bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-chain fusions of two unrelated homeodomain proteins trigger pathogenicity inUstilago maydis
Authors: Romeis Tina , Kämper Jörg , Kahmann Regine
Published: July 2002

Pathogenic and sexual development of the fungusUstilago maydis, the causal agent of corn smut disease, is regulated by heterodimerization of two unrelated homeodomain proteins bE and bW, both encoded by the multi-allelicbmating-type locus. This complex can only be formed if the two proteins are derived from different alleles. The heterodimer is believed to function as a transcriptional regulator that binds to target sites upstream of developmentally regulated genes. We have synthesized a translational fusion in which bE is tethered to bW by a designed flexible kink region.U. maydisstrains expressing this synthetic b-fusion become pathogenic for corn illustrating that the single-chain fusion substitutes for the active bE/bW heterodimer. Synthetic b-fusions in which bE and bW originate from the same allele as well as fusions deleted for the dimerization domains were shown to be active while both homeodomains were required for function. Such active fusion proteins are expected to be instrumental in the identification of pathogenicity genes.
Microperoxidase/H
2
O
2
-mediated alkoxylating dehalogenation of halophenol derivatives in alcoholic media
Authors: Osman Ahmed M. , Boeren Sjef , Boersma Marelle G. , Veeger Cees , Rietjens Ivonne M. C. M.
Published: July 2002

The results of this study report the H
2
O
2
-driven microperoxidase-8 (MP8)-catalyzed dehalogenation of halophenols such as 4-fluorophenol, 4-chlorophenol, 4-bromophenol, and 2-fluorophenol in alcoholic solvents. In methanol, the conversion of the para-halophenols and 2-fluorophenol to, respectively, 4-methoxyphenol and 2-methoxyphenol, as the major dehalogenated products is observed. In ethanol, 4-ethoxyphenol is the principal dehalogenated product formed from 4-fluorophenol. Two mechanisms are suggested for this MP8-dependent alkoxylating dehalogenation reaction. In one of these mechanisms the oxene resonant form of compound I of MP8 is suggested to react with methanol forming a cofactor-peroxide-alkyl intermediate. This intermediate reacts with the reactive π-electrons of the substrate, leading to the formation of the alkoxyphenols and the release of the fluorine substituent as fluoride anion.
Antibody catalysis of peptidyl-prolylcis-transisomerization in the folding of RNase T1
Authors: Ma Lifu , Hsieh-Wilson Linda C. , Schultz Peter G.
Published: July 2002

An antibody generated to an α-keto amide containing hapten 1 catalyzes thecis-transisomerization of peptidyl-prolyl amide bonds in peptides and in the protein RNase T1. The antibody-catalyzed peptide isomerization reaction showed saturation kinetics for thecis-substrate, Suc-Ala-Ala-Pro-Phe-pNA, with akcat/Kmvalue of 883 s−1⋅M−1; the reaction was inhibited by the hapten analog 13 (Ki= 3.0 ± 0.4 μM). Refolding of denatured RNase T1 to its native conformation also was catalyzed by the antibody, with the antibody-catalyzed folding reaction inhibitable both by the hapten 1 and hapten analog 13. These results demonstrate that antibodies can catalyze conformational changes in protein structure, a transformation involved in many cellular processes.
gp120 envelope glycoproteins of human immunodeficiency viruses competitively antagonize signaling by coreceptors CXCR4 and CCR5
Authors: Madani Navid , Kozak Susan L. , Kavanaugh Michael P. , Kabat David
Published: July 2002

Signal transductions by the dual-function CXCR4 and CCR5 chemokine receptors/HIV type 1 (HIV-1) coreceptors were electrophysiologically monitored in
Xenopus laevis
oocytes that also coexpressed the viral receptor CD4 and a G protein-coupled inward-rectifying K
+
channel (Kir 3.1). Large Kir 3.1-dependent currents generated in response to the corresponding chemokines (SDF-1α for CXCR4 and MIP-1α; MIP-1β and RANTES for CCR5) were blocked by pertussis toxin, suggesting involvement of inhibitory guanine nucleotide-binding proteins. Prolonged exposures to chemokines caused substantial but incomplete desensitization of responses with time constants of 5–7 min and recovery time constants of 12–19 min. CXCR4 and CCR5 exhibited heterologous desensitization in this oocyte system, suggesting possible inhibition of a common downstream step in their signaling pathways. In contrast to chemokines, perfusion with monomeric or oligomeric preparations of the glycoprotein of
M
r
120,000 (gp120) derived from several isolates of HIV-1 did not activate signaling by CXCR4 or CCR5 regardless of CD4 coexpression. However, adsorption of the gp120 from a T-cell-tropic virus resulted in CD4-dependent antagonism of CXCR4 response to SDF-1α, whereas gp120 from macrophage-tropic viruses caused CD4-dependent antagonism of CCR5 response to MIP-1α. These antagonisms could be partially overcome by high concentrations of chemokines and were specific for coreceptors of the corresponding HIV-1 isolates, suggesting that they resulted from direct interactions of gp120–CD4 complexes with coreceptors and that they did not involve the desensitization pathway. These results indicate that monomeric or oligomeric gp120s specifically antagonize CXCR4 and CCR5 signaling in response to chemokines, but they do not exclude the possibility that gp120s might also function as weak agonists in some cells. The gp120-mediated disruption of CXCR4 and CCR5 signaling may contribute to AIDS pathogenesis.
Aggravated decrease in the activity of nucleus basalis neurons in Alzheimer’s disease is apolipoprotein E-type dependent
Authors: Salehi A. , Dubelaar E. J. G. , Mulder M. , Swaab D. F.
Published: July 2002

