bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of the
Bacillus subtilis bcrC
Bacitracin Resistance Gene by Two Extracytoplasmic Function σ Factors
Authors: Cao Min , Helmann John D.
Published: October 2002

Bacitracin resistance is normally conferred by either of two major mechanisms, the BcrABC transporter, which pumps out bacitracin, or BacA, an undecaprenol kinase that provides C
55
-isoprenyl phosphate by de novo synthesis. We demonstrate that the
Bacillus subtilis bcrC
(
ywoA
) gene, encoding a putative bacitracin transport permease, is an important bacitracin resistance determinant. A
bcrC
mutant strain had an eightfold-higher sensitivity to bacitracin. Expression of
bcrC
initiated from a single promoter site that could be recognized by either of two extracytoplasmic function (ECF) σ factors, σ
X
or σ
M
. Bacitracin induced expression of
bcrC
, and this induction was dependent on σ
M
but not on σ
X
. Under inducing conditions, expression was primarily dependent on σ
M
. As a consequence, a
sigM
mutant was fourfold more sensitive to bacitracin, while the
sigX
mutant was only slightly sensitive. A
sigX sigM
double mutant was similar to a
bcrC
mutant in sensitivity. These results support the suggestion that one function of
B. subtilis
ECF σ factors is to coordinate antibiotic stress responses.
Presence of a Characteristic D-D-E Motif in IS1Transposase
Authors: Ohta Shinya , Tsuchida Ken , Choi Sunju , Sekine Yasuhiko , Shiga Yasuyuki , Ohtsubo Eiichi
Published: October 2002

Transposases encoded by various transposable DNA elements and retroviral integrases belong to a family of proteins with three conserved acidic amino acids, D, D, and E, constituting the D-D-E motif that represents the active center of the proteins. IS1, one of the smallest transposable elements in bacteria, encodes a transposase which has been thought not to belong to the family of proteins with the D-D-E motif. In this study, we found several IS1family elements that were widely distributed not only in eubacteria but also in archaebacteria. The alignment of the transposase amino acid sequences from these IS1family elements showed that out of 14 acidic amino acids present in IS1transposase, three (D, D, and E) were conserved in corresponding positions in the transposases encoded by all the elements. Comparison of the IS1transposase with other proteins with the D-D-E motif revealed that the polypeptide segments surrounding each of the three acidic amino acids were similar. Furthermore, the deduced secondary structures of the transposases encoded by IS1family elements were similar to one another and to those of proteins with the D-D-E motif. These results strongly suggest that IS1transposase has the D-D-E motif and thus belongs to the family of proteins with the D-D-E motif. In fact, mutant IS1transposases with an amino acid substitution for each of the three acidic amino acids possibly constituting the D-D-E motif were not able to promote transposition of IS1, supporting this hypothesis. The D-D-E motif identified in IS1transposase differs from those in the other proteins in that the polypeptide segment between the second D and third E in IS1transposase is the shortest, 24 amino acids in length. Because of this difference, the presence of the D-D-E motif in IS1transposase has not been discovered for some time.
Genome Analysis and Strain Comparison of Correia Repeats and Correia Repeat-Enclosed Elements in Pathogenic
Neisseria
Authors: Liu Shi V. , Saunders Nigel J. , Jeffries Alex , Rest Richard F.
Published: October 2002

Whole genome sequences of
Neisseria meningitidis
strains Z2491 and MC58 and
Neisseria gonorrhoeae
FA1090 were analyzed for Correia repeats (CR) and CR-enclosed elements (CREE). A total of 533, 516, and 256 copies of CR and 270, 261, and 102 copies of CREE were found in these three genomes, respectively. The lengths of CREE range from 28 to 348 bp, and the lengths of multicopy CREE appear mainly in the ranges of 154 to 156 bp and 105 to 107 bp. The distribution of CREE lengths is similar between the two
N. meningitidis
genomes, with a greater number of 154- to 156-bp CREE (163 and 152 copies in
N. meningitidis
strain Z2491 and
N. meningitidis
strain MC58, respectively) than 105- to 107-bp CREE (72 and 77 copies). In the
N. gonorrhoeae
strain FA1090 genome there are relatively more 105- to 107-bp CREE (51 copies) than 154- to 156-bp CREE (36 copies). The genomic distribution of 107-bp CREE also shows similarity between the two
N. meningitidis
strains (15 copies share the same loci) and differences between
N. meningitidis
strains and
N. gonorrhoeae
FA1090 (only one copy is located in the same locus). Detailed sequence analysis showed that both the terminal inverted repeats and the core regions of CREE are composed of distinct basic sequence blocks. Direct TA dinucleotide repeats exist at the termini of all CREE. A survey of DNA sequence upstream of the sialyltransferase gene,
lst
, in several
Neisseria
isolates showed that 5
N. meningitidis
strains contain a 107-bp CREE in this region but 25
N. gonorrhoeae
strains show an exact absence of a 105-bp sequence block (i.e., the 107-bp CREE without a 5′ TA dinucleotide) in the same region. Whole-genome sequence analysis confirmed that this 105-bp indel exists in many homologous 107-bp CREE loci. Thus, we postulate that all CREE are made of target TA with indels of various lengths. Analysis of 107-bp CREE revealed that they exist predominantly in intergenic regions and are often near virulence, metabolic, and transporter genes. The abundance of CREE in
Neisseria
genomes suggests that they may have played a role in genome organization, function, and evolution. Their differential distribution in different pathogenic
Neisseria
strains may contribute to the distinct behaviors of each
Neisseria
species.
Poly-β-Hydroxybutyrate Biosynthesis in the Facultative Methylotroph
Methylobacterium extorquens
AM1: Identification and Mutation of
gap11
,
gap20
, and
phaR
Authors: Korotkova Natalia , Chistoserdova Ludmila , Lidstrom Mary E.
Published: October 2002

