bluuebunny/crossref_metadata_2025 huggingface dataset:
Dinuclear Metal–Organic Material for Binary Optical Recording
Authors: Trouts T.D. , Tyson D.S. , Pohl R. , Kozlov D.V. , Waldron A.G. , Castellano F.N.
Published: April 2003

A diimine ligand tethered to anthracene in the 9‐position, 4′‐(9‐anthrylethyl)‐4‐methyl‐2,2′‐bipyridine (bpy‐An), was dimerized through cycloaddition photochemistry. The resultant head‐to‐tail photodimer (bpy‐PD) was used as a bridging ligand in the preparation of a new dinuclear RuII complex, [Ru(dmb)2(bpy‐PD)Ru(dmb)2]4+ (dmb = 4,4′dimethyl‐2,2′‐bipyridine). The corresponding mononuclear species containing anthracene ([Ru(dmb)2(bpy‐An)]2+ was also synthesized and serves as a model compound in this study. UV photolysis (λ < 300 nm) of the strongly luminescent RuII dinuclear complex results in cycloreversion, generating two anthracene‐containing mononuclear species, [Ru(dmb)2(bpy‐An)]2+, whose emission is largely quenched as a result of nonradiative triplet–triplet energy transfer. The photophysical and photochemical properties of the dinuclear system have been studied in CH3CN solutions and in solid polyvinyl alcohol (PVA) thin films. The “on”–“off” luminescence switching characteristics and concomitant non‐destructive readout properties suggested that these molecules could be useful in read‐only memory (ROM) applications. In the solid state, micrometer‐sized objects were imaged using visible light, taking advantage of the luminescence contrast generated from the UV photochemical reaction. These written images were stable for at least 6 months, indicating that long‐term binary data storage is indeed feasible in these ROM metal–organic materials.
Disclosure, confidentiality, and families: Experiences and attitudes of those with genetic versus nongenetic medical conditions
Authors: Plantinga Laura , Natowicz Marvin R. , Kass Nancy E. , Hull Sara Chandros , Gostin Lawrence O. , Faden Ruth R.
Published: April 2003

Despite policy attention to medical privacy and patient confidentiality, little empirical work exists documenting and comparing experiences of persons with genetic versus nongenetic medical conditions concerning persons' disclosure to others as well as their views about appropriate confidentiality to and within families. The goal of this cross‐sectional interview study with nearly 600 participants was to document and compare the experiences, attitudes, and beliefs of persons with strictly genetic conditions to those of persons with or at risk for other serious medical conditions in terms of the degree to which they have disclosed to others that they have the condition and their views about how others ought to maintain the confidentiality of that information. While almost all participants reported that family members knew about their condition, results suggest participants want to control that disclosure themselves and do not want doctors to disclose information to family members without their knowledge. Similarly, participants do not think family members should be able to get information about them without their knowledge but feel overwhelmingly that it is a person's responsibility to disclose information about hereditary conditions to other family members. Ambivalence about confidentiality was evident: while most participants did not mind doctors sharing information with other doctors when it was for their benefit, the majority also felt that doctors should be punished for releasing information without their permission. The views and experiences reported here generally did not differ by whether participants had genetic versus nongenetic conditions, suggesting that the extensive policy focus on genetic information may be unwarranted. © 2002 Wiley‐Liss, Inc.
Perceptions of reproductive risk and carrier testing among adolescent sisters of males with chronic granulomatous disease
Authors: James Cynthia A. , Holtzman Neil A. , Hadley Donald W.
Published: April 2003

Although recent research has investigated the attitudes of parents, professionals, and adult siblings toward carrier testing of minors, no studies have focused on the experiences of minor siblings of individuals with X‐linked and autosomal recessive conditions. To explore adolescent sisters' perceptions of their reproductive risks, attitudes toward carrier testing, and resources for information and support, we interviewed 14 parents and 9 sisters (ages 12–15) of males with chronic granulomatous disease (CGD), a primary immunodeficiency disorder inherited in both an X‐linked recessive and autosomal recessive fashion. Our semistructured telephone interviews were audiotaped, transcribed, and subjected to template analysis (a common qualitative methodology). Girls were all aware that CGD is an inherited condition and each had made an assessment of her reproductive risk. All girls considered their parents to be their best source of information and support, but girls had trouble initiating discussions for fear of upsetting their parents. All girls and parents considered eventual carrier testing vital for reproductive decision‐making and relationship‐building. However, girls favored carrier testing at a later age and expressed more concerns about psychological risks associated with testing than did their parents. When faced with the hypothetical situation of being offered carrier testing “tomorrow,” half of the parents and untested daughters disagreed on the desirability of the test, with parents more likely to favor testing. Including adolescent sisters in family‐based genetic counseling that provides an opportunity for age‐appropriate discussion of inheritance and the timing, risks, and benefits of carrier testing would be beneficial to them. Published 2003 Wiley‐Liss, Inc.
Computer simulations in solid‐state NMR. III. Powder averaging
Authors: Edén Mattias
Published: April 2003

As the final part in a series of articles on numerical simulations in solid‐state NMR (Concepts Magn Reson 17A: 117–154, 2003 and Concepts Magn Reson Part A 18A: 1–23, 2003), aspects of simulations of NMR responses from powders are discussed. The underlying equations for powder averaging are derived, and it is demonstrated how powder averages may be estimated numerically. Orientational symmetry in solid‐state NMR is summarized and exploited to achieve more efficient calculations. Explicit computer code in C/C++ is given for simulation of NMR spectra from powders containing (1) two homonuclear spins‐1/2 in a static sample and (2) a heteronuclear two spin‐1/2 system under magic‐angle‐spinning conditions. © 2003 Wiley Periodicals, Inc. Concepts Magn Reson Part A 18A: 24–55, 2003
Magnetic susceptibility: Solutions, emulsions, and cells
Authors: Kuchel P.W. , Chapman B.E. , Bubb W.A. , Hansen P.E. , Durrant C.J. , Hertzberg M.P.
Published: April 2003