As reported before, the metabolic activity of nucleus basalis neurons is reduced significantly in Alzheimer patients. Because the apolipoprotein E (ApoE) ɛ4 genotype is a major risk factor for Alzheimer’s disease (AD), we determined whether the decrease in metabolic activity in nucleus basalis neurons in AD is ApoE-type dependent. The size of the Golgi apparatus (GA) was determined as a measure of neuronal metabolic activity in 30 controls and 41 AD patients with a known ApoE genotype by using an image analysis system in the nucleus basalis of Meynert. A polyclonal antibody directed against MG-160, a sialoglycoprotein of the GA, was used to visualize this organelle. There was a very strong reduction in the size of the GA in the nucleus basalis of AD patients. Furthermore, a strong and significant extra reduction in the size of the GA was found in the nucleus basalis neurons of AD patients with either one or two ApoE ɛ4 alleles compared with Alzheimer patients without ApoE ɛ4 alleles. Our data show that the decreased activity of nucleus basalis neurons in AD is ApoE ɛ4 dependent and suggest that ApoE ɛ4 participates in the pathogenesis of AD by decreasing neuronal metabolism.
Reconsidering targeted toxins to eliminate HIV infection: You gotta have HAART
Authors: Berger Edward A. , Moss Bernard , Pastan Ira
Published: July 2002

The success of highly active anti-retroviral therapy (HAART) has
inspired new concepts for eliminating HIV from infected individuals. A
major obstacle is the persistence of long-lived reservoirs of latently
infected cells that might become activated at some time after cessation
of therapy. We propose that, in the context of treatment strategies to
deliberately activate and eliminate these reservoirs, hybrid toxins
targeted to kill HIV-infected cells be reconsidered in combination with
HAART. Such combinations might also prove valuable in protocols aimed
at preventing mother-to-child transmission and establishment of
infection immediately after exposure to HIV. We suggest experimental
approaches
in vitro
and in animal models to test various
issues related to safety and efficacy of this concept.
In vitro
selection of a purine nucleotide-specific hammerheadlike ribozyme
Authors: Vaish Narendra K. , Heaton Paul A. , Fedorova Olga , Eckstein Fritz
Published: July 2002

The
in vitro
selection for an intramolecular AUG-cleaving hammerhead-like ribozyme is described. One of the ribozymes selected was found to cleave after this triplet, both intramolecularly and intermolecularly, with rates comparable to the rate of the native GUC-cleaving hammerhead ribozyme. Although the selection was designed for cleavage 3′ of the AUG triplet, the ribozyme also cleaves 3′ of the AUA triplet. AUU and AUC triplets are, however, not cleaved, and thus the selected ribozyme is purine-specific for the third position in the triplet. In addition, cleavage 3′ of the AAG triplet has been observed, thus the central U is not essential. Nuclease digestion indicates that the selected ribozyme has a secondary structure similar to that of the native hammerhead ribozyme, although with an altered core and stem–loop II sequence. All nucleotides in the core, except one, are essential for activity. The nucleotides in loop II are sensitive to changes and cannot, as in the hammerhead ribozyme, be replaced by other sequences or a nonnucleotide linker. Thus there are differences between these two ribozymes even though they have similar two-dimensional structures. The new ribozyme enlarges the application of hammerhead ribozymes for the inhibition of gene expression by extending the range of cleavable triplets.
Redox-linked transient deprotonation at the binuclear site in the
aa
3
-type quinol oxidase from
Acidianus ambivalens
: Implications for proton translocation
Authors: Das Tapan Kanti , Gomes Cláudio M. , Teixeira Miguel , Rousseau Denis L.
Published: July 2002

The hyperthermophilic archaeon
Acidianus ambivalens
expresses a membrane-bound
aa
3
-type quinol oxidase, when grown aerobically, that we have studied by resonance Raman spectroscopy. The purified
aa
3
oxidase, which does not contain bound quinol, undergoes a reversible slow conformational change at heme
a
3
upon reduction, as indicated by a change in the frequency of its heme formyl stretching mode, from 1,660 cm
−1
to 1,667 cm
−1
. In contrast, upon reduction of the integral membrane enzyme or the purified enzyme preincubated with decylubiquinol, this mode appears at 1,667 cm
−1
much more rapidly, suggesting a role of the bound quinol in controlling the redox-linked conformational changes. The shift of the formyl mode to higher frequency is attributed to a loss of hydrogen bonding that is associated with a group having a pKa of ≈3.8. Based on these observations, a crucial element for proton translocation involving a redox-linked conformational change near the heme
a
3
formyl group is postulated.
Selective induction of apoptosis by the cytotoxic analog AN-207 in cells expressing recombinant receptor for luteinizing hormone-releasing hormone
Authors: Danila Daniel C. , Schally Andrew V. , Nagy Attila , Alexander Joseph M.
Published: July 2002

