bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclophynes
Authors: Tobe Yoshito , Sonoda Motohiro
Published: February 2005

For Abstract see ChemInform Abstract in Full Text.
P‐cadherin expression reduced in squamous cell carcinoma of the oral cavity
Authors: Muñoz‐Guerra Mario Fernando , Marazuela Eva G. , Fernández‐Contreras María Encarnacíon , Gamallo Carlos
Published: January 2005

BACKGROUND

The loss of cadherin expression has been shown to correlate to the invasion and metastasis of many types of carcinomas. The purpose of the current study was to evaluate whether the impaired expression of E‐cadherin (E‐cad) and P‐cadherin (P‐cad) correlated with the clinical evolution and prognosis of oral squamous cell carcinoma (OSCC).

METHODS

The authors used immunohistochemical methods to analyze the expression pattern of E‐cad and P‐cad in healthy oral mucosa, in oral carcinoma in situ (CIS), and in surgical samples of 50 patients with the early stages (Stages I–II) of OSCC.

RESULTS

E‐cad showed weak expression in the basal layer of the healthy oral mucosa and reduced expression in patients with oral CIS. P‐cad expression was conserved on the basal and suprabasal layers of the healthy mucosa and, also, in the CIS. In the group of patients with OSCC, univariate analysis demonstrated that reduced expression of E‐cad or P‐cad correlated significantly with locoregional disease recurrence in the follow‐up (P= 0.03 andP= 0.01, respectively). However, only the reduction in the expression of P‐cad emerged as an independent prognostic marker in the multivariate analysis (P= 0.04, hazard ratio = 8.06).

CONCLUSIONS

These findings suggested that a decrease in E‐cad and/or P‐cad expression may contribute to the invasive potential of early OSCC. According to the current data, P‐cad expression may be a potential independent prognostic factor in patients with OSCC. Cancer 2005. © 2005 American Cancer Society.
Percutaneous radiofrequency ablation for hepatocellular carcinoma
Authors: Tateishi Ryosuke , Shiina Shuichiro , Teratani Takuma , Obi Shuntaro , Sato Shinpei , Koike Yukihiro , Fujishima Tomonori , Yoshida Haruhiko , Kawabe Takao , Omata Masao
Published: February 2005

BACKGROUND

Radiofrequency ablation (RFA) was introduced recently as a therapeutic modality for hepatocellular carcinoma (HCC), an alternative to percutaneous ethanol injection therapy (PEIT), which is coming into use worldwide. Previously reported treatment efficacy and complication rates have varied considerably.

METHODS

Between February 1999 and February 2003, the authors performed 1000 treatments of RFA to 2140 HCC nodules in 664 patients with a cooled‐tip electrode at the University of Tokyo Hospital (Tokyo, Japan). Short‐term and long‐term complications were analyzed by treatment and session basis. Cumulative survival was also assessed in 319 patients who received RFA as primary treatment (naive patients) and 345 patients who received RFA for recurrent tumor after previous treatment including resection, PEIT, microwave coagulation therapy, and transarterial embolization (nonnaive patients).

RESULTS

A total of 40 major complications (4.0% per treatment, 1.9% per session) and 17 minor complications (1.7% per treatment, 0.82% per session) were observed during the observation period until March 31, 2004. There were no treatment‐related deaths. Surgical intervention was required in one case each of bile peritonitis and duodenal perforation. The cumulative survival rates at 1, 2, 3, 4, and 5 years were 94.7%, 86.1%, 77.7%, 67.4%, and 54.3% for naive patients, whereas the cumulative survival rates were 91.8%, 75.6%, 62.4%, 53.7%, and 38.2% for nonnaive patients, respectively.

CONCLUSIONS

The authors confirmed the safety and efficacy of RFA for HCC in a large‐scale series and long‐term prognosis was satisfactory. Cancer 2005. © 2005 American Cancer Society.
A representation of acoustic waves in unbounded domains
Authors: Alpert Bradley K. , Chen Yu
Published: February 2005

Compact, time‐harmonic, acoustic sources produce waves that decay too slowly to be square‐integrable on a line away from the sources. We introduce an inner product, arising directly from Green's second theorem, to form a Hilbert space of these waves and present examples of its computation.1 © 2005 Wiley Periodicals, Inc.
On the continuum limit of a discrete inverse spectral problem on optimal finite difference grids
Authors: Borcea Liliana , Druskin Vladimir , Knizhnerman Leonid
Published: February 2005

We consider finite difference approximations of solutions of inverse Sturm‐Liouville problems in bounded intervals. Using three‐point finite difference schemes, we discretize the equations on so‐called optimal grids constructed as follows: For a staggered grid with 2 k points, we ask that the finite difference operator (a k × k Jacobi matrix) and the Sturm‐Liouville differential operator share the k lowest eigenvalues and the values of the orthonormal eigenfunctions at one end of the interval. This requirement determines uniquely the entries in the Jacobi matrix, which are grid cell averages of the coefficients in the continuum problem. If these coefficients are known, we can find the grid, which we call optimal because it gives, by design, a finite difference operator with a prescribed spectral measure. We focus attention on the inverse problem, where neither the coefficients nor the grid are known.