Methylobacterium extorquens
AM1, a serine cycle facultative methylotroph, accumulates poly-β-hydroxybutyrate (PHB) as a carbon and energy reserve material during growth on both multicarbon- and single-carbon substrates. Recently, the identification and mutation of the genes involved in the biosynthesis and degradation of PHB have been described for this bacterium, demonstrating that two of the genes of the PHB cycle (
phaA
and
phaB
) are also involved in C
1
and C
2
metabolism, as part of a novel pathway for glyoxylate regeneration in the serine cycle (N. Korotkova and M. E. Lidstrom, J. Bacteriol. 183:1038-1046, 2001; N. Korotkova, L. Chistoserdova, V. Kuksa, and M. E. Lidstrom, J. Bacteriol. 184:1750-1758, 2002). In this work, three new genes involved in PHB biosynthesis in this bacterium have been investigated via mutation and phenotypic analysis:
gap11
,
gap20
, and
phaR
. We demonstrate that
gap11
and
gap20
encode two major granule-associated proteins (phasins) and that mutants with mutations in these genes are defective in PHB production and also in growth on C
2
compounds, while they show wild-type growth characteristics on C
1
or multicarbon compounds. The
phaR
mutant shows defects in both PHB accumulation and growth characteristics when grown on C
1
compounds and has defects in PHB accumulation but grows normally on C
3
and C
4
compounds, while both PHB accumulation and growth rate are at wild-type levels during growth on C
2
compounds. Our results suggest that this phenotype is due to altered fluxes of acetyl coenzyme A (CoA), a major intermediate in C
1
, C
2
, and heterotrophic metabolism in
M. extorquens
AM1, as well as the entry metabolite for the PHB cycle. Therefore, it seems likely that PhaR acts to control acetyl-CoA flux to PHB in this methylotrophic bacterium.
Chloride, a New Environmental Signal Molecule Involved in Gene Regulation in a Moderately Halophilic Bacterium,Halobacillus halophilus
Authors: Roeβler Markus , Müller Volker
Published: October 2002

The gram-positive, aerobic, moderately halophilic bacteriumHalobacillus halophilusis challenged in its environment by frequently changing salt (NaCl) concentrations. Recently,H. halophiluswas shown to be the first prokaryote that is dependent on Cl−for growth. In a search for the biological function of Cl−in this prokaryote, we identified different Cl−-dependent processes, which suggests a more general role for Cl−in the metabolism ofH. halophilus. To analyze the effect of Cl−in more detail, we concentrated on one model system, the Cl−-dependent production of flagella, and aimed to identify the molecular basis for the Cl−dependence of flagellum production. Here, we report that synthesis of the major subunit of the flagellum, FliC, is dependent on the Cl−concentration of the medium, as determined by Western blot analyses. The gene encoding FliC was cloned and sequenced, and Northern blot as well as reverse transcriptase PCR analyses revealed that expression offliCis Cl−dependent. FliC is the first protein of known function demonstrated to be synthesized in a Cl−-dependent manner in a prokaryote. Two-dimensional gel electrophoresis of cells grown under different conditions revealed five more Cl−-induced proteins; these were identified by N-terminal sequencing and database searches to be orthologs of proteins involved in stress response inBacillus subtilis. The data indicate that Cl−is an important environmental signal in this moderate halophile and regulates protein synthesis and gene expression. Furthermore, the data may suggest that Cl−plays a role in the signal transduction involved in salt perception by this bacterium.
Escherichia coli
Gene Expression Responsive to Levels of the Response Regulator EvgA
Authors: Masuda Nobuhisa , Church George M.
Published: October 2002

To investigate the function of the EvgA response regulator, we compared the genome-wide transcription profile of EvgA-overexpressing and EvgA-lacking
Escherichia coli
strains by oligonucleotide microarrays. The microarray measurements allowed the identification of at least 37 EvgA-activated genes, including acid resistance-related genes
gadABC
and
hdeAB
, efflux pump genes
yhiUV
and
emrK
, and 21 genes with unknown function. EvgA overexpression conferred acid resistance to exponentially growing cells. This acid resistance was abolished by deletion of
ydeP
,
ydeO
, or
yhiE
, which was induced by EvgA overexpression. These results suggest that
ydeP
,
ydeO
, and
yhiE
are novel genes related to acid resistance and that EvgA regulates several acid resistance genes. Furthermore, the deletion of
yhiE
completely abolished acid resistance in stationary-phase cells, suggesting that YhiE plays a critical role in stationary-phase acid resistance. The multidrug resistance in an
acrB
deletion mutant caused by EvgA overexpression was completely abolished by deletion of
yhiUV
, while the
emrKY
deletion had no effect on the increase in resistance by EvgA overexpression. In addition, EvgA overexpression did not confer resistance in a
tolC
-deficient strain. These results suggest that YhiUV induced by EvgA overexpression is functionally associated with TolC and contributes to multidrug resistance.
Phenotypes of
lexA
Mutations in
Salmonella enterica
: Evidence for a Lethal
lexA
Null Phenotype Due to the Fels-2 Prophage
Authors: Bunny Kim , Liu Jing , Roth John
Published: October 2002

