bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vivo Analysis of Autophagy in Response to Nutrient Starvation Using Transgenic Mice Expressing a Fluorescent Autophagosome Marker
Authors: Mizushima Noboru , Yamamoto Akitsugu , Matsui Makoto , Yoshimori Tamotsu , Ohsumi Yoshinori
Published: December 2003

Macroautophagy mediates the bulk degradation of cytoplasmic components. It accounts for the degradation of most long-lived proteins: cytoplasmic constituents, including organelles, are sequestered into autophagosomes, which subsequently fuse with lysosomes, where degradation occurs. Although the possible involvement of autophagy in homeostasis, development, cell death, and pathogenesis has been repeatedly pointed out, systematic in vivo analysis has not been performed in mammals, mainly because of a limitation of monitoring methods. To understand where and when autophagy occurs in vivo, we have generated transgenic mice systemically expressing GFP fused to LC3, which is a mammalian homologue of yeast Atg8 (Aut7/Apg8) and serves as a marker protein for autophagosomes. Fluorescence microscopic analyses revealed that autophagy is differently induced by nutrient starvation in most tissues. In some tissues, autophagy even occurs actively without starvation treatments. Our results suggest that the regulation of autophagy is organ dependent and the role of autophagy is not restricted to the starvation response. This transgenic mouse model is a useful tool to study mammalian autophagy.
Mitochondrial Localization of the Mevalonate Pathway Enzyme 3-Hydroxy-3-methyl-glutaryl-CoA Reductase in the Trypanosomatidae
Authors: Peña-Diaz Javier , Montalvetti Andrea , Flores Carmen-Lisset , Constán Aurora , Hurtado-Guerrero Ramon , De Souza Wanderley , Gancedo Carlos , Ruiz-Perez Luis M. , Gonzalez-Pacanowska Dolores
Published: December 2003

3-Hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) is a key enzyme in the sterol biosynthesis pathway, but its subcellular distribution in the Trypanosomatidae family is somewhat controversial. Trypanosoma cruzi and Leishmania HMGRs are closely related in their catalytic domains to bacterial and eukaryotic enzymes described but lack an amino-terminal domain responsible for the attachment to the endoplasmic reticulum. In the present study, digitonin-titration experiments together with immunoelectron microscopy were used to establish the intracellular localization of HMGR in these pathogens. Results obtained with wild-type cells and transfectants overexpressing the enzyme established that HMGR in both T. cruzi and Leishmania major is localized primarily in the mitochondrion and that elimination of the mitochondrial targeting sequence in Leishmania leads to protein accumulation in the cytosolic compartment. Furthermore, T. cruzi HMGR is efficiently targeted to the mitochondrion in yeast cells. Thus, when the gene encoding T. cruzi HMGR was expressed in a hmg1 hmg2 mutant of Saccharomyces cerevisiae, the mevalonate auxotrophy of mutant cells was relieved, and immunoelectron analysis showed that the parasite enzyme exhibits a mitochondrial localization, suggesting a conservation between the targeting signals of both organisms.
The α- and β′-COP WD40 Domains Mediate Cargo-selective Interactions with Distinct Di-lysine Motifs
Authors: Eugster Anne , Frigerio Gabriella , Dale Martin , Duden Rainer
Published: December 2003

Coatomer is required for the retrieval of proteins from an early Golgi compartment back to the endoplasmic reticulum. The WD40 domain of α-COP is required for the recruitment of KKTN-tagged proteins into coatomer-coated vesicles. However, lack of the domain has only minor effects on growth in yeast. Here, we show that the WD40 domain of β′-COP is required for the recycling of the KTKLL-tagged Golgi protein Emp47p. The protein is degraded more rapidly in cells with a point mutation in the WD40 domain of β′-COP (sec27-95) or in cells lacking the domain altogether, whereas a point mutation in the Clathrin Heavy Chain Repeat (sec27-1) does not affect the turnover of Emp47p. Lack of the WD40 domain of β′-COP has only minor effects on growth of yeast cells; however, absence of both WD40 domains of α- and β′-COP is lethal. Two hybrid studies together with our analysis of the maturation of KKTN-tagged invertase and the turnover of Emp47p in α- and β′-COP mutants suggest that the two WD40 domains of α- and β′-COP bind distinct but overlapping sets of di-lysine signals and hence both contribute to recycling of proteins with di-lysine signals.
Environmental Decision Making and DDT Production at Montrose Chemical Corporation of California
Authors: Kehoe Terence , Jacobson Charles
Published: December 2003

In this article, we examine the decisions made by corporate executives and government officials that led to the discharge with minimal treatment of hundreds of metric tons of dichloro-diphenyl-trichloroethane (DDT) waste into the Pacific Ocean over several decades. After World War II, Montrose Chemical Corporation of California's Los Angeles plant began making the new wonder pesticide, and Montrose executives worked with local officials to develop a waste disposal system that funneled the plant's process wastes into the county sewer system and ultimately into the ocean. Faced with increasing scientific concern about pesticides and a changed political climate in the 1960s, Montrose vigorously defended DDT and relied increasingly on exports to remain profitable. Years after the plant closed, a federal suit forced Montrose and related companies to pay the costs of environmental cleanup.
Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction
Authors: Pera Edgar M. , Ikeda Atsushi , Eivers Edward , De Robertis Eddy M.
Published: December 2003