Differences in magnetic susceptibility between various compartments in heterogeneous samples can introduce unanticipated complications to NMR spectra. On the other hand, an understanding of these effects at the level of the underlying physical principles has led to the development of several experimental techniques that provide data on cellular function that are unique to NMR spectroscopy. To illustrate some key features of susceptibility effects we present, among a more general overview, results obtained with red blood cells and a recently described model system involving diethyl phthalate in water. This substance forms a relatively stable emulsion in water and yet it has a significant solubility of ∼5 mmol L−1 at room temperature; thus, the NMR spectrum has twice as many resonances as would be expected for a simple solution. What determines the relative intensities of the two families of peaks and can their frequencies be manipulated experimentally in a predictable way? The theory used to interpret the NMR spectra from the model system and cells was first developed in the context of electrostatics nearly a century ago, and yet some of its underlying assumptions now warrant closer scrutiny. While this insight is used in a practical way in this article, the accompanying article deals with the mathematics and physics behind this new analysis. © 2003 Wiley Periodicals, Inc. Concepts Magn Reson Part A 18A: 56–71, 2003
Magnetic susceptibility: Further insights into macroscopic and microscopic fields and the sphere of Lorentz
Authors: Durrant C.J. , Hertzberg M.P. , Kuchel P.W.
Published: April 2003

To make certain quantitative interpretations of spectra from NMR experiments carried out on heterogeneous samples, such as cells and tissues, we must be able to estimate the magnetic and electric fields experienced by the resonant nuclei of atoms in the sample. Here, we analyze the relationships between these fields and the fields obtained by solving the Maxwell equations that describe the bulk properties of the materials present. This analysis separates the contribution to these fields of the molecule in which the atom in question is bonded, the “host” fields, from the contribution of all the other molecules in the system, the “external” fields. We discuss the circumstances under which the latter can be found by determining the macroscopic fields in the sample and then removing the averaged contribution of the host molecule. We demonstrate that the results produced by the, so‐called, “sphere of Lorentz” construction are of general validity in both static and time‐varying cases. This analytic construct, however, is not “mystical” and its justification rests not on any sphericity in the system but on the local uniformity and isotropy, i.e., spherical symmetry, of the medium when averaged over random microscopic configurations. This local averaging is precisely that which defines the equations that describe the macroscopic fields. Hence, the external microscopic fields, in a suitably averaged sense, can be estimated from the macroscopic fields. We then discuss the calculation of the external fields and that of the resonant nucleus in NMR experiments. © 2003 Wiley Periodicals, Inc. Concepts Magn Reson Part A 18A: 72–95, 2003
IL‐10 and TGF‐β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy
Authors: Jutel Marek , Akdis Mübeccel , Budak Ferah , Aebischer‐Casaulta Carmen , Wrzyszcz Maria , Blaser Kurt , Akdis Cezmi A.
Published: April 2003

The regulation of normal and allergic immune responses to airborne allergens in the mucosa is still poorly understood, and the mechanism of specific immunotherapy (SIT) in normalizing the allergic response to such allergens is currently not clear. Accordingly, we have investigated the immunoregulatory mechanism of both normal and allergic responses to the major house‐dust mite (HDM) and birch pollen allergens — Dermatophagoides pteroynyssinus (Der p)1 and Bet v 1, respectively — as well as the immunologic basis of SIT to HDM in rhinitis and asthma patients. In normal immunity to HDM and birch pollen, an allergen‐specific peripheral T cell suppression to Der p 1 and Bet v 1 was observed. The deviated immune response was characterized by suppressed proliferative T celland Th1 (IFN‐γ) and Th2 (IL‐5, IL‐13) cytokine responses, and increased IL‐10 and TGF‐β secretion by allergen‐specific T cells. Neutralization of cytokine activity showed that T cell suppression was induced by IL‐10 and TGF‐β during SIT and in normal immunity to the mucosal allergens. In addition, SIT induced an antigen‐specific suppressive activity in CD4+ CD25+ T cells of allergic individuals. Together, these results demonstrate a deviation towards a regulatory/suppressor T cell response during SIT and in normal immunity as a key event for the healthy immune response to mucosal antigens.
Tumor‐associated fibroblasts recruit blood monocytes into tumor tissue
Authors: Silzle Tobias , Kreutz Marina , Dobler Marcus A. , Brockhoff Gero , Knuechel Ruth , Kunz‐Schughart Leoni A.
Published: April 2003