The LexA protein of
Escherichia coli
represses the damage-inducible SOS regulon, which includes genes for repair of DNA. Surprisingly,
lexA
null mutations in
Salmonella enterica
are lethal even with a
sulA
mutation, which corrects
lexA
lethality in
E. coli
. Nine suppressors of lethality isolated in a
sulA
mutant of
S. enterica
had lost the Fels-2 prophage, and seven of these (which grew better) had also lost the Gifsy-1 and Gifsy-2 prophages. All three phage genomes included a homologue of the
tum
gene of coliphage 186, which encodes a LexA-repressed cI antirepressor. The
tum
homologue of Fels-2 was responsible for
lexA
lethality and had a LexA-repressed promoter. This basis of
lexA
lethality was unexpected because the four prophages of
S. enterica
LT2 are not strongly UV inducible and do not sensitize strains to UV killing. In
S. enterica
,
lexA
(Ind
−
) mutants have the same phenotypes as their
E. coli
counterparts. Although
lexA
null mutants express their error-prone DinB polymerase constitutively, they are not mutators in either
S. enterica
or
E. coli
.
Bacillus subtilisYhaM, a Member of a New Family of 3′-to-5′ Exonucleases in Gram-Positive Bacteria
Authors: Oussenko Irina A. , Sanchez Roberto , Bechhofer David H.
Published: October 2002

A strain ofBacillus subtilislacking two 3′-to-5′ exoribonucleases, polynucleotide phosphorylase (PNPase) and RNase R, was used to purify another 3′-to-5′ exoribonuclease, which is encoded by theyhaMgene. YhaM was active in the presence of Mn2+(or Co2+), was inactive in the presence of Mg2+, and could also degrade single-stranded DNA. The half-life of bulk mRNA in a mutant lacking PNPase, RNase R, and YhaM was not significantly different from that of the wild type, suggesting the existence of additional activities that can participate in mRNA turnover. Sequence homologues of YhaM were found only in gram-positive organisms. TheStaphylococcus aureushomologue, CBF1, which had been characterized as a double-stranded DNA binding protein involved in plasmid replication, was also shown to be an Mn2+-dependent exoribonuclease. YhaM protein has a C-terminal “HD domain,” found in metal-dependent phosphohydrolases. By structure modeling, it was shown that YhaM also contains an N-terminal “OB-fold,” present in many oligosaccharide- and oligonucleotide-binding proteins. The combination of these two domains is unique. Thus, YhaM and 10 related proteins from gram-positive organisms constitute a new exonuclease family.
Gene Structure, Organization, Expression, and Potential Regulatory Mechanisms of Arginine Catabolism inEnterococcus faecalis
Authors: Barcelona-Andrés Belén , Marina Alberto , Rubio Vicente
Published: October 2002

AlthoughEnteroccus faecalisis the paradigm for biochemical studies on the arginine deiminase (ADI) pathway of fermentative arginine catabolism, little genetic information exists on this pathway in this organism. We fill this important gap by characterizing, in an 8,228-bp region cloned from a λgt11 genomic library ofE. faecalis, a five-gene cluster forming a transcriptional unit (revealed by Northern blots and primer extension inE. faecalis) that corresponds to the ADI operon. Four additional genes in the opposite DNA strand and one in the same DNA strand are also identified. Studies on the protein products, including heterologous expression and/or sequence comparisons, allow us to ascertain or propose functions for all but 1 of the 10 genes. The ADI operon genes,arcABCRD, encode, respectively, ADI, ornithine transcarbamylase, carbamate kinase, a putative Crp/Fnr-type regulator (ArcR), and a putative ornithine-arginine antiporter (ArcD). Arginine induces the expression ofarcABCRD, most likely by means of two homologous ArgR/AhrC-type regulators encoded by two genes,argR1andargR2, that precedearcABCRDin each DNA strand and that are transcribed monocistronically, their transcription being influenced differentially by glucose and arginine. Potential ArgR1/ArgR2 (double and single) binding sequences are found in the promoter regions ofarcAand ofargR1/argR2themselves. In addition, putative binding sequences for ArcR and for CcpA are found, respectively, in theargR1/argR2andarcApromoter regions. Of the three other genes identified, two form a transcriptional unit and encode a putative metal-sensitive transcriptional regulator (ArsR) and a cysteine protease.
Genes Coding for a New Pathway of Aerobic Benzoate Metabolism in
Azoarcus evansii
Authors: Gescher Johannes , Zaar Annette , Mohamed Magdy , Schägger Hermann , Fuchs Georg
Published: October 2002

A new pathway for aerobic benzoate oxidation has been postulated for
Azoarcus evansii
and for a
Bacillus stearothermophilus
-like strain. Benzoate is first transformed into benzoyl coenzyme A (benzoyl-CoA), which subsequently is oxidized to 3-hydroxyadipyl-CoA and then to 3-ketoadipyl-CoA; all intermediates are CoA thioesters. The genes coding for this benzoate-induced pathway were investigated in the β-proteobacterium
A. evansii
. They were identified on the basis of N-terminal amino acid sequences of purified benzoate metabolic enzymes and of benzoate-induced proteins identified on two-dimensional gels. Fifteen genes probably coding for the benzoate pathway were found to be clustered on the chromosome. These genes code for the following functions: a putative ATP-dependent benzoate transport system, benzoate-CoA ligase, a putative benzoyl-CoA oxygenase, a putative isomerizing enzyme, a putative ring-opening enzyme, enzymes for β-oxidation of CoA-activated intermediates, thioesterase, and lactone hydrolase, as well as completely unknown enzymes belonging to new protein families. An unusual putative regulator protein consists of a regulator protein and a shikimate kinase I-type domain. A deletion mutant with a deletion in one gene (
boxA
) was unable to grow with benzoate as the sole organic substrate, but it was able to grow with 3-hydroxybenzoate and adipate. The data support the proposed pathway, which postulates operation of a new type of ring-hydroxylating dioxygenase acting on benzoyl-CoA and nonoxygenolytic ring cleavage. A β-oxidation-like metabolism of the ring cleavage product is thought to lead to 3-ketoadipyl-CoA, which finally is cleaved into succinyl-CoA and acetyl-CoA.
Postgenomic Analysis of Four Novel Antigens of Group A
Streptococcus
: Growth Phase-Dependent Gene Transcription and Human Serologic Response
Authors: Reid Sean D. , Green Nicole M. , Sylva Gail L. , Voyich Jovanka M. , Stenseth Elisha T. , DeLeo Frank R. , Palzkill Timothy , Low Donald E. , Hill Harry R. , Musser James M.
Published: October 2002