A key question in inversion is how to parametrize the coefficients, i.e., how to choose the grid. It is clear that, to be successful, this grid must be close to the optimal one, which is unknown. Fortunately, as we show here, the grid dependence on the unknown coefficients is weak, so the inversion can be done on a precomputed grid for an a priori guess of the unknown coefficients. This observation leads to a simple yet efficient inversion algorithm, which gives coefficients that converge pointwise to the true solution as the number k of data points tends to infinity. The cornerstone of our convergence proof is showing that optimal grids provide an implicit, natural regularization of the inverse problem, by giving reconstructions with uniformly bounded total variation. The analysis is based on a novel, explicit perturbation analysis of Lanczos recursions and on a discrete Gel'fand‐Levitan formulation. © 2005 Wiley Periodicals, Inc.
Interferon‐γ mediates antigen trafficking to MHC class II‐positive late endosomes of enterocytes
Authors: Büning Jürgen , Schmitz Martina , Repenning Birthe , Ludwig Diether , Schmidt Marcus Alexander , Strobel Stephan , Zimmer Klaus‐Peter
Published: February 2005

MHC class II‐positive late endosomes of enterocytes are thought to be involved in antigen presentation to CD4+ T cells. In contrast to enterocytes of BALB/c mice, severe combined immunodeficiency (SCID) enterocytes lack MHC class II expression and fail to transport internalized ovalbumin (OVA) into late endosomes. IFN‐γ is known to induce MHC class II in enterocytes and antigen targeting to late endosomes in macrophages. In this study, we investigated the influence of IFN‐γ and MHC class II on the processes of antigen traffic in enterocytes. Subcellular targeting of OVA and MHC class II expression within enterocytes were examined in SCID, IFN‐γ‐treated SCID, BALB/c and C57BL/6 MHC class II knockout (KO) mice after a single feed with OVA. Sorting of OVA into late endosomes was found in enterocytes from BALB/c, C57BL/6 KO and IFN‐γ‐stimulated SCID mice, but not from untreated SCID mice. MHC class II expression was restricted to enterocytes of IFN‐γ‐treated SCID and BALB/c mice, present at basolateral membranes and within endosomal compartments. These enterocytes further revealed colocalization of class II antigens and OVA in endosomes. We suggest that antigen trafficking into late endosomes of enterocytes is mediated by IFN‐γ and occurs in the absence of MHC class II.
Notch1 co‐localizes with CD4 on activated T cells and Notch signaling is required for IL‐10 production
Authors: Benson Robert A. , Adamson Karen , Corsin‐Jimenez Marta , Marley Julia V. , Wahl Karen A. , Lamb Jonathan R. , Howie Sarah E. M.
Published: February 2005

The effector function of activated CD4+ T cells and secretion of cytokines are important in the establishment of productive immune responses and tolerance. We identified expression by CD4+ T cells of Notch receptors and ligands and enhanced Notch signaling upon activation. Notch1 expression was up regulated and co‐localized with CD4 upon T cell stimulation. Disruption of Notch signaling did not affect proliferation, but attenuated cytokine secretion following CD3 ligation in the absence of anti‐CD28 antibody. Notch signaling was absolutely necessary for transcription of IL‐10 by stimulated CD4+ T cells. CD4+ T cells transfected with constitutively active Notch1 failed to proliferate, but exhibited enhanced cytokine secretion upon stimulation. Our data indicates that Notch receptor signaling can influence both proliferative and cytokine responses of CD4+ T cells. In addition, the finding that Notch signaling is required for production of IL‐10 may allude to a role in immune regulation.
CD40 signaling regulates innate and adaptive activation of microglia in response to amyloid β‐peptide
Authors: Townsend Kirk P. , Town Terrence , Mori Takashi , Lue Lih‐Fen , Shytle Doug , Sanberg Paul R. , Morgan David , Fernandez Francisco , Flavell Richard A. , Tan Jun
Published: February 2005

Although deposition of amyloid β‐peptide (Aβ) as Aβ plaques involves activation of microglia‐mediated inflammatory responses, activated microglia ultimately fail to clear Aβ plaques in the brains of either Alzheimer's disease (AD) patients or AD mouse models. Mounting evidence suggests that chronic microglia‐mediated immune response during Aβ deposition etiologically contributes to AD pathogenesis by promoting Aβ plaque formation. However, the mechanisms that govern microglia response in the context of cerebral Aβ/β‐amyloid pathology are not well understood. We show that ligation of CD40 by CD40L modulates Aβ‐induced innate immune responses in microglia, including decreased microglia phagocytosis of exogenous Aβ1–42 and increased production of pro‐inflammatory cytokines. CD40 ligation in the presence of Aβ1–42 leads to adaptive activation of microglia, as evidenced by increased co‐localization of MHC class II with Aβ. To assess their antigen‐presenting cell (APC) function, cultured microglia were pulsed with Aβ1–42 in the presence of CD40L and co‐cultured with CD4+ T cells. Under these conditions, microglia stimulate T cell‐derived IFN‐γ and IL‐2 production, suggesting that CD40 signaling promotes the APC phenotype. These data provide a mechanistic explanation for our previous work showing decreased microgliosis associated with diminished cerebral Aβ/β‐amyloid pathology when blocking CD40 signaling in transgenic Alzheimer's mice.
Shark immunity bites back: affinity maturation and memory response in the nurse shark, Ginglymostoma cirratum
Authors: Dooley Helen , Flajnik Martin F.
Published: February 2005