How do very diverse signaling pathways induce neural differentiation in Xenopus? Anti-BMP (Chordin), FGF8, and IGF2 signals are integrated in the embryo via the regulation of Smad1 phosphorylation. Neural induction results from the combined inhibition of BMP receptor serine/threonine kinases and activation of receptor tyrosine kinases that signal through MAPK and phosphorylate Smad1 in the linker region, further inhibiting Smad1 transcriptional activity. This hard-wired molecular mechanism at the level of the Smad1 transcription factor may help explain the opposing activities of IGF, FGF, and BMP signals not only in neural induction, but also in other aspects of vertebrate development.
Antagonists of Wnt and BMP signaling promote the formation of vertebrate head muscle
Authors: Tzahor Eldad , Kempf Hervé , Mootoosamy Roy C. , Poon Andy C. , Abzhanov Arhat , Tabin Clifford J. , Dietrich Susanne , Lassar Andrew B.
Published: December 2003

Recent studies have postulated that distinct regulatory cascades control myogenic differentiation in the head and the trunk. However, although the tissues and signaling molecules that induce skeletal myogenesis in the trunk have been identified, the source of the signals that trigger skeletal muscle formation in the head remain obscure. Here we show that although myogenesis in the trunk paraxial mesoderm is induced by Wnt signals from the dorsal neural tube, myogenesis in the cranial paraxial mesoderm is blocked by these same signals. In addition, BMP family members that are expressed in both the dorsal neural tube and surface ectoderm are also potent inhibitors of myogenesis in the cranial paraxial mesoderm. We provide evidence suggesting that skeletal myogenesis in the head is induced by the BMP inhibitors, Noggin and Gremlin, and the Wnt inhibitor, Frzb. These molecules are secreted by both cranial neural crest cells and by other tissues surrounding the cranial muscle anlagen. Our findings demonstrate that head muscle formation is locally repressed by Wnt and BMP signals and induced by antagonists of these signaling pathways secreted by adjacent tissues.
Tap and NXT promote translation of unspliced mRNA
Authors: Jin Li , Guzik Brian W. , Bor Yeou-cherng , Rekosh David , Hammarskjöld Marie-Louise
Published: December 2003

Tap has been proposed to play a role in general mRNA export and also functions in expression of RNA with retained introns that contain the MPMV CTE (constitutive transport element). Tap forms a functional heterodimer with NXT/p15. We have previously demonstrated that unspliced intron-containing CTE RNA is efficiently exported to the cytoplasm in mammalian cells. Here we show that Tap and NXT proteins function together to enhance translation of proteins from the exported CTE RNA. Pulse chase experiments show that Tap/NXT significantly increases the rate of protein synthesis. Sucrose gradient analysis demonstrates that Tap and NXT efficiently shift the unspliced RNA into polyribosomal fractions. Furthermore, Tap, but not NXT is detected in polyribosomes. Taken together, our results indicate that Tap and NXT serve a role in translational regulation of RNA after export to the cytoplasm. They further suggest that Tap/NXT may play a role in remodeling of cytoplasmic RNP complexes, providing a link between export pathways and cytoplasmic fate.
Post-transcriptional regulation of the E/Daughterless ortholog HLH-2, negative feedback, and birth order bias during the AC/VU decision in C. elegans
Authors: Karp Xantha , Greenwald Iva
Published: December 2003

The anchor cell/ventral uterine precursor cell (AC/VU) decision in Caenorhabditis elegans is a canonical example of lin-12/Notch-mediated lateral specification. Two initially equivalent cells interact via the receptor LIN-12 and its ligand LAG-2, so that one becomes the AC and the other a VU. During this interaction, feedback loops amplify a small difference in lin-12 activity, limiting lin-12 transcription to the presumptive VU and lag-2 transcription to the presumptive AC. Here, we find that hlh-2 appears to be required for the VU fate and directly activates lag-2 transcription in the presumptive AC. HLH-2 appears to accumulate selectively in the presumptive AC prior to differential transcription of lin-12 or lag-2, and is therefore the earliest detectable difference between the two cells undergoing the AC/VU decision. The restricted accumulation of HLH-2 to the presumptive AC reflects post-transcriptional down-regulation of HLH-2 in the presumptive VU. Our observations suggest that hlh-2 is regulated as part of the negative feedback that down-regulates lag-2 transcription in the presumptive VU. Finally, we show that the AC/VU decision in an individual hermaphrodite is biased by the relative birth order of the two cells, so that the first-born cell is more likely to become the VU. We propose models to suggest how birth order, HLH-2 accumulation, and transcription of lag-2 may be linked during the AC/VU decision.
Healthcare 2025: alternative views and underlying values
Authors: Rowley William R.
Published: December 2003

This article describes the development of scenarios to stimulate public dialog concerning healthcare values. Different values lead to different futures. America’s current healthcare system has serious difficulties and must be transformed, but the underlying problems will not be addressed until the public has enough understanding to develop a consensus on the values it desires in a new system that meets societal needs. Value driven scenarios can help by illustrating the consequences of different alternatives and thereby stimulating thinking about key value‐driven components that must be included for a functional and sustainable solution.
Forecastability, chaos and foresight
Authors: Foo Check‐Teck , Foo Check‐Tong
Published: December 2003

Roles of leadership in coping with uncertainty are explored in this paper. Through an in‐depth, empirically (CEOs of top, ASEAN publicly listed corporations) grounded discussion, the authors argued for the presence of a deep cultural divide between Eastern and Western leaders on coping with uncertainty. In the process, the authors devise a two dimensional, organic versus forecastability model of strategy behavior for polarizing East‐West leadership styles. Aspects of the Sun Tzu’s Art of War and 5,000 years old, I Ching are discussed with respect to foreknowledge and foresight respectively.
Sustainable development assessment: quality and sustainability of life indicators at global, national and regional level
Authors: Mederly Peter , Novacek Pavel , Topercer Jan
Published: December 2003