The selectivity of ligands specific for certain cells can be used to preferentially target chemotherapeutic compounds to neoplastic cells. Human breast, ovarian, endometrial, and prostatic cancers express receptors that can mediate the delivery of targeted cytotoxic compounds to neoplastic cells. Recently, a potent derivative of 2-pyrrolinodoxorubicin (AN-201) conjugated to [
d
-Lys
6
] luteinizing hormone-releasing hormone (LH-RH) (AN-207), was demonstrated to be less toxic than the nonconjugated chemotherapeutic radical and significantly more active in slowing neoplastic cellular growth. In this study we investigate the molecular mechanisms underlying the cytotoxic action of AN-207. We stably transfected COS cells with a LH-RH receptor (LH-RH-Rc) mammalian expression vector and examined the effect of AN-207 on known markers of cellular apoptosis. Apoptotic induction by AN-207, as measured by Bax and Bcl-2 protein levels, was increased in stable cells that express LH-RH-Rc compared with parental cells. DNA fragmentation also was increased by AN-207 treatment when compared with AN-201. Clinically used LH-RH antagonists partially inhibited apoptotic Bax expression and DNA fragmentation induced by AN-207, and blocked AN-207 induced down-regulation of Bcl-2 steady-state protein levels. In cell proliferation studies, after 72 h AN-207 exhibited greater cytotoxicity than AN-201 at equivalent concentrations, in COS cells expressing LH-RH-Rc but not in parental COS cells. In addition, survival of LH-RH-Rc positive cells treated with AN-207 was partially restored by LH-RH antagonist. This study demonstrates the receptor-specific cytotoxic effect of 2-pyrrolinodoxorubicin conjugated to [
d
-Lys
6
] LH-RH, exerted through induction of apoptosis and modulation of Bax, Bcl-2, and DNA fragmentation.
Mice without phosphatidylcholine transfer protein have no defects in the secretion of phosphatidylcholine into bile or into lung airspaces
Authors: van Helvoort Ardy , de Brouwer Arjan , Ottenhoff Roelof , Brouwers Jos F. H. M. , Wijnholds Jan , Beijnen Jos H. , Rijneveld Anita , van der Poll Tom , van der Valk Martin A. , Majoor Donné , Voorhout Wim , Wirtz Karel W. A. , Elferink Ronald P. J. Oude , Borst Piet
Published: July 2002

Phosphatidylcholine transfer protein (Pc-tp) is a highly specific carrier of phosphatidylcholine (PC) without known function. Proposed functions include the supply of PC required for secretion into bile or lung air space (surfactant) and the facilitation of enzymatic reactions involving PC synthesis or breakdown. To test these functions, we generated knock-out mice unable to make Pc-tp. Remarkably, these mice are normal and have no defect in any of the postulated Pc-tp functions analyzed. The lipid content and composition of the bile, as well as lung surfactant secretion and composition, of
Pc-tp
(−/−) mice, is normal. The lack of a Pc-tp contribution to biliary lipid secretion is in agreement with our finding that Pc-tp is down-regulated in adult mouse liver: whereas Pc-tp is abundant in the liver of mouse pups, Pc-tp levels decrease > 10-fold around 2 wk after birth, when bile formation starts. In adult mice, Pc-tp levels are high only in epididymis, testis, kidney, and bone marrow-derived mast cells. Absence of Pc-tp in bone marrow-derived mast cells does not affect their lipid composition or PC synthesis and degradation. We discuss how PC might reach the canalicular membrane of the hepatocyte for secretion into the bile, if not by Pc-tp.
Mimicry of erythropoietin by a nonpeptide molecule
Authors: Qureshi Sajjad A. , Kim Ronald M. , Konteatis Zenon , Biazzo Dawn E. , Motamedi Haideh , Rodrigues Robert , Boice Judith A. , Calaycay Jimmy R. , Bednarek Maria A. , Griffin Patrick , Gao Ying-Duo , Chapman Kevin , Mark David F.
Published: July 2002

Erythropoietin (EPO) controls the proliferation and differentiation of erythroid progenitor cells into red blood cells. EPO induces these effects by dimerization of the EPO receptors (EPOR) present on these cells. To discover nonpeptide molecules capable of mimicking the effects of EPO, we identified a small molecule capable of binding to one chain of EPOR and used it to synthesize molecules capable of inducing dimerization of the EPOR. We first identified compound 1 (
N
-3-[2-(4-biphenyl)-6-chloro-5-methyl]indolyl-acetyl-
l
-lysine methyl ester) by screening the in-house chemical collection for inhibitors of EPO binding to human EPOR and then prepared compound 5, which contains eight copies of compound 1 held together by a central core. Although both compounds inhibited EPO binding of EPOR, only compound 5 induced dimerization of soluble EPOR. Binding of EPO to its receptor in cells results in activation of many intracellular signaling molecules, including transcription factors like signal transducer and activator of transcription (STAT) proteins, leading to growth and differentiation of these cells. Consistent with its ability to induce dimerization of EPOR in solution, compound 5 exhibited much of the same biological activities as EPO, such as (
i
) the activation of a STAT-dependent luciferase reporter gene in BAF3 cells expressing human EPOR, (
ii
) supporting the proliferation of several tumor cell lines expressing the human or mouse EPOR, and (
iii
) the
in vitro
differentiation of human progenitor cells into colonies of erythrocytic lineage. These data demonstrate that a nonpeptide molecule is capable of inducing EPOR dimerization and mimicking the biological activities of EPO.
Domain–domain communication in a miniature archaebacterial tRNA synthetase
Authors: Steer Brian A. , Schimmel Paul
Published: July 2002

