bluuebunny/crossref_metadata_2025 huggingface dataset:
Corticospinal transmission to leg motoneurones in human subjects with deficient glycinergic inhibition
Authors: Nielsen J. B. , Tijssen M. A. J. , Hansen N. L. , Crone C. , Petersen N. T. , Brown P. , Dijk J. G. Van , Rothwell J. C.
Published: October 2002

Normal coordinated movement requires that the activity of antagonistic motoneurones may be depressed at appropriate times during the movement. Both glycinergic and GABAergic inhibitory mechanisms participate in this control. Patients with the major form of hyperekplexia (hereditary startle disease) have impaired inhibition of spinal motoneurones from local glycinergic interneurones and represent an ideal opportunity for studying the role of glycinergic inhibition in the control of antagonistic muscles. In the present study we investigated whether impaired glycinergic inhibition affects the corticospinal control of antagonistic spinal motoneurones in 10 patients with hyperekplexia and whether there are mechanisms that may compensate for the lack of glycinergic inhibition. In healthy subjects transcranial magnetic stimulation (TMS) produced a short‐latency inhibition of the soleus H‐reflex at rest and during tonic dorsiflexion. This inhibition, which has been shown to be mediated by spinal (glycinergic) inhibitory interneurones, was absent in all four patients in whom this experiment was performed. This confirms that glycinergic transmission is impaired in the patients. During voluntary dorsiflexion subthreshold TMS produced a depression of the ongoing EMG activity in the tibialis anterior (TA) muscle in both healthy subjects and all of the six tested patients. This is consistent with the idea that this EMG depression is caused by activation of cortical (GABAergic) inhibitory interneurones. Cross‐correlation analysis revealed normal short‐term synchronization of TA motor units accompanied by coherence in the 8‐12 Hz and 18‐35 Hz frequency bands in the 10 patients. As in healthy subjects, 8‐12 Hz coherence accompanied by decreased tendency to discharge synchronously (de‐synchronization) was found in recordings from the antagonistic TA and soleus muscles in 2 of the 10 patients. This suggests that glycinergic inhibition is not responsible for de‐synchronization of antagonistic motor units, but that other GABAergic‐inhibitory mechanisms must be involved. We propose that such mechanisms may compensate for the lack of glycinergic reciprocal inhibition in the hyperekplectic patients and explain why voluntary movements are not more severely affected.
Role of
Vibrio cholerae
O139 Surface Polysaccharides in Intestinal Colonization
Authors: Nesper Jutta , Schild Stefan , Lauriano Crystal M. , Kraiss Anita , Klose Karl E. , Reidl Joachim
Published: October 2002

Since the first occurrence of O139
Vibrio cholerae
as a cause of cholera epidemics, this serogroup has been investigated intensively, and it has been found that its pathogenicity is comparable to that of O1 El Tor strains. O139 isolates express a thin capsule, composed of a polymer of repeating units structurally identical to the lipopolysaccharide (LPS) O side chain. In this study, we investigated the role of LPS O side chain and capsular polysaccharide (CPS) in intestinal colonization by with genetically engineered mutants. We constructed CPS-negative, CPS/LPS O side chain-negative, and CPS-positive/LPS O side chain-negative mutants. Furthermore, we constructed two mutants with defects in LPS core oligosaccharide (OS) assembly. Loss of LPS O side chain or CPS resulted in a ≈30-fold reduction in colonization of the infant mouse small intestine, indicating that the presence of both LPS O side chain and CPS is important during the colonization process. The strain lacking both CPS and LPS O side chain and a CPS-positive, LPS O side chain-negative core OS mutant were both essentially unable to colonize. To characterize the role of surface polysaccharides in survival in the host intestine, resistance to several antimicrobial substances was investigated in vitro. These investigations revealed that the presence of CPS protects the cell against attack of the complement system and that an intact core OS is necessary for survival in the presence of bile.
Expression ofAnaplasma marginaleMajor Surface Protein 2 Operon-Associated Proteins during Mammalian and Arthropod Infection
Authors: Löhr Christiane V. , Brayton Kelly A. , Shkap Varda , Molad Thea , Barbet Anthony F. , Brown Wendy C. , Palmer Guy H.
Published: October 2002

The antigenically variant major surface protein 2 (MSP2) ofAnaplasma marginaleis expressed from a 3.5-kb operon that contains, in a 5′-to-3′ direction, four open reading frames,opag3,opag2,opag1, andmsp2. This operon structure was shown to be conserved among genotypically and phenotypically distinctA. marginale,A. ovis, andA. centralestrains.The individual OpAG amino acid sequences are highly conserved amongA. marginalestrains, with identities ranging from 95 to 99%. OpAG2 and OpAG3 were expressed by all examinedA. marginalestrains during the acute rickettsemia in the mammalian host and, like MSP2, localize to the bacterial surface. OpAG2 and OpAG3 were also expressed in an infectedIxodes scapularistick cell line. In contrast, the sameA. marginalestrains expressed only OpAG2 in two differentDermacentorspp. during transmission feeding. OpAG1 expression was not detected in the infected mammalian host, the infected tick cell line, or within infectedDermacentorticks. The differential expression of outer membrane proteins from within an operon is a novel finding in tick-transmitted bacteria, and the regulation of expression may be broadly applicable to understanding how the pathogen adapts to the mammalian host-tick vector transition.
Nature and Specificity of the Required Protective Immune Response That Develops Postchallenge in Mice Vaccinated with the 19-Kilodalton Fragment ofPlasmodium yoeliiMerozoite Surface Protein 1
Authors: Wipasa Jiraprapa , Xu Huji , Makobongo Morris , Gatton Michelle , Stowers Anthony , Good Michael F.
Published: October 2002

