bluuebunny/crossref_metadata_2025 huggingface dataset:
Pricing and Hedging Credit Derivatives with Copulas
Authors: Cherubini Umberto , Luciano Elisa
Published: December 2003

In this paper, we apply a copula function pricing technique to the evaluation of credit derivatives, namely a vulnerable default put option and a credit switch. Also in this case, copulas enable one to separate the specification of marginal default probabilities from their dependence structure. Their use is based here on no–arbitrage arguments, which provide pricing bounds and easy–to–implement super–replication strategies.

At a second stage, we specify the copula function to be a mixture one. In this case, we obtain closed form prices and hedges, which we calibrate on real market data. For the sake of comparison, we add a Clayton calibration.

(J.E.L: G11, G12).
Contrasting water management techniques in Tunisia: towards sustainable agricultural use
Authors: Hill Jennifer , Woodland Wendy
Published: December 2003

Tunisia is a marginal country hydrologically and it has adopted a number of distinctive methods of water management for agriculture. The central region supports modern dam irrigation, whilst traditional rainwater harvesting is practiced in the south. These contrasting techniques are described and evaluated in terms of sustainability using empirical field data and secondary literature for two study sites. Research focuses primarily on the physical environment, but socio‐cultural and economic viability are also examined. Analysis indicates that traditional water management advantageously partitions the continuum dividing hazards and resources through subtle manipulation of the environment. A potentially hazardous environment is rendered secure by resourceful water management based on community action and cumulative knowledge. This practice minimizes community dependency and local economic imbalance. With dam irrigation, carrying capacity is established more forcibly by centralized control in order to place society within world markets. An almost total break from environmental variability is made in the short term, but this can lead to disequilibrium over longer durations. Additionally, the spatial and social distributions of development are uneven. In Tunisia, maintenance of traditional methods can reduce the negative impacts caused by modern programmes and support their positive characteristics. A mix of both methods offers a foundation to sustainable water supply in the new millennium.
The Regime-Dependent Determination of Credibility: A New Look at European Interest Rate Differentials
Authors: Tillmann Peter
Published: December 2003

With persistence in macroeconomic variables two aspects of exchange rate credibility emerge whose relative importance varies over time. Both aspects have opposite implications for the relation between fundamentals and credibility. Hence, the effect of policy measures on interest rate differentials becomes ambiguous. In this paper a Markov-switching VAR that allows for parameter shifts across regimes is employed to test the hypothesis of regime-dependent determination of credibility for major EMS currencies. Regime-dependent impulse response functions reveal substantial differences in the response of spreads to macroeconomic shocks across regimes.
The Biological Standard of Living in the Two Germanies
Authors: Komlos John , Kriwy Peter
Published: December 2003

Physical stature is used as a proxy for the biological standard of living in the two Germanies before and after unification in an analysis of a cross-sectional sample (1998) of adult heights, as well as among military recruits of the 1990s. West Germans tended to be taller than East Germans throughout the period under consideration. Contrary to official proclamations of a classless society, there were substantial social differences in physical stature in East Germany. Social differences in height were greater in the East among females, and less among males than in the West. The difficulties experienced by the East German population after 1961 is evident in the increase in social inequality of physical stature thereafter, as well as in the considerable gap relative to the height of the West German population. After unification, however, there is a tendency for East German males, but not of females, to catch up with their West German counterparts.
Ca2+ and frequency dependence of exocytosis in isolated somata of magnocellular supraoptic neurones of the rat hypothalamus
Authors: Soldo Brandi L. , Giovannucci David R. , Stuenkel Edward L. , Moises Hylan C.
Published: December 2003

In addition to action potential‐evoked exocytotic release at neurohypophysial nerve terminals, the neurohormones arginine vasopressin (aVP) and oxytocin (OT) undergo Ca2+‐dependent somatodendritic release within the supraoptic and paraventricular hypothalamic nuclei. However, the cellular and molecular mechanisms that underlie this release have not been elucidated. In the present study, the whole‐cell patch‐clamp technique was utilized in combination with high‐time‐resolved measurements of membrane capacitance (Cm) and microfluorometric measurements of cytosolic free Ca2+ concentration ([Ca2+]i) to examine the Ca2+ and stimulus dependence of exocytosis in the somata of magnocellular neurosecretory cells (MNCs) isolated from rat supraoptic nucleus (SON). Single depolarizing steps (≥20 ms) that evoked high‐voltage‐activated (HVA) Ca2+ currents (ICa) and elevations in intracellular Ca2+ concentration were accompanied by an increase in Cm in a majority (40/47) of SON neurones. The Cm responses were composed of an initial Ca2+‐independent, transient component and a subsequent, sustained phase of increased Cm (termed ΔCm) mediated by an influx of Ca2+, and increased with corresponding prolongation of depolarizing step durations (20–200 ms). From this relationship we estimated the rate of vesicular release to be 1533 vesicles s−1. Delivery of neurone‐derived action potential waveforms (APWs) as stimulus templates elicited ICa and also induced a ΔCm, provided APWs were applied in trains of greater than 13 Hz. A train of APWs modelled after the bursting pattern recorded from an OT‐containing neurone during the milk ejection reflex was effective in supporting an exocytotic ΔCm in isolated MNCs, indicating that the somata of SON neurones respond to physiological patterns of neuronal activity with Ca2+‐dependent exocytotic activity.
Alterations of Cell Wall Structure and MetabolismAccompany Reduced Susceptibility to Vancomycin in an IsogenicSeries of Clinical Isolates of
Staphylococcusaureus
Authors: Sieradzki K. , Tomasz A.
Published: December 2003

