bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethical investment and the incentives for corporate environmental protection and social responsibility
Authors: Aslaksen Iulie , Synnestvedt Terje 
Published: November 2003

AbstractThis paper addresses some interrelated questions regarding ethical investments: does ethical screening provide any incentives for improved social responsibility within firms? Are ethical screened portfolios competitive compared with conventional funds with respect to risk‐adjusted return? Does the risk‐adjusted return of a screened portfolio depend on the screening strategy applied?Considering ethical screening as a kind of segmentation of the equity market, it is shown that screening might create incentives for changes in firms' behaviour. The strength of this incentive depends on the relative share of screened portfolios, which in turn partially depends on the financial performance of the screened portfolios. While some theoretical arguments suggest that screening imposes a handicap compared with conventional portfolios, the empirical evidence does not suggest that screened portfolios systematically under‐perform conventional portfolios. Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment.
Link‐disjoint paths for reliable QoS routing
Authors: Guo Yuchun , Kuipers Fernando , Van Mieghem Piet 
Published: November 2003

AbstractThe problem of finding link/node‐disjoint paths between a pair of nodes in a network has received much attention in the past. This problem is fairly well understood when the links in a network are only specified by a single link weight. However, in the context of quality of service routing, links are specified by multiple link weights and restricted by multiple constraints. Unfortunately, the problem of finding link/node disjoint paths in multiple dimensions faces different conceptual problems. This paper presents a first step to understanding these conceptual problems in link‐disjoint quality of service routing and proposes a heuristic link‐disjoint QoS algorithm that circumvents these problems. Copyright © 2003 John Wiley & Sons, Ltd.
Traffic locality characteristics in a parallel forwarding system
Authors: Shi W. , MacGregor M. H. , Gburzynski P. 
Published: November 2003

AbstractDue to the widening gap between the performance of microprocessors and that of memory, using caches in a system to take advantage of locality in its workload has become a standard approach to improve overall system performance. At the same time, many performance problems finally reduce to cache performance issues. Locality in system workload is the fact that makes caching possible. In this paper, we first use the reuse distance model to characterize temporal locality in Internet traffic. We develop a model that closely matches the empirical data. We then extend the work to investigate temporal locality in the workload of multi‐processor forwarding systems by comparing locality under different packet scheduling schemes. Our simulations show that for systems with hash‐based schedulers, caching can be an effective way to improve forwarding performance. Based on flow‐level traffic characteristics, we further discuss the relationship between load‐balancing and hash‐scheduling, which yields insights into system design. Copyright © 2003 John Wiley & Sons, Ltd.
Prioritized slotted multiple access protocols for bank LANs
Authors: Sklira M. , Pomportsis A. S. 
Published: November 2003

AbstractFour classes of traffic are present in a bank communication system: Alarm, BSC, SNA and IP traffic, with each class of traffic having different priority requirements. In this paper, a prioritized multiple access protocol is introduced which is capable of handling the above priority classes. The proposed protocol makes use of learning automata in order to dynamically assign the available bandwidth to the priority classes. In this way, it is capable of being adapted to the traffic conditions. The proposed protocol, is applicable to a broad range of prioritized LANs, as it can be easily extended to support multiple classes of traffic. Copyright © 2003 John Wiley & Sons, Ltd.
Uncompromised generation of a specific H‐2DM‐dependent peptide‐MHC class II complex from exogenous antigen in Leishmania mexicana‐infected dendritic cells
Authors: Bennett Clare L. , Colledge Lisa , Richards Hannah E. , Reay Philip A. , Blackburn C. Clare , Aebischer Toni 
Published: November 2003