The three-dimensional structure of tRNA is organized into two domains—the acceptor-TΨC minihelix with the amino acid attachment site and a second, anticodon-containing, stem–loop domain. Aminoacyl-tRNA synthetases have a structural organization that roughly recapitulates the two-domain organization of tRNAs—an older primary domain that contains the catalytic center and interacts with the minihelix and a secondary, more recent, domain that makes contacts with the anticodon-containing arm. The latter contacts typically are essential for enhancement of the catalytic constant
k
cat
through domain–domain communication.
Methanococcus jannaschii
tyrosyl-tRNA synthetase is a miniature synthetase with a tiny secondary domain suggestive of an early synthetase evolving from a one-domain to a two-domain structure. Here we demonstrate functional interactions with the anticodon-containing arm of tRNA that involve the miniaturized secondary domain. These interactions appear not to include direct contacts with the anticodon triplet but nonetheless lead to domain–domain communication. Thus, interdomain communication may have been established early in the evolution from one-domain to two-domain structures.
Deregulated expression of c-Myc in a translocation-negative plasmacytoma on extrachromosomal elements that carry
IgH
and
myc
genes
Authors: Wiener Francis , Kuschak Theodore I. , Ohno Shinsuke , Mai Sabine
Published: July 2002

The induced expression of c-Myc in plasmacytomas in BALB/c mice is regularly associated with nonrandom chromosomal translocations that juxtapose the c
-myc
gene to one of the
Ig
loci on chromosome 12 (
IgH
), 6 (
IgK
), or 16 (
IgL
). The DCPC21 plasmacytoma belongs to a small group of plasmacytomas that are unusual in that they appear to be translocation-negative. In this paper, we show the absence of any c
-myc
-activating chromosomal translocation for the DCPC21 by using fluorescent
in situ
hybridization, chromosome painting, and spectral karyotyping. We find that DCPC21 harbors c-
myc
and
IgH
genes on extrachromosomal elements (EEs) from which c
-myc
is transcribed, as shown by c
-myc
mRNA tracks and extrachromosomal gene transfer experiments. The transcriptional activity of these EEs is supported further by the presence of the transcription-associated phosphorylation of histone H3 (H3P) on the EEs. Thus, our data suggest that in this plasmacytoma, c-Myc expression is achieved by an alternative mechanism. The expression of the c-Myc oncoprotein is initiated outside the chromosomal locations of the c-
myc
gene, i.e., from EEs, which can be considered functional genetic units. Our data also imply that other “translocation-negative” experimental and human tumors with fusion transcripts or oncogenic activation may indeed carry translocation(s), however, in an extrachromosomal form.
A cyclin-dependent kinase inhibitor inducing cancer cell differentiation: Biochemical identification using
Xenopus
egg extracts
Authors: Rosania Gustavo R. , Merlie John , Gray Nathanael , Chang Young-Tae , Schultz Peter G. , Heald Rebecca
Published: July 2002

Cellular differentiation is a complex process involving growth arrest, exit from the cell cycle, and expression of differentiated cell-type-specific functions. To identify small molecules promoting this process, a chemical library was screened by using a myeloid leukemic cell line that retained the potential to differentiate in culture. In the presence of a purine derivative, aminopurvalanol (AP), cells acquired phenotypic characteristics of differentiated macrophages and became arrested in the cell cycle with a 4N DNA content. AP also inhibited mitosis in
Xenopus
egg extracts, suggesting that it acted on an evolutionarily conserved cell cycle regulatory pathway. Affinity chromatography and biochemical reconstitution experiments with
Xenopus
egg extracts identified cyclin-dependent kinase (CDK) 1–cyclin B as a target of the compound. Although AP potently inhibited immunoprecipitates of both human CDK1 and CDK2 from human leukemic cell extracts, our results indicate that the compound preferentially targets the G
2
/M-phase transition
in vivo
.
The mental representation and processes of spatial deductive reasoning with diagrams and sentences
Authors: Boudreau Ginette , Pigeau Ross
Published: July 2002

This study has two main objectives. The first is to specify the nature of the mental representation and processes underlying spatial reasoning with diagrams and sentences. The second is to investigate whether mental representations reproduce geometrical relations relative to spatial reference frames. Forty participants solved 64 spatial reasoning problems that were displayed using diagrams or sentences. Problems varied with respect to their logical structure and geometrical content. We measured the premise's inspection times, the responses, and the response times. Problems were significantly (p< .01) easier to represent and solve when displayed as diagrams than as sentences, indicating that participants constructed mental models. Mental representations and spatial deductions also varied consistently with the geometrical content, suggesting that mental models reproduced this content relative to a viewer‐centred reference frame.
The Position of Hungarians in Romania and Slovakia in 1996*
Authors: Szépe György
Published: July 2002

