 55% and 52% respectively and lipid hydroperoxide formation by 53%, 59% and 54% respectively. Similarly, α-tocopherol attenuated the AQ, MQ and HF-induced MDA formation by 49%, 51% and 51% in the presence of oxidants and lipid hydroperoxide formation by 61%, 62% and 47% respectively. The results indicate that rat liver microsomal lipid peroxidation could be enhanced by antimalarial drugs in the presence of reactive oxygen species and this effect could be ameliorated by treatment with antioxidants.
Phosphodiesterase expression targeted to gonadotropin-releasing hormone neurons inhibits luteinizing hormone pulses in transgenic rats
Authors: Paruthiyil Sreenivasan , Majdoubi Mohammed El , Conti Marco , Weiner Richard I.
Published: December 2002

Experiments in the GT1 gonadotropin-releasing hormone (GnRH) cell line have shown that the cAMP signaling pathway plays a central role in regulating the excitability of the cells. Lowering cAMP levels by expressing the constitutively active cAMP-specific phosphodiesterase PDE4D1 in GT1 cells inhibited spontaneous Ca
2+
oscillations and intrinsic pulsatile GnRH secretion. To address the role of cAMP levels in endogenous GnRH neurons, we genetically targeted expression of PDE4D1 (P) to GnRH neurons in transgenic rats (R) by using the GnRH gene promoter/enhancer regions (G). Three lines of transgenic rats, GPR-2, -4, and -5, were established.
In situ
hybridization and RT-PCR studies demonstrated that transgene expression was specifically targeted to GnRH neurons. Decreased fertility was observed in female but not in male rats from all three lines. The mean luteinizing hormone (LH) levels in ovariectomized rats were significantly reduced in the GPR-4 and -5 lines but not in the GPR-2 line. In castrated male and female GPR-4 rats, the LH pulse frequency was dramatically reduced. Six of twelve GPR-4 females studied did not ovulate and had polycystic ovaries. The remaining six females ovulated, but the magnitude of the preovulatory LH surge was inhibited by 63%. These findings support the hypothesis that cAMP signaling may play a central role in regulating excitability of GnRH neurons
in vivo
. The GPR-4 line of transgenic rats provides a genetic model for the understanding of the role of pulsatile gonadotropin release in follicular development.
cAMP-independent role of PKA in tonicity-induced transactivation of tonicity-responsive enhancer/ osmotic response element-binding protein
Authors: Ferraris Joan D. , Persaud Prita , Williams Chester K. , Chen Ye , Burg Maurice B.
Published: December 2002

Hypertonicity-induced increase in activity of the transcription factor tonicity-responsive enhancer/osmotic response element-binding protein (TonEBP/OREBP) protects renal cells by increasing transcription of genes, including those involved in increased accumulation of organic osmolytes. We previously showed that hypertonicity increases transactivating activity of TonEBP/OREBP. Assay with a binary GAL4 transactivation system showed that the 984 C-terminal amino acids of TonEBP/OREBP (amino acids 548–1531) contain a tonicity-dependent transactivation domain (TAD). Also, amino acids 548–1531 undergo tonicity-dependent phosphorylation, and some inhibitors of protein kinases reduce the tonicity-dependent transactivation. In the present studies we examined the role of protein kinase A (PKA). Results: (
i
) An inhibitor of PKA (H89) reduces tonicity-dependent increases in transactivation, ORE/TonE reporter activity, and induction of aldose reductase and betaine transporter mRNAs. (
ii
) Overexpression of the catalytic subunit of PKA (PKAc) increases transactivation activity of amino acids 548–1531 and activity of an ORE/TonE reporter. The increases are much greater under isotonic than under hypertonic conditions. (
iii
) A dominant-negative PKAc reduces activity of an ORE/TonE reporter. (
iv
) PKAc activity increases with tonicity but cAMP does not. (
v
) TonEBP/OREBP and PKAc coimmunoprecipitate. (
vi
) amino acids 872–1271, including N– and C-terminal polyglutamine stretches, demonstrate tonicity-dependent transactivation, albeit less than amino acids 548–1531, and a similar role for PKA. Conclusions: (
i
) PKA plays an important role in TonEBP/OREBP activation of tonicity-dependent gene expression; (
ii
) PKA activation of TonEBP/OREBP appears to be cAMP-independent; and (
iii
) amino acids 872–1271 are sufficient for tonicity-dependent transactivation of TonEBP/OREBP.
Lévy processes in free probability
Authors: Barndorff-Nielsen Ole E. , Thorbjørnsen Steen
Published: December 2002

