bluuebunny/crossref_metadata_2025 huggingface dataset:
PerlPrimer: cross-platform, graphical primer design for standard, bisulphite and real-time PCR
Authors: Marshall Owen J.
Published: April 2004

Summary: PerlPrimer is a cross-platform graphical user interface application for the design of primers for standard, bisulphite and real-time PCR, and sequencing. The program incorporates highly accurate melting-temperature and primer–dimer prediction algorithms with powerful tools such as sequence retrieval from Ensembl and the ability to BLAST search primer pairs. It aims to automate and simplify the process of primer design.

Availability: Open-source and freely available from http://perlprimer.sourceforge.net
PUNS: transcriptomic- and genomic-in silico PCR for enhanced primer design
Authors: Boutros Paul C. , Okey Allan B.
Published: April 2004

Summary: We developed a CGI/Perl-based web server to perform in silico polymerase chain reaction (PCR) on PCR primer sequences. The PUNS (Primer-UniGene Selectivity) server simulates PCR reactions by running BLASTN analysis on user-entered primer pairs against both the transcriptome and the genome to assess primer specificity. PUNS is particularly suited for the identification of highly selective primers for quantitative microarray validation.

Availability: Both system access and source-code are freely available at http://okeylabimac.med.utoronto.ca/PUNS
G-PRIMER: greedy algorithm for selecting minimal primer set
Authors: Wang Jiren , Li Kuo-Bin , Sung Wing-Kin
Published: April 2004

Summary: G-PRIMER, a web-based primer design program, has been developed to compute a minimal primer set specifically annealed to all the open reading frames in a given microbial genome. This program has been successfully used in the microarray experiment for analyzing the expression of genes in the Xanthomonas campestris genome.

Availability: It is available at http://mammoth.bii.a-star.edu.sg/gprimer/. Its source code is available upon request.
A novel role for shuttling SR proteins in mRNA translation
Authors: Sanford Jeremy R. , Gray Nicola K. , Beckmann Karsten , Cáceres Javier F.
Published: April 2004

The Ser-Arg-rich (SR) proteins comprise a large family of nuclear phosphoproteins that are required for constitutive and alternative splicing. A subset of SR proteins shuttles continuously between the nucleus and the cytoplasm, suggesting that the role of shuttling SR proteins in gene expression may not be limited to nuclear pre-mRNA splicing, but may also include unknown cytoplasmic functions. Here, we show that shuttling SR proteins, in particular SF2/ASF, associate with translating ribosomes and stimulate translation when tethered to a reporter mRNA in Xenopus oocytes. Moreover, SF2/ASF enhances translation of reporter mRNAs in HeLa cells, and this activity is dependent on its ability to shuttle from the nucleus to the cytoplasm and is increased by the presence of an exonic-splicing enhancer. Furthermore, SF2/ASF can stimulate translation in vitro using a HeLa cell-free translation system. Thus, the association of SR proteins with translating ribosomes, as well as the stimulation of translation both in vivo and in vitro, strongly suggest a role for shuttling SR proteins in translation. We propose that shuttling SR proteins play multiple roles in the posttranscriptional expression of eukaryotic genes and illustrate how they may couple splicing and translation.
A Medaka Gene Map: The Trace of Ancestral Vertebrate Proto-Chromosomes Revealed by Comparative Gene Mapping
Authors: Naruse Kiyoshi , Tanaka Minoru , Mita Kazuei , Shima Akihiro , Postlethwait John , Mitani Hiroshi
Published: April 2004

The mapping of Hox clusters and many duplicated genes in zebrafish indicated an extra whole-genome duplication in ray-fined fish. However, to reconstruct the preduplication chromosomes (proto-chromosomes), the comparative genomic studies of more distantly related teleosts are essential. Medaka and zebrafish are ideal for this purpose, because their lineages separated from their last common ancestor ∼140 million years ago. To reconstruct ancient vertebrate chromosomes, including the chromosomes of the vertebrate ancestor of humans from 450 million years ago, we mapped 818 genes and expressed sequence tags (ESTs) on a single meiotic backcross panel obtained from inbred strains of the medaka, Oryzias latipes. Comparisons of linkage relationships of orthologous genes among three species of vertebrates (medaka, zebrafish, and human) indicate the number and content of the chromosomes of the last common ancestor of ray-fined fish and lobe-fined fish (including humans), and the extra whole genome duplication event in the ray-fin lineage occurred in the common ancestor of perhaps all teleosts.
Monomer topology defines folding speed of heptamer
Authors: Bascos Neil , Guidry Jesse , Wittung‐Stafshede Pernilla
Published: April 2004

Small monomeric proteins often fold in apparent two‐state processes with folding speeds dictated by their native‐state topology. Here we test, for the first time, the influence of monomer topology on the folding speed of an oligomeric protein: the heptameric cochaperonin protein 10 (cpn10), which in the native state has seven β‐barrel subunits noncovalently assembled through β‐strand pairing. Cpn10 is a particularly useful model because equilibrium‐unfolding experiments have revealed that the denatured state in urea is that of a nonnative heptamer. Surprisingly, refolding of the nonnative cpn10 heptamer is a simple two‐state kinetic process with a folding‐rate constant in water (2.1 sec−1; pH 7.0, 20°C) that is in excellent agreement with the prediction based on the native‐state topology of the cpn10 monomer. Thus, the monomers appear to fold as independent units, with a speed that correlates with topology, although the C and N termini are trapped in β‐strand pairing with neighboring subunits. In contrast, refolding of unfolded cpn10 monomers is dominated by a slow association step.
Deciphering the function of an ORF: Salmonella enterica DeoM protein is a new mutarotase specific for deoxyribose
Authors: Assairi Liliane , Bertrand Thomas , Ferdinand Joëlle , Slavova‐Azmanova Neli , Christensen Mette , Briozzo Pierre , Schaeffer Francis , Craescu Constantin T. , Neuhard Jan , Bârzu Octavian , Gilles Anne‐Marie
Published: April 2004