A
series of isogenic methicillin-resistant
Staphylococcus aureus
isolates recovered from a bacteremic patient were shown to acquire
gradually increasing levels of resistance to vancomycin during
chemotherapy with the drug (K. Sieradzki, T. Leski, L. Borio, J. Dick,
and A. Tomasz, J. Clin. Microbiol. 41:1687-1693,
2003). We compared properties of the earliest (parental)
vancomycin-susceptible isolate, JH1 (MIC, 1 μg/ml), to two late
(progeny) isolates, JH9 and JH14 (vancomycin MIC, 8 μg/ml). The
resistant isolates produced abnormally thick cell walls and poorly
separated cells when grown in antibiotic-free medium. Chemical analysis
of the resistant isolates showed decreased cross-linkage of the
peptidoglycan and drastically reduced levels of PBP4 as determined by
the fluorographic assay. Resistant isolates showed reduced rates of
cell wall turnover and autolysis. In vitro hydrolysis of resistant cell
walls by autolytic extracts prepared from either susceptible or
resistant strains was also slow, and this abnormality could be traced
to a quantitative (or qualitative) change in the wall teichoic acid
component of resistant isolates. Some change in the structure and/or
metabolism of teichoic acids appears to be an important component of
the mechanism of decreased susceptibility to vancomycin in
S.
aureus
.
Interaction between the H
2
Sensor HupUV and the Histidine Kinase HupT Controls HupSL HydrogenaseSynthesis in
Rhodobactercapsulatus
Authors: Elsen Sylvie , Duché Ophélie , Colbeau Annette
Published: December 2003

The
photosynthetic bacterium
Rhodobacter capsulatus
contains two
[NiFe]hydrogenases: an energy-generating hydrogenase, HupSL,
and a regulatory hydrogenase, HupUV. The synthesis of HupSL is
specifically activated by H
2
through a signal transduction
cascade comprising three proteins: the H
2
-sensing HupUV
protein, the histidine kinase HupT, and the transcriptional regulator
HupR. Whereas a phosphotransfer between HupT and HupR was previously
demonstrated, interaction between HupUV and HupT was only hypothesized
based on in vivo analyses of mutant phenotypes. To visualize the in
vitro interaction between HupUV and HupT proteins, a six-His
(His
6
)-HupU fusion protein and the HupV protein were
coproduced by using a homologous expression system. The two proteins
copurified as a His
6
-HupUHupV complex present in dimeric and
tetrameric forms, both of which had H
2
uptake activity. We
demonstrated that HupT and HupUV interact and form stable complexes
that could be separated on a native gel. Interaction was also monitored
with surface plasmon resonance technology and was shown to be
insensitive to salt concentration and pH changes, suggesting that the
interactions involve hydrophobic residues. As expected, H
2
affects the interaction between HupUV and HupT, leading to a weakening
of the interaction, which is independent of the phosphate status of
HupT. Several forms of HupT were tested for their ability to interact
with HupUV and to complement
hupT
mutants. Strong interaction
with HupUV was obtained with the isolated PAS domain of HupT and with
inactive HupT mutated in the phosphorylable histidine residue, but only
the wild-type HupT protein was able to restore normal H
2
regulation.
PropaneMonooxygenase and NAD
+
-Dependent Secondary AlcoholDehydrogenase in Propane Metabolism by
Gordonia
sp.StrainTY-5
Authors: Kotani Tetsuya , Yamamoto Tazuko , Yurimoto Hiroya , Sakai Yasuyoshi , Kato Nobuo
Published: December 2003

A
new isolate,
Gordonia
sp. strain TY-5, is capable of growth on
propane and
n
-alkanes with C
13
to C
22
carbon chains as the sole source of carbon. In whole-cell reactions,
significant propane oxidation to 2-propanol was detected. A gene
cluster designated
prmABCD
, which encodes the components of a
putative dinuclear-iron-containing multicomponent monooxygenase,
including the large and small subunits of the hydroxylase, an
NADH-dependent acceptor oxidoreductase, and a coupling protein, was
cloned and sequenced. A mutant with
prmB
disrupted
(
prmB
::Kan
r
) lost the ability
to grow on propane, and Northern blot analysis revealed that
polycistronic transcription of the
prm
genes was induced
during its growth on propane. These results indicate that the
prmABCD
gene products play an essential role in propane
oxidation by the bacterium. Downstream of the
prm
genes, an
open reading frame (
adh1
) encoding an
NAD
+
-dependent secondary alcohol dehydrogenase was
identified, and the protein was purified and characterized. The
Northern blot analysis results and growth properties of a disrupted
mutant (
adh1
::Kan
r
) indicate
that Adh1 plays a major role in propane metabolism. Two additional
NAD
+
-dependent secondary alcohol dehydrogenases
(Adh2 and Adh3) were also found to be involved in 2-propanol oxidation.
On the basis of these results, we conclude that
Gordonia
sp.
strain TY-5 oxidizes propane by monooxygenase-mediated subterminal
oxidation via
2-propanol.
FunctionalDomains of the RhlR Transcriptional Regulator of
Pseudomonas
aeruginosa
Authors: Lamb Janet R. , Patel Hetal , Montminy Timothy , Wagner Victoria E. , Iglewski Barbara H.
Published: December 2003