Tumor‐associated fibroblasts (TAF) and tumor‐associated macrophages are the main stromal components in desmoplastic breast tumors. These host cell types were extensively studied individually with regard to tumor development and progression but little is known about their reciprocal interactions. To elucidate the role of TAF in the recruitment of monocytes (MO) we designed a 3D co‐culturesystem of multicellular fibroblast spheroids of different origin, co‐cultured with MO suspensions from healthy donors. Spheroids of tumor‐derived but not of normal fibroblasts were extensively infiltrated by MO. A linear correlation between number of infiltrated MO and number of MO applied per spheroid was shown, indicating a distinct migratory MO subpopulation (≈15%) within the peripheral blood MO pool. Our data imply that MO migration into fibroblastic tumor areas may partially result from high expression of CCL2 (monocyte chemotactic protein‐1), which was regulated by endogenousIL‐6 as shown by neutralization experiments. The effect of CCL2 on MO migration was inhibited by CCL2 neutralizing antibody in tumor‐derived fibroblast conditioned media in a Boyden chamber migration assay but not in spheroid culture. While this phenomenon needs further evaluation, our data clearly support the concept of fibroblasts as "sentinel cells" relevant for tumor progression.
ICAM‐1 isoforms: specific activity and sensitivity to cleavage by leukocyte elastase and cathepsin G
Authors: Robledo Olivier , Papaioannou Anne , Ochietti Benoit , Beauchemin Claire , Legault Doris , Cantin André , King Philip D. , Daniel Claude , Alakhov Valery Yu , Potworowski Edouard F. , St‐Pierre Yves
Published: April 2003

The extracellular moiety of ICAM‐1 consists of five Ig‐like domains, the first and third domains mediating adhesion to integrin ligands. The ICAM‐1 gene, however, gives rise to the expression of five alternative splice variants containing two, three, or four Ig‐like domains. In this work, we have investigated whether the rearrangement of the architecture of ICAM‐1 affects its structural properties and function. We showed that, in contrast to the common form, all alternative isoforms of ICAM‐1 were susceptible to cleavage by leukocyte elastase and cathepsin G. We found that the length of an isoform did not influence the susceptibility to proteolysis. The molecular diversity provided by the skipping of entire Ig domains and the level of expression on the APC, however, significantly influenced their ability to potentiate the proliferation of T cells. Finally, we found that the expression of minor ICAM‐1 isoforms encoding the third Ig‐like domains was sufficient to sustain neutrophil infiltration in the liver and confer exon‐5‐targeted ICAM‐1‐deficient mice susceptibility to LPS‐induced septic shock. These findings not only demonstrate that ICAM‐1 isoforms are fully functional, but support the concept that alternative RNA splicing in the Ig superfamily may fulfill distinct roles during the development of the immune response.
A recombinant bispecific single‐chain antibody induces targeted, supra‐agonistic CD28‐stimulation and tumor cell killing
Authors: Grosse‐Hovest Ludger , Hartlapp Ingo , Marwan Wolfgang , Brem Gottfried , Rammensee Hans‐Georg , Jung Gundram
Published: April 2003

Endowing tumor cells with costimulatory signals for T cell activation has emerged as a promising strategy for tumor immunotherapy. Costimulatory molecules were either transfected into tumor cells to generate vaccines or were fused, e.g. to antibodies against tumor‐associated antigens, to achieve targeted T cell costimulation in vivo. Here we report the production and purification of rM28, a recombinant bispecific single‐chain antibody directed to a melanoma‐associated proteoglycan and to the costimulatory CD28 molecule on human T cells. We found that a dimer of the recombinant molecule, bound to tumor target cells, induced pronounced T cell activation in peripheral blood mononuclear cell preparations without additional TCR/CD3 stimulation being required. Thelytic activity generated after 3 days of stimulation effectively prevented tumor cell growth. However, it was unspecific and predominantly mediated by non T cells. Our findings demonstrate that presentation of a CD28 antibody within a suitable recombinant, bispecific format may result in a "targeted supra‐agonistic stimulation" of the CD28 molecule, which leads to effective tumor cell killing after induction of unspecifically lytic cells.
Immunogenicity and protective efficacy of Plasmodium falciparum liver‐stage Ag‐3 in Aotus lemurinus griseimembra monkeys
Authors: Perlaza Blanca‐Liliana , Zapata Constanza , Valencia Anais Z. , Hurtado Silvia , Quintero Gustavo , Sauzet Jean‐Pierre , Brahimi Karima , Blanc Catherine , Arévalo‐Herrera Myriam , Druilhe Pierre , Herrera Sócrates
Published: April 2003

Three recombinant proteins spanning the Plasmodium falciparum liver‐stage Ag‐3 (LSA‐3) were used to immunize Aotus monkeys. The proteins were delivered subcutaneously withoutadjuvant, adsorbed onto polystyrene 0.5 μm particles at a concentration of 2 μg per immunization. Control animals received glutathione‐S‐transferase formulated similarly. Animals were challenged as late as 5 months after the last immunization, by intravenous inoculation of 100,000 P. falciparum sporozoites of a strain heterologous to the one from which the immunogens were derived. Sterile protection was achieved in three of the five immunized monkeys but in none of four controls. Antibodies were at low titer, but reacted with the native parasite protein and were boostedby parasite challenge. Ag‐specific IFN‐γ secretion was detectable in all LSA‐3‐immunized animals in response to the LSA‐3‐derived Ag. The protection was apparently associated with high levels of IFN‐γ production in response to in vitro recall Ag. These results lend support to the vaccine potential of LSA‐3 indicated by previous results obtained in chimpanzees, as well as the value of yet another Ag‐delivery system. They also support the value of the Aotus model for the pre‐clinical development of pre‐erythrocytic‐stage vaccines.
Visualization of peptide presentation following oral application of antigen in normal and Peyer's patches‐deficient mice
Authors: Kunkel Désirée , Kirchhoff Dennis , Nishikawa Shin‐Ichi , Radbruch Andreas , Scheffold Alexander
Published: April 2003