Immunity induced by the 19-kDa fragment ofPlasmodium yoeliimerozoite surface protein 1 (MSP119) is dependent on high titers of specific antibodies present at the time of challenge and a continuing active immune response postinfection. However, the specificity of the active immune response postinfection has not been defined. In particular, it is not known whether anti-MSP119antibodies that arise following infection alone are sufficient for protection. We developed systems to investigate whether an MSP119-specific antibody response alone both prechallenge and postchallenge is sufficient for protection. We were able to exclude antibodies with other specificities, as well as any contribution of MSP119-specific CD4+T cells acting independent of antibody, and we concluded that an immune response focused solely on MSP119-specific antibodies is sufficient for protection. The data imply that the ability of natural infection to boost an MSP119-specific antibody response should greatly improve vaccine efficacy.
The Polysaccharide Portion Plays an Indispensable Role inSalmonellaLipopolysaccharide-Induced Activation of NF-κB through Human Toll-Like Receptor 4
Authors: Muroi Masashi , Tanamoto Ken-ichi
Published: October 2002

The lipid A portion has been identified as the active center responsible for lipopolysaccharide (LPS)-induced macrophage activation. However, we found thatSalmonella(Salmonella entericaserovars Abortusequi, Minnesota, and Typhimurium) lipid A is inactive in human macrophages, despite its LPS being highly active. Thus we investigated the critical role of polysaccharide inSalmonellaLPS-induced activation of NF-κB. In human monocytic cell line THP-1,Salmonellalipid A and syntheticSalmonella-type lipid A (516) did not induce NF-κB-dependent reporter activity up to 1 μg/ml, whereas strong activation was observed in response toSalmonellaLPS. The difference in activity between this lipid A and LPS was further examined by using 293 cells expressing human CD14/Toll-like receptor 4 (TLR4)/MD-2, and similar results were obtained in these cells as well. A polysaccharide preparation obtained fromSalmonellaLPS was inactive in 293 cells expressing human CD14/TLR4/MD-2 even in combination with 516.Salmonella entericaserovar Minnesota Re LPS, whose structure consists of lipid A and two molecules of 2-keto-3-deoxyoctonic acid, but not its lipid A exhibited strong activity in THP-1 cells and 293 cells expressing human CD14/TLR4/MD-2. These results indicate that the polysaccharide portion covalently bound to lipid A plays the principal role inSalmonellaLPS-induced activation of NF-κB through human CD14/TLR4/MD-2.
Evaluation of Type 1 Immune Response in Naïve and Vaccinated Animals following Challenge withLeptospira borgpeterseniiSerovar Hardjo: Involvement of WC1+γδ and CD4 T Cells
Authors: Naiman Brian M. , Blumerman Seth , Alt David , Bolin Carole A. , Brown Rachel , Zuerner Richard , Baldwin Cynthia L.
Published: October 2002

Organisms within the Hardjo serovar ofLeptospiraspecies are harbored in cattle throughout the world, causing abortion in pregnant animals as well as being shed in the urine, thereby providing sources of zoonotic infection for humans. We recently showed that sterile immunity in vaccinated cattle is associated with induction of a type 1 (Th1) cell-mediated immune response. Here naïve and previously vaccinated pregnant cattle were challenged with a virulent strain of serovar Hardjo and subsequently evaluated for expression of a type 1 immune response. Lymphocytes that responded in a recall response to antigen by undergoing blast transformation were evident in cultures of peripheral blood mononuclear cells (PBMC) from vaccinated cattle throughout the postchallenge test period while those from naïve cattle were evident at one time point only. Nevertheless, beginning at 2 weeks after challenge, gamma interferon (IFN-γ) was measured in supernatants of antigen-stimulated PBMC cultures from nonvaccinated animals although the amount produced was always less than that in cultures of PBMC from vaccinated animals. IFN-γ+cells were also evident in antigen-stimulated cultures of PBMC from vaccinated but not from nonvaccinated animals throughout the postchallenge period. The IFN-γ+cells included CD4+and WC1+γδ T cells, and a similar proportion of these two subpopulations were found among the dividing cells in antigen-stimulated cultures as ascertained by carboxyfluorescein succinimidyl ester loading. Finally, while naïve and vaccinated animals had similar levels of antigen-specific immunoglobulin G1 (IgG1) following challenge, vaccinated animals had twofold-more IgG2. In conclusion, while infection may induce a type 1 response we suggest that it is too weak to prevent establishment of chronic infection.
Postexposure Prophylaxis against Anthrax: Evaluation of Various Treatment Regimens in Intranasally Infected Guinea Pigs
Authors: Altboum Zeev , Gozes Yehoshua , Barnea Ada , Pass Avi , White Moshe , Kobiler David
Published: October 2002