The cartilaginous fish are the oldest phylogenetic group in which all of the molecular components of the adaptive immune system have been found. Although early studies clearly showed that sharks could produce an IgM‐based response following immunization, evidence for memory, affinity maturation and roles for the other isotypes (notably IgNAR) in this group remained inconclusive. The data presented here illustrate that the nurse shark (Ginglymostoma cirratum) is able to produce not only an IgM response, but we also show for the first time a highly antigen‐specific IgNAR response. Additionally, under appropriate conditions, a memory response for both isotypes can be elicited. Analysis of the response shows differential expression of pentameric and monomeric IgM. Pentameric IgM provides the ‘first line of defense’ through high‐avidity, low‐affinity interaction with antigen. In contrast, monomeric IgM and IgNAR seem responsible for the specific, antigen‐driven response. We propose the presence of distinct lineages of B cells in sharks. As there is no conventional isotype switching, each lineage seems pre‐determined to express a single isotype (IgM versus IgNAR). However, our data suggest that there may also be specific lineages for the different forms (pentameric versus monomeric) of the IgM isotype.
Analysis of transforming growth factor‐β1‐induced Ig germ‐line γ2b transcription and its implication for IgA isotype switching
Authors: Park Seok‐Rae , Seo Goo‐Young , Choi Ae‐Jin , Stavnezer Janet , Kim Pyeung‐Hyeun
Published: February 2005

Transforming growth factor (TGF)‐β1 directs class switch recombination (CSR) to IgG2b as well as to IgA. Smad3/4, Runx3 and p300 mediate TGF‐β1‐induced germ‐line (GL) α transcription leading to IgA expression. However, the molecular mechanisms by which TGF‐β1 induces IgG2b CSR are unknown. We used luciferase reporter plasmids to investigate how TGF‐β1 regulates the activity of the promoter for GL transcripts of IgG2b constant gene (GLγ2b promoter). Similarly to the GLα promoter, overexpression of Smad3/4 and Runx3 enhances TGF‐β1‐induced GLγ2b promoter activity. Mutation analysis of the promoter identified likely Smad‐ and Runx3‐binding sites. Also similar to the GLα promoter, overexpression of p300 enhances Smad3/4‐mediated promoter activity, whereas E1A represses promoter activity. Since these regulation mechanisms underlying both GLα and GLγ2b transcription are similar, we explored the possibility that TGF‐β1 induces IgA CSR via transitional IgG2b CSR. TGF‐β1 enhances the expression of both Iα‐Cμ and Iα‐Cγ2b circle transcripts, indicative of direct (Sμ→Sα) and sequential CSR (Sμ→Sγ2b→Sα).
An extended family of Fc receptor relatives
Authors: Davis Randall S. , Ehrhardt Goetz R. A. , Leu Chuen‐Miin , Hirano Masayuki , Cooper Max D.
Published: February 2005

A surprising number of Fc receptor (FcR) relatives have been recognized recently with the potential capacity to modulate innate and adaptive immune responses. The six human FcR homologs (FcRH1–6), which belong to a phylogenetically conserved gene family, have variable numbers of extracellular immunoglobulin domains of five different subtypes. FcRH immunoregulatory potential is implicated by the presence of consensus tyrosine‐based activation or inhibition motifs in their cytoplasmic tails. All but one of these new receptors, FcRH6, are expressed on B cells at different stages in differentiation. Their ligands, function, and prospective roles as diagnostic B cell markers and therapeutic targets are topics of intense interest.
Seismic response of linear and non‐linear asymmetric systems with non‐linear fluid viscous dampers
Authors: Goel Rakesh K.
Published: January 2005

This investigation is concerned with the seismic response of one‐story, one‐way asymmetric linear and non‐linear systems with non‐linear fluid viscous dampers. The seismic responses are computed for a suite of 20 ground motions developed for the SAC studies and the median values examined. Reviewed first is the behaviour of single‐degree‐of‐freedom systems to harmonic and earthquake loading. The presented results for harmonic loading are used to explain a few peculiar trends—such as reduction in deformation and increase in damper force of short‐period systems with increasing damper non‐linearity—for earthquake loading. Subsequently, the seismic responses of linear and non‐linear asymmetric‐plan systems with non‐linear dampers are compared with those having equivalent linear dampers. The presented results are used to investigate the effects of damper non‐linearity and its influence on the effects of plan asymmetry. Finally, the design implications of the presented results are discussed. Copyright © 2005 John Wiley & Sons, Ltd.
Certified real‐time solution of the parametrized steady incompressible Navier–Stokes equations: rigorous reduced‐basis a posteriori error bounds
Authors: Veroy K. , Patera A. T.
Published: January 2005

We present a technique for the evaluation of linear‐functional outputs of parametrized elliptic partial differential equations in the context of deployed (in service) systems. Deployed systems require real‐time and certified output prediction in support of immediate and safe (feasible) action. The two essential components of our approach are (i) rapidly, uniformly convergent reduced‐basis approximations, and (ii) associated rigorous and sharp a posteriori error bounds; in both components we exploit affine parametric structure and offline–online computational decompositions to provide real‐time deployed response. In this paper we extend our methodology to the parametrized steady incompressible Navier–Stokes equations.