Orally applied antigens generate systemic unresponsiveness by induction of anergy and deletion of specific T cells at high antigen doses, and induction of regulatory T cells at low doses of antigen. These different immune reactions have been attributed to different types of antigen‐presenting cells (APC) and/or different secondary lymphoid organs participating in the induction of the immune response. We used high‐sensitivity immunofluorescence to directly identify for the first time the cells presenting orally applied antigen in vivo. At low peptide doses (<1 mg) peptide presentation was exclusively detected on dendritic cells (DC) of the Peyer's patches (PP) and mesenteric lymph nodes (mLN). At high doses (>1 mg) peptides were presented systemically and by all types of APC but presentation was still maximal on DC of the PP (up to 65%). Nevertheless, at limiting antigen doses T cell activation in the gut‐associated lymphoid tissue occurs preferentially in the mLN but not in PP. PP‐deficient mice have the same frequencies of peptide‐presenting cells in mLN, peripheral lymph nodes and spleen and activation of naive T cells in vivo is not affected. Therefore, PP are not critical for antigen presentation as well as for T cell activation in response to orally applied soluble antigens.
Effective and selective immune surveillance of the brain by MHC class I‐restricted cytotoxic T lymphocytes
Authors: Cabarrocas Julie , Bauer Jan , Piaggio Eliane , Liblau Roland , Lassmann Hans
Published: April 2003

Cytotoxic CD8+ T cells are abundantly present in human virus‐induced or putative autoimmune diseases of the central nervous system (CNS). Their direct role in the induction of inflammatory brain damage is, however, poorly understood. We have studied CD8+ T cell‐mediated brain inflammation by transferring MHC class I‐restricted hemagglutinin (HA)‐reactive T cells from a TCR transgenic mouse line into transgenic mice, which express HA in astrocytes. We show that activated CD8+ T cells alone can induce monophasic brain inflammation in immunocompetent recipient animals. Similar to previous studies, involving transfer of CD4+ cells, brain inflammation peaks after 5–7 days and then declines. The pathology of brain inflammation, however, differs fundamentally from that induced by CD4+ cells. The inflammatory reaction is dominated by T cells and activated microglia in the virtual absence of hematogenous macrophages. This is associated with exquisitely specific destruction of antigen‐containing astrocytes in the absence of any bystander damage of myelin, oligodendrocytes or neurons. Furthermore, in contrast to CD4+ T cells, some CD8+ cells accumulate in the brain and activate microglia in recipient animals, even in the absence of the specific antigen in the CNS. These data indicate that CD8+ T cells areprime candidates for immune surveillance of the CNS.
Immunostimulatory effects of plasmid DNA and synthetic oligodeoxynucleotides
Authors: Zelenay Santiago , Elías Fernanda , Fló Juan
Published: April 2003

Nucleic acid immunization is a new vaccination technology. DNA vaccines do not only carry the genetic information for the antigen of interest but also deliver an adjuvant effect due to the presence of immunostimulatory sequences within the plasmid backbone. It is generally assumed that the adjuvant properties of plasmid DNA are equal to those described for oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs. To challenge this hypothesis we have carried out a series of experiments comparing the ability of single‐ and double‐stranded ODN containing CpG motifs to induce the activation of mouse spleen cells. Moreover, we compared the immunostimulatory properties of plasmids that were modified by the addition of two to four CpG motifs. Our results establish that plasmid DNA express their adjuvanticity as either double or single strands, and no differences were observed between modified and unmodified plasmids. On the other hand, the strongest stimulatory ODN sequences lost their adjuvant properties when administered as double‐strand DNA. Furthermore, the profile of cytokines induced on spleen cells by plasmid DNA and ODN is different. Strikingly, plasmid DNA induces a moderate synthesis of IL‐6 and a strong synthesis of IFN‐γ, whereas stimulation with ODN showed an inverse profile with a higher increase in the synthesis of IL‐6 but a moderate increase in IFN‐γ. Finally, in vivo studies were consistent with the results obtained in vitro. Mice immunized with modified or unmodified plasmids encoding the glycoprotein D of HSV showed similar levels of cellular and humoral immune responses.
Schistosome N‐glycans containing core α3‐fucose and core β2‐xylose epitopes are strong inducers of Th2 responses in mice
Authors: Faveeuw Christelle , Mallevaey Thierry , Paschinger Katharina , Wilson Iain B. H. , Fontaine Josette , Mollicone Rosella , Oriol Rafael , Altmann Friedrich , Lerouge Patrice , Capron Monique , Trottein François
Published: April 2003

During murine schistosomiasis, egg‐derived glycoconjugates play a key role in skewing the immune response towards a Th2 phenotype. Among the candidates responsible for this effect, complex‐type N‐glycans containing the core α3‐fucose and core β2‐xylose determinants, two glycan epitopes found in some invertebrate‐ and plant‐derived allergens, may be important. Here, we show that core α3‐fucose and core β2‐xylose determinants are expressed in the different developmental stages of Schistosoma mansoni, particularly in the excretory‐secretory systems of schistosomula and adult worms and in eggs deposited in the liver. Glycosyltransferase assays confirmed the presence of core α3‐fucosyltransferase and core β2‐xylosyltransferase activities in egg extracts. Using a model of immunization with pulsed dendritic cells, we show that egg‐derived glycoproteins containing the core α3‐fucose and core β2‐xylose determinants generate a strong Th2‐biased cellular response in mice and that the glycan moieties of this extract are important in this effect. During murine infection, these complex‐type N‐glycans induce a glycan‐specific Th2 cellular response and elicit T‐dependent anti‐core α3‐fucose and anti‐core β2‐xylose IgG1 (a Th2‐associated isotype), but not IgG2b (a Th1‐associated isotype) Ab. Taken together, our results point out theimportance of core fucosylated/xylosylated N‐glycans in the Th2 immune response during murine schistosomiasis.
Major histocompatibility complex class II‐restricted presentation of a cytosolic antigen by autophagy
Authors: Nimmerjahn Falk , Milosevic Slavoljub , Behrends Uta , Jaffee Elizabeth M. , Pardoll Drew M. , Bornkamm Georg W. , Mautner Josef
Published: April 2003