The efficiency of postexposure prophylaxis againstBacillus anthracisinfection was tested in guinea pigs infected intranasally with either Vollum or strain ATCC 6605 spores (75 times the 50% lethal dose [LD50] and 87 times LD50,respectively). Starting 24 h postinfection, animals were treated three times per day for 14 days with ciprofloxacin, tetracycline, erythromycin, cefazolin, and trimethoprim-sulfamethoxazole (TMP-SMX). Administration of cefazolin and TMP-SMX failed to protect the animals, while ciprofloxacin, tetracycline, and erythromycin prevented death. Upon cessation of treatment all erythromycin-treated animals died; of the tetracycline-treated animals, two of eight infected with Vollum and one of nine infected with ATCC 6605 survived; and of the ciprofloxacin group injected with either 10 or 20 mg/kg of body weight, five of nine and five of five animals, respectively, survived. To test the added value of extending the treatment period, Vollum-infected (46 times the LD50) animals were treated for 30 days with ciprofloxacin or tetracycline, resulting in protection of eight of nine and nine of nine animals, respectively. Once treatment was discontinued, only four of eight and five of nine animals, respectively, survived. Following rechallenge (intramuscularly) of the survivors with 30 times the LD50of Vollum spores, all ciprofloxacin-treated animals were protected while none of the tetracycline-treated animals survived. In an attempt to confer protective immunity lasting beyond the termination of antibiotic administration, Vollum-infected animals were immunized with a protective antigen (PA)-based vaccine concurrently with treatment with either ciprofloxacin or tetracycline. The combined treatment protected eight of eight and nine of nine animals. Following cessation of antibiotic administration seven of eight and eight of eight animals survived, of which six of seven and eight of eight resisted rechallenge. These results indicate that a combined treatment of antibiotics together with a PA-based vaccine could provide long-term protection to prevent reoccurrence of anthrax disease.
Divergent Role of Gamma Interferon in a Murine Model of Pulmonary versus SystemicKlebsiella pneumoniaeInfection
Authors: Moore Thomas A. , Perry Michelle L. , Getsoian Andrew G. , Newstead Michael W. , Standiford Theodore J.
Published: October 2002

Klebsiella pneumoniaeis a leading cause of both community-acquired and nosocomial gram-negative-bacterial pneumonia. A further clinical complication of pulmonaryK. pneumoniaeinfection is dissemination of bacteria from the lung into the peripheral blood, resulting in bacteremia concurrent with the localized pulmonary infection. Here, we report studies detailing the divergent role of gamma interferon (IFN-γ) in pulmonary versus systemicK. pneumoniaeinfection. Intratracheal inoculation of IFN-γ knockout mice resulted in significantly increased mortality compared to that observed for wild-type infected animals. Increased mortality correlated with a 100-fold increase in pulmonary bacteria within 2 days postinfection and upregulation of lung-associated interleukin-10 (IL-10) mRNA. Interestingly, IFN-γ knockout mice had a twofold reduction in plasma aminospartate transferase activity, indicating diminished liver injury following peripheral blood bacterial dissemination. To study the host response towards blood-borne bacteria in the absence of the ongoing pulmonary infection, intravenous inoculation studies were initiated. IFN-γ knockout mice were no more susceptible to intravenous infection than their wild-type counterparts. The consistent observation in IFN-γ knockout mice was for improved survival correlating with increased clearance of blood- and liver-associated bacteria. Intravenous inoculation resulted in a two- to threefold increase in hepatic IL-10 production 24 and 48 h postinfection. Liver injury was also significantly reduced in IFN-γ knockout mice. These data indicate that IFN-γ secretion is a critical mediator in the resolution of localized gram-negative pulmonary pneumonia. Surprisingly, host responses towards systemic infection with the same bacteria appear to be IFN-γ independent.
Human Leukocytes Adhere to, Penetrate, and Respond to
Staphylococcus aureus
Biofilms
Authors: Leid Jeff G. , Shirtliff Mark E. , Costerton J. W. , Stoodley and Paul
Published: October 2002

Staphylococcus aureus
is a common pathogen responsible for nosocomial and community infections. It readily colonizes indwelling catheters, forming microbiotic communities termed biofilms.
S. aureus
bacteria in biofilms are protected from killing by antibiotics and the body's immune system. For years, one mechanism behind biofilm resistance to attack from the immune system's sentinel leukocytes has been conceptualized as a deficiency in the ability of the leukocytes to penetrate the biofilm. We demonstrate here that under conditions mimicking physiological shear, leukocytes attach, penetrate, and produce cytokines in response to maturing and fully matured
S. aureus
biofilm.
Transcriptional Analysis of
Rickettsia prowazekii
Invasion Gene Homolog (
invA
) during Host Cell Infection
Authors: Gaywee Jariyanart , Radulovic Suzana , Higgins James A. , Azad Abdu F.
Published: October 2002

An invasion gene homolog,
invA
, of
Rickettsia prowazekii
has recently been identified to encode a member of the Nudix hydrolase subfamily which acts specifically on dinucleoside oligophosphates (Np

n

N;
n
≥ 5), a group of cellular signaling molecules known as alarmones. InvA is thought to enhance intracellular survival by regulating stress-induced toxic nucleotide levels during rickettsial infection. To further characterize the physiological function of InvA, the gene expression pattern during various stages of rickettsial intracellular growth was investigated. Using semiquantitative reverse transcription-PCR (RT-PCR) and real-time fluorescent probe-based quantitative RT-PCR, a differential expression profile of
invA
during rickettsial host cell infection was examined. The
invA
transcript temporarily increased during the early period of infection. Expression of rickettsial
groEL
, a molecular indicator of cellular stresses, was also shown to be upregulated during the early period of infection. Furthermore,
invA
was cotranscribed in a polycistronic message with
rrp
, a gene encoding the response regulator protein homolog, which is a part of a two-component signal transduction system. These results support our earlier findings that under such stress conditions dinucleoside oligophosphate pyrophosphatase may function as a buffer, enhancing rickettsial survival within the cytoplasm of a eukaryotic cell. The expression of rickettsial dinucleoside oligophosphate pyrophosphatase may be regulated by a part of the two-component signal transduction system similar to that described for response regulators in other bacterial systems.
Structural and Functional Variation within the Alanine-Rich Repetitive Domain of Streptococcal Antigen I/II
Authors: Demuth Donald R. , Irvine Douglas C.
Published: October 2002