AbstractLeishmania infection inhibits the capacity of macrophages (MΦ) to present antigens to CD4+ T cells. Relocation of MHC class II and H‐2DM to the parasitophorous vacuole (PV) and their subsequent degradation by the parasite may contribute to this defect. Dendritic cells (DC) are critical for initiation of primary T cell responses. DC can process Leishmania antigen and elicit Leishmania‐specific T cells, but it is unknown whether exposure to Leishmania impairs this capacity. In particular, it is not clear whether DC containing live parasites efficiently process and present antigens. We investigated the ability of mouse bone marrow‐derived DC infected with L. mexicana to generate pigeon cytochrome c (PCC) peptide‐MHC class II complexes, using the mAb D4, which recognizes PCC89–104 H‐2Ek, and the PCC‐specific T cell hybridoma 2B4. We show that H‐2DM‐dependent complex generation is not compromised by infection and that complexes are fully recognized by specific T cells. We further show that in contrast to infected MΦ, in infected DC cytoplasmic H‐2DM is not down‐regulated and not relocated to the parasite‐containing vacuole. This observation may explain the continued ability of infected DC to present PCC, and also indicates differences in the habitat of these intracellular parasites in DC compared to MΦ.
Human CD4+CD25+ regulatory cells have marked and sustained effects on CD8+ T cell activation
Authors: Câmara Niels Olsen Saraiva , Sebille Fabien , Lechler Robert I. 
Published: November 2003

AbstractAmongst the many types of regulatory cells that have been described during the past few years, the spontaneously occurring population that is characterized by co‐expression of CD4 and CD25 appears to play a key role in the prevention of autoimmunity and the maintenance of transplantation tolerance. In this study we have examined the ability of CD4+CD25+ T cells to regulate human CD8+ T cells, and the behavior of CD8+ T cells following activation in the presence of regulatory CD4+CD25+ T cells. The experiments described here demonstrate that human CD4+CD25+ T cells cause pronounced and sustained inhibition of CD8+ T cell proliferation in response to polyclonal and allogeneic stimulation. The regulation of CD8+ T cell activation was cell contact‐dependent and included inhibition of perforin, granzyme B and IFN‐γ cytokine production at the transcriptional level and impaired cytotoxicity. The regulated CD8+ T cell population showed sustained hyporesponsiveness and refractoriness to exogenous IL‐2. These data provide insights into the short‐ and long‐term effects of CD4+CD25+ T cells on CD8+ T cells that could be of considerable value in optimizing vaccination against tumor and viral antigens.
p300 cooperates with Smad3/4 and Runx3 in TGFβ1‐induced IgA isotype expression
Authors: Park Seok‐Rae , Lee Eun‐Kyoung , Kim Byung‐Chul , Kim Pyeung‐Hyeun 
Published: November 2003

AbstractWe have shown previously that Smad3 and Smad4 mediate TGF‐β1‐induced IgA expression. In the present study, we examined the involvement of Runx3 in this process. Overexpression of Runx3 in mice increased germ‐line α (GLα) transcription, and transcription was further augmented when B lymphoma and LPS‐activated murine spleen cells were co‐transfected with Smad3/4. Overexpressionof Runx3 and Smad3/4 increased IgA secretion by both cell types in response to TGF‐β1. p300, which has histone acetyltransferase activity, further augmented TGF‐β1‐induced GLα transcription promoted by Smad3/4 and Runx3. These observations were confirmed by examining the influence of Smad3/4, Runx3 and p300 on the expression of endogenous GLα and post‐switch α transcripts.E1A, an inhibitor of p300, blocked both GLα promoter activity and the enhancement of endogenous GLα transcription by Smad3/4 and Runx3. We conclude that p300 cooperates with Smad3/4 and Runx3 in stimulating TGF‐β1‐induced GLα transcription and subsequent IgA isotype expression, while E1A inhibits these cooperative effects.
OX40/OX40L interaction induces the expression of CXCR5 and contributes to chronic colitis induced by dextran sulfate sodium in mice
Authors: Obermeier Florian , Schwarz Herbert , Dunger Nadja , Strauch Ulrike G. , Grunwald Nicole , Schölmerich Jürgen , Falk Werner 
Published: November 2003

