bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic factors of early distant recurrence in hormone receptor‐positive, postmenopausal breast cancer patients receiving adjuvant tamoxifen therapy
Authors: Debled Marc , MacGrogan Gaëtan , Brouste Véronique , Mathoulin‐Pelissier Simone , Durand Michel , Mauriac Louis
Published: April 2007

BACKGROUND

Current adjuvant hormone therapy in postmenopausal women with breast cancer is debatable between upfront aromatase inhibitors (AIs) and sequential treatment with tamoxifen. A major concern is the higher rate of early recurrences observed with sequential treatment. The authors conducted a retrospective analysis to identify risk factors of early recurrences in hormone receptor (HR)‐positive, postmenopausal women within the first 3 years of adjuvant tamoxifen.

METHODS

Between 1986 and 2000, operable breast cancer patients who received exclusively adjuvant tamoxifen for at least 3 years were selected from the authors' institutional database. Age, histology, pathologic tumor size, modified Scarff‐Bloom‐Richardson (mSBR) grade, mitotic index, tumor necrosis, peritumoral vascular emboli (PVE), HR status, and the number of involved axillary lymph‐node were considered as prognostic factors of recurrence.

RESULTS

Among 715 patients who met the inclusion criteria, a distant recurrence occurred in 38 patients (5.3%) within the first 3 years of tamoxifen therapy. Significant prognostic factors of early recurrence were mSBR, axillary lymph node involvement, tumor necrosis, mitotic index, PVE, and pathologic tumor size. Grade 1 and/or lymph node‐negative tumors were excluded from the multivariate analysis (1 recurrence in 208 patients). In this model, mSBR grade 3 was the only significant predictive factor of early recurrence (hazard ratio, 3.72; P < .001).

CONCLUSIONS

In this study, a subset of patients was identified that was at low‐risk of early recurrence (mSBR grade 1 and/or negative lymph node status). Women in that subset could be treated using sequential hormone therapy with tamoxifen and AIs. In women with mSBR grade 3 or lymph node‐positive tumors, an upfront treatment with AIs seemed to be the current optimal strategy. Cancer 2007. © 2007 American Cancer Society.
On group‐theoretic computation of natural frequencies for spring–mass dynamic systems with rectilinear motion
Authors: Zingoni A.
Published: April 2007

In this article, group theory is employed to simplify the computation of natural circular frequencies for spring–mass dynamic systems with rectilinear motion. The systems are by themselves not physically symmetric (or they exhibit only very weak symmetry properties), but they can be transformed into graphs that preserve all the connectivities between masses and springs, while featuring the maximum possible symmetry. For physical dynamic systems exhibiting symmetry, a well‐known group‐theoretic approach involves the computation of the full stiffness matrix of the system first, followed by transformation of this matrix in order to cast it into block‐diagonal form. The present approach involves the direct assembly of much smaller stiffness matrices within the decomposed subspaces of the problem, and is therefore computationally more efficient. Of particular focus in this study are transformed configurations belonging to ‘triangular’ symmetry groups, whose symmetries are difficult to exploit using conventional methods. It is shown how the repeating eigenvalues associated with the degenerate subspaces of such symmetry groups can easily be obtained. Copyright © 2007 John Wiley & Sons, Ltd.
Calsenilin is required for endocrine pancreas development in zebrafish
Authors: Stetsyuk V. , Peers B. , Mavropoulos A. , Verbruggen V. , Thisse B. , Thisse C. , Motte P. , Duvillié B. , Scharfmann R.
Published: April 2007

Calsenilin/DREAM/Kchip3 is a neuronal calcium‐binding protein. It is a multifunctional protein, mainly expressed in neural tissues and implicated in regulation of presenilin processing, repression of transcription, and modulation of A‐type potassium channels. Here, we performed a search for new genes expressed during pancreatic development and have studied the spatiotemporal expression pattern and possible role of calsenilin in pancreatic development in zebrafish. We detected calsenilin transcripts in the pancreas from 21 somites to 39 hours postfertilization stages. Using double in situ hybridization, we found that the calsenilin gene was expressed in pancreatic endocrine cells. Loss‐of‐function experiments with anti‐calsenilin morpholinos demonstrated that injected morphants have a significant decrease in the number of pancreatic endocrine cells. Furthermore, the knockdown of calsenilin leads to perturbation in islet morphogenesis, suggesting that calsenilin is required for early islet cell migration. Taken together, our results show that zebrafish calsenilin is involved in endocrine cell differentiation and morphogenesis within the pancreas. Developmental Dynamics 236:1517–1525, 2007. © 2007 Wiley‐Liss, Inc.
OVSF code allocation and two‐stage combining method to reduce intercode interference in OFCDM system
Authors: Hasegawa Kazuhiko , Shimura Ryuichiro , Sasase Iwao
Published: April 2007