We invoke the Brezzi–Rappaz–Raviart theory for analysis of variational approximations of non‐linear partial differential equations to construct rigorous, quantitative, sharp, inexpensive a posteriori error estimators. The crucial new contribution is offline–online computational procedures for calculation of (a) the dual norm of the requisite residuals, (b) an upper bound for the ‘L4(Ω)‐H1(Ω)’ Sobolev embedding continuity constant, (c) a lower bound for the Babuška inf–sup stability ‘constant,’ and (d) the adjoint contributions associated with the output. Numerical results for natural convection in a cavity confirm the rapid convergence of the reduced‐basis approximation, the good effectivity of the associated a posteriori error bounds in the energy and output norms, and the rapid deployed response. Copyright © 2005 John Wiley & Sons, Ltd.
A Lagrangian level‐set approach for the simulation of incompressible two‐fluid flows
Authors: Sousa F. S. , Mangiavacchi N.
Published: January 2005

A Lagrangian level‐set method to solve incompressible two‐dimensional two‐fluid flows is presented. The Navier–Stokes equations are discretized by a Galerkin finite element method. A projection method is employed to decouple the system of non‐linear equations. The interface between fluids is represented by the zero level set of a function ϕ plus additional marker points of the computational mesh. In the standard Eulerian level‐set method, this function is advected through the domain by solving a pure advection equation. To reduce mass conservation errors that can arise from this step, our method employs a Lagrangian technique which moves the nodes of the finite element mesh, and consequently, the information stored in each node. The quality of the mesh is controlled by a remeshing procedure, avoiding bad triangles by flipping edges, inserting or removing vertices from the triangulation. Results of numerical simulations are presented, illustrating the improvements in mass conservation and accuracy of this new methodology. Copyright © 2005 John Wiley & Sons, Ltd.
Breast tumor cell soluble factors induce monocytes to produce angiogenic but not angiostatic CXC chemokines
Authors: Toulza Frédéric , Eliaou Jean‐François , Pinet Valérie
Published: February 2005

Tumor cells are known to interact closely with nontumoral infiltrating cells in order to grow and proliferate. Monocyte‐derived cells constitute a major component of the tumoral infiltrate and a high level of these cells has been associated with increased tumor growth and poor prognosis in patients with breast cancer. For their growth and metastatic propagation, solid tumors are dependant on angiogenesis and accumulated evidences suggest that monocyte‐derived cells could also play an important role in this phenomenon. However, the precise nature of proangiogenic factors secreted by these cells in breast carcinomas, and their direct influence on vessel formation, has not been determined. In the present study, we show that soluble factors secreted by breast tumor cells induce monocytes to produce a variety of proangiogenic CXC chemokines without secretion of angiostatic CXC chemokines. Using in vitro tubule formation in Matrigel, we demonstrated that the CXC chemokines secreted by MTSs (monocytes cultured with tumor cell supernatants) were able to induce microvessel formation. The profile of secreted CXC chemokines was characteristic for each tumor cell line or fresh tumor cells. This last result points out that a precise profiling of secreted proangiogenic factors inside the tumor, by tumor cells themselves or tumor‐infiltrating monocyte‐derived cells, is important for a precise targeting of therapeutic agents against neovascularization. © 2005 Wiley‐Liss, Inc.
Expression and localization of human multidrug resistance protein (ABCC) family members in pancreatic carcinoma
Authors: König Jörg , Hartel Mark , Nies Anne T. , Martignoni Marc E. , Guo Junchao , Büchler Markus W. , Friess Helmut , Keppler Dietrich
Published: February 2005

Pancreatic ductal adenocarcinoma is among the top 10 causes of death from cancer in industrialized countries. In comparison with other gastrointestinal malignancies, pancreatic cancer is one of the tumors most resistant to chemotherapy. An important mechanism of tumor multidrug resistance is increased drug efflux mediated by several transporters of the ABC superfamily. Especially BCRP (ABCG2), MDR1 P‐glycoprotein (ABCB1) and members of the MRP (ABCC) family are important in mediating drug resistance. The MRP family consists of 9 members (MRP1–MRP9) with MRP1–MRP6 being best characterized with respect to protein localization and substrate selectivity. Here, we quantified the mRNA expression of BCRP and of all MRP family members in normal human pancreas and pancreatic carcinoma and analyzed the mRNA level of the transporters most abundantly expressed in pancreatic tissue, BCRP, MRP1, MRP3, MRP4 and MRP5, in 37 tissue samples. In addition, we determined the localization of the 4 MRP proteins in normal human pancreas and in pancreatic carcinoma. The expression of BCRP, MRP1 and MRP4 mRNA did not correlate with tumor stage or grading. On the other hand, the expression of MRP3 mRNA was upregulated in pancreatic carcinoma samples and was correlated with tumor grading. The MRP5 mRNA level was significantly higher in pancreatic carcinoma tissue compared to normal pancreatic tissue. These data suggest that MRP3 and MRP5 are involved in drug resistance of pancreatic tumors and that quantitative analysis of their expression may contribute to predict the benefit of chemotherapy in patients with pancreatic cancer. © 2005 Wiley‐Liss, Inc.
Anginex synergizes with radiation therapy to inhibit tumor growth by radiosensitizing endothelial cells
Authors: Dings Ruud P.M. , Williams Brent W. , Song Chang W. , Griffioen Arjan W. , Mayo Kevin H. , Griffin Robert J.
Published: February 2005