Biochemical and functional studies have demonstrated major histocompatibility complex (MHC) class II‐restricted presentation of peptides derived from cytosolic proteins, but the underlying processing and presentation pathways have remained elusive. Here we show that endogenous presentation of an epitope derived from the cytosolic protein neomycin phosphotransferase II (NeoR) on MHC classII is mediated by autophagy. This presentation pathway involves the sequestration of NeoR into autophagosomes, and subsequent delivery into the lytic compartment. These results identify endosomes/lysosomes as the processing compartment for cytosolic antigens and furthermore link endogenous antigen presentation on MHC class II with the process of cellular protein turnover by autophagy.
TGF‐β1 modulates Fas (APO‐1/CD95)‐mediated apoptosis of human pre‐B cell lines
Authors: Lanvin Olivia , Guglielmi Paul , Fuentes Vincent , Gouilleux‐Gruart Valérie , Mazière Cécile , Bissac Eliane , R´egnier Aline , Benlagha Kamel , Gouilleux Fabrice , Lassoued Kaiss
Published: April 2003

We have previously shown that Fas‐induced apoptosis is markedly enhanced by IL‐7 in human pre‐B but not pro‐B cell lines. In addition, pre‐B cell receptor (pre‐BCR) ligation significantly potentiates the IL‐7 effects on Fas‐triggered pre‐B cell death. We show herein that transforming growth factor (TGF)‐β1 sharply reduces Fas‐induced death rate of pre‐B but not pro‐B cells. TGF‐β1 causes inhibition of Fas‐mediated disruption of mitochondrial transmembrane potential and cleavage of caspase 8, Bid and caspase 3. Bcl2 expression is markedly increased in TGF‐β1‐treated pre‐B cells, whereas cellular FLICE‐like inhibitory protein long (c‐FLIPL), Bcl‐XL, Bax, and Bad expression remains unchanged. TGF‐β1 causes a selective growth arrest of pre‐B cells in G0/G1 phase of the cell cycle and induces a partial down‐modulation of both Fas and pre‐BCR expression. All TGF‐β1‐mediated effects, but Bcl2 up‐regulation, can be reproduced by the LY294002 phosphatidylinositol 3‐kinase (PI3K)/Akt inhibitor but not by inhibitors of the MAPK/ERK (MEK) and Janus kinase (Jak)/STAT pathways, which promote cell death. Akt phosphorylation is strongly inhibited by TGF‐β1 in pre‐B but not pro‐B cells and is not modified by Fas engagement. Altogether, our findings suggest that TGF‐β1 prevents Fas‐induced apoptosis of pre‐B lines by inhibiting PI3K pathway and by enhancing expression of Bcl2. They also suggest that the PI3K/Akt pathway is involved in the control of Fas and pre‐BCR expression, a checkpoint in B cell development.
Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes
Authors: Zaccone Paola , Fehérvári Zoltán , Jones Frances M. , Sidobre Stéphane , Kronenberg Mitchell , Dunne David W. , Cooke Anne
Published: April 2003

Infection with Schistosoma mansoni (S. mansoni) or exposure to eggs from this helminth inhibits the development of type 1 diabetes in NOD mice. In this study we show that soluble extracts of S. mansoni worm or egg completely prevent onset of type 1 diabetes in these mice but only if injection is started at 4 weeks of age. T cells from diabetes‐protected mice make IL‐10 in recall responses to parasite antigens. These cells are furthermore impaired in their ability to transfer diabetes to NOD‐SCID recipients. Bone marrow dendritic cells derived from NOD mice are found to make more IL‐10 and less IL‐12 following culture with S. mansoni soluble egg antigens in conjunction with lipopolysaccharides. NOD mice are deficient in NKT cells. Soluble worm and egg antigens increase the numbers of Vα14i NKT cells in NOD mice. These effects of schistosome antigens on the innate immune system provide a mechanism for their ability to prevent type 1 diabetes in NOD mice.
Exchange Coupling in Metal Complexes of the Second Transition Series: A Theoretical Exploration
Authors: Desplanches Cédric , Ruiz Eliseo , Alvarez Santiago
Published: April 2003

Theoretical methods based on density functional theory using hybrid functionals provide good estimates of the exchange coupling constants for complexes with metals of the second transition series, with accuracy similar to that previously obtained for complexes with lighter transition metals. The influence of the basis set and effective core potentials has been analyzed. The more diffuse nature of the 4d orbitals, in comparison with the 3d ones, considerably modifies the electronic structure and, consequently, the magnetic properties enhancing the antiferromagnetic contributions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Organotin‐Drug Interactions. Organotin Adducts of Lornoxicam, Synthesis and Characterisation of the First Complexes of Lornoxicam
Authors: Galani Angeliki , Demertzis Mavroudis A. , Kubicki Maciej , Kovala‐Demertzi Dimitra
Published: April 2003