The official language of the medieval Kingdom of Hungaria was Latin until the mid-nineteenth century (Szekfű, 1926); the throne was occupied from the second half of the sixteenth century by the Hapsburgs. The subsequent change to Hungarian was due to several factors, but was caused above all by the ideas of the French Revolution, and by the early anti-Austrian nationalistic endeavors of the Hungarian gentry, endeavors which also expressed the economic interests of the country. As soon as the official idiom of the kingdom became Hungarian, it triggered similar aspirations among the non-Magyar minority groups against the dominating and assimilating Hungarian majority. These aspirations were prominent among the causes of the dissolution of the Austro-Hungarian monarchy at the end of World War I. Within the former Kingdom of Hungary the Felvidék (Upper Land) roughly coincided with what was, after 1919, Slovakia. The eastern part of the kingdom, Ardeal/Erdély/Siebenbürgen/Transylvania, which had enjoyed a certain autonomy between the sixteenth and mid-nineteenth centuries, became a part of Romania in the same year. Thus, both in Romania and in Slovakia (as also in Yugoslavia and to a lesser extent in Austria) a Hungarian minority was created by the 1919 borders. Revision of the peace treaties became the focal point of Hungarian politics in the inter-war period. During World War II Hungary attained a partial revision in respect to, first, the southern part of Slovakia, and also the entire Ruténföld/Rusinsko, which had from the 1920s been administered by the Czechoslovak State); second, northern Transylvania; and third, two further areas which had belonged to the then-dissolved Yugoslav kingdom. As a consequence of these revisions, a considerable number of non-Hungarians once again became minorities in the Hungarian State. After World War II, the 1919 borders were reinstated (with two exceptions: the major exception being that Ruténföld became part of Ukraine). The situation of the minorities was also reinstated, but differently in each instance. This was the age when some kind of democratic reconciliation was on the agenda in Romania (Balogh, 1985; Lázok and Vincze, 1995; “Mit kíván,” 1946/1988), after a period of thorough self-searching and a synthesizing of historical research and political experience (see Bibó, 1946).
Spherical functions of the symmetric space 𝐺(𝔽_{𝕢²})/𝔾(𝔽_{𝕢})
Authors: Henderson Anthony
Published: July 2002

We apply Lusztig’s theory of character sheaves to the problem of calculating the spherical functions ofG(Fq2)/G(Fq)G(\mathbb {F}_{q^{2}})/G(\mathbb {F}_q), whereGGis a connected reductive algebraic group. We obtain the solution for generic spherical functions for anyGG, and for all spherical functions whenG=GLnG=GL_n. The proof includes a result about convolution of character sheaves and its interaction with the associated two-sided cells.
SChiSM: creating interactive web page annotations of molecular
structure models using Chime
Authors: Cammer Stephen A.
Published: July 2002

Summary: SChiSM is a program for creating World Wide Web (WWW) pages that include embedded interactive molecular models using the browser plug-in, Chime, for visualization. The program works with Netscape 4.x and Internet Explorer 5 browsers to facilitate Chime/Rasmol scripting control of a molecular display.

Availability: The program can be accessed from the following address: http://mmlsun2.pha.unc.edu/schism.html.

Contact: cammer@email.unc.edu
ACCRUAL BUDGETING AND FISCAL CONSOLIDATION IN THE EMU
Authors: Salinas F. Javier
Published: July 2002

Drawing on modern macroeconomic literature focusing on the study of politico‐institutional determinants of public policies, this article analyzes the institutional design of the European fiscal policy laid down by the Treaty of Amsterdam and the Stability and Growth Pact. Both documents provide countries in the EU, and in particular those that have adopted the euro, with a common code of fiscal conduct that is expected to uphold discipline in the management of government finances. Nevertheless, a simple review of this code of conduct shows the existence of serious drawbacks mainly derived from the asymmetry between the treatment given to outcomes of fiscal policy in comparison with that given to the procedures followed in generating them. It seems that the current design of the European fiscal coordination system does not really take into account the findings of modern macroeconomics and does not pay due attention to the relation between budgetary processes/institutions and outcomes in fiscal policy. Moreover, this article argues that in the implementation of the broad reforms needed to achieve a sustainable fiscal consolidation, there are political complementarities (in the sense that the ability to gain political consent for one reform depends on the acceptance of other reforms) between the setting up of new fiscal policies of expenditure containment and new fiscal procedures.

All in all, this analysis points to a sorely needed procedural reform in public sector budgeting as the best contribution to pursuing the stabilization of European public finances: the fuller use of accrual concepts in budget reporting. Much more than an isolated technical exercise, the shift to accrual budgeting could be quite a useful tool to facilitate wider reforms aimed at improving public sector financial management and performance while enhancing transparency and accountability.
Can High Prices Ensure Product Quality When Buyers do not Know the Sellers' Cost?
Authors: Rasmusen Eric B. , Perri Timothy J.
Published: July 2002

The 1981 Klein‐Leffler model of product quality does not explain why high‐quality firms would dissipate the rents they earn from quality‐assuring price premia, and it relies on consumers knowing the cost functions of firms. In the present article, consumers do not know any firm's cost of producing quality goods, so firms with a low cost of producing high quality engage in conspicuous spending to demonstrate they earn a profitable mark‐up over cost. Complete rent dissipation does occur if such firms have the same cost of producing low‐quality items as other firms that are worse at producing high quality.
Introduction: Enterprise and State in the Italian “Economic Miracle”
Authors: Tolliday Steven W.
Published: July 2002

The first two articles in this issue ofEnterprise & Societyshed new light on the performance of the postwar Italian economy, an intriguing paradox for economic and business historians. Italy has been notorious for its political instability, inflation, massive public debt, and clientelism. Its political and economic institutions are often derided and labeled dysfunctional. Yet, in historical perspective, the country has frequently performed better than its more stable and “efficient” European neighbors and other developed economies. Between 1950 and 1973, for example, Italy’s Gross National Product grew at 6.8 percent per annum and its Gross Domestic Product (GDP) per capita at a rate of 4.8 percent (matching Germany and second only to Japan). Even more remarkably, since 1973 its GDP, manufacturing output, exports, and productivity have all grown faster than that of any other major European economy.
Knowledge and Competitive Advantage in the Synthetic Dye Industry, 1850–1914: The Coevolution of Firms, Technology, and National Institutions in Great Britain, Germany, and the United States
Authors: Murmann Johann Peter
Published: July 2002