Gross domestic product as an indicator of wealth and therefore quality of life have long been criticised. GDP places too much emphasis on consumption and ignores wealth distribution. Importantly it also takes no account of environmental issues. This article considers the development of an integrated environmental sustainability index and its application in the case of the Czech Republic.
Increase in endothelial cell Ca2+ in response to mouse cremaster muscle contraction
Authors: Duza Tasmia , Sarelius Ingrid H.
Published: December 2003

We addressed the role of endothelial cells (ECs) in metabolic dilatation of skeletal muscle arterioles in anaesthetized mice in situ. Electrical field stimulation was used to contract the cremaster muscle for 15 s at 30 Hz. Diameter was observed using bright field microscopy. In controls, muscle contraction produced a 15.7 ± 1.5 μm dilatation from a baseline of 17.4 ± 1.6 μm. Endothelial denudation (−EC) via intraluminal perfusion of air abolished this response (1.6 ± 1.2 μm in −EC, P < 0.05), identifying endothelium as the primary vascular cell type initiating the dilatation. To investigate the role of EC Ca2+ in metabolic dilatation, arteriolar ECs were loaded with Fluo‐4 AM or BAPTA AM by intraluminal perfusion, after which blood flow was re‐established. Ca2+ activity of individual ECs was monitored as a function of change from baseline fluorescence using confocal microscopy. In ECs, whole cell Ca2+ increased (>10%, P < 0.05) during muscle contraction, and localized Ca2+ transients were increased (>20%, P < 0.05) during the first minute after contraction. Chelation of EC Ca2+ abolished the dilatations in response to muscle contraction (1.1 ± 0.7 μm, P < 0.05). Inhibition of P1 purinergic receptors (with xanthine amine congener) did not alter the rate of onset of the dilatation (P > 0.05) but decreased its magnitude immediately post stimulation (7.1 ± 0.9 μm, P < 0.05) and during recovery. These findings demonstrate obligatory roles for endothelium and EC Ca2+ during metabolic dilatation in intact arterioles. Furthermore, they suggest that at least two separate pathways mediate the local response, one of which involves stimulation of endothelial P1 purinergic receptors via endogenous adenosine produced during muscle activity.
Distinctive membrane and discharge properties of rat spinal lamina I projection neurones in vitro
Authors: Ruscheweyh Ruth , Ikeda Hiroshi , Heinke Bernhard , Sandkühler Jürgen
Published: December 2003

Most lamina I neurones with a projection to the brainstem express the neurokinin 1 receptor and thus belong to a small subgroup of lamina I neurones that are necessary for the development of hyperalgesia in rat models of persisting pain. These neurones are prone to synaptic plasticity following primary afferent stimulation in the noxious range while other nociceptive lamina I neurones are not. Here, we used whole‐cell patch‐clamp recordings from lamina I neurones in young rat spinal cord transverse slices to test if projection neurones possess membrane properties that set them apart from other lamina I neurones. Neurones with a projection to the parabrachial area or the periaqueductal grey (PAG) were identified by retrograde labelling with the fluorescent tracer DiI. The properties of lamina I projection neurones were found to be fundamentally different from those of unidentified, presumably propriospinal lamina I neurones. Two firing patterns, the gap and the bursting firing pattern, occurred almost exclusively in projection neurones. Most spino‐parabrachial neurones showed the gap firing pattern while the bursting firing pattern was characteristic of spino‐PAG neurones. The underlying membrane currents had the properties of an A‐type K+ current and a Ca2+ curent with a low activation threshold, respectively. Projection neurones, especially those of the burst firing type, were more easily excitable than unidentified neurones and received a larger proportion of monosynaptic input from primary afferent C‐fibres. Intracellular labelling with Lucifer yellow showed that projection neurones had larger somata than unidentified neurones and many had a considerable extension in the mediolateral plane.
Slow inactivation of the CaV3.1 isotype of T‐type calcium channels
Authors: Hering Julien , Feltz Anne , Lambert Régis C.
Published: December 2003

T‐type calcium channels (the CaV3 channel family) are involved in defining the resting membrane potential and in neuronal activities such as oscillations and rebound depolarization. Their physiological roles depend upon the channel activation and inactivation kinetics. A fast inactivation that stops the ionic flux of calcium in tens of milliseconds has already been described in both native and heterologously expressed channels. Here, using HEK 293 cells expressing the rat CaV3.1 channel and whole‐cell voltage clamp, we investigate an additional inactivation process, which can be distinguished from the previously described fast inactivation by its slow time course of recovery from inactivation (τ= 1 s) and by its sensitivity to external calcium. Steady‐state slow inactivation is voltage dependent around the resting membrane potential (the potential of half‐inactivation (V0.5) =−70 mV, slope factor = 7.4 mV) and can reduce the calcium current by up to 50%. Near resting potential, the slow inactivation displays a half‐time of induction of tens of seconds. The slow inactivation therefore modulates the availability of T‐type calcium channels depending upon recent cell history, providing a mechanism to store information in a time scale of seconds.
Inhibition of α‐adrenergic vasoconstriction in exercising human thigh muscles
Authors: Wray D. Walter , Fadel Paul J. , Smith Michael L. , Raven Peter , Sander Mikael
Published: December 2003