Analysis of three group A
Streptococcus
genomes (serotypes M1, M3, and M18) recently identified four previously undescribed genes that encode extracellular proteins. Each of these genes encode proteins with an LPXTG amino acid motif that covalently links many virulence factors produced by gram-positive bacteria to the cell surface. Western immunoblot analysis of serum samples obtained from 80 patients with invasive infections, noninvasive soft tissue infections, pharyngitis, and rheumatic fever indicated that these four proteins are expressed in vivo. However, the level of gene transcript and the time of maximal gene transcription varied in representative serotype M1, M3, and M18 strains. Surface expression of two proteins was confirmed by flow cytometry. Studies using a mouse infection model suggest that antibodies specific for one of the proteins (Spy0843) may contribute to a protective host immune response against a serotype M1 infection. These results are additional evidence that postgenomic strategies provide new ways to identify and investigate novel bacterial proteins that may participate in host-pathogen interactions or serve as targets for therapeutics research.
Novel Two-Component Regulatory System Involved in Biofilm Formation and Acid Resistance inStreptococcus mutans
Authors: Li Yung-Hua , Lau Peter C. Y. , Tang Nan , Svensäter Gunnel , Ellen Richard P. , Cvitkovitch Dennis G.
Published: October 2002

The abilities ofStreptococcus mutansto form biofilms and to survive acidic pH are regarded as two important virulence determinants in the pathogenesis of dental caries. Environmental stimuli are thought to regulate the expression of several genes associated with virulence factors through the activity of two-component signal transduction systems. Yet, little is known of the involvement of these systems in the physiology and pathogenicity ofS. mutans. In this study, we describe a two-component regulatory system and its involvement in biofilm formation and acid resistance inS. mutans. By searching theS. mutansgenome database with tblastn with the HK03 and RR03 protein sequences fromS. pneumoniaeas queries, we identified two genes, designatedhk11andrr11, that encode a putative histidine kinase and its cognate response regulator. To gain insight into their function, a PCR-mediated allelic-exchange mutagenesis strategy was used to create thehk11(Emr) andrr11(Emr) deletion mutants fromS. mutanswild-type NG8 named SMHK11 and SMRR11, respectively. The mutants were examined for their growth rates, genetic competence, ability to form biofilms, and resistance to low-pH challenge. The results showed that deletion ofhk11orrr11resulted in defects in biofilm formation and resistance to acidic pH. Both mutants formed biofilms with reduced biomass (50 to 70% of the density of the parent strain). Scanning electron microscopy revealed that the biofilms formed by the mutants had sponge-like architecture with what appeared to be large gaps that resembled water channel-like structures. The mutant biofilms were composed of longer chains of cells than those of the parent biofilm. Deletion ofhk11also resulted in greatly diminished resistance to low pH, although we did not observe the same effect whenrr11was deleted. Genetic competence was not affected in either mutant. The results suggested that the gene product ofhk11inS. mutansmight act as a pH sensor that could cross talk with one or more response regulators. We conclude that the two-component signal transduction system encoded byhk11andrr11represents a new regulatory system involved in biofilm formation and acid resistance inS. mutans.
Regulation and Physiological Significance of ClpC and ClpP in
Streptococcus mutans
Authors: Lemos José A. C. , Burne Robert A.
Published: October 2002

Tolerance of environmental stress, especially low pH, by
Streptococcus mutans
is central to the virulence of this organism. The Clp ATPases are implicated in the tolerance of, and regulation of the response to, stresses by virtue of their protein reactivation and remodeling activities and their capacity to target misfolded proteins for degradation by the ClpP peptidase. The purpose of this study was to dissect the role of selected
clp
genes in the stress responses of
S. mutans
, with a particular focus on acid tolerance and adaptation. Homologues of the
clpB
,
clpC
,
clpE
,
clpL
,
clpX
, and
clpP
genes were identified in the
S. mutans
genome. The expression of
clpC
and
clpP
, which were chosen as the focus of this study, was induced at low pH and at growth above 40°C. Inactivation of
ctsR
, the first of two genes in the
clpC
operon, demonstrated that CtsR acts as a repressor of
clp
and
groES-EL
gene expression. Strains lacking ClpP, but not strains lacking ClpC, were impaired in their ability to grow under stress-inducing conditions, formed long chains, aggregated in culture, had reduced genetic transformation efficiencies, and had a reduced capacity to form biofilms. Comparison of two-dimensional protein gels from wild-type cells and the
ctsR
and
clpP
mutants revealed many changes in the protein expression patterns. In particular, in the
clpP
mutant, there was an increased production of GroESL and DnaK, suggesting that cells were stressed, probably due to the accumulation of denatured proteins.
WEAK UCP AND PERTURBED MONOPOLE EQUATIONS
Authors: BOOSS-BAVNBEK BERNHELM , MARCOLLI MATILDE , WANG BAI-LING
Published: October 2002

We give a simple proof of weak Unique Continuation Property for perturbed Dirac operators, using the Carleman inequality. We apply the result to a class of perturbations of the Seiberg–Witten monopole equations that arise in Floer theory.
PROGRAM DEVELOPMENT FOR COMPUTATIONAL GRIDS USING SKELETONS AND PERFORMANCE PREDICTION
Authors: ALT MARTIN , BISCHOF HOLGER , GORLATCH SERGEI
Published: October 2002