The synthesis and spectral characterisation of novel organotin complexes [SnMe2(lorn)] (1) and [SnBu2(lorn)] (2) of the potent and widely used anti‐inflammatory drug lornoxicam, H2lorn, are reported. Crystal structure determinations of complexes1 and 2 showed that the ligand is doubly deprotonated at the oxygen and amide nitrogen atoms and is coordinated to the SnR2 fragment via four‐ and six‐membered chelate rings. The monomers of 1 are linked through intermolecular hydrogen bonds of C−H‐‐O type and through C−H−π intermolecular interactions. There are two similar molecules in the asymmetric unit of 2. The dimers of 2 are arranged in polymers with a stacking of alternate parallel chains and are linked through intermolecular hydrogen bonds of C−H‐‐O type, and through C−H−π intermolecular interactions. An extended network of Sn−O−Sn, C−H‐‐O and C−H‐‐π contacts lead to aggregation and a supramolecular assembly. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Self‐Assembly of Five Cadmium(II) Coordination Polymers from 4,4′‐Diaminodiphenylmethane
Authors: Luo Junhua , Hong Maochun , Wang Ruihu , Cao Rong , Shi Qian , Weng Jiabao
Published: April 2003

Five cadmium(II) coordination polymers formed from dadpm (dadpm = 4,4′‐diaminodiphenylmethane), namely, [Cd(dadpm)(I)2]n (1), [{Cd(dadpm)2(Cl)}(dca)]n (2) [dca = dicyanamide anion, N(CN)2−], [{Cd(dadpm)2(Br)}(dca)]n (3), [Cd(dadpm)(SCN)2]n (4) and [Cd(dadpm)(dca)2]n (5) have been synthesized and characterized by NMR, IR, and fluorescence spectroscopy as well as TG analysis. The ligand dadpm in 1 bridges the metal centers to form a zigzag chain where the halide anion I− acts as a terminal ligand. Weak Cd···I interactions between adjacent chains extend the zig‐zag chains into a wave‐like layer. Complexes 2 and 3 are isomorphous, the metal centers are bridged by dadpm to generate a double‐stranded chain containing the metallacycles of [Cd2(dadpm)2], and the halide anions (Cl− in 2 and Br− in 3) link adjacent chains into 2D layer structures in a trans mode. Dicyanamide anions in the two complexes lie between the layers as supported anions and link the adjacent layers into 3D structures through hydrogen bonds. In complex 4, the metal centers are bonded by the thiocyanate anions to form double‐stranded chains, which are linked by dadpm in different orientations resulting in a cross‐linked 3D structure. In 5, dicyanamide anions connect the cadmium(II) centers to form a [Cd(dca)2]n 2D layer, which contains 24‐membered ring units [Cd4(μ1,1‐dca‐N,N)4]. The dadpm ligand links the adjacent layers into an α‐Po‐like 3D network structure. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Cyanide‐Bridged Oligonuclear Complexes Containing Ni‐CN‐Cu and Pt‐CN‐Cu Linkages
Authors: Flay Marie‐Louise , Vahrenkamp Heinrich
Published: April 2003

The central building blocks Ni(CN)42− and Pt(CN)42− can be combined with one, two or four CuIIL units (L = tren, Me6tren, tpa) to form di‐, tri‐ and pentanuclear complexes with Ni‐CN‐Cu and Pt‐CN‐Cu linkages. Structure determinations of these and the side product [(tren)Cu−CN−Cu(tren)] (ClO4)2 reveal mostly linear M‐C‐N‐Cu arrays and cis‐, trans‐ and star‐like arrangements of the CN‐Cu units around the central Ni or Pt ions. The $\tilde {\nu}$
(CN) IR data for the bridging cyanides show a characteristic hypsochromic effect compared to the data for the free M(CN)42− complexes. The absorption bands in the visible spectra of the oligonuclear complexes are shifted to shorter wavelengths than those of the free LCuII‐X complexes. The CuII/CuI redox steps in the cyclic voltammograms allow the conclusion that there is electronic communication between the external CuL units when they are arranged in a trans‐orientation at PtII, but not NiII, centers. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Electroanalytical Flow Measurements–Recent Advances
Authors: Trojanowicz Marek , Szewczynska Malgorzata , Wcislo Marzena
Published: April 2003

As general trends in current development of chemical analysis, including electroanalysis, one can indicate a search for methods fast and multianalyte, for miniaturized measuring devices, mechanization and automation of analytical processes. In all these trends a significant role is played by measurements in flow conditions. The major advantage of flow electroanalysis is a possibility of utilizing a kinetic discrimination in potentiometric measurements and enhancement of mass transport in voltammetric techniques. Flow injection techniques provide shortening of time of a single analytical determination due to reproducible use of transient signal from the detector without need of obtaining a steady‐state equilibrium signal. Electrochemical detection in HPLC gives often improved selectivity and detection limit for electroactive solutes, whereas in capillary electrophoresis it allows a convenient design of portable, integrated chips for field application. This review presents state‐of‐the ‐art of flow electroanalysis based on 226 cited literature references
Electrochemical Detection of Copper(II) at an Electrode Modified by a Carnosine–Silica Hybrid Material
Authors: Sayen Stéphanie , Gérardin Christine , Rodehüser Ludwig , Walcarius Alain
Published: April 2003