The
RhlR transcriptional regulator of
Pseudomonas
aeruginosa
, along with its cognate autoinducer,
N
-butyryl homoserine lactone (C
4
-HSL), regulates
gene expression in response to cell density. With an
Escherichia coli
LexA-based protein interaction
system, we demonstrated that RhlR multimerized and that the degree of
multimerization was dependent on the C
4
-HSL concentration.
Studies with an
E. coli
lasB
::
lacZ
lysogen demonstrated
that RhlR multimerization was necessary for it to function as a
transcriptional activator. Deletion analysis of RhlR indicated that the
N-terminal domain of the protein is necessary for C
4
-HSL
binding. Single amino acid substitutions in the C-terminal domain of
RhlR generated mutant RhlR proteins that had the ability to bind
C
4
-HSL and multimerize but were unable to activate
lasB
expression, demonstrating that the C-terminal domain is
important for target gene activation. Single amino acid substitutions
in both the N-terminal and C-terminal domains of RhlR demonstrated that
both domains possess residues involved in multimerization. RhlR with a
C-terminal deletion and an RhlR site-specific mutant form that
possessed multimerization but not transcriptional activation
capabilities were able to inhibit the ability of wild-type RhlR to
activate
rhlA
expression in
P. aeruginosa
.
We conclude that C
4
-HSL binding is necessary for RhlR
multimerization and that RhlR functions as a multimer in
P
.
aeruginosa
.
Transcriptional Regulation and PosttranslationalActivity of the Betaine Transporter BetL in
Listeriamonocytogenes
Are Controlled by EnvironmentalSalinity
Authors: Sleator Roy D. , Wood Janet M. , Hill Colin
Published: December 2003

While
the genetic elements contributing to the salinity tolerance of
Listeria monocytogenes
have been well characterized, the
regulatory signals and responses (genetic and/or biochemical) that
govern these mechanisms have yet to be elucidated. Encoded by
betL
, the first genetic element to be linked to listerial
osmotolerance, the secondary betaine uptake system BetL is a member of
the betaine-carnitine-choline transporter family. Preceded by consensusσ
A
- and σ
B
-dependent promoter
sites,
betL
is constitutively expressed and transcriptionally
up-regulated in response to salt stress. The nisin-controlled
expression system was used to achieve salinity-independent, controlled
betL
expression in
Listeria
. In the absence of
NaCl-activated transcriptional control, BetL activity was found to be a
function of environmental salinity, showing optimal activity in buffer
supplemented with 1 to 2% NaCl (osmolality, 417 to 719
mosmol/kg). In addition, BetL was activated rapidly (half-life, 2 min)
in response to an osmotic upshift imposed by adding 2% NaCl to
50 mM potassium phosphate
buffer.
The CroRS Two-Component Regulatory System Is Requiredfor Intrinsic β-Lactam Resistance in
Enterococcusfaecalis
Authors: Comenge Yannick , Quintiliani Richard , Li Ling , Dubost Lionnel , Brouard Jean-Paul , Hugonnet Jean-Emmanuel , Arthur Michel
Published: December 2003

Enterococcus
faecalis
produces a specific penicillin-binding protein (PBP5)
that mediates high-level resistance to the cephalosporin class ofβ
-lactam antibiotics. Deletion of a locus encoding a previously
uncharacterized two-component regulatory system of
E. faecalis
(
croRS
) led to a 4,000-fold reduction in the MIC of the
expanded-spectrum cephalosporin ceftriaxone. The cytoplasmic domain of
the sensor kinase (CroS) was purified and shown to catalyze
ATP-dependent autophosphorylation followed by transfer of the phosphate
to the mated response regulator (CroR). The
croR
and
croS
genes were cotranscribed from a promoter (
croRp
)
located in the
rrnC-croR
intergenic region. A putative
seryl-tRNA synthetase gene (
serS
) located immediately
downstream from
croS
did not appear to be a target of CroRS
regulation or to play a role in ceftriaxone resistance. A plasmid-borne
croRp-lacZ
fusion was
trans
-activated by the CroRS
system in response to the presence of ceftriaxone in the culture
medium. The fusion was also induced by representatives of other classes
of β-lactam antibiotics and by inhibitors of early and late
steps of peptidoglycan synthesis. The
croRS
null mutant
produced PBP5, and expression of an additional copy of
pbp5
under the control of a heterologous promoter did not restore
ceftriaxone resistance. Deletion of
croRS
was not associated
with any defect in the synthesis of the nucleotide precursor
UDP-MurNAc-pentapeptide or of the
d
-Ala
4
→
l
-Ala-
l
-Ala-Lys
3
peptidoglycan cross-bridge. Thus, the
croRS
mutant was
susceptible to ceftriaxone despite the production of PBP5 and the
synthesis of wild-type peptidoglycan precursors. These observations
constitute the first description of regulatory genes essential for
PBP5-mediated β-lactam resistance in
enterococci.
The
Klebsiella pneumoniae wabG
Gene: Role inBiosynthesis of the Core Lipopolysaccharide andVirulence
Authors: Izquierdo Luis , Coderch Núria , Piqué Nuria , Bedini Emiliano , Corsaro Maria Michela , Merino Susana , Fresno Sandra , Tomás Juan M. , Regué Miguel
Published: December 2003