Members of the antigen I/II family of cell surface proteins are highly conserved, multifunctional adhesins that mediate interactions of oral streptococci with other oral bacteria, with cell matrix proteins (e.g., type I collagen), and with salivary glycoproteins, e.g., gp340. The interaction of gp340 (formerly designated salivary agglutinin) with
Streptococcus mutans
requires an alanine-rich repetitive domain (A region) of antigen I/II that is highly conserved in all members of this family of proteins. In this report, we show that the A regions from the two
Streptococcus gordonii
M5 antigen I/II proteins (SspA and SspB) interact differently with the salivary gp340 glycoprotein and appear to be structurally distinct. Recombinant polypeptides encompassing the A region of SspA or from a highly related
S. mutans
antigen I/II protein (SpaP) competitively inhibited the interaction of gp340 with intact
S. gordonii
and
S. mutans
cells, respectively. In contrast, an A region polypeptide from SspB was inactive, and furthermore, it did not bind to purified gp340 in vitro. Circular dichroism spectra suggested that all three polypeptides were highly α-helical and may form coiled-coil structures. However, the A region of SspB underwent a conformational change and exhibited reduced α-helical structure at pH 8.5, whereas the A region polypeptides from SspA and SpaP were relatively stable under these conditions. Melt curves also indicated that at physiological pH, the A region of SspB lost α-helical structure more rapidly than that of SspA or SpaP when the temperature was increased from 10 to 40°C. Furthermore, the SspB A region polypeptide denatured completely at a temperature that was 7 to 9°C lower than that required for the A region polypeptide of SspA or SpaP. The full-length SspB protein and the three A region peptides migrated in native gel electrophoresis and column chromatography with apparent molecular masses that were approximately 2- to 2.5-fold greater than their predicted molecular masses. However, sedimentation equilibrium ultracentrifugation data showed that the A region peptides sedimented as monomers, suggesting that the peptides may form nonglobular intramolecular coiled-coil structures under the experimental conditions used. Taken together, our results suggest that the A region of SspB is less stable than the corresponding A regions of SspA and SpaP and that this structural difference may explain, at least in part, the functional variation observed in their interactions with salivary gp340.
Evidence Inconsistent with a Negative Influence of T Helper 2 Cells on Protection Afforded by a Dominant T Helper 1 Response againstMycobacterium tuberculosisLung Infection in Mice
Authors: Jung Yu-Jin , LaCourse Ronald , Ryan Lynn , North Robert J.
Published: October 2002

Mice incapable of generating an efficient Th2 response because of functional deletion of the genes for signal transducer and activation of transcription 6 (Stat6), interleukin-4 receptor alpha chain (IL-4Rα), or IL-4 plus IL-13 (IL-4/IL-13) were no more resistant than wild-type (WT) mice to airborne infection with virulentMycobacterium tuberculosis. WT mice were able to control infection and hold it at a stationary level following 20 days of log linearM. tuberculosisgrowth. Likewise, infection was kept under control and was held at the same stationary level in IL-4/IL-13−/−mice but progressed to a slightly higher level in Stat6−/−and IL-4Rα−/−mice. The onset of stationary-level infection in WT mice was associated with the expression of Th1-mediated immunity, as evidenced by an approximately 100- to 1,000-fold increase in the lungs in the synthesis of mRNA for IL-12, gamma interferon (IFN-γ), and inducible nitric oxide synthase (NOS2) that was sustained for at least 100 days. IL-12 is essential for the induction of Th1 immunity, IFN-γ is a key Th1 cytokine involved in mediation of immunity, and NOS2 is an inducible enzyme of macrophages and is needed by these cells to express immunity. In response to infection, the lungs of Stat6−/−mice showed increases in synthesis of mRNA for IL-12, IFN-γ, and NOS2 similar to that seen in WT mice. In IL-4/IL-13−/−mice, however, synthesis of mRNA for IFN-γ and NOS2 reached higher levels than in WT mice. These results argue against the notion that a Th2 response is partly or wholly responsible for the inability of Th1-mediated immunity to resolve infection with a virulent strain ofM. tuberculosis.
A Comparison of Murine and Human Immunoproteomes of
Helicobacter pylori
Validates the Preclinical Murine Infection Model for Antigen Screening
Authors: Bumann Dirk , Holland Petra , Siejak Frank , Koesling Jan , Sabarth Nicolas , Lamer Stefanie , Zimny-Arndt Ursula , Jungblut Peter R. , Meyer Thomas F.
Published: October 2002

Preclinical mouse infection models are widely used for
Helicobacter
vaccine development, but how well such models mimic important aspects of human infections is unknown. A comparison of
Helicobacter pylori
immunoproteomes of infected mice with previously reported patient data reveals a high agreement in the antigens recognized, suggesting that
H. pylori
in vivo protein composition and recognition by the host immune system are comparable in mice and humans. Murine
Helicobacter
models may thus be valid to screen antigens for human vaccination.
OPTICAL PROPERTIES OF ACCEPTORS IN SEMIMAGNETIC QUANTUM WELL SYSTEMS
Authors: JAYAM Sr. GERARDIN , NAVANEETHAKRISHNAN K.
Published: October 2002