We have demonstrated that the designed peptide anginex displays potent antiangiogenic activity. The aim of our study was to investigate the effect of anginex on established tumor vasculature as an adjuvant to radiation therapy of solid tumors. In the MA148 human ovarian carcinoma athymic mouse model, anginex (10 mg/kg) in combination with a suboptimal dose of radiation (5 Gy once weekly for 4 weeks) caused tumors to regress to an impalpable state. In the more aggressive SCK murine mammary carcinoma model, combination of anginex and a single radiation dose of 25 Gy synergistically increased the delay in tumor growth compared to the tumor growth delay caused by either treatment alone. Immunohistochemical analysis also demonstrated significantly enhanced effects of combined treatment on tumor microvessel density and tumor or endothelial cell proliferation and viability. In assessing physiologic effects of anginex, we observed a reduction in tumor perfusion and tumor oxygenation in SCK tumors after 5–7 daily treatments with anginex with no reduction in blood pressure. To test anginex as a radiosensitizer, additional studies using SCK tumors were performed. Three daily i.p. injections of anginex were able to enhance the effect of 2 radiation doses of 10 Gy, resulting in 50% complete responses, whereas the known antiangiogenic agent angiostatin did not enhance the radiation response of SCK tumors. Mechanistically, it appears that anginex functions as an endothelial cell‐specific radiosensitizer because anginex showed no effect on in vitro radiosensitivity of SCK or MA148 tumor cells, whereas anginex significantly enhanced the in vitro radiosensitivity of 2 endothelial cell types. This work supports the idea that the combination of the antiangiogenic agent anginex and radiation may lead to improved clinical outcome in treating cancer patients. © 2005 Wiley‐Liss, Inc.
Occupational X‐ray examinations and lung cancer risk
Authors: Boffetta Paolo , Mannetje Andrea't , Zaridze David , Szeszenia‐Dabrowska Neonila , Rudnai Peter , Lissowska Jolanta , Fabiánová Eleonóra , Mates Dana , Bencko Vladimir , Navratilova Marie , Janout Vladimir , Cardis Elisabeth , Fevotte Joelle , Fletcher Tony , Brennan Paul
Published: February 2005

Occupational X‐ray examination programs have been conducted in many countries to screen for occupational and nonoccupational respiratory diseases, resulting in widespread exposure to X‐radiation. We conducted a multicentre case‐control study of lung cancer in the Czech Republic, Hungary, Poland, Romania, Russia and Slovakia, including 2,589 cases and 2,859 controls enrolled during 1998–2002. We collected detailed information on occupational X‐ray examinations, occupations and tobacco smoking. We calculated odds ratios of lung cancer via multiple logistic regression after adjustment for age, sex, center and tobacco smoking.

Among controls 24.9% reported no X‐ray examination, 62.9% reported 1–30 examinations and 12.2% reported more than 30 examinations. When we chose individuals with no examination as the reference group, the odds ratios of lung cancer were 1.21 (95% confidence interval [CI] 0.99–1.48), 1.33 (95% CI 1.08–1.64), 1.49 (95% CI 1.18–1.87), 1.52 (95% CI 1.17–1.99) and 2.15 (95% CI 1.50–3.08) for 1–10, 11–20, 21–30, 31–40 and more than 40 examinations, respectively (p‐value of test for linear trend <0.0001). The association between X‐ray examinations and lung cancer risk was strong in countries with low prevalence of exposure and absent in countries with high prevalence of exposure. Odds ratios for X‐ray examinations were lower among smokers than among nonsmokers. The magnitude of the increased risk observed is higher than expected on the basis of other studies of radiation‐exposed populations. Although the association we detected between X‐ray examinations and lung cancer risk may reflect a carcinogenic effect of repeated exposure to low‐level ionizing radiation, reporting bias and particularly uncontrolled confounding by occupational exposure to carcinogens are also likely explanations of the results. © 2005 Wiley‐Liss, Inc.
Quantitative analysis of lymphangiogenic markers for predicting metastasis of human gastric carcinoma to lymph nodes
Authors: Kitadai Yasuhiko , Kodama Michiyo , Cho Songde , Kuroda Tsuyoshi , Ochiumi Takehiko , Kimura Shigeru , Tanaka Shinji , Matsumura Shunji , Yasui Wataru , Chayama Kazuaki
Published: February 2005

The spread of tumor cells to regional lymph nodes is an early event of gastric cancer metastasis. In our study, we assessed the expression of lymphangiogenic factors and lymphatic endothelial markers in gastric carcinoma tissues and compared expression levels with the status of lymph node metastasis. We also examined the correlation between lymphatic vessel density (LVD) in primary tumors and lymph node metastasis. Paired biopsy samples (tumor and corresponding normal mucosa) of gastric tissue were obtained from 39 patients with gastric carcinoma. The expression of VEGF‐C, VEGF‐D, VEGFR‐3 and podoplanin mRNAs was assessed by real‐time quantitative PCR. The expression of VEGF‐C (but not of VEGF‐D) was significantly greater in patients with lymph node metastasis than in those without metastasis. The expression of lymphatic endothelial markers VEGFR‐3 and podoplanin was also significantly greater in the node‐positive group. LVD, as assessed by immunohistochemistry for podoplanin, was correlated with lymph node metastasis. These results indicate that quantitative analysis of lymphangiogenic markers in gastric biopsy specimens may be useful in predicting metastasis of gastric cancer to regional lymph nodes. © 2005 Wiley‐Liss, Inc.
GSTT1 and GSTM1 gene polymorphisms and gastric cancer in a high‐risk italian population
Authors: Palli Domenico , Saieva Calogero , Gemma Simonetta , Masala Giovanna , Gomez‐Miguel Maria Jesus , Luzzi Ida , D'Errico Mariarosaria , Matullo Giuseppe , Ozzola Giulio , Manetti Roberto , Nesi Gabriella , Sera Francesco , Zanna Ines , Dogliotti Eugenia , Testai Emanuela
Published: February 2005