We address the challenging problem of algorithm and program design for the Computational Grid by providing the application user with a set of high-level, parameterised components called skeletons. We descrile a Java-based Grid programming system in which algorithmns are composed of skeletons and the computational resources for executing individual skeletons are chosen using performance prediction. The advantage of our approach is that skeletons are reusable for different applications and that skeletons' implementation can be tuned to particular machines. The focus of this paper is on predicting performance for Grid applications constructed using skeletons.
USING METAPROGRAMMING TO PARALLELIZE FUNCTIONAL SPECIFICATIONS
Authors: HERRMANN CHRISTOPH A. , LENGAUER CHRISTIAN
Published: October 2002

Metaprogramming is a paradigm for enhancing a general-purpose programming language with features catering for a special-purpose application domain, without a need for a reimplementation of the language. In a staged compilation, the special-purpose features are translated and optimised by a domain-specific preprocessor, which hands over to the general-purpose compiler for translation of the domain-independent part of the program. The domain we work in is high-performance parallel computing. We use metaprogramming to enhance the functional language Haskell with features for the efficient, parallel implementation of certain computational patterns, called skeletons.
AN OPERATIONAL SEMANTICS FOR THE PARALLEL LANGUAGE EDEN
Authors: HIDALGO-HERRERO MERCEDES , ORTEGA-MALLÉN YOLANDA
Published: October 2002

The functional parallel language Eden — suitable for the description of parallel and concurrent algorithms in a distributed setting — is an extension of Haskell with a set of coordination features. In this paper we present a formal operational semantics for the kernel of Eden, or more precisely, for a λ-calculus widened with explicit parallelism and potentially infinite communication channels. Eden overrides the lazy nature of Haskell on behalf of parallelism. This interplay between laziness and eagerness is accurately described by the semantics proposed here, which is based on Launchbury's natural semantics for lazy evaluation, and is expressed through a two-level transition system: a lower level for the local and independent evaluation of each process, and an upper one for the coordination between all the parallel processes in the system. As processes are created either under demand or in a speculative way, different scheduling strategies are possible — ranging from a minimal one that only allows the main thread to evolve, to a maximal one that evolves in parallel every active binding.
TURING UNIVERSALITY OF RECURSIVE PATTERNS FOR PARALLEL PROGRAMMING
Authors: FISCHER JÖRG , GORLATCH SERGEI
Published: October 2002

Dijkstra's famous thesis "goto considered harmful", which paved the way for structured programming, was formally substantiated by the result of Böhm and Jacopini on the Turing universality of the three well-known basic programming constructs. We argue for a similar ideal in parallel programming — "send-receive considered harmful" — i.e. abandoning explicit send-receive statements between processors and expressing programs using a restricted set of parallel constructs. We deal with recursive patterns of parallelism, represented formally as morphisms in a suitable calculus.

The aim of this paper is to study the expressive power of two morphisms – catamorphisms and anamorphisms. For a restricted program calculus based on these morphisms, we constructively prove two formal results, whose pragmatic message is: (1) A programming language based on catamorphisms is computationally equivalent to the class of primitive recursive functions; (2) A programming language based on both catamorphisms and anamorphisms is equivalent to the class of partial recursive functions and is therefore Turing-universal. We present a case study on numerical integration, demonstrating the expressive power of ana- and catamorphisms for parallel programming.
LIFTING SEQUENTIAL FUNCTIONS TO PARALLEL SKELETONS
Authors: NITSCHE THOMAS
Published: October 2002

This paper describes the transformation of (almost arbitrary) sequential functions on covers to parallel, collective operations (skeletons). This allows the direct re-use of existing, but sequential, code on parallel machines without the necessity to hand-code the desired parallel operations. A necessary pre-requisite for this skeleton lifting is the availability of a cover which holds the mapping information of the local subobjects, including their topology information. The lifting transformation distinguishes sequential values, which are available on each processor, from parallel values, which are only stored once. Accesses to parallel values are either ignored locally if they will be computed on another processor, or they induce communication messages to transfer the necessary data, depending on the behavior of the original function.
THE CASE FOR DISCRETE ENERGY LEVELS OF A BLACK HOLE
Authors: BEKENSTEIN JACOB D.
Published: October 2002

The adiabatic invariant nature of black hole horizon area in a classical gravity suggests that in quantum theory the corresponding operator has a discrete spectrum. I here develop further an algebraic approach to black hole quantization which starts from very elementary assumptions, and proceeds by exploiting symmetry. It predicts a uniformly spaced area spectrum for all charges and angular momenta. Area eigenvalues are degenerate; correspondence with black hole entropy then dictates a precise value for the interval between eigenvalues.
INFLATION AND STRING COSMOLOGY
Authors: LINDE ANDREI
Published: October 2002

I will give a brief review of the various versions of inflationary theory, from Starobinsky model to chaotic inflation, and of recent observational data supporting inflationary theory. In the second part of the talk I will discuss the recently proposed ekpyrotic scenario and argue that in its present form it does not provide a viable alternative to inflation.
GAUGE FIELDS AND SPACE-TIME
Authors: POLYAKOV A. M.
Published: October 2002

In this article I attempt to collect some ideas, opinions and formulae which may be useful in solving the problem of gauge/string/space-time correspondence. This includes the validity of D-brane representation, counting of gauge-invariant words, relations between the null states and the Yang-Mills equations and the discussion of the strong coupling limit of the string sigma model. The article is based on the talk given at the "Odyssey 2001" conference.
MAKING SENSE OF THE NEW COSMOLOGY
Authors: TURNER MICHAEL S.
Published: October 2002

Over the past three years we have determined the basic features of the Universe — spatially flat; accelerating; comprised of 1/3 a new form of matter, 2/3 a new form of energy, with some ordinary matter and a dash of massive neutrinos; and apparently born from a burst of rapid expansion during which quantum noise was stretched to astrophysical size seeding cosmic structure. The New Cosmology greatly extends the highly successful hot big-bang model. Now we have to make sense of all this: What is the dark matter particle? What is the nature of the dark energy? Why this mixture? How did the matter — antimatter asymmetry arise? What is the underlying cause of inflation (if it indeed occurred)?
GEOMETRY AND SPACETIME
Authors: YAU SHING TUNG
Published: October 2002

The geometry of spacetime has a deep influence on our physical world. Hence any significant understanding of our physical world gives rise to important insights into geometry. The exchange of ideas between geometry and fundamental physics have been extensive in the past twenty years. Ideas from string theory have been vital in unifying several disciplines in mathematics.