AbstractInteractions between APC and T lymphocytes have been implicated as a major factor contributing to inflammatory bowel disease. To test whether OX40/OX40L interaction plays a role in chronic intestinal inflammation, we induced chronic colitis using dextran sulfate sodium and treated the mice with a murine fusion protein (OX40–IgG). Treatment resulted in a dose‐dependent and significant reduction of intestinal inflammation (46%) as measured by a histologic score. IL‐10 and IL‐5 production from mesenteric lymph node cells increased 20‐fold and 18‐fold, respectively. In colonic tissue, IL‐10 mRNA levels increased and the expression of T‐bet was decreased to 30%. IL‐10 neutralization partly inhibited the beneficial effects of OX40–IgG treatment. Surprisingly, despite the reduction of inflammation we found the number and size of colonic lymphoid follicles increased, with an accumulation of CD4+ cells in the mantle area. In contrast, the number of CD4+ cells infiltrating the mucosa was significantly reduced, as was their CXCR5 expression (24‐fold). We conclude that OX40/OX40L interaction contributes to the perpetuation of chronic colitis partly by suppressing IL‐10 production. Furthermore, our data suggest that the OX40/OX40L‐induced CXCR5 expression on CD4+ cells may be important for the inflammatory process by allowing migration to the germinal center for further differentiation of CD4+ cells before they infiltrate the chronically inflamed mucosa.
Antigen‐specific production of interleukin (IL)‐13 and IL‐5 cooperate to mediate IL‐4Rα‐independent airway hyperreactivity
Authors: Webb Dianne C. , Mahalingam Surendran , Cai Yeping , Matthaei Klaus I. , Donaldson Debra D. , Foster Paul S. 
Published: November 2003

AbstractThe pathogenesis of human asthma and the development of key features of pulmonary allergy in mouse models has been critically linked to IL‐13. Analyses of the receptor components employed by IL‐13 have shown that delivery of this cytokine to the airways of naive IL‐4Rα gene targeted (IL‐4Rα–/–) mice fails to induce disease, suggesting that this membrane protein is critical for transducing IL‐13‐mediated responses. The current study demonstrates that, in contrast to naive mice, T helper 2 bias, airways hyperreactivity (AHR) and tissue eosinophilia develop in Ovalbumin‐sensitized IL‐4Rα–/– mice and that these responses can be inhibited by the IL‐13 antagonist sIL‐13Rα2Fc. Therefore, antigen stimulation induces an IL‐13‐regulated response that is independent of IL‐4Rα. To determine the role of IL‐5 and eosinophils in the development of disease in antigen‐exposed IL‐4Rα–/– mice, pulmonary allergy was examined in mice deficient in both factors. IL‐4Rα/IL‐5–/– mice were significantly defective in their ability to produce IL‐13 and failed to develop AHR, suggesting that IL‐5 indirectly regulates AHR in allergic IL‐4Rα–/– mice by an IL‐13‐dependent mechanism. Collectively, these results demonstrate that IL‐13‐dependent processes regulating the development of AHR and T helper bias persist in the inthe lungs of allergic IL‐4Rα–/– mice.
B cell defects in SLP65/BLNK‐deficient mice can be partially corrected by the absence of CD22, an inhibitory coreceptor for BCR signaling
Authors: Gerlach Judith , Ghosh Snigdha , Jumaa Hassan , Reth Michael , Wienands Jürgen , Chan Andrew C. , Nitschke Lars 
Published: November 2003