This is the continuation of a previous article that studied the relationship between the classes of infinitely divisible probability measures in classical and free probability, respectively, via the Bercovici–Pata bijection. Drawing on the results of the preceding article, the present paper outlines recent developments in the theory of Lévy processes in free probability.
The Forkhead Box m1b transcription factor is essential for hepatocyte DNA replication and mitosis during mouse liver regeneration
Authors: Wang Xinhe , Kiyokawa Hiroaki , Dennewitz Margaret B. , Costa Robert H.
Published: December 2002

The Forkhead Box (Fox) proteins are an extensive family of transcription factors that shares homology in the winged helix DNA-binding domain and whose members play essential roles in cellular proliferation, differentiation, transformation, longevity, and metabolic homeostasis. Liver regeneration studies with transgenic mice demonstrated that FoxM1B regulates the onset of hepatocyte DNA replication and mitosis by stimulating expression of cell cycle genes. Here, we demonstrate that albumin-promoter-driven Cre recombinase-mediated hepatocyte-specific deletion of the
Foxm1b
Floxed (fl) targeted allele resulted in significant reduction in hepatocyte DNA replication and inhibition of mitosis after partial hepatectomy. Reduced DNA replication in regenerating
Foxm1b
−/−
hepatocytes was associated with sustained increase in nuclear staining of the cyclin-dependent kinase (Cdk) inhibitor p21
Cip1
(p21) protein between 24 and 40 h after partial hepatectomy. Furthermore, increased nuclear p21 levels and reduced expression of Cdc25A phosphatase coincided with decreases in Cdk2 activation and hepatocyte progression into S-phase. Moreover, the significant reduction in hepatocyte mitosis was associated with diminished mRNA levels and nuclear expression of Cdc25B phosphatase and delayed accumulation of cyclin B1 protein, which is required for Cdk1 activation and entry into mitosis. Cotransfection studies demonstrate that FoxM1B protein directly activated transcription of the Cdc25B promoter region. Our present study shows that the mammalian Foxm1b transcription factor regulates expression of cell cycle proteins essential for hepatocyte entry into DNA replication and mitosis.
A robust and scalable microfluidic metering method that allows protein crystal growth by free interface diffusion
Authors: Hansen Carl L. , Skordalakes Emmanuel , Berger James M. , Quake Stephen R.
Published: December 2002

Producing robust and scalable fluid metering in a microfluidic device is a challenging problem. We developed a scheme for metering fluids on the picoliter scale that is scalable to highly integrated parallel architectures and is independent of the properties of the working fluid. We demonstrated the power of this method by fabricating and testing a microfluidic chip for rapid screening of protein crystallization conditions, a major hurdle in structural biology efforts. The chip has 480 active valves and performs 144 parallel reactions, each of which uses only 10 nl of protein sample. The properties of microfluidic mixing allow an efficient kinetic trajectory for crystallization, and the microfluidic device outperforms conventional techniques by detecting more crystallization conditions while using 2 orders of magnitude less protein sample. We demonstrate that diffraction-quality crystals may be grown and harvested from such nanoliter-volume reactions.
POTE
, a highly homologous gene family located on numerous chromosomes and expressed in prostate, ovary, testis, placenta, and prostate cancer
Authors: Bera Tapan K. , Zimonjic Drazen B. , Popescu Nicholas C. , Sathyanarayana Bangalore K. , Kumar Vasantha , Lee Byungkook , Pastan Ira
Published: December 2002