In this talk, I shall discuss a few examples in geometry that are related to physics.
FEYNMAN PATH INTEGRAL REPRESENTATIONS FOR THE CLASSICAL DAMPED HARMONIC OSCILLATOR WITH STOCHASTIC FREQUENCY
Authors: BOTELHO LUIZ C. L.
Published: October 2002

We propose a Feynman path-integral solution for classical damped harmonic oscillator motions with stochastic frequency.
PERSISTENCE PROBABILITY IN FINANCIAL DYNAMICS
Authors: ZHENG B.
Published: October 2002

The persistence probability in the dynamics of a German stock index (DAX) is investigated using daily data from 1959 to 1997 and minute-to-minute records from 1994 to 1997. Scaling behavior is found extending at least from half an hour to some months, and it is characterized by two exponents. One exponent originates from the evolution of the background.
BERRY PHASE IN AN EFFECTIVE SU(1,1) SYSTEM
Authors: JIN YANHONG , LI ZHIJIAN , LIANG J.-Q.
Published: October 2002

We study the dynamics of a quantum system with a time-dependent Hamiltonian which is given by a linear combination of SU(1,1) generators and coupled with a heat bath. An effective Hamiltonian of this dissipative system is derived. With the help of a time-dependent gauge transformation, we obtain the exact solutions of the time-dependent Schrödinger equation, from which the time-evolution operator and the non-adiabatic and adiabatic Berry phases, which depend on time, are calculated explicitly. In the weak dissipation limit, an additional term besides the original Berry phase is found. The additional phase does not have a geometrical meaning due to the dissipation.
Prevention of Hypertrophy by Overexpression of Kv4.2 in Cultured Neonatal Cardiomyocytes
Authors: Zobel Carsten , Kassiri Zameneh , Nguyen The-Tin T. , Meng Yang , Backx Peter H.
Published: October 2002

Background—

Prolonged action potentials (APs) and decreased transient outward K
+
currents (
I
to
) are consistent findings in hypertrophic myocardium. However, the connection of these changes with cardiac hypertrophy is unknown. The present study investigated the effects of changes in
I
to
and the associated alterations in AP on myocyte hypertrophy induced by phenylephrine.

Methods and Results—

Chronic incubation of cultured neonatal ventricular rat myocytes (NVRMs) with phenylephrine (PE) reduced
I
to
density and prolonged AP duration, leading to a 2-fold increase in the net Ca
2+
influx per beat and a 1.4-fold increase in Ca
2+
-transient amplitude. PE treatment of chronically paced (2-Hz) NVRM also induced increases in cell size, protein/DNA ratio, atrial natriuretic factor mRNA expression, as well as β/α myosin mRNA ratio. These hypertrophic changes were associated with a 2.4-fold increase in activation of nuclear factor of activated T-cells (NFAT), indicating increased activity of the Ca
2+
-dependent phosphatase calcineurin. Overexpression of Kv4.2 channels using adenovirus prevented the AP duration prolongation as well as the increases in Ca
2+
influx and Ca
2+
-transient amplitude induced by PE. Kv4.2 overexpression also prohibited the PE-induced increases in cell size, protein/DNA ratio, atrial natriuretic factor expression, β/α myosin mRNA ratio, and NFAT activation.

Conclusions—

Our results demonstrate that PE-mediated hypertrophy in NRVMs seems to require
I
to
reductions and AP prolongation associated with increased Ca
2+
influx and Ca
2+
transients as well as calcineurin activation. The clinical implications of these studies and the possible involvement of other signaling pathways are discussed.
Plasminogen Activator Inhibitor-1 Promotes Formation of Endothelial Microparticles With Procoagulant Potential
Authors: Brodsky Sergey V. , Malinowski Kazimierz , Golightly Marc , Jesty Jolyon , Goligorsky Michael S.
Published: October 2002

Background—

Endothelial dysfunction is emerging as a common denominator for diverse and highly prevalent cardiovascular diseases. Increased level of plasminogen activator inhibitor-1 (PAI-1) and procoagulant activity have been recognized as hallmarks of endothelial dysfunction. This study was aimed at investigating cellular actions of PAI-1 and a potential link between PAI-1 and procoagulant state.

Methods and Results—

Human umbilical vein endothelial cells treated with PAI-1 were subjected to laser confocal fluorescence microscopy, immunoprecipitation and Western blotting, and FACS analysis for isolation and identification of endothelial microparticles. PAI-1 treatment resulted in a reduced expression of uPAR, its colocalization with caveolin, and the concomitant increase of uPAR abundance in the culture medium. FACS analysis revealed that PAI-1 rapidly and dose-dependently increased the number of endothelial microparticles expressing uPAR and α
V
β
3
integrin. This process was attenuated by pretreatment with neutralizing anti-uPAR antibodies. PAI-1 knockout mice showed a significantly decreased number of circulating endothelial microparticles than wild-type mice; however, PAI-1–deficient animals responded to infusion of PAI-1 with a more pronounced rise in the number of microparticles. PAI-1 treatment increased the number of microparticles stained with Annexin V, evidence for the expression of anionic phospholipids. This was accompanied by the accelerated generation of thrombin.