We identified in Salmonella enterica serovar Typhi a cluster of four genes encoding a deoxyribokinase (DeoK), a putative permease (DeoP), a repressor (DeoQ), and an open reading frame encoding a 337 amino acid residues protein of unknown function. We show that the latter protein, called DeoM, is a hexamer whose synthesis is increased by a factor over 5 after induction with deoxyribose. The CD spectrum of the purified recombinant protein indicated a dominant contribution of βtype secondary structure and a small content of α‐helix. Temperature and guanidinium hydrochloride induced denaturation of DeoM indicated that the hexamer dissociation and monomer unfolding are coupled processes. DeoM exhibits 12.5% and 15% sequence identity with galactose mutarotase from Lactococcus lactis and respectively Escherichia coli, which suggested that these three proteins share similar functions. Polarimetric experiments demonstrated that DeoM is a mutarotase with high specificity for deoxyribose. Site‐directed mutagenesis of His183 in DeoM, corresponding to a catalytically active residue in GalM, yielded an almost inactive deoxyribose mutarotase. DeoM was crystallized and diffraction data collected for two crystal systems, confirmed its hexameric state. The possible role of the protein and of the entire gene cluster is discussed in connection with the energy metabolism of S. enterica under particular growth conditions.
Critical nucleation size in the folding of small apparently two‐state proteins
Authors: Bai Yawen , Zhou Hongyi , Zhou Yaoqi
Published: April 2004

For apparently two‐state proteins, we found that the size (number of folded residues) of a transition state is mostly encoded by the topology, defined by total contact distance (TCD) of the native state, and correlates with its folding rate. This is demonstrated by using a simple procedure to reduce the native structures of the 41 two‐state proteins with native TCD as a constraint, and is further supported by analyzing the results of eight proteins from protein engineering studies. These results support the hypothesis that the major rate‐limiting process in the folding of small apparently two‐state proteins is the search for a critical number of residues with the topology close to that of the native state.
Expression of genes encoding the rice translation initiation factor, eIF5A, is involved in developmental and environmental responses
Authors: Chou Wan‐Chi , Huang Ya‐Wen , Tsay Wen‐Su , Chiang Tzen‐Yuh , Huang Dinq‐Ding , Huang Hao‐Jen
Published: April 2004

Eukaryotic translation initiation factor 5 A (eIF5A) is the only cellular protein known to contain the unusual amino acid hypusine. However, the precise cellular function of eIF5A is to date unknown. In the present study, we report on the characterization of two cDNA clones encoding eIF5A in rice (Oryza sativa). Sequence analysis revealed that the two cDNAs share 93% amino acid sequence identity. Phylogenetic analysis of the eIF5A genes revealed paraphyly of OseIF5A‐1 and OseIF5A‐2. Analysis at the mRNA level has shown that OseIF5A‐1 and OseIF5A‐2 are expressed in rice leaves and panicles and high relative amounts of both genes were detected in old leaves. In addition, both OseIF5A‐1 and OseIF5A‐2 were spatially regulated during rice leaf development. In suspension‐cultured cells, the transcripts of OseIF5A genes were strongly reduced after sugar starvation. Abiotic stresses, salt and heavy metal, induce the accumulation of OseIF5A‐1 and OseIF5A‐2 mRNAs in rice cells. These results suggested that both OseIF5A genes might be regulated by plant development and environmental stresses.
Phloem specific expression driven by wheat dwarf geminivirus V‐sense promoter in transgenic dicotyledonous species
Authors: Dinant Sylvie , Ripoll Christophe , Pieper Mark , David Chantal
Published: April 2004

Wheat dwarf geminivirus (WDV) is a single‐stranded DNA Mastrevirus. The large intergenic region (LIR) of WDV contains cis‐acting elements essential for the replication of the genome as well as for the bidirectional transcription of virus genes. The LIR was fused to the GUS (uidA) reporter gene and the WDV viral sense (V‐sense) promoter activity derived from the stable integration of that promoter was analysed in transgenic dicot plants. Various dicot species were tested, including Nicotiana tabacum, Nicotiana benthamiana, Arabidopsis thaliana and Cucumis melo. The GUS activity driven by the WDV promoter was also compared to that obtained in plants transformed with the GUS gene controlled by the CaMV 35S promoter as well as two phloem‐specific promoters derived from the Arabidopsis thaliana AtSUC2 and AtAHA3 genes. Histochemistry showed that the WDV V‐sense promoter consistently induced an expression pattern restricted to the vascular tissues, predominantly in the phloem of all organs. This promoter exhibited levels of GUS activity comparable to that driven by AtSUC2 and AtAHA3 promoters. A vascular expression pattern was observed in the four dicots tested. This was stable during plant development and was not altered following viral infection by an unrelated geminivirus. The uses of such a promoter are discussed regarding the targeting to the phloem of molecules active against vascular pests or pathogens.
Purification and properties of apoplastic amylase from oat (Avena sativa) seedlings
Authors: Uno‐Okamura Kuniko , Soga Kouichi , Wakabayashi Kazuyuki , Kamisaka Seiichiro , Hoson Takayuki
Published: April 2004