To
determine the function of the
wabG
gene in the biosynthesis of
the core lipopolysaccharide (LPS) of
Klebsiella pneumoniae
, we
constructed
wabG
nonpolar mutants. Data obtained from the
comparative chemical and structural analysis of LPS samples obtained
from the wild type, the mutant strain, and the complemented mutant
demonstrated that the
wabG
gene is involved in attachment toα
-
l
-glycero-
d
-manno-heptopyranose II
(
l
,
d
-Hep
p
II) at the O-3 position of anα
-
d
-galactopyranosyluronic acid
(α-
d
-GalA
p
) residue.
K. pneumoniae
nonpolar
wabG
mutants were devoid of the cell-attached
capsular polysaccharide but were still able to produce capsular
polysaccharide. Similar results were obtained with
K.
pneumoniae
nonpolar
waaC
and
waaF
mutants, which
produce shorter LPS core molecules than do
wabG
mutants. Other
outer core
K. pneumoniae
nonpolar mutants in the
waa
gene cluster were encapsulated.
K. pneumoniae waaC
,
waaF
, and
wabG
mutants were avirulent when tested in
different animal models. Furthermore, these mutants were more sensitive
to some hydrophobic compounds than the wild-type strains. All these
characteristics were rescued by reintroduction of the
waaC
,
waaF
, and
wabG
genes from
K.
pneumoniae
.
Transcription of Quorum-Sensing System Genes inClinical and Environmental Isolates of
Pseudomonasaeruginosa
Authors: Cabrol Ségolène , Olliver Anne , Pier Gerald B. , Andremont Antoine , Ruimy Raymond
Published: December 2003

Quorum
sensing (QS)-based transcriptional responses in
Pseudomonas
aeruginosa
have been defined on the basis of increases in
transcript levels of QS-controlled genes such as
lasB
and
aprA
following the hierarchical transcriptional increases of
central controllers such as the
lasR
gene. These
increases occur at high bacterial concentrations such as
early-stationary-phase growth in vitro. However, the extent to which
the increases occur in a variety of clinical and environmental isolates
has not been determined nor is there extensive information on allelic
variation in
lasR
genes. An analysis of the sequences of the
lasR
gene among 66 clinical and environmental isolates showed
that 81% have a sequence either identical to that of strain PAO1
or with a silent mutation, 15% have nucleotide changes resulting
in amino acid changes, and 5% have an insertion sequence in the
lasR
gene. Using real-time PCR to quantify transcript levels
of
lasR
,
lasB
, and
aprA
in the early log and
early stationary phases among 35 isolates from bacteremia and pneumonia
cases and the environment, we found most (33 of 35) strains had
increases in
lasR
transcripts in early stationary phase but
with a very wide range of final transcript levels per cell. There was a
strong correlation (
r
2
= 0.84) between
early-log- and early-stationary-phase transcript levels in all strains,
but this finding remained true only for the 50% of strains above
the median level of
lasR
found in early log phase. There were
significant (
P
< 0.05) but weak-to-modest correlations
of
lasR
transcript levels with
aprA
(r
2
=
0.2) and
lasB
(
r
2
= 0.5)
transcript levels, but again this correlation occurred only in the
50% of
P. aeruginosa
strains with the highest levels of
lasR
transcripts in early stationary phase. There were no
differences in distribution of
lasR
alleles among the
bacteremia, pneumonia, or environmental isolates. Overall, only about
50% of
P. aeruginosa
strains from clinical and
environmental sources show a
lasR
-dependent increase in the
transcription of
aprA
and
lasB
genes, indicating that
for about 50% of clinical isolates this regulatory system may
not play a significant role in
pathogenesis.
Novel Type of Specialized Transduction forCTXφ or Its Satellite Phage RS1 Mediated by Filamentous PhageVGJφ in
Vibriocholerae
Authors: Campos Javier , Martínez Eriel , Marrero Karen , Silva Yussuan , Rodríguez Boris L. , Suzarte Edith , Ledón Talena , Fando Rafael
Published: December 2003

The
main virulence factor of
Vibrio cholerae
, the cholera toxin,
is encoded by the
ctxAB
operon, which is contained in the
genome of the lysogenic filamentous phage CTXφ. This phage
transmits
ctxAB
genes between
V. cholerae
bacterial
populations that express toxin-coregulated pilus (TCP), the
CTXφ receptor. In investigating new forms of
ctxAB
transmission, we found that
V. cholerae
filamentous phage
VGJφ, which uses the mannose-sensitive hemagglutinin (MSHA)
pilus as a receptor, transmits CTXφ or its satellite phage RS1
by an efficient and highly specific TCP-independent mechanism. This is
a novel type of specialized transduction consisting in the
site-specific cointegration of VGJφ and CTXφ (or RS1)
replicative forms to produce a single hybrid molecule, which generates
a single-stranded DNA hybrid genome that is packaged into hybrid viral
particles designated HybPφ (for the VGJφ/CTXφ
hybrid) and HybRSφ (for the VGJφ/RS1 hybrid). The
hybrid phages replicate by using the VGJφ replicating functions
and use the VGJφ capsid, retaining the ability to infect via
MSHA. The hybrid phages infect most tested strains more efficiently
than CTXφ, even under in vitro optimal conditions for TCP
expression. Infection and lysogenization with HybPφ revert the
V. cholerae
live attenuated vaccine strain 1333 to virulence.
Our results reinforce that TCP is not indispensable for the acquisition
of CTXφ. Thus, we discuss an alternative to the current
accepted evolutionary model for the emergence of new toxigenic strains
of
V. cholerae
and the importance of our findings for the
development of an environmentally safer live attenuated cholera
vaccine.
Horizontal Transfer of Segments of the 16S rRNA Genesbetween Species of the
Streptococcus anginosus
Group
Authors: Schouls Leo M. , Schot Corrie S. , Jacobs Jan A.
Published: December 2003