The mechanisms underlying metabolic inhibition of sympathetic responses within exercising skeletal muscle remain incompletely understood. The aim of the present study was to test whether α2‐adrenoreceptor‐mediated vasoconstriction was more sensitive to metabolic inhibition than α1‐vasoconstriction during dynamic knee‐extensor exercise. We studied healthy volunteers using two protocols: (1) wide dose ranges of the α‐adrenoreceptor agonists phenylephrine (PE, α1selective) and BHT‐933 (BHT, α2selective) were administered intra‐arterially at rest and during 27 W knee‐extensor exercise (n= 13); (2) flow‐adjusted doses of PE (0.3 μg kg−1l−1) and BHT (15 μg kg−1l−1) were administered at rest and during ramped exercise (7 W to 37 W;n= 10). Ultrasound Doppler and thermodilution techniques provided direct measurements of femoral blood flow (FBF). PE (0.8 μg kg−1) and BHT (40 μg kg−1) produced comparable maximal reductions in FBF at rest (−58 ± 6versus−64 ± 4%). Despite increasing the doses, PE (1.6 μg kg−1min−1) and BHT (80 μg kg−1min−1) caused significantly smaller changes in FBF during 27 W exercise (−13 ± 4versus−3 ± 5%). During ramped exercise, significant vasoconstriction at lower intensities (7 and 17 W) was seen following PE (−16 ± 5 and −16 ± 4%), but not BHT (−2 ± 4 and −4 ± 5%). At the highest intensity (37 W), FBF was not significantly changed by either drug. Collectively, these data demonstrate metabolic inhibition of α‐adrenergic vasoconstriction in large postural muscles of healthy humans. Both α1‐ and α2‐adrenoreceptor agonists produce comparable vasoconstriction in the resting leg, and dynamic thigh exercise attenuates α1‐ and α2‐mediated vasoconstriction similarly. However, α2‐mediated vasoconstriction appears more sensitive to metabolic inhibition, because α2is completely inhibited even at low workloads, whereas α1becomes progressively inhibited with increasing workloads.
Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications
Authors: Berry Cristine E. , Hare Joshua M.
Published: December 2003

There is substantial evidence that oxidative stress participates in the pathophysiology of cardiovascular disease. Biochemical, molecular and pharmacological studies further implicate xanthine oxidoreductase (XOR) as a source of reactive oxygen species in the cardiovascular system. XOR is a member of the molybdoenzyme family and is best known for its catalytic role in purine degradation, metabolizing hypoxanthine and xanthine to uric acid with concomitant generation of superoxide. Gene expression of XOR is regulated by oxygen tension, cytokines and glucocorticoids. XOR requires molybdopterin, iron–sulphur centres, and FAD as cofactors and has two interconvertible forms, xanthine oxidase and xanthine dehydrogenase, which transfer electrons from xanthine to oxygen and NAD+, respectively, yielding superoxide, hydrogen peroxide and NADH. Additionally, XOR can generate superoxide via NADH oxidase activity and can produce nitric oxide via nitrate and nitrite reductase activities. While a role for XOR beyond purine metabolism was first suggested in ischaemia–reperfusion injury, there is growing awareness that it also participates in endothelial dysfunction, hypertension and heart failure. Importantly, the XOR inhibitors allopurinol and oxypurinol attenuate dysfunction caused by XOR in these disease states. Attention to the broader range of XOR bioactivity in the cardiovascular system has prompted initiation of several randomised clinical outcome trials, particularly for congestive heart failure. Here we review XOR gene structure and regulation, protein structure, enzymology, tissue distribution and pathophysiological role in cardiovascular disease with an emphasis on heart failure.
Purinergic regulation of epithelial transport
Authors: Bucheimer R. Elaine , Linden Joel
Published: December 2003

Purinergic receptors are a family of ubiquitous transmembrane receptors comprising two classes, P1 and P2 receptors, which are activated by adenosine and extracellular nucleotides (i.e. ATP, ADP, UTP and UDP), respectively. These receptors play a significant role in regulating ion transport in epithelial tissues through a variety of intracellular signalling pathways. Activation of these receptors is partially dependent on ATP (or UTP) release from cells and its subsequent metabolism, and this release can be triggered by a number of stimuli, often in the setting of cellular damage. The function of P2Y receptor stimulation is primarily via signalling through the Gq/PLC‐β pathway and subsequent activation of Ca2+‐dependent ion channels. P1 signalling is complex, with each of the four P1 receptors A1, A2A, A2B, and A3 having a unique role in different epithelial tissue types. In colonic epithelium the A2B receptor plays a prominent role in regulating Cl− and water secretion. In airway epithelium, A2B and A1 receptors are implicated in the control of Cl− and other currents. In the renal tubular epithelium, A1, A2A, and A3 receptors have all been identified as playing a role in controlling the ionic composition of the lumenal fluid. Here we discuss the intracellular signalling pathways for each of these receptors in various epithelial tissues and their roles in pathophysiological conditions such as cystic fibrosis.
Membrane potential stabilization in amphibian skeletal muscle fibres in hypertonic solutions
Authors: Ferenczi Emily A. , Fraser James A. , Chawla Sangeeta , Skepper Jeremy N. , Schwiening Christof J. , Huang Christopher L.‐H.
Published: December 2003