AbstractCD22 is an inhibitory coreceptor for B cell receptor (BCR) signaling. The inhibition is most likely mediated by activation of SHP‐1. We found that SLP65/BLNK reaches maximal tyrosine‐phosphorylation at earlier time points in CD22–/– than in wild type B cells upon BCR cross‐linking, suggesting that SLP65/BLNK is a substrate of SHP‐1. However, in contrast to the defective Ca2+ mobilization of SLP65/BLNK–/– B cells, there was a clear Ca2+ response in SLP65/BLNK×CD22 double‐deficient B cells. This implies that SLP65/BLNK is not the sole target of SHP‐1 in the regulation of the Ca2+ signaling strength. While SLP65–/– mice show several blocks of B cell differentiation, in SLP65/BLNK×CD22 double‐deficient mice the maturationblock of B cells in the spleen was partially rescued. However, the proliferative responses of B cells from both SLP65/BLNK–/– and double‐deficient mice were defective after IgM‐ or CD40‐stimulation. These results show that SLP65/BLNK is not absolutely essential for Ca2+ induction in B cells, because the deficiency of this adapter can be by‐passed by the additional deletion of an inhibitory receptor. Furthermore, these experiments suggest that B cell maturation in the spleen is directly dependent on the strength of BCR‐derived Ca2+ signals.
Complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) cooperate in the binding of hydrolyzed complement factor 3 (C3i) to human B lymphocytes
Authors: Leslie Robert Graham Quinton , Prodinger Wolfgang Maria , Nielsen Claus Henrik 
Published: November 2003

AbstractThe C3b‐binding receptor, CR1/CD35, supports CR2/CD21‐mediated activation of complement by human B lymphocytes, possibly by associating with CR2 to promote or stabilize the binding of hydrolyzed C3 (C3i), the primary component of the AP convertase, C3i‐Bb. To evaluate this hypothesis, we examined the uptake kinetics and binding equilibria for C3i dimer interaction with human blood cells in the absence and presence of CR1‐ and CR2‐blocking mAb. C3i displayed dual uptake kinetics to B lymphocytes, comprising of rapid binding to CR1 and slower binding to CR2. The forward rate constants (k1) for CR1 and CR2, operating independently, differed ca. 9‐fold (k1=193±9.4 and 22.2±6.0×103 M–1s–1, respectively). Equilibrium binding of C3i to B lymphocytes was also complex, varying in strength by ca. 13‐fold over the C3i concentration range examined. The maximum association constant (Ka, max=109±27.2×107 l/mole) was ca. 9‐ and 6‐fold greater, respectively, than those for CR1 or CR2 acting alone (Ka=13.2±5.3 and 18.5±3.5×107 l/mole). The high avidity of the CR1‐CR2 complex for C3i is consistent with its rates of C3i uptake and release being determined by CR1 and CR2, respectively.
Efficient generation and expansion of antigen‐specific CD4+ T cells by recombinant influenza viruses
Authors: Nimmerjahn Falk , Kobelt Dieter , Steinkasserer Alexander , Menke Annette , Hobom Gerd , Behrends Uta , Bornkamm Georg W. , Mautner Josef 
Published: November 2003

AbstractAdoptive transfer of in vitro generated antigen‐specific T cells has been successfully used to treat viral infections in immunodeficient patients. Therefore, methods for the rapid in vitro expansion of antigen‐specific T cells are needed. Influenza virus efficiently infects dendritic cells, and peptides derived from viral proteins are processed and presented to CD8+ cytotoxic T cells. However, both, CD4+ and CD8+ T cells are necessary for the efficient control of viral infections, and it is becoming increasingly clear that a T helper cell response is very important for the maintenance and strength of the immune response. Here we show that recombinant influenza virus efficiently infects a wide range of professional antigen‐presenting cells and does not interfere with antigen presentation pathways. Using T cell clones for three different MHC class II‐restricted antigens we demonstrate that peptides derived from these antigens are efficiently presented on MHC class II molecules. Importantly, it was possible to generate and expand antigen‐specific CD4+ T cells following in vitro infection of professional antigen‐presenting cells with recombinant influenza virus. These findings support the notion that recombinant influenza virus is a valuable tool for the expansion of antigen‐specific CD4+ T cells in vitro.
Diabetogenic T cells are primed both in pancreatic and gut‐associated lymph nodes in NOD mice
Authors: Jaakkola Ilkka , Jalkanen Sirpa , Hänninen Arno 
Published: November 2003