The binding energy of a shallow acceptor in an isolated quantum well of the CdTe / Cd 1-x Mn x Te system has been investigated in an external magnetic field, assuming an empirical relationship between the barrier height and the magnetic field. Photoionization cross-sections for different magnetic fields have been estimated. Taking into account the confined phonons in the electron-phonon interaction, carrier capture times for various magnetic fields and different hydrostatic pressures have been computed. The results obtained are discussed in the light of the existing literature.
A JOINT EMPIRICAL AND THEORETICAL INVESTIGATION OF THE MODES OF DEFORMATION OF SWAPTION MATRICES: IMPLICATIONS FOR MODEL CHOICE
Authors: REBONATO RICCARDO , JOSHI MARK
Published: October 2002

We present a joint empirical/theoretical analysis of the changes in the implied volatility swaption matrix for two currencies (USD and DEM/EUR). We recognize the existence of a small number of recognizable shape patterns, and comment about the speed of transition between them. By Principal/Component/Analyzing the associated correlation and covariance matrices we highlight a non/trivial interpretation for the leading eigenvectors. We also compare the empirically obtained eigenvectors and eigenvalues with the corresponding quantities produced by the stochastic/volatility LIBOR market model of Joshi and Rebonato[10]. This allows us to perform a measure-independent comparison that is of intrinsic interest, and that can also provide a general blueprint for analyzing the realism of and choosing among similarly-fitting stochastic models. We find that mean reversion of the instantaneous volatility is a necessary condition in order to obatin the market-observed shape of the first eigenvector associated with the covariance matrix.
ON THE PRICING OF AN ISLAMIC CONVERTIBLE MORTGAGE FOR INFRASTRUCTURE PROJECT FINANCING
Authors: EBRAHIM MUHAMMED-SHAHID , KHAN TARIQULLAH
Published: October 2002

This paper models a default-free convertible facility to finance infrastructure projects in emerging Muslim countries. The mortgage is designed as a combination of an Islamic credit facility (allowing the collateralization of debt by the assets of the firm as espoused in Scott[32], Stulz and Johnson[36]) and inclusion of real warrants (as espoused in Green[12], Haugen and Senbet[15]) to mitigate the agency cost of debt discussed in Myers[27]. Numerical simulation is employed to endogenously solve for the rate of return, tenure and fractional ownership to be conveyed to financier upon conversion of the facility without resorting to any interest based (ribawi) index. Finally, sensitivity analysis is conducted to study the impact of exogenous variables and to reconcile with the existing mainstream finance literature such as Barclay and Smith[3], Stohs and Mauer [35] and Guedes and Opler [13].
ON EXPLICIT SOLUTIONS FOR THE PROBLEM OF MUMFORD AND SHAH
Authors: DE PAUW THIERRY , SMETS DIDIER
Published: October 2002

We look for explicit image segmentations in the framework of the variational model proposed by Mumford and Shah. We first treat the symmetric case when the "screen" is a disk Ω and the image is a concentric disk D⊂Ω. We prove the optimal segmentation is either the given disk D or the solution of the associated Neumann problem, depending on both the difference of intensity between the background and the disk, and the distance separating ∂Ω and ∂D. Both segmentations are optimal in some critical cases which we characterize. Our main result is a first step towards a generalization of this behaviour. In case Ω and D are convex, we prove the following for an optimal segmentation (u,K) such that K⊂D: K tends to ∂D (in the Hausdorff distance) when the difference of intensity between Ω and D goes to infinity.
MORSE–NOVIKOV CRITICAL POINT THEORY, COHN LOCALIZATION AND DIRICHLET UNITS
Authors: FARBER M.
Published: October 2002

In this paper we construct a Universal chain complex, counting zeros of closed 1-forms on a manifold. The Universal complex is a refinement of the well known Novikov complex; it relates the homotopy type of the manifold, after a suitable noncommutative localization, with the numbers of zeros of different indices which may have closed 1-forms within a given cohomology class. The main theorem of the paper generalizes the result of a joint paper with A. Ranicki, which treats the special case of closed 1-forms having integral cohomology classes. The present paper also describes a number of new inequalities, giving topological lower bounds on the minimum number of zeros of closed 1-forms. In particular, such estimates are provided by the homology of flat line bundles with monodromy described by complex numbers, which are not Dirichlet units.
AUBRY–MATHER THEORY AND IDEMPOTENT EIGENFUNCTIONS OF BELLMAN OPERATOR
Authors: SOBOLEVSKIĬ A. N.
Published: October 2002

We study the connection between Aubry–Mather theory of invariant sets of a dynamical system described by a Lagrangian L(t,x,v) = L0(v) - U(t,x) with periodic potential U(t,x), on the one hand, and idempotent spectral theory of Bellman operator of the corresponding optimization problem, on the other hand. This connection is applied to obtain a uniqueness result for an eigenfunction of Bellman operator in the case of irrational rotation number.
FORMAL FROBENIUS MANIFOLD STRUCTURE ON EQUIVARIANT COHOMOLOGY
Authors: CAO HUAI-DONG , ZHOU JIAN
Published: October 2002

For a closed Kähler manifold with a Hamiltonian action of a connected compact Lie group by holomorphic isometries, we construct a formal Frobenius manifold structure on the equivariant cohomology by exploiting a natural DGBV algebra structure on the Cartan model.
Engagement of Glycoprotein IIb/IIIa (α
IIb
β
3
) on Platelets Upregulates CD40L and Triggers CD40L-Dependent Matrix Degradation by Endothelial Cells
Authors: May Andreas E. , Kälsch Thorsten , Massberg Steffen , Herouy Yared , Schmidt Roland , Gawaz Meinrad
Published: October 2002

Background—

CD40L-CD40 interactions induce inflammatory signals in cells of the vascular wall. We evaluated the effects of glycoprotein (GP) IIb/IIIa (α
IIb
β
3
) engagement that occurs during platelet-endothelium interactions on CD40L surface exposure on platelets and initiation of proteolytic activity in human umbilical vein endothelial cells (HUVECs).