The protein fraction extracted with a high ionic strength buffer from the cell wall preparation of oat (Avena sativa L.) coleoptiles and first leaves contained starch‐degrading (amylase) activity. The activity of apoplastic amylase in the coleoptiles and first leaves continued to increase in parallel with organ growth. One of the apoplastic amylases recovered from shoot cell wall preparations was purified by sequential ion exchange and gel filtration chromatography, and the catalytic properties of the enzyme were analysed. The purified enzyme gave a single 25 kDa protein band on SDS‐PAGE. The enzyme exhibited maximum activity at pH 5.0 against maltooligosaccharides. The purified enzyme hydrolysed soluble starch and maltooligosaccharides larger than tetraose at maltose unit, but did not hydrolyse β‐limit dextrin or p‐nitrophenyl‐α‐d‐glucopyranoside. These results as well as the findings that the molecular size and the catalytic properties of the purified enzyme are different from those of known amylases obtained from Gramineae caryopses suggest that this enzyme is a novel type of β‐amylase present in cell walls of vigorously elongating Gramineae shoot organs.
Modulation by cytosolic components of proton pump activities in plasma membrane and tonoplast from Cucumis sativus roots during salt stress
Authors: Kłobus Grażyna , Janicka‐Russak Małgorzata
Published: April 2004

The effect of NaCl on the plasma membrane and tonoplast ATPases measured as the hydrolytic and H+‐pumping activity was studied. Treatment of cucumber seedlings with salt increased the membrane‐bound ATPases of the plasma membrane as well as the tonoplast. In both types of membranes the stimulation of ATP‐hydrolysis was much higher than the stimulation of H+‐transport suggesting that the salt‐ treatment of plants partially uncoupled the membrane proton pumps. It was shown that the soluble fraction obtained from the unstressed or NaCl‐stressed roots stimulated the ATPase activities in both membranes isolated from unstressed plants. A stimulatory effect of the soluble fraction on the proton pump activities was considerably enhanced in the salt conditions indicating the presence of a salt‐inducible factor (s) in the soluble fraction, which could rapidly modulate the membrane‐bound ATPases. Staurosporine, a specific protein kinase inhibitor, totally abolished the stimulatory action of the soluble fractions on the membrane proton pumps, whereas okadaic acid, a phosphatase inhibitor, had no effect. Inclusion of calcium in the mixture of membranes and the soluble fraction from unstressed roots elevated the ATPase activities to the levels determined with the soluble fraction isolated from NaCl‐stressed roots. Cation chelators (EGTA), as well as calmodulin antagonist (W7) cancelled the stimulatory effect of calcium ions. The above results strongly suggest the involvement of specific calcium–calmodulin‐dependent protein kinases in the activation of the membrane ATPases under salt‐stress conditions.
Prevalence of dens invaginatus in Jordanian adults
Authors: Hamasha A. A. , Alomari Q. D.
Published: April 2004

Aim  To assess the prevalence of dens invaginatus in a sample of Jordanian dental patients.

Methodology  The data were collected from examination of 3024 radiographs from a random sample of 1660 patients showing 9377 teeth. A tooth was considered having dens invaginatus if an infolding of a radiopaque ribbon‐like structure equal in density to enamel was seen extending from the cingulum into the root canal.

Results  Teeth with dens invaginatus were found in 49 subjects out of 1660 subjects examined; thus, the person prevalence was 2.95%. Bilateral dens invaginatus was seen in 12 patients, whereas unilateral dens invaginatus was demonstrated in 37 patients. Dens invaginatus was detected in 61 teeth out of a total of 9377 for a tooth prevalence of 0.65%. Maxillary lateral incisors were the most common teeth affected with the condition (90% of cases).

Conclusions  Dens invaginatus is not common, but it is an important anomaly. The availability of such data may alert the dental practitioner to anticipate the percentage of teeth having difficulties during endodontic treatment.
Undergraduate teaching and clinical use of rotary nickel–titanium endodontic instruments: a survey of French dental schools
Authors: Arbab‐Chirani R. , Vulcain J. M.
Published: April 2004

Aim  To evaluate the impact of rotary nickel–titanium (NiTi) instruments on undergaduate teaching and clinical use in French dental schools and to evaluate the impressions of dental students when learning and using these techniques.

Methodology  A questionnaire was mailed to all 16 French undergraduate dental schools. Data were gathered on a range of issues concerning teaching and use of NiTi endodontic techniques.

Results  The response rate was 100%. The need for teaching NiTi techniques to dental students was agreed by all schools. Lectures and laboratory courses for rotary NiTi techniques were organized in all of the schools. In 13 of the 16 teaching hospitals, students could use rotary NiTi techniques for canal preparation under the supervision of teaching staff. Similarities were observed in the majority of responses, e.g. type of rotary system taught and used clinically. Some differences were also observed, e.g. the association of hand files to rotary NiTi instruments and at what stage in the undergraduate curriculum rotary instruments were introduced.

Conclusion  There was a national consensus over the need for undergraduate teaching of rotary NiTi systems in France. These techniques had made a substantial impact in endodontic teaching and were widely taught and used in French dental schools.
Marginal adaptation of mineral trioxide aggregate (MTA) compared with amalgam as a root‐end filling material: a low‐vacuum (LV) versus high‐vacuum (HV) SEM study
Authors: Shipper G. , Grossman E. S. , Botha A. J. , Cleaton‐Jones P. E.
Published: April 2004

Aim  To compare the marginal adaptation of mineral trioxide aggregate (MTA) or amalgam root‐end fillings in extracted teeth under low‐vacuum (LV) versus high‐vacuum (HV) scanning electron microscope (SEM) viewing conditions.