Conclusions—

The data disclose a novel effect of PAI-1 to dose-dependently promote formation of endothelial microparticles with the reduced transmembrane asymmetry of phospholipids. This phenomenon may be responsible for the observed increase in in vitro thrombin generation. These findings could potentially link these hallmarks of endothelial dysfunction—elevated levels of PAI-1 and propensity toward thrombosis.
Oral Everolimus Inhibits In-Stent Neointimal Growth
Authors: Farb Andrew , John Michael , Acampado Eduardo , Kolodgie Frank D. , Prescott Margaret Forney , Virmani Renu
Published: October 2002

Background—

Rapamycin (sirolimus)-eluting stents are associated with reduced restenosis rates in animal studies and initial human trials. The present study evaluated whether orally administered everolimus (a macrolide of the same family as sirolimus) inhibits in-stent neointimal growth in rabbit iliac arteries.

Methods and Results—

New Zealand white rabbits were randomized to everolimus 1.5 mg/kg per day starting 3 days before stenting and reduced to 1 mg/kg per day from days 14 to 28 (group 1), everolimus 1.5 mg/kg given 1 day before stenting followed by 0.75 mg/kg per day for 28 days (group 2), or matching placebo for each group. Drugs were administered by oral gavage. Stents were deployed in both iliac arteries, and arteries were harvested 28 days after stenting. Group 1 everolimus-treated rabbits experienced weight loss and anorexia, which resolved after the everolimus dose was lowered on day 14. Group 2 animals were healthy for the duration of everolimus dosing. Both everolimus treatment groups significantly reduced in-stent neointimal growth (46% reduction and 42% reduction in intimal thickness in groups 1 and 2, respectively). In group 2 everolimus-treated animals, the neointima was healed or healing, characterized by stent struts covered by a thin neointima, overlying endothelial cells, and only small foci of fibrin. Scanning electron microscopy showed >80% stent surface endothelialization in group 2 everolimus-treated rabbits.

Conclusions—

Oral everolimus suppresses in-stent neointimal growth in the rabbit iliac artery. At a dose of 1.5 mg/kg given 1 day before stenting followed by 0.75 mg/kg per day for 28 days, everolimus was well tolerated and was associated with significant neointimal healing.
Prostacyclin-Deficient Mice Develop Ischemic Renal Disorders, Including Nephrosclerosis and Renal Infarction
Authors: Yokoyama Chieko , Yabuki Tomoko , Shimonishi Manabu , Wada Masayuki , Hatae Toshihisa , Ohkawara Susumu , Takeda Junji , Kinoshita Taroh , Okabe Masaru , Tanabe Tadashi
Published: October 2002

Background—

Prostacyclin (PGI
2
) is a short-lived endogenous inhibitor of platelet aggregation and a potent vasodilator and regulator of the growth of vascular smooth muscle cells. To study the role of PGI
2
in the vascular system in vivo, PGI
2
-deficient (PGID) mice were established by genetic disruption of the PGI
2
synthase gene.

Methods and Results—

PGI
2
synthase–null mice were generated by replacing the exons of PGI
2
synthase gene that encodes for the catalytic site of the enzyme with a neomycin resistance gene. In these mice, PGI
2
levels in the plasma, kidneys, and lungs were reduced, whereas thromboxane and prostaglandin E
2
levels became elevated. Blood pressure and the amounts of urea nitrogen and creatinine in plasma of the PGID mice were significantly higher than those of wild-type mice (
P
<0.05). They developed progressive morphological abnormalities in the kidneys, accompanied by atrophy, surface irregularity, fibrosis, cyst, arterial sclerosis, and hypertrophy of vessel walls. Thickening of the thoracic aortic media and adventitia were observed in aged PGID mice. Importantly, these phenotypes have not been reported in PGI
2
receptor–deficient mice.

Conclusions—

PGI
2
deficiency resulted in the development of vascular disorders with the thickening of vascular walls and interstitial fibrosis, especially in mouse kidneys. The findings demonstrated in vivo that PGI
2
is important in the homeostasis of blood vessels. Our established PGID mice are useful for studies on the initiation and development of vascular diseases, such as ischemic renal disorders with arterial sclerosis and infarction, and also for studies on the novel signaling pathway of PGI
2
.
Left Ventricular Remodeling After Primary Coronary Angioplasty
Authors: Bolognese Leonardo , Neskovic Aleksandar N. , Parodi Guido , Cerisano Giampaolo , Buonamici Piergiovanni , Santoro Giovanni M. , Antoniucci David
Published: October 2002

Background—

We prospectively evaluated the prevalence, pattern, and prognostic impact of left ventricular (LV) remodeling after acute myocardial infarction (AMI) successfully treated with primary PTCA. The prevalence, course, and prognostic value of LV remodeling after primary PTCA are still to be clarified.

Methods and Results—

In 284 consecutive patients with AMI treated with primary PTCA, serial echocardiographic and angiographic studies, within 24 hours (T1), at 1 (T2) and 6 months (T3) after AMI were performed. Long-term (61±14 months) clinical follow-up data were collected for 98.6% patients enrolled in the study. Overall, 85 (30%) patients showed LV dilation (>20% end-diastolic volume increase) at T3 as compared with T1. Early (from T1 to T2), late (from T2 to T3), and progressive dilation patterns (from T1 to T2 to T3) were detected in 42 (15%), 41 (14%), and 36 (13%) patients, respectively. Cardiac death and combined events rate was significantly higher among patients with than among those without LV dilation (
P
=0.005 and
P
=0.025, respectively). The pattern of LV dilation during 6 months did not significantly affect survival. Cox survival analysis identified end-systolic volume at T1 and age as baseline predictors and end-systolic volume at T3 and age as 6-month predictors of cardiac death, respectively.