A new solid‐phase extractant based on carnosine moieties covalently attached to a silica backbone (S‐Car) was introduced into a carbon paste electrode (CPE), and the resulting modified electrode (S‐Car‐MCPE) was applied to the preconcentration and subsequent voltammetric quantification of copper(II). The electrode modifier was a solid organic‐inorganic hybrid prepared by co‐condensation of tetraethoxysilane with an organotri‐ethoxysilane containing a carnosine dipeptide (β‐alanyl‐l‐histidine) derivative. This hybrid material has propensity for binding CuII species from aqueous solutions. The basic voltammetric characterization of S‐Car‐MCPE, previously loaded with CuII, indicates clearly that its electrochemical activity requires desorption of the analyte out of the solid material prior to undergoing charge transfer. A two‐step analytical procedure was then applied, involving the sequence “accumulation at open‐circuit – voltammetric detection by anodic stripping differential pulse voltammetry”. Both these steps have been optimized with respect to various experimental parameters (electrode composition, pH and composition of both detection and accumulation media, preconcentration time, detection mode, presence of interference). Linear response to copper(II) was found in the 5×10−8 M to 10−6 M concentration range, with a detection limit estimated at 4×10−9 M (0.06 ppb). This new immobilization approach for peptide‐based materials on electrode surfaces is promising for further developments of organic‐inorganic hybrids in electroanalysis.
Two‐Surface Strategy in Electrochemical DNA Hybridization Assays: Detection of Osmium‐Labeled Target DNA at Carbon Electrodes
Authors: Fojta Miroslav , Havran Ludek , Billova Sabina , Kostecka Pavel , Masarik Michal , Kizek Rene
Published: April 2003

Target DNAs, including a 71‐mer oligonucleotide, a PCR product and a plasmid DNA, all containing oligo(A) stretches, were hybridized at magnetic Dynabeads oligo(dT)25 (DBT). The hybridization events were detected using a technique based on chemical modification of the target DNA with a complex of osmium tetroxide with 2,2′‐bipyridine (Os, bipy) and voltammetric detection at carbon electrodes. DNA was modified with Os, bipy prior to capture at DBT, at the beads, or after release from the beads. In the latter case, DNA‐Os, bipy was detected in the reaction mixture using adsorptive transfer stripping voltammetry involving extraction of unreacted Os, bipy from the electrode by organic solvents. Pre‐labeling of the target plasmid DNA and the PCR product with Os, bipy significantly increased the yield of DNA captured at the beads. Tens of femtomoles of both short (the 71‐mer oligonucleotide) and long (the 3‐kilobase plasmid) target DNAs in a 20‐microliter hybridization sample can be easily detected by means of these techniques. Various carbon electrode materials, including pyrolytic graphite (PGE), highly oriented pyrolytic graphite (HOPGE), carbon paste (CPE), glassy carbon and pencil graphite, were tested regarding their suitability for the detection of osmium‐labeled DNA. Among them, PGE and HOPGE appeared usable in the measurements of both purified DNA‐Os, bipy and its mixtures with unreacted Os, bipy while CPE was suitable for the detection purified osmium‐labeled DNA.
Catalytic Voltammetric Determination of Cladribine in Biological Samples
Authors: de‐los‐Santos‐Álvarez Noemí , Lobo‐Castañón María Jesús , Miranda‐Ordieres Arturo J. , Tuñón‐Blanco Paulino
Published: April 2003

An electrochemical method for the citotoxic prodrug cladribine determination is proposed. Graphite electrodes modified with cladribine showed a redox process with a formal potential of 0.173 V at pH 6, after the oxidation of the adenine moiety of the drug, whose current can be employed as analytical signal with a detection limit of 75 nM by square‐wave voltammetry. As these oxidation products exhibit great electrocatalytic activity toward the electro‐oxidation of NADH at low potentials, the analytical response can further be amplified. As a result, the detection limit was improved up to 1 nM using differential pulse voltammetry. The method was applied to the determination of cladribine in serum and urine samples after solid‐phase extraction. No electroactive interferences were found in both fluids. The method allows the selective detection of the drug in the presence of the main metabolite, 2‐chloroadenosine, which is not able to electrocatalize the NADH oxidation.
Eighty Years of Polarography – History and Future
Authors: Barek Jiří , Zima Jiří
Published: April 2003

Since 1922, when Professor Jaroslav Heyrovský carried out his pioneering experiment with a dropping mercury electrode, polarography showed remarkable ability to adjust to ever increasing demands on the sensitivity and selectivity and up to now mercury electrodes are among the best sensors for electroanalytical measurements. The aim of this contribution is to show both the historical development of these techniques and their presence and possible future developments and to show that even today in certain cases polarographic and voltammetric techniques on mercury electrodes can successfully compete with modern separation and spectrometric techniques.
Amperometric Ion Sensing Using Polypyrrole Membranes
Authors: Michalska Agata , Walkiewicz Sebastian , Maksymiuk Krzysztof
Published: April 2003

Oxidation/reduction of conducting polymers, coupled with ion exchange between the polymer and electrolyte solution can be utilized for amperometric ion sensing. Electrochemically deposited “model” polypyrrole membranes doped by chloride (PPyCl) and hexacyanoferrate (PPyFeCN) anions were studied from the point of view of their advantages and limits for amperometric determination of electroinactive anions and cations, respectively. Monotonous dependences of the current on electrolyte concentration were obtained for short reading times after potential step application (in the range of ms). The experimental conditions were optimized to obtain linear dependences: log (current) vs. log (KCl concentration) within the range 10−6−1 M. The advantages of the amperometric method over the potentiometric one are highlighted: much lower effect of redox and pH interferences, wider concentration range, elimination of long conditioning procedure.
Statistical performance analysis of seismic‐excited structures with active interaction control
Authors: Zhang Yunfeng , Iwan Wilfred D.
Published: April 2003

