bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new model for network traffic forecast based on user's mobility in cellular networks with highway stretches
Authors: Bolla Raffaele , Repetto Matteo 
Published: September 2004

AbstractWireless communications have always faced the scarceness of bandwidth and until today the cellular division has solved this problem by making radio cells always smaller. However, as cell size is reduced, more users will probably require handoffs, and signaling can overload the system. Further, the decrease in cell dimension cannot ensure the best utilization of system resources, because user density in the cell is not constant over the time. Dynamic allocation might be the solution, but it is a complex task, basically due to complexity of the models for the mobility prediction, especially in those environments where users move very fast (e.g. highways). This last one is a typical environment where high mobility of vehicles does not allow small cell sizes and thus system capacity is intrinsically bounded.In this paper, we deploy an analytical model for a cellular network operating in a high mobility environment. Such a model is capable of representing and forecasting wireless system evolution in terms of channel occupancy, starting from the current state of the mobile network and road traffic. This model has been defined by integrating a vehicular traffic model with a wireless cellular communication one. With such approach the dynamic behaviour of the most critical mobile terminals, those associated with vehicles, are described in a very precise and specific way with respect to mobility.Many results obtained with specific simulation tools and herein reported show the good behaviour of our proposal. Copyright © 2004 John Wiley & Sons, Ltd.
GPSPA: a new adaptive algorithm for maintaining shortest path routing trees in stochastic networks
Authors: Misra Sudip , Oommen B. John 
Published: September 2004

AbstractThis paper presents a new efficient solution to the Dynamic Shortest Path Routing Problem, using the principles of Generalized Pursuit Learning. It proposes an efficient algorithm for maintaining shortest path routing trees in networks that undergo stochastic updates in their structure. It involves finding the shortest path in a stochastic network, where there are continuous probabilistically based updates in link‐costs. In vast, rapidly changing telecommunications (wired or wireless) networks, where links go up and down continuously and rapidly, and where there are simultaneous random updates in link costs, the existing algorithms are inefficient. In such cases, shortest paths need to be computed within a very short time (often in the order of microseconds) by scanning and processing the minimal number of nodes and links. The proposed algorithm, referred to as the Generalized Pursuit Shortest Path Algorithm (GPSPA), will be very useful in this regard, because after convergence, it seems to be the best algorithm to‐date for this purpose. Indeed, it has the advantage that it can be used to find the shortest path within the ‘statistical’ average network, which converges irrespective of whether there are new changes in link‐costs or not. Existing algorithms are not characterized by such a behaviour inasmuch as they would recalculate the affected shortest paths after each link‐cost update. The algorithm has been rigorously evaluated experimentally, and it has been found to be a few orders of magnitude superior to the algorithms available in the literature. Copyright © 2004 John Wiley & Sons, Ltd.
Pharmacodynamic differences between species exemplified by the novel anticancer agent CHS 828
Authors: Lindhagen Elin , Vig Hjarnaa Pernille‐Julia , Friberg Lena E. , Latini Scilla , Larsson Rolf 
Published: September 2004

AbstractWhen a candidate drug enters clinical trials, decisions regarding dosing are mainly based on animal data. Occasionally, toxicity problems are faced in the clinic because of unexpected species differences in pharmacokinetics or pharmacodynamics between humans and preclinical species. Fludarabine and topotecan are examples of such drugs. In the first clinical trials of the new agent CHS 828, the maximum tolerated dose was reached earlier than expected from animal data. This paper discusses the issue of species differences in the development of anticancer drugs, and preclinical models for detection and quantification of such differences. Pharmacokinetic and hematological toxicity data of CHS 828 from studies in rats and humans are presented. In vitro sensitivity to CHS 828 and some established cytotoxic agents was measured in lymphocytes from humans and rats and in a panel of human and rodent cell‐lines. 10–100 times higher CHS 828 exposure was tolerated by rats than by patients. In both in vitro cell systems, CHS 828 showed higher potency in human cells compared to rodent cells. A species difference was evident also for fludarabine, but not for doxorubicin and cisplatin. CHS 828 pharmacokinetics were similar across species. In conclusion, the lower tolerance of CHS 828 in humans than in rats could be detected in vitro in cultures of peripheral lymphocytes. Preclinical studies of species differences could help the interpretation of in vivo effect studies as well as the choice of starting dose for clinical trials. We suggest peripheral lymphocytes from different species as a potential model system for such studies. Drug Dev. Res. 61:218–226, 2004. © 2004 Wiley‐Liss, Inc.
Northern ring conformation of methanocarba‐adenosine 5′‐triphosphate required for activation of P2X receptors
Authors: Dunn Philip M. , Kim Hak Sung , Jacobson Kenneth A. , Burnstock Geoffrey 
Published: September 2004