Glutathione S‐Transferases (GSTs) are a family of phase II enzymes involved in the detoxification of potential carcinogens and provided of a strong antioxidant function by neutralizing electrophiles and free radicals. The GSTM1 and GSTT1 isoenzymes exhibit deletion polymorphisms, resulting in a lack of activity, and the null genotypes have been associated with increased cancer risk at several sites, including the stomach, although with contrasting results. We carried out a case‐control study to evaluate whether these polymorphisms modulate the risk of developing gastric cancer (GC). Genotypes for GSTM1 and GSTT1 were obtained from a series of 175 histologically confirmed GC patients and a large series of 546 healthy controls randomly sampled from the general population of Tuscany, an area at high GC risk. No difference in the frequency of GSTM1 null genotype was observed between cases and controls, whereas the GSTT1 null genotype was more frequent among cases (p = 0.04). Multivariate single‐gene analyses adjusted for possible confounders showed that the GSTT1 null genotype, but not the GSTM1 null genotype, was associated with an increased GC risk. Combined‐genotype analyses showed a significantly increased GC risk only for the double null (GSTM1‐GSTT1) genotype (OR = 2.27; 95% CI: 1.14–4.53). A statistically significant positive interaction between the 2 null genotypes was observed (p = 0.02). Our findings suggest that only subjects lacking both GSTM1 and GSTT1 activity are at increased GC risk. This study provides further support to the hypothesis that the risk of developing GC is influenced by inter‐individual variation in both carcinogen detoxification and antioxidant capacity. © 2005 Wiley‐Liss, Inc.
Relationship of hepatocellular carcinoma to soya food consumption: A cohort‐based, case‐control study in Japan
Authors: Sharp Gerald B. , Lagarde Frederic , Mizuno Terumi , Sauvaget Catherine , Fukuhara Toshiyuki , Allen Naomi , Suzuki Gen , Tokuoka Shoji
Published: February 2005

To determine if the risk of hepatocellular carcinoma (HCC) is reduced by consumption of soya foods, we conducted a case‐control study within a cohort of Japanese A‐bomb survivors. We compared the prediagnosis consumption of isoflavone‐rich miso soup and tofu to HCC risk, adjusting for hepatitis B (HBV) and C (HCV) viral infections, the major HCC risk factors in this population. The study included 176 pathologist‐confirmed cases of HCC diagnosed in 1964–1988 and 560 controls who died of diseases other than liver cancer. We examined dietary information collected at least 2 years before diagnosis or death and tissue‐based measures of viral hepatitis. Using logistic regression, crude ORs were 0.5 (95% CI 0.29–0.95) and 0.5 (95% CI 0.20–0.99) for high vs. low miso soup and tofu intake, respectively. Adjusting for year of birth, sex, HBV, HCV and other factors, the OR for miso soup was unchanged at 0.5 (95% CI 0.14–1.55), and miso results were similar when ORs were recalculated separately for earlier and later birth cohorts to assess consistency of results. The adjusted OR for tofu was 0.9 (95% CI 0.20–3.51). We also found a statistically significant (p < 0.0001) interaction between sex and HCV, with risk of HCC being substantially higher for women. We conclude that consumption of miso soup and other soya foods may reduce HCC risk. © 2005 Wiley‐Liss, Inc.
Differences in phenotype and function between spontaneously occurring melan‐A‐, tyrosinase‐ and influenza matrix peptide‐specific CTL in HLA‐A*0201 melanoma patients
Authors: Maczek Christian , Berger Thomas G. , Schuler‐Thurner Beatrice , Schultz Erwin S. , Hamann Anett , Dunbar P. Rod , Cerundolo Vincenzo , Steinkasserer Alexander , Schuler Gerold
Published: February 2005

Melanoma‐specific T cells can occur spontaneously or in response to vaccination or other therapies, but the frequency is much lower than observed in viral infections. The presence of tumor‐specific T cells does not necessarily translate into clinical regressions for a variety of reasons such as an insufficient frequency, activation state or homing capacity of the T cells or escape strategies of the tumor. Having screened melanoma patients prior to inclusion in vaccination trials for spontaneous tumor‐specific T cells either by Elispot or tetramer‐staining, we have identified 3 patients with sufficient numbers of tumor‐reactive T cells to more than 1 TAA and at least 1 virus‐antigen to perform phenotypic and functional analysis directly ex vivo. These stage IV melanoma patients showed specific CTL against melan‐A.A2, tyrosinase.A2 and influenza matrix peptide (IMP).A2 readily detectable in peripheral blood. T‐cell receptor (TCR) staining using the tetramer technology was combined with phenotypic characterization and functional assays. In contrast to IMP‐specific CTL, melanoma‐specific CTL were predominantly terminally differentiated effector cells. However, analysis of melan‐A‐ and tyrosinase‐specific T‐cell lines showed that only a part of the melanoma‐specific CTL were able to lyse peptide‐loaded target cells. Interestingly, the described phenotypic and functional differences of melan‐A‐ and tyrosinase‐specific CTL appeared not only between patients but were also evident within patients, suggesting that the immune response against various tumor antigens is regulated independently. © 2005 Wiley‐Liss, Inc.
Non‐syndromic X‐linked mental retardation: From a molecular to a clinical point of view
Authors: Renieri A. , Pescucci C. , Longo I. , Ariani F. , Mari F. , Meloni I.
Published: February 2005