In this paper, we propose an OVSF (Orthogonal Variable Spreading Factor) code allocation in OFCDM (Orthogonal Frequency and Code Division Multiplexing) system. In the proposed OVSF code allocation, codes which have a different ancestor code are allocated to users. When the proposed OVSF code allocation is used, a receiver can use a despreading which utilizes chips shorter than the spreading factor. Thus, symbols are generated. Furthermore, we propose a two‐stage combining method. After first stage combining, by despreading, the symbols are multiplied by weights and combined in second stage combining. We show that the proposed scheme achieves better BER performance than the conventional scheme by computer simulations. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 90(9): 16– 24, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20381
MIMO‐STBC scheme for intervehicle communications using decision feedback channel estimation method based on propagation feature at intersection
Authors: Ito Kenji , Itoh Nobuo , Sa()nda Katsushi , Karasawa Yoshio
Published: April 2007

This paper investigates an intervehicle communication method as a safe driving support system for intersection collision avoidance warnings. In this kind of system, realization of highly reliable communications in the physical layer is an absolute requirement. As a result, we propose a new MIMO‐STBC (Space‐Time Block Coding) method based on intersection propagation channel characteristics. MIMO transmission characteristics are determined by the propagation channel characteristics. First, we use a ray‐tracing method simulation to clarify the propagation channel conditions, and then model the intersection propagation channel. We use the characteristics of this propagation channel to propose a MIMO‐STBC method that utilizes decision feedback channel estimation, and verify the effectiveness of the proposed method in computer simulations. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 90(9): 1–15, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20400
NRD‐guide and waveguide H‐plane transition and its application for lens antenna feeding structure
Authors: Shimizu Takashi , Yoneyama Tsukasa
Published: April 2007

In this paper, NRD‐guide and waveguide H‐plane transitions are proposed to propagate a millimeter wave from the dielectric strip to the upper surface of the conductor plate through a waveguide made by excavating the conductor plate. As a result, they have a bandwidth of about 4 GHz with |S11|≤−15 dB and a low transition loss of 0.2 dB in the 60‐GHz band. An NRD‐guide upper side dielectric lens antenna was designed and fabricated as an application of the proposed transition. It had a wide bandwidth of about 6 GHz with |S11|≤−15 dB, high efficiency of about 78%, and a low sidelobe strength of less than −27 dB. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(5): 39–48, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20294
Highly reliable SiO2/SiN/SiO2(ONO) gate dielectric on 4H‐SiC
Authors: Tanimoto Satoshi
Published: April 2007

The marked lack of long‐term reliability in thermal gate oxides has thwarted practical applications of SiC power MOS devices. Gate dielectrics with a SiO2/SiN/SiO2(ONO) structure have been studied and optimized on a commercial 4H‐SiC epitaxial substrate as a fundamental resolution to this problem. A medium charge‐to‐failure value of more than 400C/cm2 was achieved for polycrystalline gate MONOS capacitors with an equivalent SiO2 thickness of 40 nm and fabricated with a typical power MOS process. The medium time‐to‐failure at an operating field of 3 MV/cm was extrapolated to be over 2 million years at room temperature. An ONO gate dielectric DMOS was demonstrated to show stable normally‐off transistor operation on 4H‐SiC. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(5): 1– 10, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20329
BAST: BIST‐aided scan test. A new method for test cost reduction
Authors: Aikyo Takashi , Hiraide Takahisa , Emori Michiaki
Published: April 2007

It is common to use ATPG of scan‐based design for high fault coverage in LSI testing. However, significant increases in test cost arise with increasing design complexity. Recent strategies for test cost reduction combine ATPG and BIST techniques. Unfortunately, these strategies have serious constraints. We propose a new method that employs ATE and BIST structures to apply coded test patterns to LSI circuits. Results obtained using practical circuits show drastic test cost reduction capability of the proposed method. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 90(5): 58– 65, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20356
A comparative study of micellar and microemulsion EKC for the analysis of benzoylurea insecticides and their analogs
Authors: Yang Xia , Xia Yan , Tao Chuanjiang , Liao Yiping , Zuo Yumin , Liu Huwei
Published: April 2007

An investigation of the basic factors which govern the microemulsion EKC (MEEKC) and MEKC for the separation of four benzoylurea (BU) insecticides and their four analogs was carried out. In MEEKC, the separation of eight BU compounds was optimized by changing the microemulsion composition, such as concentration of SDS, octane, n‐butanol, and isopropanol percentages, as well as capillary temperature. Separation optimization was also carried out for MEKC, showing that ACN and a high level of another additive γ‐CD were needed to achieve effective separation of these analytes. Although separation with baseline resolution was achieved by either MEEKC or MEKC methods, the separation selectivity resulting from the proposed MEEKC method was completely different from that of MEKC. In addition, analytical time in MEEKC was longer than that in MEKC, but in view of theoretical plate numbers, detection limits, and reproducibility, both methods were effective for the analysis of BU insecticides and their analogs.
Electrochromatography in poly(dimethyl)siloxane microchips using organic monolithic stationary phases
Authors: Faure Karine , Blas Maximilien , Yassine Omar , Delaunay Nathalie , Crétier Gérard , Albert Monique , Rocca Jean‐Louis
Published: April 2007