Conclusions—

LV remodeling after successful PTCA occurs despite sustained patency of the infarct-related artery and preservation of regional and global LV function. LV dilation at 6 months after AMI but not the specific pattern of LV dilation is clearly associated with worse long-term clinical outcome.
Cardiac Sympathetic Dysautonomia in Chronic Orthostatic Intolerance Syndromes
Authors: Goldstein David S. , Holmes Courtney , Frank Steven M. , Dendi Raghuveer , Cannon Richard O. , Sharabi Yehonatan , Esler Murray D. , Eisenhofer Graeme
Published: October 2002

Background—

In postural tachycardia syndrome (POTS) and repeated neurocardiogenic presyncope (NCS), orthostatic intolerance occurs without persistent sympathetic neurocirculatory failure. Whether these conditions involve abnormal cardiac sympathetic innervation or function has been unclear.

Methods and Results—

Patients with POTS or NCS underwent measurements of neurochemical indices of cardiac release, reuptake, and synthesis of the sympathetic neurotransmitter norepinephrine based on entry of norepinephrine into the cardiac venous drainage (cardiac norepinephrine spillover), cardiac extraction of circulating
3
H-norepinephrine, and cardiac production of dihydroxyphenylalanine and measurement of left ventricular myocardial innervation density using 6-[
18
F]fluorodopamine positron emission tomographic scanning. Mean cardiac norepinephrine spillover in POTS (171±30 pmol/min, N=16) was higher and in NCS (62±9 pmol/min, N=20) was lower than in a large group of healthy volunteers (102±9 pmol/min, N=52) and in a subgroup of age-matched healthy women (106±18 pmol/min, N=11). Both patient groups had normal cardiac extraction of
3
H-norepinephrine, normal cardiac production of dihydroxyphenylalanine, and normal myocardial 6-[
18
F]fluorodopamine-derived radioactivity.

Conclusions—

POTS and NCS differ in tonic cardiac sympathetic function, with increased cardiac norepinephrine release in the former and decreased release in the latter. Both groups had normal values for indices of function of the cell membrane norepinephrine transporter, norepinephrine synthesis, and density of myocardial sympathetic innervation. Because POTS and NCS both include specific abnormalities of cardiac sympathetic function, both can be considered forms of dysautonomia.
Magnetic Resonance Imaging Determination of Cardiac Prognosis
Authors: Hundley W. Gregory , Morgan Timothy M. , Neagle Christina M. , Hamilton Craig A. , Rerkpattanapipat Pairoj , Link Kerry M.
Published: October 2002

Background—

Regional assessments of left ventricular (LV) wall motion obtained during MRI cardiac stress tests can be used to identify myocardial injury and ischemia, but the utility of MRI stress test results for the assessment of cardiac prognosis is not known.

Methods and Results—

Two hundred seventy-nine patients referred (because of poor LV endocardial visualization with echocardiography) for dobutamine/atropine MRI for the detection of inducible ischemia were followed for an average of 20 months. After MRI stress testing, the occurrence of myocardial infarction, cardiac death, death attributable to any cause, coronary arterial revascularization, and unstable angina or congestive heart failure requiring hospitalization was determined. In a multivariate analysis, the presence of inducible ischemia (hazard ratio 3.3, CI 1.1 to 9.7) or an LV ejection fraction <40% (hazard ratio 4.2, CI 1.3 to 13.9) was associated with future MI or cardiac death independent of the presence of risk factors for coronary arteriosclerosis.

Conclusions—

In patients with poor echocardiograms, the results of cardiac MRI stress tests can be used to forecast myocardial infarction or cardiac death.
Reproducibility of Chronic Infarct Size Measurement by Contrast-Enhanced Magnetic Resonance Imaging
Authors: Mahrholdt Heiko , Wagner Anja , Holly Thomas A. , Elliott Michael D. , Bonow Robert O. , Kim Raymond J. , Judd Robert M.
Published: October 2002

Background—

The reproducibility of contrast-enhanced MRI has not been established. We compared MRI reproducibility for infarct size determination with that of
99m
Tc-sestamibi (MIBI) single photon emission computed tomography (SPECT).

Methods and Results—

Patients with chronic myocardial infarction defined by enzymes (peak creatine kinase-MB 173±119 U/L) were scanned twice by MRI (MRI I and MRI II, n=20) and twice by SPECT (SPECT I and SPECT II, n=15) on the same day. The MRI contrast agent was injected during MRI I but not MRI II to test the effect of imaging time after contrast. Resting Tc-MIBI SPECT images were acquired and infarct size was determined with commercial software. Infarct size in patients scanned by MRI and SPECT was 14±6% of left ventricular mass (%LV) by MRI (range 4%LV to 27%LV) and 14±7%LV by SPECT (range 4%LV to 26%LV). MRI I and II scans were performed 10±2 and 27±3 minutes after contrast, respectively. For MRI, the difference in infarct size between scans I and II (bias) was −0.1%LV, and the coefficient of repeatability was ±2.4%LV. For SPECT, bias was −1.3%LV, and the coefficient of repeatability was ±4.0%LV. Within individual patients, no systematic differences in infarct size were detected when the 2 MRI scans were compared, the 2 SPECT scans were compared, or MRI was compared to SPECT.

Conclusion—

The size of healed infarcts measured by contrast-enhanced MRI does not change between 10 and 30 minutes after contrast. The clinical reproducibility of contrast-enhanced MRI for infarct size determination compares favorably with that of routine clinical SPECT.