We have identified a gene located on chromosomes 21 that is expressed in normal and neoplastic prostate, and in normal testis, ovary, and placenta. We name this gene
POTE
(expressed in prostate, ovary, testis, and placenta). The
POTE
gene has 11 exons and 10 introns and spans ≈32 kb of chromosome 21q11.2 region. The 1.83-kb mRNA of
POTE
encodes a protein of 66 kDa. Ten paralogs of the gene have been found dispersed among eight different chromosomes (2, 8, 13, 14, 15, 18, 21, and 22) with preservation of ORFs and splice junctions. The synonymous:nonsynonymous ratio indicates that the genes were duplicated rather recently but are diverging at a rate faster than the average for other paralogous genes. In prostate and in testis, at least five different paralogs are expressed.
In situ
hybridization shows that
POTE
is expressed in basal and terminal cells of normal prostate epithelium. It is also expressed in some prostate cancers and in the LnCAP prostate cancer cell line. The POTE protein contains seven ankyrin repeats between amino acids 140 and 380. Expression of POTE in prostate cancer and its undetectable expression in normal essential tissues make POTE a candidate for the immunotherapy of prostate cancer. The existence of a large number of closely related but rapidly diverging members, their location on multiple chromosomes and their limited expression pattern suggest an important role for the
POTE
gene family in reproductive processes.
Direct regulation of Arp2/3 complex activity and function by the actin binding protein coronin
Authors: Humphries Christine L. , Balcer Heath I. , D'Agostino Jessica L. , Winsor Barbara , Drubin David G. , Barnes Georjana , Andrews Brenda J. , Goode Bruce L.
Published: December 2002

Mechanisms for activating the actin-related protein 2/3 (Arp2/3) complex have been the focus of many recent studies. Here, we identify a novel mode of Arp2/3 complex regulation mediated by the highly conserved actin binding protein coronin. Yeast coronin (Crn1) physically associates with the Arp2/3 complex and inhibits WA- and Abp1-activated actin nucleation in vitro. The inhibition occurs specifically in the absence of preformed actin filaments, suggesting that Crn1 may restrict Arp2/3 complex activity to the sides of filaments. The inhibitory activity of Crn1 resides in its coiled coil domain. Localization of Crn1 to actin patches in vivo and association of Crn1 with the Arp2/3 complex also require its coiled coil domain. Genetic studies provide in vivo evidence for these interactions and activities. Overexpression of CRN1 causes growth arrest and redistribution of Arp2 and Crn1p into aberrant actin loops. These defects are suppressed by deletion of the Crn1 coiled coil domain and by arc35-26, an allele of the p35 subunit of the Arp2/3 complex. Further in vivo evidence that coronin regulates the Arp2/3 complex comes from the observation that crn1 and arp2 mutants display an allele-specific synthetic interaction. This work identifies a new form of regulation of the Arp2/3 complex and an important cellular function for coronin.
XdomView: protein domain and exon position visualization
Authors: Vivek Gopalan , Tan Tin Wee , Ranganathan Shoba
Published: December 2002

Summary: The relationship between intron distribution in the eukaryotic gene and protein structural elements is essential for understanding the origin and evolution of genes. XdomView is a web-based viewer mapping protein structural domains and intron positions in eukaryotic homologues to its tertiary structure. The association of sequence signals to 3D structure in XdomView provides a valuable visualization environment for eukaryotic gene organization, gene evolution, protein folding and protein structure classification.

Availability: Freely available from http://surya.bic.nus.edu.sg/xdom

Contact: shoba@bic.nus.edu.sg

* To whom correspondence should be addressed.
Facial and Vocal Expressions of Emotion
Authors: Russell James A. , Bachorowski Jo-Anne , Fernández-Dols José-Miguel
Published: December 2002

A flurry of theoretical and empirical work concerning the production of and response to facial and vocal expressions has occurred in the past decade. That emotional expressions express emotions is a tautology but may not be a fact. Debates have centered on universality, the nature of emotion, and the link between emotions and expressions. Modern evolutionary theory is informing more models, emphasizing that expressions are directed at a receiver, that the interests of sender and receiver can conflict, that there are many determinants of sending an expression in addition to emotion, that expressions influence the receiver in a variety of ways, and that the receiver's response is more than simply decoding a message.
Signalers and Receivers in Animal Communication
Authors: Seyfarth Robert M. , Cheney Dorothy L.
Published: December 2002