The
nature in variation of the 16S rRNA gene of members of the
Streptococcus anginosus
group was investigated by
hybridization and DNA sequencing. A collection of 708 strains was
analyzed by reverse line blot hybridization. This revealed the presence
of distinct reaction patterns representing 11 different hybridization
groups. The 16S rRNA genes of two strains of each hybridization group
were sequenced to near-completion, and the sequence data confirmed the
reverse line blot hybridization results. Closer inspection of the
sequences revealed mosaic-like structures, strongly suggesting
horizontal transfer of segments of the 16S rRNA gene between different
species belonging to the
Streptococcus anginosus
group.
Southern blot hybridization further showed that within a single strain
all copies of the 16S rRNA gene had the same composition, indicating
that the apparent mosaic structures were not PCR-induced artifacts.
These findings indicate that the highly conserved rRNA genes are also
subject to recombination and that these events may be fixed in the
population. Such recombination may lead to the construction of
incorrect phylogenetic trees based on the 16S rRNA
genes.
Controlof
Pseudomonas aeruginosa algZ
Expression bythe Alternative Sigma FactorAlgT
Authors: Wozniak Daniel J. , Sprinkle April B. , Baynham Patricia J.
Published: December 2003

AlgZ
controls
Pseudomonas aeruginosa
alginate synthesis by
activating
algD
, yet
algZ
expression is not
detectable in nonmucoid strains. Mobility shift and Western blot assays
revealed that
algZ
expression requires the sigma factor AlgT.
The mapped
algZ
transcription start site revealed a consensus
AlgT-dependent promoter that, when mutated, substantially reduced
algZ
transcription.
IMPLICATIONS OF WEAK-INTERACTION SPACE DEFORMATION FOR NEUTRINO MASS MEASUREMENTS
Authors: ŠIMIČEVIĆ NEVEN
Published: December 2003

The negative values for the squares of both electron and muon neutrino masses obtained in recent experiments are explained as a possible consequence of a change in metric within the weak-interaction volume in the energy–momentum representation. Using a model inspired by a combination of the general theory of relativity and the theory of deformation for continuous media, it is shown that the negative value of the square of the neutrino mass can be obtained without violating allowed physical limits. The consequence is that the negative value is not necessarily unphysical.
QUANTUM INTERFERENCE TO MEASURE SPACETIME CURVATURE: A PROPOSED EXPERIMENT AT THE INTERSECTION OF QUANTUM MECHANICS AND GENERAL RELATIVITY
Authors: CHIAO RAYMOND Y. , SPELIOTOPOULOS ACHILLES D.
Published: December 2003

An experiment in Low Earth Orbit (LEO) is proposed to measure components of the Riemann curvature tensor using atom interferometry. We show that the difference in the quantum phase Δϕ of an atom that can travel along two intersecting geodesics is given by mR0i0j/ℏ times the spacetime volume contained within the geodesics. Our expression for Δϕ also holds for gravitational waves in the long wavelength limit.
THE LIGHT SPEED AND THE INTERPLAY OF THE QUANTUM VACUUM, THE GRAVITATION OF ALL THE UNIVERSE AND THE FOURTH HEISENBERG RELATION
Authors: RAÑADA ANTONIO F.
Published: December 2003

A recently proposed model which accounts for the observed time dependence of the fine structure constant is summarized. The model is based on the combined effect of the fourth Heisenberg relation and the gravitation of all the expanding universe on the quantum vacuum. As is shown here, it predicts that the light must have now an acceleration close to H0c≃6.9×10-10 m/s2. This suggests an explanation of the anomalous acceleration aP≃8.5×10-10 m/s2 found in the Pioneer 10 spacecraft, because an acceleration of light has the same radio observational signature as an acceleration of the ship.
THE ASYMPTOTIC STRUCTURE OF SPACE-TIME
Authors: ADAMS FRED C. , BUSHA MICHAEL T. , EVRARD AUGUST E. , WECHSLER RISA H.
Published: December 2003

Astronomical observations strongly suggest that our universe is now accelerating and contains a substantial admixture of dark vacuum energy. Using numerical simulations to study this newly consolidated cosmological model (with a constant density of dark energy), we show that astronomical structures freeze out in the near future and that the density profiles of dark matter halos approach the same general form. Every dark matter halo grows asymptotically isolated and thereby becomes the center of its own island universe. Each of these isolated regions of space-time approaches a universal geometry and we calculate the corresponding form of the space-time metric.
NEW HINTS FROM GENERAL RELATIVITY
Authors: DREYER OLAF
Published: December 2003