Methods and Results—

Transient (60-minute) adhesion of thrombin-prestimulated platelets enhanced HUVEC expression of urokinase-type plasminogen activator receptor and membrane type-1 matrix metalloproteinase (MT1-MMP) (reverse transcriptase–polymerase chain reaction, flow cytometry) and secretion of urokinase-type plasminogen activator, tissue-type plasminogen activator, and MMP-1 (ELISA) and induced proteolytic activity via MMP-2 and MMP-9 (gelatin zymography). These effects were abrogated by hindrance of physical platelet-endothelial contacts using transwell systems or inhibited by GRGDSP, mAbs anti–GP IIb/IIIa (7E3), anti-α
v
β
3
(LM609), or anti-CD40L (TRAP1). In addition, MMP-2 and MMP-9 were inhibited by specific GP IIb/IIIa antagonists tirofiban, lamifiban, or integrelin. On endothelial cells, induction of proteolytic activity by activated platelets was mimicked by CD40 engagement using soluble CD40L but not affected by antibody clustering of α
v
β
3
. On platelets, CD40L and CD62P exposure was enhanced on adhesion to HUVECs or immobilized fibrinogen and was abrogated by GRGDSP or LM609. In suspension, cross-linking of GP IIb/IIIa by fibrinogen plus secondary mAb upregulated CD40L surface exposure. Consistently, bivalent mAb 7E3 upregulated CD40L, whereas ligation of GP IIb/IIIa by soluble fibrinogen alone or monovalent Fab-fragment c7E3 had no effect.

Conclusions—

Platelet adhesion via GP IIb/IIIa upregulates CD40L and CD62P surface exposure. Proteolytic activity of HUVEC is induced by the concerted action of β
3
-integrin–mediated platelet adhesion and subsequent CD40L-induced signals in HUVECs. Effective anti–GP IIb/IIIa or anti-CD40L strategies might, therefore, contribute to plaque stabilization.
Cardiac-Specific Overexpression of GLUT1 Prevents the Development of Heart Failure Attributable to Pressure Overload in Mice
Authors: Liao Ronglih , Jain Mohit , Cui Lei , D’Agostino Jessica , Aiello Francesco , Luptak Ivan , Ngoy Soeun , Mortensen Richard M. , Tian Rong
Published: October 2002

Background—

Increased rates of glucose uptake and glycolysis have been repeatedly observed in cardiac hypertrophy and failure. Although these changes have been considered part of the fetal gene reactivation program, the functional significance of increased glucose utilization in hypertrophied and failing myocardium is poorly understood.

Methods and Results—

We generated transgenic (TG) mice with cardiac-specific overexpression of insulin-independent glucose transporter GLUT1 to recapitulate the increases in basal glucose uptake rate observed in hypertrophied hearts. Isolated perfused TG hearts showed a greater rate of basal glucose uptake and glycolysis than hearts isolated from wild-type littermates, which persisted after pressure overload by ascending aortic constriction (AAC). The in vivo cardiac function in TG mice, assessed by echocardiography, was unaltered. When subjected to AAC, wild-type mice exhibited a progressive decline in left ventricular (LV) fractional shortening accompanied by ventricular dilation and decreased phosphocreatine to ATP ratio and reached a mortality rate of 40% at 8 weeks. In contrast, TG-AAC mice maintained LV function and phosphocreatine to ATP ratio and had <10% mortality.

Conclusions—

We found that increasing insulin-independent glucose uptake and glycolysis in adult hearts does not compromise cardiac function. Furthermore, we demonstrate that increasing glucose utilization in hypertrophied hearts protects against contractile dysfunction and LV dilation after chronic pressure overload.
REVISITING KARL BARTH'S EXEGESIS OF 1 KINGS 13
Authors: Bosworth David
Published: October 2002

The present article seeks to re-present Karl Barth's exegesis of 1 Kings 13 with additional support that Barth neglected to include. Changes in biblical scholarship over the past few decades have resulted in an environment in which Barth's interpretation may not be as readily rejected as it was in the past. Barth's exegesis of 1 Kings 13 was not accepted among biblical scholars for several reasons. He was thought to be an enemy of historical criticism whose exegetical work was not a serious contribution to biblical studies. Furthermore, he interpreted the chapter holistically at a time when scholars were preoccupied with analytical questions concerning sources and composition. Barth related the chapter to the whole history of the divided kingdom by suggesting that the man of God and the old prophet represent the kingdoms from which they come and that the relationship between the two prophetic figures mirrors the relationship between Israel and Judah as told in Kings. This analogy seemed unlikely to scholars convinced of the fragmentary nature of Kings. The present article begins with an overview of Barth's relationship to modern biblical scholarship followed by a summary presentation of his exegesis of 1 Kings 13. Next, the major objections to Barth's interpretation are critically assessed, and recent research on the chapter is evaluated. Finally, the analogy indicated by Barth is elaborated, so that his interpretation may seem more plausible and future research may benefit from his insights.
THE BEGINNING OF MARK: A COLONIAL/ POSTCOLONIAL CONUNDRUM
Authors: Samuel Simon
Published: October 2002