It is London 1856. William Henry Perkin serendipitously invents the first synthetic dye while he is trying to synthesize quinine, a medicine for malaria. The nineteen-year-old Perkin leaves the Royal College of Chemistry and quickly commercializes his aniline purple dye, launching the synthetic dye industry. From that time on, the industry continues to dazzle the eye with ever new and appealing dye colors. Perkin, along with entrepreneurs from Britain and France, dominates the synthetic dye industry for the next eight years. During this period, British and French firms introduce most other innovative synthetic dyes onto the market, and they hold the largest global market share.
Hydrogen peroxide reversibly inhibits epidermal growth factor (EGF) receptor internalization and coincident ubiquitination of the EGF receptor and Eps15
Authors: de Wit Renate , Makkinje Miriam , Boonstra Johannes , Verkleij Arie J. , Post Jan Andries
Published: July 2002

Recently, we demonstrated that hydrogen peroxide (H2O2) inhibits the internalization of the epidermal growth factor (EGF) receptor and the EGF‐induced mono‐ubiquitination of EGF receptor pathway substrate clone #15 (Eps15) in fibroblasts. In addition, it was suggested that EGF receptor internalization might be inhibited by H2O2 by inhibition of ubiquitination of proteins involved in endocytosis. Here, we show that H2O2 also inhibits the poly‐ubiquitination of the EGF receptor in fibroblasts. Furthermore, recovery of the cells resulted in re‐establishment of ubiquitination of both the EGF receptor and Eps15 and coincided with restoration of internalization of those receptors that had bound EGF in the presence of H2O2. In addition, EGF receptor internalization was inhibited by the sulphydryl reagent N‐ethylmaleimide (NEM), indicating that intact SH groups might be required for receptor‐mediated endocytosis. Furthermore, H2O2 rapidly induced an increase in the cellular ratio of GSSG:GSH (oxidized glutathione:reduced glutathione) and removal of H2O2 resulted in a fast restoration of the ratio of GSSG:GSH. Therefore, these results suggest a relation between the inhibition of internalization ubiquitination and an increase in GSSG:GSH ratio, which strengthens the hypothesis that H2O2 inhibits EGF receptor internalization by an inhibition of ubiquitination of proteins involved in EGF receptor‐mediated endocytosis.
Base–compositional biases and the bat problem. I. DNA–hybridization melting curves based on AT– and GC–enriched tracers
Authors: Pettigrew John D. , Kirsch John A. W.
Published: July 2002

We explored the interordinal relationships of mammals using DNA–DNA hybridization, with particular reference to the much–debated problem of whether the megabats and microbats are more closely related to each other than the megabats are to primates. To try to improve resolution when taxa are distantly related and the melting points of hybrids are low and difficult to distinguish, we increased the GC–content of DNA by a fractionation method that used the same melting–point apparatus also used in the hybridization studies. When we used GC–rich DNA as the tracer to make hybrids, the melting point of the self–hybrid shifted to a higher temperature as expected, but the behaviour of heterologous hybrids varied with the taxa being compared. When the melting point of the heterologous hybrid also shifted to a higher temperature so that the two compared taxa maintained the same or proportional distance, we called this ‘following behaviour’, because the heterologous hybrid made with GC– tracer ‘followed’ the GC– self– to higher temperatures. We also commonly saw anomalous behaviour, where the melting point of the heterologous hybrid shifted to a lower temperature when compared with an AT– hybrid. In these anomalous cases, the distance measured between the taxa increased markedly as a result of GC–, indicating that an underestimate of distance may have resulted from AT– in DNA. This inference was supported by the finding that it was rare to observe a decrease in measured distance between taxa using GC– DNA, but very common to find an increase as would be expected from the generally higher AT–contents of eutherian DNAs. Moreover, the most extreme cases, where distances changed most using GC–rich DNA, were usually those involving comparisons between taxa known to have the most extreme AT–biases among mammals, such as the megabats and rhinolophoid (including megadermatid) microbats. Our results show that AT–bias in eutherian DNA leads to consistent underestimates of measured differences between taxa with extreme AT–biases.
Neuropsychological studies of perception and visuomotor control
Authors: Milner A. D.
Published: July 2002

According to recent conceptualizations, there are two separate cortical visual systems—each with its own distinctive cortical and subcortical links—and these two systems respectively serve the functions of perception and of motor control. These ideas have been arrived at through a confluence of neuroanatomical, electrophysiological, behavioural, and neuropsychological research. It is proposed that this distinction between two broad purposes of vision and their neural bases can provide useful working procedures for analysing both: (i) the nature of visuomotor processing in the normal brain; and also (ii) the abnormal patterns of visual processing that are seen in certain neurological conditions.
Thermodynamic stability measurements on multimeric proteins using a new H/D exchange‐ and matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry‐based method
Authors: Powell Kendall D. , Wales Thomas E. , Fitzgerald Michael C.
Published: July 2002