AbstractActivation of an islet‐specific immune response is an early yet essential step in autoimmune diabetes. The immune cells and antigen(s) involved in this early step and its anatomical site remain incompletely understood. To directly evaluate the site where islet‐specific and diabetogenic lymphocytes are activated, we isolated lymphocytes from spleen and from pancreas‐draining, gut‐associated and subcutaneous lymph nodes of diabetic NOD mice and of young NOD mice, and transferred these into NOD scid/scid recipients devoid of endogenous islet‐specific immune responses themselves. Although spleen lymphocytes from diabetic NOD mice induced diabetes more rapidly than lymphocytes from any other lymphoid tissue, spleen lymphocytes from young NOD donors were not superior to other lymphocytes from the same donors. At a donor‐age of 6 weeks, the most‐diabetogenic lymphocytes were found in pancreas‐draining lymph node whereas gut‐associated lymph nodes and the spleen were sources of intermediate diabetogenic activity. Lymphocytes from peripheral lymph nodes were only weakly diabetogenic at this age, and also remained the least efficient later. Surprisingly, lymphocytes isolatedeven from 3‐week‐old NOD mice had diabetogenic potential. However, such cells were almost exclusively found in gut‐associated lymph nodes. This suggests that initial priming of diabetogenic cells takes place in the gut whereas pancreas‐draining lymph nodes may serve as the site of amplification of the autoimmune response.
Dendritic cell‐derived IL‐15 controls the induction of CD8 T cell immune responses
Authors: Rückert René , Brandt Katja , Bulanova Elena , Mirghomizadeh Farhad , Paus Ralf , Bulfone‐Paus Silvia 
Published: November 2003

AbstractThe development and the differentiation of CD8+ T cells are dependent on IL‐15. Here, we have studied the source and mechanism of how IL‐15 modulates CD8+ T cell‐mediated Th1immune responses by employing two delayed‐type hypersensitivity (DTH) models. IL‐15‐deficient (IL‐15–/–) mice or mice treated with soluble IL‐15Rα as an IL‐15 antagonist showed significantly reduced CD8+ T cell‐dependent DTH responses, while activation of CD4+ T cell and B cell functions remained unaffected. Injection of antigen‐labeled dendritic cells (DC) fromIL‐15+/+, IL‐15–/– or IL‐15Rα–/– mice revealed that DC‐derived IL‐15 is an absolute requirement for the initiation of DTH response. The re‐establishment of the interaction of IL‐15 with the IL‐15Rα by incubating IL‐15–/– DC with IL‐15 completely restored the capacity to prime T cells for DTH induction in vivo. Moreover, IL‐15 also enhanced secretion of pro‐inflammatory cytokines by DC and triggered in vitro CD8+ T cell proliferation and IL‐2 release. Taken together, the data suggest that an autocrine IL‐15/IL‐15Rα signaling loop in DC is essential for inducing CD8+‐dependent Th1 immune responses in mice. Therefore, targeted manipulation of this loop promises to be an effective, novel strategy for therapeuticmodulation of clinically relevant DTH reactions.
Boron Clusters − A New Entity for DNA‐Oligonucleotide Modification
Authors: Lesnikowski Zbigniew J. 
Published: November 2003