AbstractReplacement of the ribose moiety of adenosine 5′‐triphosphate (ATP) with a carbocyclic ring constrained in either the Northern (N) or Southern (S) conformation produces agonists with widely differing activities at P2Y receptors (Kim et al. [2002] J Med Chem 45:208–218). We have used whole cell patch clamp recording to investigate the agonist activity of these two methanocarba analogs of ATP at four different P2X receptors (P2X1, P2X2, P2X3, and P2X2/3). On dorsal root ganglion neurons, (N) methanocarba‐ATP ((1′S,2′R,3′S,4′R,5′S)‐4‐(6‐amino‐9H‐purin‐9‐yl)‐1‐[triphosphoryloxymethyl] bicyclo[3.1.0]hexane‐2,3‐diol; MRS 2340) activated rapidly‐desensitizing (P2X3) and slowly‐desensitizing (P2X2/3) receptors with a similar potency to ATP. In contrast, (S) methanocarba‐ATP ((±)‐5‐(6‐amino‐9H‐purin‐9‐yl)‐1‐[triphosphoryloxymethyl] bicycle [3.1.0]hexane‐2,3‐diol MRS 2312) was devoid of agonist activity. On nodose ganglion neurones, that express mainly P2X2/3 receptors, ATP evoked a slowly desensitizing inward current with an EC50 value of 26 µM. MRS 2340 was an effective agonist, but less potent than ATP, while MRS 2312 at concentrations up to 100 µM produced a barely detectable response. On mammalian cell lines expressing recombinant hP2X1 and hP2X2 receptors, MRS 2340 evoked inward currents similar in amplitude to those produced by the same concentration of ATP or α,β‐mATP. In contrast, MRS 2312 failed to give a detectable response. Although the conformation of the ribose affects agonist activity at P2Y receptors, there is a strong requirement for the (N) conformation for the activation of these P2X receptors. Furthermore, the region of the agonist binding site that accommodates the ribose moiety appears to be highly conserved among different P2X receptors. Drug Dev Res 61:227–232, 2004. © 2004 Wiley‐Liss, Inc.
Characterization of mouse MAGE‐derived H‐2Kb‐restricted CTL epitopes
Authors: Eggert Andreas O. , Andersen Mads H. , Voigt Heike , Schrama David , Kämpgen Eckhardt , Straten Per thor , Becker Jürgen C. 
Published: September 2004

AbstractImmunogenic peptide epitopes from tumor‐associated antigens serve as targets for cellular immune responses in numerous clinical trials for therapeutic vaccinations. From these it became evident that prevailing questions can only be addressed in animal models. Hence, problems arise from the fact that while for human melanoma many different immunogenic peptide epitopes are known, for mouse melanoma the available selection is very restricted. To overcome this limitation, we applied reverse immunology to identify Kb‐restricted epitopes derived of mouse MAGE. Two epitopes which bind strongly to Kb were selected to test for their immunogenicity in vivo. Spleen cells from mice vaccinated by intradermal injection of mature dendritic cells pulsed with these peptides displayed reactivity to the respective epitopes as measured by enzyme‐linked immunospot assays and tetramer staining. The processing and presentation of these epitopes was evident by the killing of melanoma cells by the vaccination‐induced T cells. Moreover, intravenous challenge with syngeneic melanoma cells demonstrated the protective immunity induced by this vaccination. In summary, we demonstrate the immunogenicity of two Kb‐restricted peptide epitopes derived from mouse MAGE proteins which may serve as valuable tool for preclinical evaluation of vaccination strategies.
Expression of selectin ligands on murine effector and IL‐10‐producing CD4+ T cells from non‐infected and infected tissues
Authors: Kretschmer Ute , Bonhagen Kerstin , Debes Gudrun F. , Mittrücker Hans‐Willi , Erb Klaus J. , Liesenfeld Oliver , Zaiss Dietmar , Kamradt Thomas , Syrbe Uta , Hamann Alf 
Published: September 2004