The search for a quantum theory of gravity has followed two parallel but different paths. One aims at arriving at the final theory starting from a priori assumptions as to its form and building it from the ground up. The other tries to infer as much as possible about the unknown theory from the existing ones and use our current knowledge to constrain the possibilities for the quantum theory of gravity. Probably the biggest success of the second path has been the results of black hole thermodynamics. The subject of this essay is a new, highly promising such result, the application of quasinormal modes in quantum gravity.
BLACK HOLE SINGULARITIES, CRITICAL PHENOMENA, THE RUNAWAY UNIVERSE AND HYPERSPACE TRAVEL
Authors: BURKO LIOR M.
Published: December 2003

Black holes are always irradiated by the cosmic background radiation. This captured radiation field determines the physical and geometrical nature of the singularity inside the black hole. We find that non-compact radiation fields (similar to the cosmic background radiation) affect dramatically the singularity, and may determine the fate of a falling astronaut. In particular, the dark energy which accelerates the expansion of the universe determines whether the "tunnel" inside the black hole is blocked, or whether the possibility of using the black hole as a portal for hyperspace travel cannot be ruled out as yet.
ANALOGUE MODELS FOR FRW COSMOLOGIES
Authors: BARCELÓ CARLOS , LIBERATI STEFANO , VISSER MATT
Published: December 2003

It is by now well known that various condensed matter systems may be used to mimic many of the kinematic aspects of general relativity, and in particular of curved-spacetime quantum field theory. In this essay we will take a look at what would be needed to mimic a cosmological spacetime — to be precise a spatially flat FRW cosmology — in one of these analogue models. In order to do this one needs to build and control suitable time dependent systems. We discuss here two quite different ways to achieve this goal. One might rely on an explosion, physically mimicking the big bang by an outflow of whatever medium is being used to carry the excitations of the analogue model, but this idea appears to encounter dynamical problems in practice. More subtly, one can avoid the need for any actual physical motion (and avoid the dynamical problems) by instead adjusting the propagation speed of the excitations of the analogue model. We shall focus on this more promising route and discuss its practicality.
CLOSED TIMELIKE CURVES IN CLASSICAL RELATIVITY
Authors: BONNOR W. B.
Published: December 2003

Spacetimes of general relativity containing closed timelike curves (CTC) are usually dismissed as non-physical. However, it is now known that CTC may appear in spacetimes modelling simple laboratory experiments, and two such experiments are described in this essay. We therefore need a realistic interpretation of CTC. I suggest that a region containing CTC may represent a new type of singularity, called a torsion singularity.
TRADING RESTRICTIONS, PRICE DYNAMICS AND ALLOCATIVE EFFICIENCY IN DOUBLE AUCTION MARKETS: ANALYSIS BASED ON AGENT-BASED MODELING AND SIMULATIONS
Authors: CHEN SHU-HENG , TAI CHUNG-CHING
Published: December 2003

In this paper we conduct two experiments within an agent-based double auction market. These two experiments allow us to see the effect of learning and smartness on price dynamics and allocative efficiency. Our results are largely consistent with the stylized facts observed in experimental economics with human subjects. From the amelioration of price deviation and allocative efficiency, the effect of learning is vividly seen. However, smartness does not enhance market performance. In fact, the experiment with smarter agents (agents without a quote limit) results in a less stable price dynamics and lower allocative efficiency.
A STUDY ON RESEARCH PERFORMANCE IN JAPANESE UNIVERSITIES: WHICH IS MORE EFFICIENT — A PROFESSOR WHO IS LEADING HIS RESEARCH GROUP OR ONE WHO IS WORKING ALONE? THE MULTI-AGENT SIMULATION KNOWS
Authors: TANIMOTO JUN , FUJII HARUYUKI
Published: December 2003

In recent years, we have been interested in the up-and-down prospects of academic societies, including both universities and academies. We have developed a University-Academy Coupling Model, which is built on the multi-agent simulation technique. In the artificial society, there exist both funding and "research seeds" that are requisite simultaneously for researchers to survive. The "seed" means a clue, source or new topic for his research activity. This paper focuses on how different efficiencies are observed in different types of organizing processes or personnel systems for research activity in universities.
THE EFFECTS OF VARYING PARAMETER VALUES AND HETEROGENEITY IN AN INDIVIDUAL-BASED MODEL OF PREDATOR-PREY INTERACTION
Authors: CHIVERS WILLIAM J. , HERBERT RIC D.
Published: December 2003

An individual-based model which produces nonlinear predator-prey dynamics is described. The importance of individual variation to the stability of the population dynamics predicted by the model and the advantages of the individual-based approach to modelling ecological systems is discussed. The individual-based model is compared with the traditional approach of population ecology — the modelling of populations with state variable equations. The individual-based model built here produces similar patterns of mutual dependence of the populations to those produced by the state variable model but has additional utility. It greatly simplifies the adjustment of individual environmental parameters which may be built into the model and it makes it possible to follow individuals or individual parameter values through the simulation. The cost of the utility of the individual-based approach is in the complexity of the model itself, which is more difficult to build than many state variable models. A common finding in the literature of individual-based modelling in ecology is the importance of individual variation. The individual-based model described here is built with a minimum of biological complexity, but still we find that individual variation in the model has profound effects on the stability of the population levels over long time periods.
Endothelial Nitric Oxide Synthase
Authors: Tai Sharon C. , Robb G. Brett , Marsden Philip A.
Published: December 2003