This study investigated membrane transport mechanisms influencing relative changes in cell volume (V) and resting membrane potential (Em) following osmotic challenge in amphibian skeletal muscle fibres. It demonstrated a stabilization of Em despite cell shrinkage, which was attributable to elevation of intracellular [Cl−] above electrochemical equilibrium through Na+–Cl− and Na+−K+−2Cl− cotransporter action following exposures to extracellular hypertonicity. Fibre volumes (V) determined by confocal microscope xz‐scanning of cutaneous pectoris muscle fibres varied linearly with [1/extracellular osmolarity], showing insignificant volume corrections, in fibres studied in Cl−‐free, normal and Na+‐free Ringer solutions and in the presence of bumetanide, chlorothiazide and ouabain. The observed volume changes following increases in extracellular tonicity were compared with microelectrode measurements of steady‐state resting potentials (Em). Fibres in isotonic Cl−‐free, normal and Na+‐free Ringer solutions showed similar Em values consistent with previously reported permeability ratios PNa/PK(0.03–0.05) and PCl/PK (∼2.0) and intracellular [Na+], [K+] and [Cl−]. Increased extracellular osmolarities produced hyperpolarizing shifts in Em in fibres studied in Cl−‐free Ringer solution consistent with the Goldman‐Hodgkin‐Katz (GHK) equation. In contrast, fibres exposed to hypertonic Ringer solutions of normal ionic composition showed no such Em shifts, suggesting a Cl−‐dependent stabilization of membrane potential. This stabilization of Em was abolished by withdrawing extracellular Na+ or by the combined presence of the Na+–Cl− cotransporter (NCC) inhibitor chlorothiazide (10 μm) and the Na+−K+−2Cl− cotransporter (NKCC) inhibitor bumetanide (10 μm), or the Na+−K+‐ATPase inhibitor ouabain (1 or 10 μm) during alterations in extracellular osmolarity. Application of such agents after such increases in tonicity only produced a hyperpolarization after a time delay, as expected for passive Cl− equilibration. These findings suggest a model that implicates the NCC and/or NKCC in fluxes that maintain [Cl−]i above its electrochemical equilibrium. Such splinting of [Cl−]i in combination with the high PCl/PK of skeletal muscle stabilizes Em despite volume changes produced by extracellular hypertonicity, but at the expense of a cellular capacity for regulatory volume increases (RVIs). In situations where PCl/PK is low, the same cotransporters would instead permit RVIs but at the expense of a capacity to stabilize Em.
CHARACTERIZING THE MONETARY TRANSMISSION MECHANISM IN A SMALL OPEN ECONOMY: THE CASE OF MALAYSIA
Authors: GAN WEE BENG , SOON LEE YING
Published: December 2003

This paper evaluates the monetary policy response of Malaysia's central bank and the nature of monetary transmission mechanism in the 1990s when the exchange rate was on a managed float and the capital account was open. Structural vector autogression analysis is employed to evaluate how the central bank sets short term interest rates taking into consideration the constraints faced in adjusting the policy instrument to shocks to the economy. The impulse response functions and the variance decomposition indicate that the central bank preferred to use foreign exchange intervention rather than interest rate to stabilize the ringgit exchange rate. The results suggest that a sustained high level of interest rates would have caused a prolonged and deep contraction in output during the East Asian financial crisis.
A RE-STATEMENT OF SINGAPORE'S EXCHANGE RATE AND MONETARY POLICIES
Authors: YIP PAUL S. L.
Published: December 2003

This policy note, which focuses on Singapore's monetary and exchange rate policies, has a number of objectives. First, it highlights the fact that the Monetary Authority of Singapore (MAS) is equipped with a powerful tool to target the exchange rate level it desires (within limits). Second, it reviews Singapore's exchange rate policy since 1980 and explains that the de facto policy is far more complicated and flexible than the simplistic but oft-noted description of the MAS pursuing a "strong Singapore dollar" policy. Specifically, the paper argues that Singapore's exchange rate regime is an ideal example of the monitoring band system favoured by John Williamson. Third, the paper contrasts the Singapore currency regime with the relatively more inflexible currency board arrangement (CBA) operated in Hong Kong. The relative advantages of Singapore's flexible monitoring band arrangement over Hong Kong's rigidly fixed CBA are highlighted.
ECONOMIC GROWTH IN INDIA: "DOES FOREIGN DIRECT INVESTMENT INFLOW MATTER?"
Authors: SAHOO DUKHABANDHU , MATHIYAZHAGAN MAATHAI K.
Published: December 2003

The main objective of this paper is to examine the role of Foreign Direct Investment (FDI) in promoting the growth of the economy via export promotion by using the annual data from 1979–80 to 2000–01. This study uses the Johansen co-integration test and the results demonstrate that there is a long run relationship between Gross Domestic Product (GDP), FDI and Export (EX). The same relationship is also established when the Index of Industrial Production (IIP) replaces GDP. However, the positive elasticity coefficients between FDI, GDP and FDI, IIP are less than the positive elasticity coefficient between EX, GDP and EX, IIP. It implies that EX plays a comparatively better role in the growth of the Indian economy than FDI. Thus, on the eve of India's plan for further opening up of the economy, it is advisable to open up the export-oriented sectors so that a higher growth of the economy can be achieved through the growth of these sectors.
Information from quantum blackhole physics
Authors: Govindarajan T. R.
Published: December 2003