AbstractEndothelial selectins are crucial for the recruitment of leukocytes into sites of inflammation. On T cells, ligands for selectins become induced upon differentiation into the effector/memory stage. Initial in vitro studies suggested a correlation between the Th1 phenotype and ligand expression, but whether this also holds true in vivo remained uncertain. We here analyzed selectin ligands on CD4+ T cells producing IFN‐γ, IL‐4 or IL‐10, prototypic cytokines of the Th1, Th2 and Tr1 subset, respectively. We analyzed mice infected with influenza virus, the bacterium Listeria, and the parasites Toxoplasma (all Th1 models) or Nippostrongylus (Th2 model). A link between the Th1 phenotype and ligand expression was not found in vivo. Surprisingly, the potentially regulatory IL‐10‐producing T cells displayed the highest frequency of ligand‐positive cells in general. Within the inflamed tissues, the frequencies of P‐selectin‐binding cells increased in the dominant subset, either Th1 or Th2. Up‐regulation was also found for E‐selectin ligands during influenza, but not Nippostrongylus infection. In conclusion, conditions driving T cell polarization into either Th1 or Th2 in vivo do not affect the expression of selectin ligands, but acquisition of P‐selectin binding and hence migration into inflamed tissues is boosted by an inflammatory milieu.
Allergen‐induced traffic of bone marrow eosinophils, neutrophils and lymphocytes to airways
Authors: Johansson Anna‐Karin , Sergejeva Svetlana , Sjöstrand Margareta , Lee James J. , Lötvall Jan 
Published: September 2004

AbstractWe evaluated whether bone marrow (BM) inflammatory cells have capacity to traffic into the airways following allergen exposure in a mouse model of allergen‐induced airway inflammation. We also evaluated the effect of IL‐5 overexpression on (i) the production of eosinophils in BM, (ii) the accumulation of eosinophils, neutrophils and lymphocytes in blood and airways and (iii) the changes in CD34+ cell numbers in BM, blood and airways. Bromodeoxyuridine (BrdU) was used to label cells produced during the exposure period. Furthermore, CD3 splenocytes were adoptively transferred to investigate the BM inflammatory response. Allergen exposure induced traffic of BM eosinophils, neutrophils and lymphocytes to the airways and increased the number of BrdU+ eosinophils, neutrophils, lymphocytes and CD34+ cells in BALf. IL‐5 overexpression enhanced the eosinophilopoiesis and increased the presence of BrdU+ eosinophils and CD34+ cells in airways and enhanced the number of CD34+ cells in BM and blood after allergen exposure. Adoptive transfer of CD3 lymphocytes overexpressing IL‐5 caused increased BM eosinophilia. In conclusion, allergen exposure induces traffic of not only newly produced eosinophils but also newly produced neutrophils and lymphocytes into the airways.
Reduced antigen concentration and costimulatory blockade increase IFN‐γ secretion in naive CD8+ T cells
Authors: Hall Håkan T. L. , Petrovic Jelena , Höglund Petter 
Published: September 2004

AbstractCD8+ T cells are killer cells but also major producers of IFN‐γ. We have investigated the effects of peptide antigen titration and costimulatory blockade on IFN‐γ production and proliferation by naive CD8+ T cells. Mature dendritic cells (DC) pulsed with high amounts of agonist peptide triggered proliferation but little IFN‐γ secretion in individual T cells. In contrast, immature DC pulsed with similar amounts of peptide induced IFN‐γ secretion in a larger fraction of T cells but triggered less proliferation. Blocking B7.2 or lowering the amount of peptide on mature DC led to a response similar to that induced by immature DC, suggesting that differences in stimulatory strength were responsible for the different responses. Using splenic antigen‐presenting cells (APC) we demonstrate that reducing the amount of peptide in combination with B7 blockage enhanced IFN‐γ secretion and decreased proliferation in naive CD8+ T cells in an additive way. Our data suggest that IFN‐γ secretion and proliferation are independently and inversely controlled by stimulatory strength in naive CD8+ T cells. This may enable CD8+ T cells to respond with IFN‐γ secretion to immature APC with few peptide ligands consistent with an early immunoregulatory role of CD8+ T cells.
Frontline: The p85α isoform of phosphoinositide 3‐kinase is essential for a subset of B cell receptor‐initiated signaling responses
Authors: Hess Kristen L. , Donahue Amber C. , Ng Kwan L. , Moore Travis I. , Oak Jean , Fruman David A. 
Published: September 2004