Methodology  Root‐end fillings were placed in 20 extracted single‐rooted maxillary teeth. Ten root ends were filled with MTA and the other 10 root ends were filled with amalgam. Two 1 mm thick transverse sections of each root‐end filling were cut 0.50 mm (top) and 1.50 mm (bottom) from the apex. Gap size was recorded at eight fixed points along the dentine–filling material interface on each section when uncoated wet (LV wet (LVW)) and dry under LV (0.3 Torr) in a JEOL JSM‐5800 SEM and backscatter emission (LV dry uncoated (LVDU)). The sections were then air‐dried, gold‐coated and gap size was recorded once again at the fixed points under HV (10−6 Torr; HV dry coated (HVDC)). Specimen cracking, and the size and extent of the crack were noted.

Results  Gap sizes at fixed points were smallest under LVW and largest under HVDC SEM conditions. Gaps were smallest in MTA root‐end fillings. A General Linear Models Analysis, with gap size as the dependent variable, showed significant effects for extent of crack in dentine, material and viewing condition (P = 0.0001).

Conclusions  This study showed that MTA produced a superior marginal adaptation to amalgam, and that LVW conditions showed the lowest gap size. Gap size was influenced by the method of SEM viewing. If only HV SEM viewing conditions are used for MTA and amalgam root‐end fillings, a correction factor of 3.5 and 2.2, respectively, may be used to enable relative comparisons of gap size to LVW conditions.
The Benefits and Costs of Disclosing Information about Risks: What Do We Know about Right‐to‐Know?
Authors: Beierle Thomas C.
Published: April 2004

Following the attacks of September 11, 2001, the Environmental Protection Agency and other government agencies removed information from their websites that they feared could invite attacks on critical public and private infrastructure. Accordingly, the benefits and costs of environmental information disclosure programs have come under increasing scrutiny. This article describes a framework for examining these benefits and costs and illustrates the framework through brief case studies of two information disclosure programs: risk management planning and materials accounting. The article outlines what we know and still need to find out about information disclosure programs in order to appropriately balance benefits and costs.
Evaluating the Efficacy of a Mental Models Approach for Improving Occupational Chemical Risk Protection
Authors: Niewöhner Jörg , Cox Patrick , Gerrard Simon , Pidgeon Nick
Published: April 2004

Chemical risk protection in the workplace relies partly on informing workers about possible risks using material safety data sheets (MSDS). This article reports on phase 2 of a project (phase 1 reported in Cox et al.), which employed a mental models approach to improve on data sheets as communicative interventions for perchloroethylene in dry cleaning and rosin‐based solder flux in the electronics industry within small businesses in the United Kingdom (small enterprises (SEs) < 25 employees in the workplace). It focuses on the efficacy of a multimethod evaluation strategy to assess (1) the capacity of a mental models approach to yield contextually relevant data for intervention design and (2) the effectiveness of the strategy itself in validating the mental models data. The evaluation was conducted using postal questionnaires and semi‐structured verbal protocols to provide responses to the alternative intervention content and to prioritize risk messages. User discussion groups were then employed, particularly as a means of establishing whether contextual information could be obtained that would differ qualitatively from the kind elicited through individual (semi) structured methods. We conclude that the mental models approach as part of an iterative process including systematic multimethod evaluation is successful in supporting the design of relevant communications to the users of chemicals. The overall viability of communicative interventions in the context of health and safety in small businesses remains in question. Future research might aim to develop a more holistic approach to interventions in complex occupational contexts.
Ecological Risk Ranking: Development and Evaluation of a Method for Improving Public Participation in Environmental Decision Making
Authors: Willis Henry H. , DeKay Michael L. , Morgan M. Granger , Florig H. Keith , Fischbeck Paul S.
Published: April 2004

This article reports an extension of the Carnegie Mellon risk‐ranking method to incorporate ecological risks and their attributes. On the basis of earlier risk‐perception studies, we identified a set of 20 relevant attributes for describing health, safety, and environmental hazards in standardized risk summary sheets. In a series of three ranking sessions, 23 laypeople ranked 10 such hazards in a fictional Midwestern U.S. county using both holistic and multiattribute ranking procedures. Results were consistent with those from previous studies involving only health and safety hazards, providing additional evidence for the validity of the method and the replicability of the resulting rankings. Holistic and multiattribute risk rankings were reasonably consistent both for individuals and for groups. Participants reported that they were satisfied with the procedures and results, and indicated their support for using the method to advise real‐world risk‐management decisions. Agreement among participants increased over the course of the exercise, perhaps because the materials and deliberations helped participants to correct their misconceptions and clarify their values. Overall, health and safety attributes were judged more important than environmental attributes. However, the overlap between the importance rankings of these two sets of attributes suggests that some information about environmental impacts is important to participants’ judgments in comparative risk‐assessment tasks.
Dose Response for Infection by Escherichia coli O157:H7 from Outbreak Data
Authors: Teunis Peter , Takumi Katsuhisa , Shinagawa Kunihiro
Published: April 2004

In 1996, an outbreak of E. coli O157:H7‐associated illness occurred in an elementary school in Japan. This outbreak has been studied in unusual detail, making this an important case for quantitative risk assessment. The availability of stored samples of the contaminated food allowed reliable estimation of exposure to the pathogens. Collection of fecal samples allowed assessment of the numbers infected, including asymptomatic cases. Comparison to other published dose‐response studies for E. coli O157:H7 show that the strain that caused the outbreak studied here must have been considerably more infectious. We use this well‐documented incident as an example to demonstrate how such information on the response to a single dose can be used for dose‐response assessment. In particular, we demonstrate how the high infectivity limits the uncertainty in the low‐dose region.
Environmental Risk, Precaution, and Scientific Rationality in the Context of WTO/NAFTA Trade Rules
Authors: Crawford‐Brown Douglas , Pauwelyn Joost , Smith Kelly
Published: April 2004