This review focuses on the 19 identified genes involved in X‐linked “non‐syndromic” mental retardation (MR) and defines the signaling pathways in which they are involved, focusing on emerging common mechanisms. The majority of proteins are involved in three distinct pathways: (1) Rho GTPases pathway modulating neuronal differentiation and synaptic plasticity; (2) Rab GTPases pathway regulating synaptic vesicle cycling; (3) gene expression regulation. The function of four proteins (ACSL4, AT2, SLC6A8, and SAP102) could not be reconciled to a common pathway. From a clinical point of view, the review discusses whether some common dysmorphic features can be identified even in non‐syndromic MR patients and whether it is correct to maintain the distinction between “non‐syndromic” and “syndromic” MR. © 2005 Wiley‐Liss, Inc.
Intramolecular charge delocalization and nonlinear optical
properties of Methyl 3-(4-methoxy phenyl) prop-2-enoate from
vibrational spectra
Authors: Sajan D , Joe I H , Zaleski J , Jayakumar V S
Published: January 2005

The density functional computations of MMP are
performed at B3LYP/6-31G (d,p) level to derive equilibrium
geometry, vibrational wavenumbers and intensities, and first
hyperpolarizability. Large NLO efficiency predicted for the first
time in this new class of compounds has been confirmed by powder
efficiency experiments. DFT calculation reveals that endocyclic
angle at the junction of the propenoate group and the phenyl ring
is decreased from 120° by 2.5°, whereas two
neighbouring angles around the ring are increased by 2.1°
and 1.2° respectively, associated with intramolecular
charge transfer interaction. The vibrational spectra confirm the
charge transfer interaction between -COOCH3 group and phenyl
ring through the ethylenic bridge with simultaneous infrared and
Raman activation of C7=C18 stretching and ring modes 8
and 19. The large intensity differences observed between 8a
and 8b modes in both IR and Raman spectrum due to the algebraic
difference of the electronic effects of the substitutents have
been discussed. The charge transfer interaction between -COOCH3
group and phenyl ring through the ethylenic bridge resulting in
π-electron cloud movement from donor to acceptor can make the
molecule highly polarized and must be responsible for the NLO
activity of MMP.
Medical informatics: Market for IS/IT
Authors: Morris Theodore Allan
Published: January 2005

Following on the lead from earlier pilot studies, the present work uses co‐occurrence analysis of INSPEC classification codes and thesaurus terms assigned to Medical Informatics journal articles and proceedings papers to reveal a more complete perspective of how information science and information technology authors view Medical Informatics. An important underlying dimension to this perspective portrays a continuum of interest from biophysics through biomechanics to biomedicine to (presumably) biology (which is noticeable in its absence). Medical Informatics may be described as the application of information science and information technology to the theoretical and practical problems of biomedical research, clinical practice, and medical education. However, study results suggest IS/IT considers its relationship to Medicine within Medical Informatics as that of supplier vs. market.
Laying the foundation for a virtual department
Authors: Barreau Deborah
Published: January 2005

Advances in telecommunications and networking have potentially as much to offer faculty and educational institutions as they offer to distance students in expanded opportunities and cost efficiency. While academic libraries often take advantage of networking to share a variety of resources and services, academic departments utilize the medium primarily to offer distance courses, collaborate on research, coordinate administrative functions, or to communicate with students and alumni. Distance programs expand a university's reach, but they have yet to challenge the structure of departments or to shift from the traditional paradigm of a “delivery” view of education (Brown and Duguid, 1998). This paper describes an experiment to create a virtual department for international scholars with similar interests who are somewhat out of the mainstream research areas in their own institutions. We describe briefly the evaluation of the project and some of the challenges of sustaining such communities, including the need for administrative support and adequate electronic resources.
Investigating the relationship between learning style preferences and teaching collaboration skills and technology: An exploratory study
Authors: Kim Seung‐Lye , Sonnenwald Diane H.
Published: January 2005

This paper reports on an exploratory study that investigates the relationship between participants' learning style preferences and their perceptions of a professional workshop on collaboration and technology to support collaboration. The Learning Preference Scale‐Students (LPSS) (Owens & Barnes, 1992) was administered to identify participants' learning style preferences as cooperative, competitive and/or individualized. Using cluster analysis two groups, or categories, of learning style preferences among the participants emerged. Group 1 showed a strong preference for the cooperative learning style, and Group 2 showed a strong preference for competitive and cooperative learning styles. Group 1 rated the workshop more positively than Group 2. However, Group 2 reported a larger increase in self‐efficacy compared to those in Group 1 (18.9% vs. 6.0%). Both groups provided different suggestions regarding the content of the workshop. Group 1 suggested adding more discussions and group exercises, whereas Group 2 suggested adding explicit theory or rules to govern behavior. These findings indicate that learning styles should be considered as a potential variable that influences learning outcomes and preferences.
Government & community building: A study of Michigan local governments online
Authors: Brueckner Allison R. K.
Published: January 2005

Today's policymakers are being called upon to embrace a new way of government. A learning economy requires a smart and responsive government—one that works in partnership with all sectors of society to provide services and support systems that are essential to building strong communities.