This article reads the Markan beginning (Mark 1:1), arguably the superscription, from a postcolonial perspective. It examines whether or not Mark begins the story of Jesus as a pro- or anti- or postcolonial response to the colonist Roman and certain relatively dominant native Jewish nationalistic and collaborative discourses of power. This reading is informed by the postcolonial theoretical concepts of mimicry, ambivalence and hybridity. It examines the consensual-conflictual hybridity of 'Aρχη τoυ ευαγγελιoυ 'Iησoυ Xριστoυ [υιoυ εoυ], firstly in the Roman imperial context of 'Aρχη τoυ ευαγγελιoυ Kαισαρoυ υιoυ εoυ, and secondly in the native Jewish nationalistic and collaborative discursive contexts. Attention is given to the potential interface of this category of words, codes and symbols in Mark with their occurrences in the imperial cult and in the biblical and postbiblical discourses. I argue that, while adhering to these words, codes and symbols of the Roman and Jewish discourses, Mark potentially creates an element of indetminancy and disruption of meaning. This may perhaps be with a view to create a voice of its own that is affiliative and disruptive to both the Roman colonial and the native Jewish nationalistic and collaborative voices. This article thus sheds light to the affiliative alterity of Mark, a characteristic of most postcolonial discourses whether ancient or modern. This reading is informed by my own postcolonial experience of being born and bred in a minority community in postcolonial 'India' and also by the experiences of being the 'other' in the former colonial masters' mother country. My own ambivalent affiliative-antagonistic attitude toward both countries and their discourses of power inform my reading.
Neuroinflammation in Alzheimer's disease and prion disease
Authors: Eikelenboom P. , Bate C. , Van Gool W.A. , Hoozemans J.J.M. , Rozemuller J.M. , Veerhuis R. , Williams A.
Published: October 2002

Alzheimer's disease (AD) and prion disease are characterized neuropathologically by extracellular deposits of Aβ and PrP amyloid fibrils, respectively. In both disorders, these cerebral amyloid deposits are co‐localized with a broad variety of inflammation‐related proteins (complement factors, acute‐phase protein, pro‐inflammatory cytokines) and clusters of activated microglia. The present data suggest that the cerebral Aβ and PrP deposits are closely associated with a locally induced, non‐immune‐mediated chronic inflammatory response. Epidemiological studies indicate that polymorphisms of certain cytokines and acute‐phase proteins, which are associated with Aβ plaques, are genetic risk factors for AD. Transgenic mice studies have established the role of amyloid associated acute‐phase proteins in Alzheimer amyloid formation. In contrast to AD, there is a lack of evidence that cytokines and acute‐phase proteins can influence disease progression in prion disease. Clinicopathological and neuroradiological studies have shown that activation of microglia is a relatively early pathogenetic event that precedes the process of neuropil destruction in AD patients. It has also been found that the onset of microglial activation coincided in mouse models of prion disease with the earliest changes in neuronal morphology, many weeks before neuronal loss and subsequent clinical signs of disease. In the present work, we review the similarities and differences between the involvement of inflammatory mechanisms in AD and prion disease. We also discuss the concept that the demonstration of a chronic inflammatory‐like process relatively early in the pathological cascade of both diseases suggests potential therapeutic strategies to prevent or to retard these chronic neurodegenerative disorders. GLIA 40:232–239, 2002. © 2002 Wiley‐Liss, Inc.
Microglial activation by purines and pyrimidines
Authors: Inoue Kazuhide
Published: October 2002

Microglial activation by purines and pyrimidines is reviewed, with emphasis on the actions of adenosine 5′‐triphosphate (ATP) on chemotaxis or releases of plasminogen and cytokines from microglia. ATP activates microglia, causing morphological changes with membrane ruffling. Activated microglia exhibit chemotaxis to ATP. Microglia stimulated by a low concentration of ATP (∼30–50 μM) rapidly release plasminogen (within 5–10 min), which may protect neurons. Microglia stimulated by a higher concentration of ATP release tumor necrosis factor‐α (TNF‐α), 2–3 h after the stimulation and interleukin‐6 (IL‐6), 6 h after the stimulation. It is reported that TNF‐α stimulation causes an increase in the expression of IL‐6 receptor mRNA and expression in neuronal cells (März et al. 1996. Brain Res 706:71–79). After binding with gp130, the IL‐6 receptor matures and can accept IL‐6 molecules. It is speculated that neurons may require several hours to prepare for the full reception of IL‐6, which induces a more efficient protective effect by IL‐6 after stimulation with TNF‐α. After neurons are ready to accept IL‐6 fully, microglia release IL‐6 to neurons. Stronger and longer stimulation by ATP may change the function of microglia and cause cell death. The conditions evoking the heavy stimulation would result from serious injury. Activated microglia act as scavenger cells that induce apoptosis in damaged neurons by releasing toxic factors, including NO, and removing dead cells, their remnants, or dangerous debris by phagocytosis. These actions lead to a suitable environment for tissue repair and neural regeneration. The fate of neurons may therefore be regulated in part by ATP through the activation of microglia. GLIA 40:156–163, 2002. © 2002 Wiley‐Liss, Inc.
Role of p38 and p44/42 mitogen‐activated protein kinases in microglia
Authors: Koistinaho Milla , Koistinaho Jari
Published: October 2002