This article considers the role of scientific rationality in understanding statements of risk produced by a scientific community. An argument is advanced that, while scientific rationality does impose constraints on valid scientific justifications for restrictions on products and practices, it also provides flexibility in the judgments needed to both develop and apply characterizations of risk. The implications of this flexibility for the understanding of risk estimates in WTO and NAFTA deliberations are explored, with the goal of finding an intermediate ground between the view that science unambiguously justifies or rejects a policy, and the view that science is yet another cultural tool that can be manipulated in support of any decision. The result is a proposal for a dialogical view of scientific rationality in which risk estimates are depicted as confidence distributions that follow from a structured dialogue of scientific panels focused on judgments of evidence, evidential reasoning, and epistemic analysis.
The Weakest Link: Demonstrating the Inconsistency of “Appropriate Levels of Protection” in Australia‐Salmon
Authors: Atik Jeffery
Published: April 2004

In Australia‐Salmon, the WTO Appellate Body found Australia to be in violation of the WTO SPS Agreement based on the inconsistency of the “appropriate level of protection” underlying various SPS measures. Article 5.5 of the SPS Agreement prohibits arbitrary or unjustifiable distinctions in “appropriate levels of protection” if such distinctions result in discrimination or a disguised restriction on international trade. In Australia‐Salmon, Canada challenged Australia's import ban on salmon. Australia permitted the entry of other fish products that were known to host some of the same diseases cited by Australia in justifying its salmon import ban. The distinction in the “appropriate levels of protection” between Australia's regulation of salmon and its treatment of these other fish products was found to be “arbitrary or unjustified” and to have “resulted in a restriction on international trade.”Australia‐Salmon was the first WTO decision to find an Article 5.5 violation. Canada successfully made a “weakest link” argument to undercut Australia's regulatory justification. The decision rests on the relationship between the risk purportedly justifying the salmon import ban and the risk seemingly ignored in Australia's treatment of other fish products—the regulatory “situations” compared concerned the identical pathogens with the identical potential consequences. As such, Australia‐Salmon may be an example of a category of regulatory “chains” that are peculiarly exposed to Article 5.5 challenge. In responding to the Appellate Body's ruling, Australia reduced its limits on salmon and imposed new restrictions on the other fish products. The outcome suggests that a challenge of one SPS measure under Article 5.5 may lead to the imposition of new restrictions on other imported products—an unexpected result for the free trade regime.
Efficacy of antibiotics to strains of periodontopathogenic bacteria within a single species biofilm – an in vitro study
Authors: Eick S. , Seltmann T. , Pfister W.
Published: April 2004

Objectives: This study examined differences in the efficacy of antibiotics against a single strain of three periodontal pathogens grown in an artificial biofilm.

Methods: Single species biofilms were established with artificial saliva and one of the following bacterial strains: Actinobacillus actinomycetemcomitans Y4, Streptococcus constellatus 384b (a clinical isolate) and Porphyromonas gingivalis ATCC 33277. The efficacy of the antibiotics clindamycin, doxycycline, metronidazole, and moxifloxacin to these bacteria was determined using concentrations up to 100‐fold minimal inhibitory concentration (MIC) to planctonic bacteria over 48 h.

Results: The ability of the bacteria to form a biofilm varied. The biofilms of S. constellatus 384b and A. actinomycetemcomitans Y4 contained more viable bacteria and showed a larger thickness in SEM photographs than those of P. gingivalis ATCC 33277. The antibiotics tested showed different efficacy for the different strains. Moxifloxacin was the most efficient antibiotic: onefold MIC was sufficient to eliminate A. actinomycetemcomitans Y4 and P. gingivalis ATCC 33277 after 48 h. However, only the 50‐fold MIC completely eradicated S. constellatus 384b. SEM photographs underlined the damaging effect of moxifloxacin on the biofilm structure.

Conclusion: The complete removal of bacteria by the use of antibiotics alone seems to be impossible when taking into account MIC values and the level of antibiotics in gingival fluid.
Closed‐End Fund Discounts and Expected Investment Performance
Authors: Ferguson Robert , Leistikow Dean
Published: April 2004

This article provides empirical support for the theory that closed‐end fund discounts reflect expected investment performance. Evidence is presented to explain how equity closed‐end fund initial public offerings (IPOs) can sell at a premium when existing funds sell at a discount and why the initial IPO premiums decay after the IPO. Relative premium decay data are presented. Tests on (1) the relation between relative premium changes and investment performance following IPOs, (2) relative premium mean‐reversion following management changes, and (3) net redemptions following closed‐end fund open‐endings for funds trading at pre‐open‐ending announcement discounts individually support and collectively strongly support the theory.
Bank Mergers and Insider Nontrading
Authors: Madison Tom , Roth Greg , Saporoschenko Andy
Published: April 2004

Insiders with nonpublic information that their firms are acquisition targets can profit by purchasing their firms' stock or by delaying planned sales of their firms' stock. Under current securities laws, insiders who execute the former strategy expose themselves to civil and criminal liability, whereas insiders who execute the latter strategy do not. Using a sample of bank mergers, we find that target bank insiders significantly decrease both share purchases and share sales before merger announcements. These findings suggest that securities laws effectively deter some forms of illegal insider trading and that insiders exploit opportunities to profit legally from nonpublic information.
The Pricing of Sequential Bank Loans
Authors: Athavale Manoj , Edmister Robert O.
Published: April 2004