One of the most important features of the Internet is its ability to connect people with information and with one another. For many this means finding affordable housing, local jobs and dependable daycare. Increasingly local government units are trying to use the Internet, especially the World Wide Web, to provide their citizens with valuable information to enhance the community's quality of life and to increase civic participation.

To help these government units to improve their use of the World Wide Web, cyber‐state.org is undertaking an initiative to assess each of Michigan's local government Web sites, using a national assessment tool called WAES

The Website Attribute Evaluation System (WAES) was developed by the Cyberspace Policy Research Group (CyPRG), http://www.cyprg.arizona.edu/. CyPRG is based at the University of Arizona, Tucson and George Mason University and conducts research on the openness and transparency of national government websites across the globe. The National Science Foundation's Social Behavior and Economic Research, and Computer Information Science Divisions have funded their work since 1996.

, and to provide national benchmarks and models. The poster presentation will address the value of e‐government, using the Michigan case study, where it's at and where it's going – current trends and future possibilities. The methodology and results will be shared from this year's report, Michigan's local governments onlne status and their usage.
Mapping “a beautiful mind:” A comparison of the author cocitation PFNets for John Nash, John Harsanyi, and Reinhard Selten—the three winners of the 1994 Nobel Prize for Economics
Authors: McCain Katherine W. , McCain Roger A.
Published: January 2005

We present the results of an Author Cocitation Analysis focusing on Nash, Harsanyi, and Selten and the top 24–27 authors with which each is cocited in the five years prior to their (1994) receipt of the Nobel Prize for Economics (1989:1993) and the five years following (1995:1999). We explore the different impacts that these three authors' work had on scholarship in these two time periods. Preliminary results show a substantial core of game theory authors anchoring the center of all three PFNets and unique sets of “penumbral” authors frequently cocited with each of the three winners.
Reducing the information gap: Digital library development in Brazil
Authors: McCarthy Cavan , da Cunha Marilo Bastos
Published: January 2005

Principal Brazilian digital library initiatives were identified and characterized. Significant projects in the area of science and research include gateway sites for research (Prossiga), set up and maintained cooperatively, also a multinational access system for regional electronic journals (SciELO). Systems which offer access to texts of the Brazilian classics predominate in the field of literature and hmanities. Digital libraries have had a significant impact on Brazil. Government financing was critical for implanting these new services. Institutions which already have a strong background in advanced technology have significantly better chances of success in the digital library field. Cooperative projects have also had significant impact.
Attorneys interacting with legal information systems: Tools for mental model building and task integration
Authors: Komlodi Anita , Soergel Dagobert
Published: January 2005

This paper reports (1) on the results of a user study and (2) search‐history‐based user interface tools developed based on the results of the study. The research described is part of a dissertation (Komlodi 2002) that examined the use of search histories in legal information seeking and derived interface design recommendations for information storage and re trieval systems. The study examined legal information seekers' use of their memory and externally recorded search histories in searching for and using information through qualitative research methods. The data collected was analyzed to identify potential task areas where search histories can support information seeking and use. The results show that many information‐seeking tasks can take advantage of automatically and manually recorded history information, including mental model building of a topical area, the integration of searching for and using infrmation, and integrating these into larger tasks contexts, which are reported in this paper. These findings encouraged the design of user interface tools building on search history information: direct search history displays, history‐enabled scratchpad facilities, and organized results collection tools.
Information gathering: The information behaviors of line‐managers within a business environment
Authors: Mackenzie Maureen L.
Published: January 2005

The information needs faced by managers are not always clear and straightforward. Therefore, the motivation behind a manager's information gathering behavior is not easily defined. In this research study it is suggested that managers have a tendency to seek and accumulate information for which they have no explicit or known need. This tendency to accumulate informatio enables managers to behave as they do, for example, making rapid decisions, jumping from problem to problem and foregoing the formal information search process that non‐managers may follow when seeking to close a gap in knowledge. Three hypotheses will be empirically tested by statistically comparing line managers to non‐managers. A questionnaire is used to gather quantitative data on the line‐managers' perceptions and information behaviors. The results offer some evidence to the difference in behavior between managers and non‐managers.
Hermes, the information messenger. Integrating information services and delivering them to the end user
Authors: Coello‐Coutiño Gerardo , Ainsworth Shirley , Escalante‐Gonzalbo Ana María
Published: January 2005

The boom of the internet during the last 10 years has produced an accelerated and slightly chaotic growth in information services. User frustration with multiple databases, confusing interfaces, bewildering query languages, search protocols, and differing results formats has also increased. These services need to be both integrated and homogenized. Hermes is a research tool that uses specially designed acquisition, parsing and presentation methods to integrate information resources, from searching in disparate bibliographic databases, to accessing the full text articles online, and developing a web of information associated with each reference, via one seamless common interface. The system has been developed with Open Source software and has a Web interface. At present it searches 17 bibliographic databases on several different platforms, and delivers results from more than 7,000 full text electronic journals. We also discuss the obstacles that exist for the development of this kind of tool, due to the lack of acceptance and implementation of standards, and compare Hermes with other similar projects.