We recently reported on a new H/D exchange‐ and matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry‐based technique, termed SUPREX, that removes several important limitations associated with measuring the thermodynamic stability of proteins. In contrast to conventional spectroscopy‐based techniques for characterizing the equilibrium unfolding behavior of proteins, SUPREX is amenable to the thermodynamic analysis of both purified and unpurified proteins using mg to ng quantities of material. Here we report on the application of SUPREX to the analysis of multimeric protein systems. Included in this work are the SUPREX results we obtained in studies on six model multimeric proteins including the GCN4p1 dimer, the coil‐VaLd trimer, the 4‐oxalocrotonate tautomerase (4‐OT) hexamer, the Trp repressor (TrpR) dimer, the Arc repressor (ArcR) dimer, and an ArcR mutant (the (DOA20)ArcR) dimer which contained two destabilizing mutations including an Asp to Ala mutation at position 20 and an amide to ester bond mutation between amino acid (aa) residues 19 and 20. As part of the work described here, we present a new method for the analysis of SUPREX data that is generally applicable to both monomeric and multimeric protein systems. Our results on the model proteins in this study indicate that this new method can be used to determine folding free energies for proteins with the accuracy and precision of conventional spectroscopy‐based methods.
Dosimetry close to an HDR source using N‐vinylpyrrolidone based polymer gels and magnetic resonance imaging
Authors: Papagiannis P. , Pappas E. , Kipouros P. , Angelopoulos A. , Sakelliou L. , Baras P. , Karaiskos P. , Seimenis I. , Sandilos P. , Baltas D.
Published: July 2002

In this work, the utilization of polymer gel–MRI dosimetry for measurements at distances relevant to clinical brachytherapy and intravascular applications [i.e., in the mm range, where steep three‐dimensional (3‐D) dose gradients exist] is investigated using N‐vinylpyrrolidone‐based gels. Transverse axis radial dose distributions, dose distributions parallel to the source axis, and 2‐D dose distributions around the commonly used microSelectron HDR source are measured for single source dwell position irradiations. Experimental results are found in good agreement with verified Monte Carlo calculations, even for distances less than 3 mm from the source. The effect of various MRI parameters, such as slice thickness, slice mispositioning, and in‐plane resolution, on the accuracy of the method is also investigated. Possible limitations of the method are discussed, and its' overall potential in brachytherapy dosimetry is evaluated. Experimental 2‐D dose distributions for an intravascular application following the Paris irradiation protocol are compared to corresponding commercial treatment planning system calculations. Results suggest that polymer gel–MRI dosimetry is capable of experimentally verifying dose distributions in relevant clinical intravascular applications.
Head insulation and heat loss in naked and clothed newborns using a thermal mannequin
Authors: Elabbassi Elmountacer Billah , Chardon Karen , Bach Véronique , Telliez Frédéric , Delanaud Stéphane , Libert Jean‐Pierre
Published: July 2002

In newborns, large amounts of heat are lost from the head, due to its high skin surface area. Insulating the head (for example, with a hat or bonnet) can be a simple and effective method of reducing dry heat loss. In the present study, we evaluated the safety aspects of insulating the head of low‐birth‐weight naked or clothed newborns by using a heated mannequin that simulates a low‐birth‐weight newborn. Experimental conditions (comprising a nude and three clothed setups) were performed in a closed incubator at three different air temperatures (29 °C, 32 °C, and 34 °C) and with and without the head being covered with a bonnet in each case, i.e., 24 experimental conditions in all. The study shows that added clothing elements and insulating the head decreases the total heat loss of the mannequin as a whole. As regards the dry heat exchange from the head, wearing a bonnet decreases the local heat loss by an average of 18.9% in all clothed and thermal conditions. This phenomenon could be at the origin of brain overheating in heavily dressed newborns, when unrestricted heat loss is limited to the face only. Our results suggest that—apart from accidental hypothermia—in order to achieve thermal equilibrium of the body, it is preferable to leave the head unprotected and to increase the level of clothing insulation over the rest of the body.
Verification of the omni wedge technique
Authors: Milliken Barrett D. , Turian Julius V. , Hamilton Russell J. , Rubin Steven J. , Kuchnir Franca T. , Yu Cedric X. , Wong John W.
Published: July 2002

The optimal field shape achieved using a multileaf collimator (MLC) often requires collimator rotation to minimize the adverse effects of the scalloped dose distribution the leaf steps produce. However, treatment machines are designed to deliver wedged fields parallel or perpendicular to the direction of the leaves. An analysis of cases from our clinic showed that for 25% of the wedged fields used to treat brain and lung tumors, the wedge direction and optimal MLC orientation differed by 20° or more. The recently published omni wedge technique provides the capability of producing a wedged field with orientation independent of the orientation of the collimator. This paper presents a comparison of the three‐dimensional (3D) dose distributions of the omni wedged field with distributions of wedged fields produced using both the universal and dynamic wedge techniques. All measurements were performed using film dosimetry techniques. The omni wedge generated fields closely matched the conventional wedged fields. Throughout 95% of the irradiated volume (excluding the penumbra), the dose distribution of the omni wedged field ranged from +5.5 to of that of the conventionally wedged fields. Calculation of the omni wedged field is as accurate as conventional wedged field calculation when using a 3D treatment planning systems. For two‐dimensional treatment planning systems, where one must assume that the omni wedged field is identical to a conventional field, the calculated field and the delivered field differs by a small amount.
The effect of pitch in multislice spiral/helical CT
Authors: Wang Ge , Vannier Michael W.
Published: July 2002