The theory of financial intermediation assigns banks a unique role in the resolution of information asymmetry. Banks, in general, obtain private information about the borrower and the project during the screening of loan applicants and during the monitoring of loan recipients. Incumbent banks, in particular, utilize information obtained while monitoring previous loan extensions to resolve information asymmetry when granting subsequent loans. We examine the rate on a sequence of loans to a borrower and find that the incumbent bank information advantage has finite magnitude and is quickly reflected in the pricing of the second loan. We also find that the lending relationship does not deteriorate to the detriment of the borrower. This study also provides further evidence supporting the hypothesis that an incumbent bank resolves information asymmetry during the monitoring of loan extensions.
Specialists, Limit‐Order Traders, and the Components of the Bid‐Ask Spread
Authors: Chung Kee H. , Van Ness Bonnie F. , Van Ness Robert A.
Published: April 2004

This study compares the components of the bid‐ask spread estimated from quotes that reflect the trading interest of specialists with those estimated from limit‐order quotes and all available quotes for a sample of New York Stock Exchange (NYSE) stocks. The results show that the adverse selection component of the spread estimated from specialist quotes is significantly smaller than the corresponding figures from limit‐order quotes and entire quotes. We interpret this as evidence that NYSE specialists transfer at least a part of adverse selection costs to outsiders through the discretionary use of limit orders. Our results show that the estimation/interpretation of the components of the spread using quote data that include both specialist and limit‐order interests is problematic.
To Trade or Not to Trade: The Effect of Broker Search and Discretionary Trading on Securities Market Performance
Authors: Zhang Wei , Li Jinliang , Wu Chunchi
Published: April 2004

In this article we examine the interaction of brokerage search with the Bayesian learning behavior of competitive dealers under asymmetric information. We particularly focus on the effects of price search and discretionary trading on the performance of a dealer market. A search process is incorporated into a model in which brokers determine their reservation price and whether to continue their trades. The model enables us to uncover the interrelationships among search cost, bid‐ask spread, and price volatility. We show that both spread revision and price volatility are dependent upon the optimal search process, inventory fluctuation, and search cost. Furthermore, our model predicts a negative relationship between price volatility and liquidity trading volume.
Quantitative evaluation of severity in psoriatic lesions using three‐dimensional morphometry
Authors: Park Sang Yong , Ha Seung‐Han , Yu Dong‐Sao , Son Sang‐Wook , Kim Dong‐Jun , Kim Il‐Hwan , Moon Jong‐Sub , Kim Min‐Ki , Oh Chil‐Hwan
Published: April 2004

Abstract:  The severity of psoriasis has been traditionally assessed by measures, such as the psoriasis area and severity index (PASI), the psoriasis severity scores, and the lesional severity scores. As a result, even experienced dermatologists show variations when attempting to determine the severity of psoriasis. Therefore, a better non‐invasive and objective measurement of clinical signs is needed. In this study, an instrument, a so‐called ‘stereoimage optical topometer’ (SOT), based on a new concept of ‘stereoimaging’ was used to measure the three‐dimensional skin surface. The aim of this study was to compare the results obtained by the SOT with the visual score of psoriasis lesion. Thirty psoriatic patients were enrolled in this study. Initially, the severity of the infiltration and the scale of 134 psoriatic lesions were assessed by using a visual scoring system (0: none, 1: mild, 2: moderate, 3: severe, and 4: very severe), as scored by five dermatologists. The SOT was then used to quantify the severity of each psoriatic lesion using four three‐dimensional SOT parameters (Sa, SL, SA, and SV). Secondly, the involved skin‐surface area in the psoriasis cases was scored by the naked eye by the five dermatologists and by image analysis. Statistically significant differences were observed between grades 0, 1, 2, and 3 in terms of the severity measurements of the individual psoriatic lesions by SOT when using the parameters Sa, SL, SA, and SV. Therefore, it was concluded that there is a strong correlation between the results measured by visual scoring and by SOT in psoriasis.
Thymus‐ and activation‐regulated chemokine (TARC/CCL17) induces a Th2‐dominated inflammatory reaction on intradermal injection in mice
Authors: Vestergaard Christian , Deleuran Mette , Gesser Borbala , Larsen Christian Grønhøj
Published: April 2004

Abstract:  TARC/CCL17 (thymus‐ and activation‐regulated chemokine) is a CC chemokine, which binds to the CC chemokine receptor‐4 (CCR4) known to be distinctively expressed on Th2 lymphocytes. In atopic dermatitis (AD), the skin is invaded by Th2 lymphocytes in the acute phase. TARC/CCL17 is produced by the keratinocytes in AD lesions, and CCR4 is overexpressed on CLA+ (cutaneous lymphocyte‐associated antigen) lymphocytes in the skin and blood. We, therefore, hypothesized that TARC/CCL17 is pivotal in mediating a Th2‐dominated inflammation in the skin. To examine this, we injected BALB/c mice with murine TARC/CCL17 in concentrations ranging from 0.1 µg/ml to 10 µg/ml and examined the skin after 48 h. This revealed that TARC/CCL17 induces lymphocytic infiltration of the skin by CD4+ lymphocytes in a dose‐dependent manner with a maximum response at 1 µg/ml. Additionally, TARC/CCL17 induced interleukin‐4 mRNA but not interferon‐γ mRNA expression in the skin, suggesting that the lymphocytes invading the skin are Th2 cells. Additionally, TARC/CCL17 induced its own production in the keratinocytes along with cutaneous T‐cell‐attracting chemokine (CTACK/CCL27) mRNA. We, therefore, conclude that TARC/CCL17 induces a Th2‐dominated inflammatory reaction when injected into the skin.
Interaction of hairless and thyroid hormone receptor is not involved in the pathogenesis of atrichia with papular lesions
Authors: Djabali Karima , Zlotogorski Abraham , Metzker Arye , Ben‐Amitai Dani , Christiano Angela M.
Published: April 2004