The study of BTZ blackhole physics and the cosmological horizon of 3D de Sitter spaces are carried out in unified way using the connections to the Chern Simons theory on three manifolds with boundary. The relations to CFT on the boundary is exploited to construct exact partition functions and obtain logarithmic corrections to Bekenstein formula in the asymptotic regime. Comments are made on the dS/CFT correspondence frising from these studies.
TIME AND GEOMETRIC QUANTIZATION
Authors: ABRIKOSOV A. A. , GOZZI E. , MAURO D.
Published: December 2003

In this paper we briefly review the functional version of the Koopman-von Neumann operatorial approach to classical mechanics. We then show that its quantization can be achieved by freezing to zero two Grassmannian partners of time. This method of quantization presents many similarities with the one known as Geometric Quantization.
Quantum Inverse Square Interaction
Authors: Gupta Kumar S.
Published: December 2003

Hamiltonians with inverse square interaction potential occur in the study of a variety of physical systems and exhibit a rich mathematical structure. In this talk we briefly mention some of the applications of such Hamiltonians and then analyze the case of the N-body rational Calogero model as an example. This model has recently been shown to admit novel solutions, whose properties are discussed.
Non-linear σ-models in noncommutative geometry: fields with values in finite spaces
Authors: Dabrowski Ludwik , Krajewski Thomas , Landi Giovanni
Published: December 2003

We study σ-models on noncommutative spaces, notably on noncommutative tori. We construct instanton solutions carrying a nontrivial topological charge q and satisfying a Belavin-Polyakov bound. The moduli space of these instantons is conjectured to consists of an ordinary torus endowed with a complex structure times a projective space [Formula: see text].
Simulating the scalar field using the fuzzy sphere
Authors: MARTIN XAVIER
Published: December 2003

Fuzzy spaces provide a new approximation scheme using (non–commutative) matrix algebras to approximate the algebra of function of the continuous space. This paper describes how to implement a numerical scheme based on a fuzzy space approximation. In this first attempt, the simplest fuzzy space and field theory, respectively the fuzzy two–sphere and the real scalar field, are used to simulate the real scalar field on the plane. Along the way, this method is compared to its traditional lattice discretisation equivalent.
THE PHYSICS OF BIOLOGY
Authors: MEGGS WILLIAM J.
Published: December 2003

Biological processes seem magical from the standpoint of physics. Simple biological processes such as cell division and protein synthesis take place billions of times a day. Molecules rapidly move into place to form intricate structures which can in turn rapidly dissipate. The physicist asks: What are the forces that move these molecules just to the right place at the right time? Here it is proposed that there are attractive forces between complementary sites on biological molecules. Like a self-assembling jigsaw puzzle, edges that fit together are attracted to each other. An example of how such a force could arise is given by complementary charge distributions, in which binding sites have identical charge distributions except of opposites charges. Attractive electrostatic forces between complementary sites sum coherently, leading to an enhancement that can "drive" living processes. It is proposed that internal electric fields are generated by current flows in cells arising from ionic pumps, and that these fields align polar molecules to form polymers that parallel field lines.
Generalized Coherent States and Operator Descriptions in Quantum Mechanics
Authors: Mukunda N.
Published: December 2003

"The possibility of describing noncommuting operators in quantum mechanics by classical type functions, and the associated expression of operator multiplication, is of considerable interest. The well known Wigner-Weyl-Moyal theory is an important example. Another is the diagonal representation of operators using standard coherent states. We develop general necessary and sufficient conditions for the existence of the diagonal representation in the context of a family of generalised coherent states associated with any unitary irreducible Lie group representation. Several examples illustrating these conditions, and interesting results in the Heisenberg-Weyl case, are presented".
Adventures in Eleven Dimensions
Authors: Ramond P.
Published: December 2003

In ten dimensions, SO(8) triality encourages confusion between fermions ans bosons, but in eleven dimensions, SO(9) has no such features. Yet this is the domain of M — theory whose infrared limit is the divergent supergravity field theory. Curtright ascribes this divergence to an incomplete cancellation among the Dynkin indices between the supergravity representations. We speculate that an infinite number of the recently discovered Euler triplets, describing massless particles of higher spin, can cancel the divergences of eleven dimensional supergravity, perhaps providing a clue to M — theory.
Superintegrable Systems and Recursion Operators
Authors: Sparano Giovanni
Published: December 2003

Geometric structures underlying noncommutative integrable (superintegrable) dynamics are analyzed. They lead to a new characterization of noncommutative integrability in terms of spectral properties and of Nijenhuis torsion of an invariant (1,1) tensor field. The construction of compatible symplectic structures is also discussed.
Edge States from Defects on the Noncommutative Plane
Authors: Pinzul A. , Stern A.
Published: December 2003

We illustrate how boundary states are recovered when going from a noncommutative manifold to a commutative one with a boundary. Our example is the noncommutative plane with a defect, whose commutative limit was found to be a punctured plane - so here the boundary is one point. Defects were introduced by removing states from the standard harmonic oscillator Hilbert space. For Chern-Simons theory, the defect acts as a source, which was found to be associated with a nonlinear deformation of the w∞ algebra. The undeformed w∞ algebra is recovered in the commutative limit, and here we show that its spatial support is in a tiny region near the puncture.
COEXISTENCE OF FERROMAGNETISM AND SUPERCONDUCTIVITY IN THE TWO-DIMENSIONAL FERROMAGNETIC t–J MODEL
Authors: YANG FAN , WANG YUPENG , HAN RUSHAN
Published: December 2003