AbstractPhosphoinositide 3‐kinase (PI3K) is a ubiquitously expressed signaling enzyme that plays an integral role in development and activation of B cells. B cell receptor (BCR)‐driven proliferation is completely blocked either in cells lacking the p85α regulatory isoform of PI3K or in wild‐type cells treated with pharmacological PI3K inhibitors. However, the contribution of p85α to early signaling events has not been fully investigated. Here we show that B cells lacking p85α have signaling impairments that are both quantitatively and qualitatively different from those in cells treated with PI3K inhibitors. Loss of p85α results in partial reductions in Ca2+ mobilization and IκB phosphorylation, whereas ERK phosphorylation is not diminished. Moreover, although Akt phosphorylation is partially reduced, phosphorylation of several proteins downstream of Akt is preserved. These partial impairments suggest that there are other routes to PI3K activation in B cells apart from p85α‐associated catalytic subunits. Notably, addition of phorbol ester restores BCR‐mediated proliferation in p85α‐deficient cells but not wild‐type cells treated with PI3K inhibitors. These findings suggest that the primary BCR signaling defect in B cells lacking p85α is a failure to activate diacylglycerol‐regulated signaling enzymes, most likely protein kinase C.See accompanying article: http://dx.doi.org/10.1002/eji.200425593
The development of early and mature B cells is impaired in mice deficient for the Ets‐1 transcription factor
Authors: Eyquem Stéphanie , Chemin Karine , Fasseu Magali , Chopin Martine , Sigaux François , Cumano Ana , Bories Jean‐Christophe 
Published: September 2004

AbstractThe Ets‐1 transcription factor is essential for normal development of the natural killer and T cell lineages; however, its role in B cell development remains poorly understood. To address this issue, we used gene targeting to inactivate Ets‐1 in mice (Ets‐1–/–). We show here that the development of B cell precursors, particularly steps requiring pre‐B cell receptor function, is defective in Ets‐1–/– mice. Peripheral B cell subsets were analyzed in RAG2‐deficient mice reconstituted with Ets‐1–/– fetal liver cells. In such Ets‐1–/– chimeric mice, B cell precursors develop into IgM/IgD‐bearing cells, but B‐1a cells as well as transitional‐2 and marginal zone B cell subsets of the spleen are absent. In response to B cell receptor stimulation, Ets‐1–/– splenic B cells fail to express the CD69 and CD25 activation markers. Furthermore, despite activation of ERK and JNK signaling pathways, Ets‐1‐deficient B cells do not proliferate and die following BCR engagement. These findings demonstrate that the effect of Ets‐1 inactivation is not restricted to the terminal B cell differentiation stage, but also affects the development and function of earlier B cell subsets.
Responses to the soluble flagellar protein FliC are Th2, while those to FliC on Salmonella are Th1
Authors: Cunningham Adam F. , Khan Mahmood , Ball Jennifer , Toellner Kai‐Michael , Serre Karine , Mohr Elodie , MacLennan Ian C. M. 
Published: September 2004

AbstractFeatures of the Th1 or Th2 phenotype start to develop during CD4 T cell priming. This study of the response to the bacterial flagellar protein FliC shows that either Th1 or Th2 responses can be induced in mice depending upon how FliC is presented. This is shown by assessing the cytokine mRNA and class of FliC‐specific plasma cells induced in situ. Soluble recombinant (r)FliC and polymerized FliC are strongly Th2 polarizing, inducing IL‐4, NIP45 and c‐Maf mRNA as well as ϵ and γ1 switch transcripts and switching to IgG1. CD28‐requirement for this switching shows its T cell dependence. rFliC was unable to induce markers of Th1 activity including IL‐12, T‐bet and IFN‐γ. Conversely, when FliC is presented in its native context surface‐bound on live, flagellated Salmonella, switching is predominantly to IgG2a (IgG2c in C57BL/6 mice), reflecting Th1 activity. The development of divergent FliC‐specific polarization to either Th1 or Th2 indicates that the context in which this antigen is encountered rather than its intrinsic immunostimulatory properties determines the direction of Th polarization.
Frontline: An in‐depth evaluation of the production of IL‐2 by antigen‐specific CD8 T cells in vivo
Authors: D'Souza Warren N. , Lefrançois Leo 
Published: September 2004