Advances in our understanding of the molecular mechanisms involved in the constitutive and regulated expression of endothelial nitric oxide synthase (eNOS) mRNA expression present a new level of complexity to the study of endothelial gene regulation in health and disease. Recent studies highlight the contribution of both transcription and RNA stability to net steady-state mRNA levels of eNOS in vascular endothelium, introducing a new paradigm to gene regulation in the injured blood vessel. Constitutive eNOS expression is dependent on basal transcription machinery in the core promoter, involving positive and negative protein–protein and protein–DNA interactions. Chromatin-based mechanisms and epigenetic events also regulate expression of eNOS at the transcriptional level in a cell-restricted fashion. Although constitutively active, important physiological and pathophysiologic stimuli alter eNOS gene transcription rates. For instance, eNOS transcription rates increase in response to lysophosphatidylcholine, shear stress, and TGF-β, among others. Under basal conditions, eNOS mRNA is extremely stable. Surprisingly, posttranscriptional mechanisms have emerged as important regulatory pathways in the observed decreases in eNOS expression in some settings. In models of inflammation, proliferation/injury, oxidized low-density lipoprotein treatment, and hypoxia, eNOS mRNA destabilization plays a significant role in the rapid downregulation of eNOS mRNA levels.
Weight Reduction With Very-Low-Caloric Diet and Endothelial Function in Overweight Adults: Role of Plasma Glucose
Authors: Raitakari Maria , Ilvonen Thomas , Ahotupa Markku , Lehtimäki Terho , Harmoinen Aimo , Suominen Pauli , Elo Juhani , Hartiala Jaakko , Raitakari Olli T.
Published: December 2003

Objective—

Obesity is associated with endothelial dysfunction that may contribute to the development of atherosclerosis. We studied whether weight reduction improves endothelial function in overweight individuals.

Methods and Results—

Flow-mediated endothelium-dependent vasodilation of the brachial artery was measured in 67 adults (age: 46±7 years, body mass index: 35.2±5.4 kg/m
2
) before and after a 6-week weight reduction program induced by very-low-calorie diet (daily energy: 580 kcal/2.3 MJ). Caloric restriction reduced body weight from 101±18 to 90±17 kg. Flow-mediated vasodilation increased from 5.5%±3.7 to 8.8%±3.7% (
P
<0.0001). Nitrate-mediated vasodilation was not significantly affected. The improvement in flow-mediated dilation was associated with the reduction in plasma glucose concentration (
P
=0.0003). This relationship was independent of changes in weight, serum lipids, oxidized LDL, C-reactive protein, adiponectin, blood pressure, and insulin.

Conclusions—

Weight reduction with very-low-calorie diet improves flow-mediated vasodilation in obese individuals. This improvement is related to the reduction in plasma glucose concentration. These observations suggest that changes in glucose metabolism may determine endothelial vasodilatory function in obesity.
Modulation of Factor V Levels in Plasma by Polymorphisms in the C2 Domain
Authors: Scanavini Daniela , Girelli Domenico , Lunghi Barbara , Martinelli Nicola , Legnani Cristina , Pinotti Mirko , Palareti Gualtiero , Bernardi Francesco
Published: December 2003

Objective—Functional polymorphisms contributing to coagulation factor levels are preferential markers for association studies aimed at identifying prothrombic genetic components.

Methods and Results—Factor V (FV) microsatellite genotypes were found to be associated with FV levels (P=0.003). Single nucleotide polymorphisms analysis and sequencing of the promoter and of coding regions identified two polymorphisms (Met2120Thr, Asp2194Gly) present in 20% of the population (n=1013) that are responsible for genotype-phenotype associations. The effect of the Met2120Thr polymorphism, both in plasma (mean reduction of FV level in the heterozygous condition: 25%) and in recombinant FV studies (34% reduction), was comparable to that of the Asp2194Gly change (20% and 34%, respectively). The study of 10 subjects with a rare genotype indicated that the Asp2194Gly substitution is the functional determinant of the reduced FV levels associated with the FVHR2 haplotype. Among Leiden carriers, the doubly heterozygous condition for FV2120Thr was found to be associated with a significantly increased activated protein-C resistance (APCR) (P<0.05), and the doubly heterozygous condition for FV2194Gly was found to be more frequent (P=0.009) in symptomatic than in asymptomatic subjects.

Conclusions—Extensive analysis of FV polymorphisms indicated that changes in the C2 domain modulate FV levels and might increase APCR and thrombotic risk in FV Leiden carriers through a pseudohomozygous mechanism.
Nitric Oxide May Prevent Hypertension Early in Diabetes by Counteracting Renal Actions of Superoxide
Authors: Brands Michael W. , Bell Tracy D. , Gibson Bradford
Published: December 2003