Abstract:  Atrichia with papular lesions (APL) (MIM 209 500) is a rare autosomal recessive disease characterized by early onset of atrichia, followed by a papular eruption within the first years of life. Recent studies demonstrating linkage to chromosome 8p21 and further mutation detection in the hairless gene (HR) have established the molecular basis of APL. This study describes the case of a 16‐year‐old female with APL due to a missense mutation, D1012N, in the hr–thyroid hormone receptor interacting domain 2 (TRID2) of the HR. Using functional and biochemical analysis, it was determined that this mutation does not significantly affect hr‐thyroid hormone receptor interaction. This result suggests that the TRID2 domain either is dispensable in the hr–TR interaction or is not involved in the pathogenesis of APL.
The hairless promoter is differentially regulated by thyroid hormone in keratinocytes and neuroblastoma cells
Authors: Engelhard Andrew , Christiano Angela M.
Published: April 2004

Abstract:  The hair cycle is an extraordinarily complex process relying on spatially and temporally coordinated integration of intercellular signaling, cell division and death, cell migration, and gene expression. The hairless gene (hr) is expressed with hair‐cycle‐dependent kinetics, and pathogenic mutations in hr are responsible for the hairless and rhino phenotypes in mice and atrichia with papular lesions in humans. In addition to its expression in the skin and hair follicle, hr is also highly expressed in the brain, yet the factors governing its differential cell‐type‐specific expression have not yet been defined. A thyroid hormone responsive element was previously identified in the rat hr promoter which confers thyroid hormone (T3) responsiveness to heterologous promoter constructs; however, prior studies have not focused on the hr promoter itself. The hairless promoter was cloned, and it is shown that the hr promoter is transactivated by T3 in neuroblastoma cells but not in keratinocytes. Therefore, while T3 has a significant role in the regulation of neuronal expression of hairless, its upregulation in keratinocytes is T3 independent. Furthermore, hr is subject to cell‐type‐specific negative autoregulation, inhibiting the activity of its own promoter in keratinocytes but not neuroblastoma cells. These findings illustrate a molecular distinction between the regulation of hr expression in defined cell populations.
Force‐independent expression of c‐fos mRNA by endothelin‐1 in rat intact small mesenteric arteries
Authors: Buus C. L. , Kristensen H. B. , Bakker E. N. T. P. , Eskildsen‐Helmond Y. E. G. , Mulvany M. J.
Published: April 2004

Aim:  Wall stress‐independent signalling pathways were studied for endothelin‐1 (ET‐1)‐induced c‐fos expression in rat intact mesenteric small arteries.

Methods:  Arteries were kept unmounted in Krebs buffer, equilibrated for 1 h and stimulated with vasoactive substances for 15–60 min. The c‐fos mRNA expression was determined by real‐time polymerase chain reaction.

Results:  Stimulation with fetal bovine serum (FBS), phorbol 12‐myristate 13‐acetate (PMA) and ET‐1 caused about a doubling of c‐fos mRNA. The ET‐1‐induced c‐fos expression was steady (15–60 min) and was inhibited by the inhibitor of the ETA receptor, BQ‐123. Platelet‐derived growth factor‐B, angiotensin II and U46619 did not cause increased c‐fos mRNA levels. The broad specificity inhibitor staurosporine inhibited the response to ET‐1, but inhibitors of Rho‐A kinase and phosphatidylinositol 3‐kinase had no effect. However, inhibitors to tyrosine kinases, the MAP kinases [extracellular signal‐regulated kinase 1/2 (ERK1/2), c‐Jun amino‐terminal kinase, p38], and to conventional protein kinase C showed no inhibition. Consistent with these findings, ET‐1 did not cause activation of ERK1/2, a finding also seen in vessels held under pressure. In contrast, ET‐1‐induced c‐fos expression was inhibited by the calcium chelator BAPTA, suggesting a role for intracellular calcium. This possibility was supported by the finding that raising the extracellular K+ concentration caused increased expression of c‐fos in a concentration‐dependent manner.

Conclusion:  The results suggest that in the absence of wall stress, ET‐1 is able to induce increased expression of c‐fos independent of traditional growth pathways, such as MAP kinase. The mechanism appears to be calcium‐dependent.
Haemodynamic effects of dopexamine on postprandial splanchnic hyperaemia
Authors: Bartsch S. , Brüning A. , Reimann F. M. , Ludwig D.
Published: April 2004

Background  The synthetic β2‐adrenergic and dopaminergic agonist dopexamine is supposed to prevent splanchnic hypoperfusion in critically ill patients, thus potentially interacting with haemodynamic effects of early enteral nutrition. However, precise mechanism of action and interaction with postprandial splanchnic hyperaemia of the drug are largely unknown, even in healthy subjects.

Materials and methods  Twelve healthy volunteers received dopexamine 1 µg kg−1 min−1 and dopexamine and placebo (NaCl 0·9%) 3 µg kg−1 min−1 in a randomized, double‐blinded order (crossover‐design). Splanchnic (Doppler ultrasound) and systemic (noninvasive cardiac monitoring) haemodynamic parameters were assessed at baseline and during infusion (fasted as well as 15, 30, 45 and 60 min after a standard liquid meal).