The purpose of this study is to understand the effect of pitch on raw data interpolation in multislice spiral/helical computed tomography (CT) and provide guidelines for scanner design and protocol optimization. Multislice spiral CT is mainly characterized by the three parameters: the number of detector arrays, the detector collimation, and the table increment per x‐ray source rotation. The pitch in multislice spiral CT is defined as the ratio of the table increment over the detector collimation in this study. In parallel to the current framework for studying longitudinal image resolution, the central fan‐beam rays of direct and opposite directions are considered, assuming a narrow cone‐beam angle. Generally speaking, sampling in the Radon domain by the direct and opposite central rays is nonuniform along the longitudinal axis. Using a recently developed methodology for quantifying the sensitivity of signal reconstruction from nonuniformly sampled finite points, the effect of pitch on raw data interpolation is analyzed in multislice spiral CT. Unlike single‐slice spiral CT, in which image quality decreases monotonically as the pitch increases, the sensitivity of raw data interpolation in multislice spiral CT increases in an alternating way as the pitch increases, suggesting that image quality does not decrease monotonically in this case. The most favorable pitch can be found from the sensitivity‐pitch plot for any given set of multislice spiral CT parameters. An example for four‐slice spiral CT is provided. The study on the effect of pitch using the sensitivity analysis approach reveals the fundamental characteristics of raw data interpolation in multislice spiral CT, and gives insights into interaction between pitch and image quality. These results may be valuable for design of multislice spiral CT scanners and imaging protocol optimization in clinical applications.
Patient‐dependent beam‐modifier physics in Monte Carlo photon dose calculations
Authors: Schach von Wittenau A. E. , Bergstrom P. M. , Cox L. J.
Published: July 2002

Model pencil‐beam on slab calculations are used as well as a series of detailed calculations of photon and electron output from commercial accelerators to quantify level(s) of physics required for the Monte Carlo transport of photons and electrons in treatment‐dependent beam modifiers, such as jaws, wedges, blocks, and multileaf collimators, in photon teletherapy dose calculations. The physics approximations investigated comprise (1) not tracking particles below a given kinetic energy, (2) continuing to track particles, but performing simplified collision physics, particularly in handling secondary particle production, and (3) not tracking particles in specific spatial regions. Figures‐of‐merit needed to estimate the effects of these approximations are developed, and these estimates are compared with full‐physics Monte Carlo calculations of the contribution of the collimating jaws to the on‐axis depth‐dose curve in a water phantom. These figures of merit are next used to evaluate various approximations used in coupled photon/electron physics in beam modifiers. Approximations for tracking electrons in air are then evaluated. It is found that knowledge of the materials used for beam modifiers, of the energies of the photon beams used, as well as of the length scales typically found in photon teletherapy plans, allows a number of simplifying approximations to be made in the Monte Carlo transport of secondary particles from the accelerator head and beam modifiers to the isocenter plane.
Psychophysical customization of directional transfer functions for virtual sound localization
Authors: Middlebrooks John C. , Macpherson Ewan A. , Onsan Zekiye A.
Published: July 2002

The accuracy of virtual localization when using nonindividualized external-ear transfer functions can be improved by scaling the transfer functions in frequency [Middlebrooks, J. Acoust. Soc. Am. 106, 1493–1510 (1999)]. The present letter describes a psychophysical procedure by which listeners identified appropriate scale factors. The procedure ran on nonspecialized equipment, took as little as 20 min, and could be used successfully by inexperienced listeners. Scale factors obtained from the psychophysical procedure approximated factors computed from acoustical measurements from individual listeners. Roughly equivalent virtual-localization accuracy was obtained using scale factors derived from acoustical measurements, from the psychophysical procedure, or from listeners’ physical dimensions.
Distinguishing cochlear pathophysiology in 4-aminopyridine and furosemide treated ears using a nonlinear systems identification technique
Authors: Bian Lin , Chertoff Mark E.
Published: July 2002

To test the adequacy of physiologic indices derived from a third-order polynomial model quantifying cochlear mechano-electric transduction (MET), 24 Mongolian gerbils were exposed to either 250-mM glucose (control), 150-mM 4-aminopyridine (4-AP), or 30-mM furosemide solutions applied to the round window (RW) membrane. The cochlear microphonic (CM) was recorded from the RW in response to 68- and 88-dB SPL Gaussian noise. A nonlinear systems identification technique (NLID) provided the frequency-domain parameters and physiologic indices of the polynomial model of MET. The control group showed no change in both compound action potential (CAP) thresholds and CM. Exposure to 4-AP and furosemide resulted in a similar elevation in CAP thresholds and a reduction in CM. However, the polynomial model of MET showed different changes. The operating point, slope, and symmetry of the MET function, the polynomial model parameters, and related nonlinear coherences differed between the experimental groups. It is concluded that the NLID technique is sensitive and specific to alterations in the cochlear physiology.
Coherent backscattering of elastic waves: Specific role of source, polarization, and near field
Authors: van Tiggelen B. A. , Margerin L. , Campillo M.
Published: July 2002

Calculation of coherent backscattering of elastic waves in an infinite isotropic random medium is presented. Despite the simplicity of this geometry, this calculation highlights several specific aspects for seismic detection: near field detection, polarization, and the symmetry of the source. Line profiles and enhancement factors are seen to be time independent and are calculated for kinetic, shear, and compressional energy.