AbstractIL‐2 is an important cytokine that is capable of inducing both proliferation and apoptosis of activated T cells. CD4 T cells are thought to be the major producers of IL‐2, but CD8 T cells also produce copious amounts of this cytokine. However, our current understanding regarding the kinetics of IL‐2 production by antigen‐specific CD8 T cells, and the proportion of these cells that produce IL‐2 in vivo, is extremely limited. We now demonstrate that virus‐specific CD8 T cells initiate IL‐2 production by 6 h post‐infection and prior to cell division in vivo. Interestingly, peak levels of IL‐2 production were achieved very early during the response and prior to the proliferative peak. We also show – using transgenic mice expressing herpes simplex virus‐1 thymidine kinase under the control of the IL‐2 promoter – that, unlike what has been reported for antigen‐specific CD4 T cells, the majority of antigen‐specific CD8 T cells produce IL‐2 during primary as well as secondary immune responses in vivo.
Cover Picture: Synthesis, Structure and Complexation Ability of Novel Metalloreceptors Containing Two Pincer Complexes of Palladium(II) (Eur. J. Inorg. Chem. 19/2004)
Authors: Nabeshima Tatsuya , Nishida Daisuke , Akine Shigehisa , Saiki Toshiyuki 
Published: September 2004

AbstractThe cover picture shows a flexible Pd metallocrown ether that has two SCS‐pincer ligand moieties. A long bidentate ligand binds to the host in a bridging fashion to close the crown cavity, whereas a short one divides the cavity to give two small polyether rings. Details are discussed in the Short Communication by T. Nabeshima et al. on p. 3779 ff.
Frequent silencing of fragile histidine triad gene (FHIT) in Burkitt's lymphoma is associated with aberrant hypermethylation
Authors: Hussain Azhar , Gutiérrez Marina I. , Timson Georgina , Siraj Abdul K. , Deambrogi Clara , Al‐Rasheed Maha , Gaidano Gianluca , Magrath Ian , Bhatia Kishor 
Published: September 2004

AbstractThe fragile histidine triad (FHIT) gene, a potential tumor‐suppressor gene, is frequently inactivated in multiple human cancers. However, the FHIT gene remains largely unexplored in Burkitt's lymphoma (BL). Hence, we assessed whether loss of FHIT expression occurs in BL, and, if so, what is the mechanism of such loss. Lack of protein expression was observed in 50% of BL cell lines. Methylation‐specific polymerase chain reaction (MSP) showed that 45% of BL cell lines carried aberrantly methylated FHIT alleles. Sequencing of bisulfite‐treated DNA confirmed these data and indicated a very high density of methylation in all methylated alleles. Real‐time, quantitative reverse‐transcription PCR analysis indicated that attenuation of full‐length FHIT transcription was correlated with methylation. Sequencing of transcripts illustrated that aberrant transcription resulting in loss of FHIT exons occurred more commonly in BL containing unmethylated FHIT genes. However, such transcripts often coexisted with full‐length FHIT transcripts. Not surprisingly, therefore, loss of FHIT protein in BL correlated with CpG island methylation, rather than with aberrant transcription. FHIT methylation also was detected in 31% (16 of 51) of the primary BLs examined, including 2 samples whose derived cell lines also manifested FHIT hypermethylation. Aberrant methylation can thus occur in vivo. In summary, this report provides evidence that epigenetic modification frequently results in loss of FHIT expression in BL. © 2004 Wiley‐Liss, Inc.
Aberrant alternative exon use and increased copy number of human metalloprotease‐disintegrin ADAM15 gene in breast cancer cells
Authors: Ortiz Rebekka M. , Kärkkäinen Iivari , Huovila Ari‐Pekka J. 
Published: September 2004

AbstractADAM genes have been associated with cancer, with ADAM expression, genomic rearrangements, and, by implication of ADAM proteins in the altered behavior found in tumor cells. In the present study, increased copy number of the ADAM15 gene in human breast cancer cell lines was demonstrated by fluorescence in situ hybridization. This was not reflected in mRNA levels, however. Instead, the use of alternative ADAM15 exons appeared erratic, leading to aberrant combinations of ADAM15 mRNA isoforms in the cancer cells. Clustering analysis indicated that these isoform patterns were nonrandom, suggesting a failure in the regulation mechanism or mechanisms of the alternative exon usage. Altered regulation of alternative exon usage may provide a useful target for cancer diagnostics development. ADAM15 would be particularly appropriate for breast cancer diagnostics because the various combinations of its three alternatively used exons can be readily examined with a simple, straightforward PCR protocol. © 2004 Wiley‐Liss, Inc.