Results  In fasted humans, dopexamine enhanced time‐averaged maximum velocity (TAMX) in the superior mesenteric artery (1 µg + 40%; 3 µg + 82%, P < 0·05), portal vein (+ 63%; + 121%, P < 0·05) and femoral artery (+ 66%; + 87%, P < 0·05), in proportion to the increase of cardiac index (+ 33%; + 77%, both P < 0·05). In the postprandial state, TAMX rose significantly in the superior mesenteric artery (+ 139%) and portal vein (+ 68%) in the placebo group, showing the same absolute extent as dopexamine. The physiological postprandial buffer response of hepatic artery was conserved under all conditions.

Conclusions  Continuous infusion of dopexamine enhances mesenterial and portal perfusion in a dose‐dependent manner without affecting the extent of physiological postprandial hyperaemia. Thus, dopexamine and enteral nutrition may interact with splanchnic haemodynamics by different pathways.
Vasodilator mRNA levels are increased in the livers of portal hypertensive NO‐synthase 3‐deficient mice
Authors: Biecker E. , Sägesser H. , Reichen J.
Published: April 2004

Background/aims  Nitric oxide synthase (NOS) 3‐deficient (NOS‐3 KO) mice have an increased systemic arterial pressure but develop portal hypertension to the same extent as wildtype (WT) mice. We hypothesized that other vasodilators in the portal circulation compensate for the lack in NOS‐3 activity. We used quantitative PCR as a screening method to identify mediators that possibly compensate for NOS‐3 in NOS‐3 KO mice.

Methods  Mean arterial pressure (MAP) and portal venous pressure (PVP) were measured in the anaesthetized animal. mRNA levels in whole liver tissue were determined by quantitative RT‐PCR.

Results  NOS‐3 KO mice had a significantly higher mean arterial pressure than WT mice, but portal venous pressure did not differ. Bile duct ligation (BDL) induced a drop in MAP and a rise in PVP in both groups. Bile duct ligation induced a significant increase in mRNA levels of the cannabinoid receptor (CB)‐1, adrenomedullin and NOS‐2 in the liver of NOS‐3 KO and WT mice. Nitric oxide synthase‐1 and NOS‐3 mRNA levels were elevated in BDL WT mice compared with sham‐operated WT mice. Higher mRNA levels of CB‐1, NOS‐1 and the adrenomedullin receptor were found in sham‐operated NOS‐3 KO mice compared with sham‐operated WT mice.

Conclusions  We used quantitative PCR as a screening method to identify vasodilative mediators that might be involved in the compensation for the lack of NOS‐3 activity in NOS‐3 KO mice. Elevated mRNA levels in sham‐operated NOS‐3 KO mice compared with sham‐operated WT mice were demonstrated for CB‐1, NOS‐1 and the adrenomedullin receptor.
Effect of homocysteine‐lowering treatment with folic acid plus vitamin B6 on cerebrovascular atherosclerosis and white matter abnormalities as determined by MRA and MRI: a placebo‐controlled, randomized trial
Authors: Vermeulen E. G. J. , Stehouwer C. D. A. , Valk J. , Van Der Knaap M. , Van Den Berg M. , Twisk J. W. R. , Prevoo W. , Rauwerda J. A.
Published: April 2004

Background  A high plasma homocysteine concentration is an independent risk factor for large and possibly small vessel disease. We investigated the effects of homocysteine‐lowering treatment with folic acid plus vitamin B6 on markers of cerebrovascular atherosclerosis and cerebral microangiopathy.

Materials and Methods  Using 158 healthy siblings (mean age 46·0 ± 7·6 years) of patients with premature atherosclerotic disease, we performed a randomized, placebo‐controlled trial using 5 mg of folic acid plus 250 mg of vitamin B6 daily (n = 78) or placebo medication (n = 80). Participants were followed for 2 years with magnetic resonance angiography (MRA) (carotid stenosis; carotid and/or vertebral elongation) and magnetic resonance imaging (MRI) (white matter abnormalities; cerebral atrophy).

Results  Seventeen (10·8%) subjects refused MRA/MRI owing to claustrophobia and were excluded. From the remaining 141 participants, 68 received vitamin and 73 received placebo medication [42 (61·8%) and 48 (65·8%) had postmethionine hyperhomocysteinaemia, respectively]. Twenty‐four participants (15·2%; 10 in the treatment and 14 in the placebo group) did not complete both years of the trial. Vitamin treatment was associated with an increase in plasma folate (13‐fold vs. placebo; P < 0·001) and vitamin B6 (8·8‐fold; P < 0·001). Fasting and postmethionine total homocysteine concentrations decreased 38·7% (95% CI, 27·4–50·0) and 29·1% (95% CI, 19·2–39·0) vs. placebo (all P < 0·001). During follow up six individuals in the vitamin‐treated and 11 in the placebo‐treated group deteriorated in their outcome measurements. Vitamin treatment, as compared with placebo, was associated with nonsignificantly improved outcomes on both MRA and MRI outcome measurements (odds ratio 0·48; 95% CI 0·17–1·41; P = 0·18 and 0·48; CI 0·14–1·60; P = 0·23, respectively).

Conclusions  These results could indicate a possible favourable effect of homocysteine‐lowering treatment on cerebrovascular atherosclerosis and cerebral microangiopathy among healthy siblings of patients with premature atherosclerotic disease, but larger trials are required to establish this with certainty.