Although microglial cells are thought to play a beneficial role in the regeneration and plasticity of the central nervous system (CNS), recent studies have indicated that at least some molecules released by microglia may be harmful in acute brain insults and neurodegenerative diseases. Therefore, the pathways mediating the synthesis and release of these neurotoxic compounds are of importance. p38 and p44/42 families of mitogen‐activated protein kinases (MAPKs) in microglia respond strongly to various extracellular stimuli, such as ATP, thrombin, and β‐amyloid, a peptide thought to be responsible for the neuropathology in Alzheimer's disease. In this review we describe in vivo evidence implicating that p38 and p44/42 MAPKs may play a critical role in harmful microglial activation in acute brain injury, such as stroke, and in more chronic neurodegenerative diseases, such as Alzheimer's disease. We also clarify the extracellular signals responsible for activation of p38 and p44/42 MAPK in microglia and review the responses so far reported to be mediated by these kinases. GLIA 40:175–183, 2002. © 2002 Wiley‐Liss, Inc.
Consistent pricing of warrants and traded options
Authors: Hanke Michael , Pötzelberger Klaus
Published: October 2002

Warrants issuance affects the stock price process of the issuing company. This change in the stock price process leads to subsequent changes in the prices of options written on the issuing company's stocks. In this paper, we investigate the effects of warrants issuance on the prices of traded options (bought and sold by third parties) already outstanding at the time of warrants issuance. We show how these options can be valued as portfolios of standard and compound options written on the stock of an otherwise similar company without warrants and derive a closed‐form solution for the Black‐Scholes model. An application of these results to empirical data shows that warrants issuance can have very large effects on the prices of outstanding traded options.
Financial development and economic growth
Authors: Khalifa Al‐Yousif Yousif
Published: October 2002

The present paper examines the nature and direction of the relationship between financial development and economic growth using both time‐series and panel data from 30 developing countries for the period 1970–1999. The choice of the sample was determined by the availability of data. As such, the exclusion of other developing countries is due to the fact that the data on these countries are missing for some years. The empirical results strongly support the view that financial development and economic growth are mutually causal, that is, causality is bidirectional. There is also some support for the other views presented in the literature (supply‐leading, demand‐leading, and no relationship) but it is not as strong as that for the bidirectional causality. Moreover, the findings of the present paper accords with the view of the World Bank and other empirical studies that the relationship between financial development and economic growth cannot be generalized across countries because economic policies are country specific and their success depends, among others things, on the efficiency of the institutions implementing them.
Interrelationships among regional stock indices
Authors: Ratanapakorn Orawan , Sharma Subhash C
Published: October 2002

This study investigates the short‐run and long‐run relationships among stock indices of the US, Europe, Asia, Latin America, and Eastern Europe–Middle East for the pre‐Asian crisis and for the crisis period. The findings from these two periods are compared and contrasted. No long‐run relationship is observed among these indices during the pre‐Asian crisis period. However, during the crisis period, one significant cointegrating vector is observed and more short‐run (i.e., causal) relations are observed in this period as compared to the pre‐crisis period. Based on the analysis, we infer that during the Asian crisis period, the globalization increased and only the European markets directly effected the US market, while the other regional markets indirectly influenced the US market via the European market. As regards the effect of shocks, we observe that during the pre‐Asian crisis period, the response of all regional markets to shocks in other markets is transitory, whereas during the crisis period, the response of the US stock market is transitory but that of EU market is permanent to all other markets.
Analysis and the hierarchy of nature in eighteenth-century chemistry
Authors: SIMON JONATHAN
Published: October 2002

What was the impact of Lavoisier's new elementary chemical analysis on the conception and practice of chemistry in the vegetable kingdom at the end of the eighteenth century? I examine how this elementary analysis relates both to more traditional plant analysis and to philosophical and mathematical concepts of analysis current in the Enlightenment. Thus I explore the relationship between algebra, Condillac's philosophy and Lavoisier's chemical system, as well as comparing Lavoisier's analytical approach to those of his predecessors, such as Baumé and Bucquet. With reference to the aims of vegetable analysis, I show how the dominance of elementary analysis devalued a tradition that sought to isolate immediate principles (plant extracts), marginalizing the chemical practices of many doctors and pharmacists in the context of the new chemistry in France.
AVOIDING TENANCY LEGISLATION: SHAM AND CONTRACTING OUT REVISITED
Authors: Bright Susan
Published: October 2002

THIS article considers the approach taken to devices that are designed to avoid tenancy legislation, exploring the doctrines of sham, pretence, contracting out and the “artificial device doctrine” developed in tax cases. It is argued that the legal response takes two stages. The first judicial task is to determine which legal route is being followed, an enquiry which is designed to identify what the genuine relationship is between the parties and incorporating the doctrines of sham, pretence and labelling. Having determined the true nature of the legal relationship, the task of the court is then to apply the legislation to that relationship, which will include a consideration of whether any “contracting out” by the tenant is lawful. Having reviewed the legal response to devices, the article discusses the decision of the Court of Appeal in Bankway Properties v Pensfold-Dunsford.
PHYSICAL DAMAGE IN NEGLIGENCE
Authors: Witting Christian
Published: October 2002

BEING an action on the case, it has long been supposed that negligence is consummated only upon the occurrence of damage. Physical damage ordinarily occurs where there is some change in the state or structure of a person’s body, or where there is some change in the state or structure of tangible property. The author argues that courts have, in recent wrongful conception and contamination cases, widened the orthodox notion of what constitutes physical damage. The courts have employed an ordinary bystander test in order to determine whether particular failures of care, arising in circumstances of high or unnecessary risk of physical harm, should be treated as if they give rise to physical damage. These are cases of a new form of actionable damage, that is, damage of a socially constructed kind.