This paper presents a statistical performance analysis of a semi‐active structural control system for suppressing the vibration response of building structures during strong seismic events. The proposed semi‐active mass damper device consists of a high‐frequency mass damper with large stiffness, and an actively controlled interaction element that connects the mass damper to the structure. Through actively modulating the operating states of the interaction elements according to pre‐specified control logic, vibrational energy in the structure is dissipated in the mass damper device and the vibration of the structure is thus suppressed. The control logic, categorized under active interaction control, is defined directly in physical space by minimizing the inter‐storey drift of the structure to the maximum extent. This semi‐active structural control approach has been shown to be effective in reducing the vibration response of building structures due to specific earthquake ground motions. To further evaluate the control performance, a Monte Carlo simulation of the seismic response of a three‐storey steel‐framed building model equipped with the proposed semi‐active mass damper device is performed based on a large ensemble of artificially generated earthquake ground motions. A procedure for generating code‐compatible artificial earthquake accelerograms is also briefly described. The results obtained clearly demonstrate the effectiveness of the proposed semi‐active mass damper device in controlling vibrations of building structures during large earthquakes. Copyright © 2003 John Wiley & Sons, Ltd.
Optimal location of sensors for reconstruction of seismic responses through spline function interpolation
Authors: Limongelli M. P.
Published: April 2003

In this paper, a criterion is proposed for the choice of the optimal location of a limited number of recording sensors for reconstruction of seismic responses of multistorey frames. Reconstruction of unknown responses is performed by modelling through a spline shape function the evolution of the relative acceleration along the height of the building. The coefficients of the spline function are determined by interpolating available responses in terms of absolute accelerations taking into account boundary conditions. The optimal location for a given number of recording sensors is defined as the one corresponding to the minimum value of the global error evaluated on the whole set of reconstructed responses. The criterion has been verified by using simulated responses of numerical models of multistorey frames and responses recorded on real buildings during the Northridge earthquake.

A physical characterization of the location of available sensors leading to the minimum global error between calculated and real responses is proposed in terms of effective modal participation factors relevant to the principal modes of the structure. This characterization allows for frames of known modal characteristics the definition of a criterion for the choice of the location of a limited number of sensors for monitoring or vibration control purposes. Copyright © 2003 John Wiley & Sons, Ltd.
Empirical attenuation relationship for Arias Intensity
Authors: Travasarou Thaleia , Bray Jonathan D. , Abrahamson Norman A.
Published: April 2003

Arias Intensity is a ground motion parameter that captures the potential destructiveness of an earthquake as the integral of the square of the acceleration–time history. It correlates well with several commonly used demand measures of structural performance, liquefaction, and seismic slope stability. A new empirical relationship is developed to estimate Arias Intensity as a function of magnitude, distance, fault mechanism, and site category based on 1208 recorded ground motion data from 75 earthquakes in active plate‐margins. Its functional form is derived from the point‐source model, and the coefficients are determined through non‐linear regression analyses using a random‐effects model. The results show that for large magnitude earthquakes (M > 7) Arias Intensity was significantly overestimated by previous relationships while it was underestimated for smaller magnitude events (M ⩽ 6). The average horizontal Arias Intensity is not significantly affected by forward rupture directivity in the near‐fault region. The aleatory variability associated with Arias Intensity is larger than that of most other ground motion parameters such as spectral acceleration. However, it may be useful in assessing the potential seismic performance of stiff engineering systems whose response is dominated by the short‐period characteristics of ground motions. Copyright © 2003 John Wiley & Sons, Ltd.
Chlorotoxin‐sensitive Ca2+‐activated Cl− channel in type R2 reactive astrocytes from adult rat brain
Authors: Dalton Stanislava , Gerzanich Volodymyr , Chen Mingkui , Dong Yafeng , Shuba Yaroslav , Simard J. Marc
Published: April 2003

Astrocytes express four types of Cl− or anion channels, but Ca2+‐activated Cl− (ClCa) channels have not been described. We studied Cl− channels in a morphologically distinct subpopulation (∼ 5% of cells) of small (10–12 μm, 11.8 ± 0.6 pF), phase‐dark, GFAP‐positive native reactive astrocytes (NRAs) freshly isolated from injured adult rat brains. Their resting potential, −57.1 ± 4.0 mV, polarized to −72.7 ± 4.5 mV with BAPTA‐AM, an intracellular Ca2+ chelator, and depolarized to −30.7 ± 6.1 mV with thapsigargin, which mobilizes Ca2+ from intracellular stores. With nystatin‐perforated patch clamp, thapsigargin activated a current that reversed near the Cl− reversal potential, which was blocked by Cl− channel blockers, 5‐nitro‐2‐(3‐phenylpropylamino)‐benzoate (NPPB) and Zn2+, by I− (10 mM), and by chlorotoxin (EC50 = 47 nM). With conventional whole‐cell clamp, NPPB‐ and Zn2+‐sensitive currents became larger with increasing [Ca2+]i (10, 150, 300 nM). Single‐channel recordings of inside‐out patches confirmed Ca2+ sensitivity of the channel and showed open‐state conductances of 40, 80, 130, and 180 pS, and outside‐out patches confirmed sensitivity to chlorotoxin. In primary culture, small phase‐dark NRAs developed into small GFAP‐positive bipolar cells with chlorotoxin‐sensitive ClCa channels. Imaging with biotinylated chlorotoxin confirmed the presence of label in GFAP‐positive cells from regions of brain injury, but not from uninjured brain. Chlorotoxin‐tagged cells isolated by flow cytometry and cultured up to two passages exhibit positive labeling for GFAP and vimentin, but not for prolyl 4‐hydroxylase (fibroblast), A2B5 (O2A progenitor), or OX‐42 (microglia). Expression of a novel chlorotoxin‐sensitive ClCa channel in a morphologically distinct subpopulation of NRAs distinguishes these cells as a new subtype of reactive astrocyte. GLIA 42:325–339, 2003. © 2003 Wiley‐Liss, Inc.