In animal communication natural selection favors callers who vocalize to affect the behavior of listeners and listeners who acquire information from vocalizations, using this information to represent their environment. The acquisition of information in the wild is similar to the learning that occurs in laboratory conditioning experiments. It also has some parallels with language. The dichotomous view that animal signals must be either referential or emotional is false, because they can easily be both: The mechanisms that cause a signaler to vocalize do not limit a listener's ability to extract information from the call. The inability of most animals to recognize the mental states of others distinguishes animal communication most clearly from human language. Whereas signalers may vocalize to change a listener's behavior, they do not call to inform others. Listeners acquire information from signalers who do not, in the human sense, intend to provide it.
The role of depressive symptoms in recovery from injuries to the extremities in older persons. A prospective study
Authors: Kempen Gertrudis I. J. M. , Sanderman Robbert , Scaf‐Klomp Winnie , Ormel Johan
Published: December 2002

Background

Previous research suggested that depressive symptoms play a role in recovery after hip fracture. However none of these studies were prospective and included only patients with hip fractures.

Objective

To examine the effect of depressive symptoms on the recovery of (instrumental) activities of daily living after fall‐related injuries to the extremities in older persons.

Design

Prospective cohort study.

Methods

Data were collected from 168 older persons at baseline, prior to their injuries (hip fractures, other fractures or contortions and dislocations), and 8 weeks, 5 months and 12 months after their accident. Hierarchical multiple regression analysis was used to study the impact of depressive symptoms (as assessed with the Hospital Anxiety and Depression Scale; HADS) on disability (as assessed with the Groningen Activity Restriction Scale; GARS) after the injury while adjusting for several covariates.

Results

Depressive symptoms at baseline were not predictive for disability after the injury when covariates were taken into account. However, depressive symptoms 8 weeks after the fall were significantly related to disability at 8 weeks, 5 months and even 12 months after the injury. In addition, disability levels before the injury were highly predictive for recovery later on. Severity of injury was particularly predictive for disability at 8 weeks while age (which may generally represent the amount of physiological reserve) predicted disability at 5 and 12 months after the injury. Cognitive functioning 8 weeks post‐injury was, in contrast to previous research, not predictive for recovery when covariates were taken into account.

Conclusions

Pre‐injury levels of disability and post‐injury depressive symptoms are associated with recovery and may warrant concern and special attention in clinical practice. Copyright © 2002 John Wiley & Sons, Ltd.
Ethics and dementia: mapping the literature by bibliometric analysis
Authors: Baldwin Clive , Hughes Julian , Hope Tony , Jacoby Robin , Ziebland Sue
Published: December 2002

Objectives

This paper reports on a bibliometric analysis of keywords in the literature on ethics and dementia during the period 1980–2000.

Methods

Keywords were drawn from titles, abstracts and keyword fields of 14 bibliographic databases and clustered in to 19 categories. These categories were then examined for their frequency and co‐occurrences. The strength of relationships between these categories is mapped using the metaphor of the ‘night sky’ showing constellations of issues and changes over time.

Results

Four categories appear consistently and frequently in the literature: professional care, end‐of‐life issues, decision‐making and treatment. Other issues come and go (such as quality‐of‐life issues) while others appear to respond to outside events (e.g. feeding issues). The research literature is based predominantly on surveys or studies soliciting responses to predefined issues. Little research has been undertaken to establish the range of ethical issues for either family members or professionals.

Discussion

We discuss the domination of the literature by four categories of ethical issues, the new and emerging areas of ethical interest and those areas that are triggered by external events such as legal cases. We also discuss some of the limitations of the study and note some omissions in the literature.

Conclusion

During the period 1980–2000 the research literature has been dominated by surveys and studies soliciting views on predefined issues with relatively few in‐depth, open‐ended qualitative studies. Copyright © 2002 John Wiley & Sons, Ltd.