The two-dimensional ferromagnetic t–J model is studied in the framework of slave-boson mean field theory. After solving the mean field self-consistent equations, we find that there exists a hole-doping region δ1<δ<δ2 in which p-wave superconductivity and ferromagnetism coexist. There also exists a T* line, under which pre-paired p-wave cooper pairs appear. The similarity and differences between our theoretical results and the experimental ones made for UGe 2 are compared.
PRESSURE EFFECT ON THE INTERFACE EXCITONS IN A TYPE-II ZnTe/CdSe HETEROJUNCTION
Authors: GUO Z. Z. , LIANG X. X. , BAN S. L.
Published: December 2003

A variational method is used to study the ground-state binding energies of interface light-hole excitons in ZnTe/CdSe type-II heterojunctions under the influence of hydrostatic pressure. The finite triangle potential well approximation is introduced considering the band bending near the interface. The asymptotic transfer method is adopted to obtain the sub-band energies and wave functions of the electrons and light holes. The pressure influence on the band offsets, the effective masses and the dielectric constant are considered in the calculation. The obvious pressure-induced increase of the exciton binding energy is demonstrated and the influences of the pressure-depended parameters on the binding energy are compared.
MAGNETIC PROPERTIES OF U1-xDyxAlyNi5-y (y=0,1) SYSTEMS
Authors: LUPSA ILEANA
Published: December 2003

The magnetic properties of U 1-x Dy x Al y Ni 5-y (y=0,1) systems were investigated in the 2(5)–600 K temperature range and for fields up to 80 kOe. The systems having x≥0.2 are magnetically ordered with low transition temperatures and magnetization mainly due to the Dy contribution. The nickel exhibits magnetic moments, very weak in the low temperature range and well-defined effective moments over transition temperatures. The nickel behavior is discussed in terms of the spin fluctuation model.
CHARACTERISTIC WAVEFUNCTIONS OF ONE-DIMENSIONAL PERIODIC, QUASIPERIODIC AND RANDOM LATTICES
Authors: HUANG X. Q. , JIANG S. S. , PENG R. W. , LIU Y. M. , QIU F. , HU A.
Published: December 2003

We obtain analytically a universal expression of the resonant energies for any one-dimensional (1D) models with the defects having symmetric internal structures. In a 1D periodic system with the on-site energy ε0=0 and a nearest-neighbor matrix element t0=1.0, two classes of the most interesting and simplest wavefunction behaviors are numerically obtained for the resonant energies around (a) 0, ±1, (b) [Formula: see text], respectively. We show that similar wavefunction behaviors can be found widely in many quasiperiodic and random systems where the delocalization phenomena are predicted. We suggest that the envelope of these wavefunctions can be generally used as a criterion of delocalization of electronic states in 1D random and quasiperiodic lattices.
On the Steenrod operations in cyclic cohomology
Authors: Elhamdadi Mohamed , Gouda Yasien Gh.
Published: December 2003

For a commutative Hopf algebra A over ℤ/p, where p is a prime integer, we define the Steenrod operations pi in cyclic cohomology of A using a tensor
product of a free resolution of the symmetric group Sn and the
standard resolution of the algebra A over the cyclic category
according to Loday (1992). We also compute some of these
operations.
On a system of Hamilton‐Jacobi‐Bellman inequalities associated to a minimax problem with additive final cost
Authors: Di Marco Silvia C. , González Roberto L. V.
Published: December 2003

We study a minimax optimal control problem with finite horizon
and additive final cost. After introducing an auxiliary problem,
we analyze the dynamical programming principle (DPP) and we
present a Hamilton‐Jacobi‐Bellman (HJB) system. We prove the
existence and uniqueness of a viscosity solution for this system.
This solution is the cost function of the auxiliary problem and
it is possible to get the solution of the original problem in
terms of this solution.
Upregulation of SR-PSOX/CXCL16 and Recruitment of CD8
+
T Cells in Cardiac Valves During Inflammatory Valvular Heart Disease
Authors: Yamauchi Ryoko , Tanaka Makoto , Kume Noriaki , Minami Manabu , Kawamoto Takahiro , Togi Kiyonori , Shimaoka Takeshi , Takahashi Shu , Yamaguchi Junko , Nishina Takeshi , Kitaichi Masanori , Komeda Masashi , Manabe Toshiaki , Yonehara Shin , Kita Toru
Published: December 2003

Objective—

SR-PSOX/CXCL16 is a transmembrane chemokine and is implicated in activated CD8
+
T cell trafficking. In the present study, we examined the expression pattern of SR-PSOX/CXCL16 in the heart and investigated a potential role of SR-PSOX/CXCL16 in inflammatory valvular heart disease.

Methods and Results—

Initial expression of SR-PSOX/CXCL16 in murine embryos was detected in endothelial cells lining endocardial cushions in the forming heart at E11.5. From mid-gestation to adult, expression of this gene in the heart was exclusively observed in valvular endothelial cells. Examination of SR-PSOX/CXCL16 expression in human cardiac valves demonstrated that SR-PSOX/CXCL16 was strongly expressed in valvular and neocapillary endothelial cells in patients with infective endocarditis. SR-PSOX/CXCL16 expression in neocapillary endothelial cells was also observed in patients with rheumatic and atherosclerotic valvular disease. Moreover, CD8
+
T cells were distributed closely to endothelial cells expressing SR-PSOX/CXCL16. In vitro adhesion assays showed that SR-PSOX/CXCL16 induced adhesion of activated CD8
+
T cells to vascular cell adhesion molecule-1 (VCAM-1) through very late antigen-4 (VLA-4) activation. Furthermore, SR-PSOX/CXCL16 stimulated interferon-γ (IFN-γ) production by CD8
+
T cells.