AbstractThe carboranyl cluster is a new and versatile modifying entity for nucleotides and nucleic acids. Three types of carboranyl (−C2B10H11) group‐containing DNA‐oligonucleotides are described: (1) CBMP‐oligonucleotides, consisting of the carborane cage within an internucleotide linkage; (2) CDU‐oligonucleotides, containing the carborane cage attached to a nucleobase; and (3) 2′‐CBM‐oligonucleotides, with the carborane cage linked to a sugar residue at the 2′ position. The method of synthesis and the physicochemical and biochemical features of these novel modifications are discussed, together with structure−property relationships. The carboranyl cluster‐containing oligonucleotides form a crossover between (carba)borane chemistry and molecular biology. They are potentially useful as antisense agents for antisense oligonucleotide therapy (AOT) and boron carriers for boron neutron capture therapy (BNCT). The chemistry of carborane‐modified nucleic acids has implications beyond BNCT and AOT. Owing to the unique properties of carborane clusters they have potential for further development as molecular probes for molecular medical diagnostics and bioinorganic material for emerging technologies. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Efficient Solution‐Phase Parallel Synthesis of 4‐Substituted N‐Protected Piperidines
Authors: Wang Xiaoyang , Kauppi Anna M. , Olsson Roger , Almqvist Fredrik 
Published: November 2003

AbstractPractical conditions for the synthesis of 4‐substituted N‐protected piperidines through CuCN·2LiBr‐catalyzed organozinc additions to 1‐acylpyridinium salts and subsequent hydrogen‐transfer hydrogenation have been established. The reaction sequence is performed at room temperature and provides 4‐substituted N‐protected piperidines in excellent overall yields without the isolation of intermediate dihydropyridines. In those cases in which the organozinc addition results in mixtures of 2‐ and 4‐substituted dihydropyridines, the 2‐substituted isomers are efficiently scavenged with maleic anhydride and subsequently removed by a mild extractive workup with NaHCO3 (sat.). The N‐acyl group can conveniently be exchanged from N‐phenoxycarbonyl to N‐tBoc, thus allowing orthogonal deprotection strategies. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
The Synthesis of Two Furan‐Based Analogues of the α′,β′‐Epoxy Ketone Proteasome Inhibitor Eponemycin
Authors: Bennacer Bibia , Trubuil Dominique , Rivalle Christian , Grierson David S. 
Published: November 2003

AbstractMyers’s methodology for enantioselective amino acid synthesis was employed to prepare the N‐Boc didehydroleucine amide derivative 15 and to effect its conversion into the acylfuran intermediate 17. Coupling of 19 (R = H) with N‐(isooctanoyl)serine provided the furan‐based analogue 4 of eponemycin (de = 96 %), a peptide epoxide with potent cytotoxic and anti‐angiogenesis properties. In an identical fashion the corresponding unsaturated analogue 5 of eponemycin was prepared (de = 48 %). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003
A Novel Route to Chiral trans‐6‐Alkyl‐2‐hydroxymethyl‐1,2,5,6‐tetrahydropyridines by Allylation of Chiral Imines and Ring‐Closing Metathesis − Total Synthesis of (−)‐3‐epi‐Deoxoprosopinine
Authors: Felpin François‐Xavier , Boubekeur Kamal , Lebreton Jacques 
Published: November 2003

AbstractA novel route to enantiomerically pure trans‐6‐alkyl‐2‐hydroxymethyl‐1,2,5,6‐tetrahydropyridines is reported in five steps from Garner’s aldehyde with overall yields higher than 35 %. This strategy is based on the allylation of chiral imino alcohols formed in situ followed by a ring‐closing metathesis. This new method was used for the first total synthesis of (−)‐3‐epi‐deoxoprosopinine. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Aza‐MIRC Reactions of Sulfonyl‐Activated Hydroxycarbamates with α,β‐Difunctionalised Acrylates
Authors: Fioravanti Stefania , Morreale Alberto , Pellacani Lucio , Tardella Paolo A. 
Published: November 2003

AbstractHighly functionalised aziridines are readily obtained in high yields (up to 95%) under mild conditions from the reaction of trisubstituted olefins bearing different groups with nosyloxycarbamates in the presence of calcium oxide. We propose a possible explanation for the different reactivities observed between these olefins and the aminating agents. Reagent‐controlled stereoselective amination reactions led to the expected products with high conversions and purities. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)