The dependence of blood pressure on a balance between superoxide and nitric oxide may be amplified in diabetes. We have shown that the first occurrence of sustained hyperglycemia in type I diabetes causes hypertension when induced in rats that have had nitric oxide synthesis blocked chronically (L-NAME, 10 μg/kg per minute IV). This study used tempol (18 μmol/kg per hour IV) to test the hypothesis that superoxide mediates that hypertensive response. Induction of diabetes in untreated rats had no significant effect on mean arterial pressure (MAP, measured 18 h/d), and glomerular filtration rate (GFR) increased significantly during the 2 weeks of diabetes. Chronic infusion of L-NAME in a separate group of rats increased baseline MAP from ≈90 mm Hg to a stable level of ≈120 mm Hg after 6 days of infusion, and induction of diabetes (streptozotocin, 40 mg/kg IV) in those rats caused a rapid, progressive increase in MAP that averaged 156±5 mm Hg by day 14 of diabetes that was associated with a decrease in GFR and 4-fold increase in isoprostane excretion. Tempol infusion was begun on day 2 of diabetes in a subgroup of those rats, and the progressive hypertensive response was prevented, with MAP averaging 134±10 mm Hg by day 14. In addition, the normal renal hyperfiltration response was restored by tempol and the increase in isoprostane did not occur. Thus, the hypertension and decrease in GFR caused by onset of diabetes in rats without a functioning nitric oxide system was prevented by chronic administration of the superoxide dismutase mimetic tempol.
Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
Authors: Chobanian Aram V. , Bakris George L. , Black Henry R. , Cushman William C. , Green Lee A. , Izzo Joseph L. , Jones Daniel W. , Materson Barry J. , Oparil Suzanne , Wright Jackson T. , Roccella Edward J. ,   the National High Blood Pressure Education Program Coordinating Committee
Published: December 2003

The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120–139 mm Hg or diastolic BP 80–89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician’s judgment remains paramount.
Catecholamine-Induced Vascular Wall Growth Is Dependent on Generation of Reactive Oxygen Species
Authors: Bleeke Tina , Zhang Hua , Madamanchi Nageswara , Patterson Cam , Faber James E.
Published: December 2003

α
1
-Adrenoceptor–dependent proliferation of vascular smooth muscle cells (VSMCs) is strongly augmented by vascular injury, and may contribute to intimal growth and lumen loss. Because reactive oxygen species (ROS) are increased by injury and have been implicated as second messengers in proliferation of VSMCs, we investigated the role of ROS in catecholamine-induced VSMC growth. Rat aortae were isolated 4 days after balloon injury, maintained in organ culture under circumferential wall tension, and exposed to agents for 48 hours. The antioxidants N-acetylcysteine (NAC, 10 mmol/L) and Tiron (5 mmol/L) and the flavin-inhibitor diphenylene iodonium (DPI, 20 μmol/L) abolished norepinephrine-induced increases in protein synthesis and DNA content in media. In aortic sections, norepinephrine augmented ROS production (dihydroethidium confocal microscopy), which was dose-dependently inhibited by NAC, Tiron, and DPI. In cultured VSMCs, phenylephrine caused time- and dose-dependent ROS generation (aconitase activity), had similar efficacy to thrombin (1 U/mL), and was eliminated by the superoxide dismutase (SOD) mimetic Mn-(III)-tetrakis-(4-benzoic-acid)-porphyrin-chloride (200 μmol/L) and Tiron. Phenylephrine-induced ROS production and increases in DNA and protein content were blocked by prazosin (0.3 μmol/L) and abolished in p47

phox
−/−

cells. PEG-SOD (25 U/mL) had little effect, whereas PEG-catalase (50 U/mL) eliminated phenylephrine-induced proliferation in VSMCs. DPI (10 μmol/L) and apocynin (30 μmol/L) abolished phenylephrine-stimulated mitogenesis, whereas inhibitors of other intracellular ROS sources had not effect. Furthermore, PE increased p47

phox

expression (RT-PCR). These data demonstrate that the trophic effect of catecholamines on vascular wall cells is dependent on a ROS-sensitive step that we hypothesize consists of activation of the NAD(P)H-dependent vascular oxidase.
Hemoglobin Scavenger Receptor CD163 Mediates Interleukin-10 Release and Heme Oxygenase-1 Synthesis
Authors: Philippidis P. , Mason J.C. , Evans B.J. , Nadra I. , Taylor K.M. , Haskard D.O. , Landis R.C.
Published: December 2003

The recently described hemoglobin scavenger receptor CD163 mediates the endocytosis of hemoglobin:haptoglobin (Hb:Hp) complexes and thereby counters Hb-induced oxidative tissue damage after hemolysis. Although CD163 has been indirectly associated with antiinflammatory and atheroprotective activity, no ligand-receptor-effector pathway has yet been described for this receptor. To understand the significance of CD163 and more clearly define downstream pathways linked to inflammatory resolution, we studied the expression and function of CD163 in human monocytes/macrophages using both in vitro and in vivo models. Differentiation of human blood monocytes into macrophages either by in vitro culture or in resolving cantharidin-induced skin blisters led to an equivalent increase (>15×) in CD163 expression. Elevated CD163 levels were also noted on circulating monocytes in cardiac surgical patients during the resolution phase of the systemic inflammatory response to cardiopulmonary bypass surgery. In each case, binding of Hb:Hp to CD163-bearing cells elicited potent interleukin-10 secretion, and this was inhibited by the anti-CD163 antibody RM3/1. Release of interleukin-10, in turn, induced heme oxygenase-1 stress protein synthesis via an autocrine mechanism. Such induction of heme oxygenase-1 was observed in vivo 24 to 48 hours after the onset of cardiopulmonary bypass surgery. These results identify novel antiinflammatory and cytoprotective effector pathways in human monocytes/macrophages related to Hb scavenging and metabolism, which may have relevance in atheroprotection, wound healing, and patient recovery postoperatively.