Conclusions—

SR-PSOX/CXCL16 may be involved in CD8
+
T cell recruitment through VLA-4 activation and stimulation of IFN-γ production by CD8
+
T cells during inflammatory valvular heart disease.
Transforming Growth Factor β and Atherosclerosis: So Far, So Good for the Protective Cytokine Hypothesis
Authors: Grainger David J.
Published: December 2003

The role of the anti-inflammatory cytokine transforming growth factor β (TGF-β) in atherosclerosis has been the subject of considerable debate for a decade. In the early 1990s, we postulated that TGF-β played an important role in maintaining normal vessel wall structure and that loss of this protective effect contributed to the development of atherosclerosis. We termed this the protective cytokine hypothesis. This proposal was slow to gain broad acceptance, however, because at that time there were little data available on the role of TGF-β during the development of atherosclerosis but much information about its role during trauma-induced neointima formation. Because TGF-β apparently aggravates neointima formation, both by inhibiting endothelial regeneration and by promoting fibrosis, it was difficult to accept that its presence might ameliorate the superficially similar atherogenesis process. But several recent studies revealed beyond doubt the fact that TGF-β protects against lipid lesion formation, at least in mouse models of atherosclerosis. Therefore, two important questions remain. First, is the role of TGF-β in vascular biology similar in humans and in mice? Secondly, how important, compared with defects in thrombosis or lipoprotein metabolism, is the protective role of TGF-β during atherogenesis?
Effect of Lower Dosage of Oral Conjugated Equine Estrogen on Inflammatory Markers and Endothelial Function in Healthy Postmenopausal Women
Authors: Wakatsuki Akihiko , Ikenoue Nobuo , Shinohara Koichi , Watanabe Kazushi , Fukaya Takao
Published: December 2003

Objective—Although oral estrogen replacement therapy (ERT) in postmenopausal women improves endothelial function, it also increases plasma C-reactive protein (CRP) and interleukin-6 (IL-6) concentration. The proinflammatory effect of oral ERT may explain the increased risk of coronary heart disease (CHD) associated with this treatment. Recent observational studies have demonstrated that a lower dose of oral estrogen reduces the risk for CHD. The purpose of the present study was to investigate the effects of low-dose oral estrogen on vascular inflammatory markers and endothelium-dependent vasodilation in postmenopausal women.

Methods and Results—Postmenopausal women were randomized into 3 groups to receive no treatment (n=14) or oral conjugated equine estrogen (CEE) at a dosage of 0.625 mg (n=15) or 0.3125 mg (n=15) daily for 3 months. CEE at a dosage of 0.625 mg resulted in significant increases in plasma concentrations of CRP from 690.9±749.5 to 1541.9±1608.0 ng/mL, serum amyloid A from 6.12±4.15 to 8.25±4.40 μg/mL, and IL-6 from 1.45±0.73 to 2.35±1.16 pg/mL. In contrast, CEE at a dosage of 0.3125 mg had no effect on these inflammatory markers. Both dosages of estrogen significantly decreased E-selectin concentration, whereas the concentrations of intercellular and vascular cell adhesion molecules remained unchanged. In both CEE groups, flow-mediated vasodilation in the brachial artery was increased significantly, whereas nitroglycerine-induced vasodilation was unaltered.

Conclusions—Oral CEE at a low dose of 0.3125 mg in postmenopausal women eliminated the adverse effects of high-dosage oral CEE on vascular inflammatory markers in addition to preserving the favorable effects of estrogen on cell adhesion molecules and endothelial function.
Angiotensin-Converting Enzyme Inhibitors and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase in Cardiac Syndrome X
Authors: Pizzi Carmine , Manfrini Olivia , Fontana Fiorella , Bugiardini Raffaele
Published: December 2003

Background—

Morbidity of patients with Syndrome X (SX; chest pain and normal coronary angiograms) is high and is associated with continuing episodes of chest pain and hospitalization. Impairment of microvascular endothelial function caused by increased oxidative stress has been suggested to be a mechanism of the disease. Superoxide dismutase (SOD) is the major antioxidant enzyme system of the vascular wall. This study sought to establish whether combination treatment with ACE inhibitors and statins reduces oxidative stress and improves quality of life of patients with cardiac SX.

Methods and Results—

Forty-five patients with SX were randomly assigned to receive either a combination of ramipril (10 mg/d) and atorvastatin (40 mg/d) or placebo for 6 months. We determined the activity of extracellular SOD and its relation to flow-dependent endothelium-mediated dilation (FMD) and quality of life (exercise capacity and score with Seattle Angina Questionnaire [SAQ]) before and after treatment. After 6 months, patients with SX who received atorvastatin and ramipril had significantly reduced (
P
=0.001) SOD levels (188.1±29.6 U/mL). No significant changes were seen on placebo (262.9±48.8 U/mL). Reduction of SOD after therapy was negatively correlated with FMD (
r
=0.38;
P
=0.01) and positively with total cholesterol (
r
=−0.56;
P
<0.001). At follow-up, patients taking atorvastatin and ramipril improved their quality of life both in terms of exercise duration (by 23.46%) and SAQ (by 64.1%).

Conclusions—

Six months of therapy with atorvastatin and ramipril improves endothelial function and quality of life of patients with SX. Reduced SOD activity may reflect low superoxide anion production. Benefits of these drugs may be related to reduction of oxidative stress.