This paper shows the in situ synthesis of an hexyl acrylate monolith in PDMS microfluidic devices and its subsequent use as stationary phase for electrochromatography on chip. To overcome the ability of PDMS material to absorb organic monomers, surface modification of the enclosed channels was realized by UV‐mediated graft polymerization. This grafting procedure is based on the preliminary adsorption of a photoinitiator onto the PDMS surface and polymerization of charged monomers. Next, hexyl acrylate monoliths were cast in situ using photopolymerization process. The chromatographic behavior of the monolithic column was confirmed by the successful separation of derivatized catecholamines in the PDMS device using a 30 mm effective separation length (100 μm×100 μm section). Efficiencies reached up to 200 000 plates per meter.
Separation of cold medicine ingredients using a precise MEKC method at elevated pH
Authors: Hasemann Phillip , ter Balk Marieke , Preu Lutz , Wätzig Hermann
Published: April 2007

An MEKC method was developed in order to separate a cold medicine formulation containing acetaminophen, ephedrine sulfate, doxylamine succinate, and dextromethorphan hydrobromide as active pharmaceutical ingredients. Because of their similar physical and chemical properties, it was a challenge to separate the basic compounds without sample pretreatment. In addition, the high content of alcohol and sucrose together with the variety of further excipients had to be considered. Thus, the complex matrix required several optimization steps. These included the search for the optimum pH and for a suitable sodium dodecyl sulfate concentration to avoid matrix‐capillary wall interaction and to ensure precision. As a second developing step, an internal standard (benzocaine) was chosen to guarantee a high level of quantitative performance. An RSD% value of the peak areas between 1.0 and 2.0 was reached. The employed method development strategy can be generalized to similar separation approaches in the future.
Fabrication and characterization of open‐tubular CEC modified with tentacle‐type metal‐chelating polymer chains
Authors: Xu Liang , Sun Yan
Published: April 2007

A novel stationary phase with tentacle‐type metal‐chelating polymer chains was fabricated for open‐tubular CEC. The preparation procedure of the stationary phase included the synthesis of monomer, silanization of capillary inner wall, in situ polymerization, and metal complexation. The effects of initiator concentration and reaction time on the column capacity were investigated. To compare with the tentacle‐type metal‐chelating capillary column, a monolayer ligand‐modified capillary was also prepared. Immobilized copper(II) capacity of the tentacle‐type polymer stationary phase was nearly 900 times higher than that of the monolayer one. The electroosmotic mobility was examined for its dependence on pH as well as phosphate and ACN concentrations. The tentacle‐type metal‐chelating capillary with high ligand capacity has proven to afford better retention and resolution for the separation of phenylalanine, tryptophan, and tyrosine mixtures and three purine derivatives. The separation was considered to be effected by a combination of ligand exchange and electrophoretic mobility.
Decrease in glucose metabolism in frontal cortex associated with deterioration of microstructure of corpus callosum measured by diffusion tensor imaging in healthy elderly
Authors: Inoue Kentaro , Ito Hiroshi , Uchida Shinya , Taki Yasuyuki , Kinomura Shigeo , Tsuji Ichiro , Sato Shigeru , Horie Kaoru , Kawashima Ryuta , Ito Masatoshi , Fukuda Hiroshi
Published: April 2007

The neural functions of signaling are carried out by the interconnection of neurons via neuronal fibers. Diffusion tensor imaging has recently become an established technique that enables the in vivo visualization of white matter (WM) fibers. Studies of normal aging have suggested the disruption of WM fiber microstructures with anterior–posterior gradient. Because neuronal activity is tightly coupled with glucose metabolism, neuronal death or a decrease in synaptic activity with aging may cause a decrease in glucose metabolism in the brain. We examined whether the disruption of callosal fiber microstructures in the healthy elderly is accompanied by changes in regional glucose metabolism (rMGlu) in the brain. Fifteen healthy volunteers in their seventies participated. Fractional anisotropies (FAs) of the genu and splenium of the corpus callosum (CC) were measured for each subject, and their correlations with rMGlu were analyzed using SPM2 software. We found a statistically significant positive correlation of rMGlu in the bilateral frontal cortices with the FA of the genu of the CC, whereas there was no correlation of the FA of the splenium of the CC and rMGlu. By voxel‐based morphometry, we found no decrease in gray matter concentration associated with FA. The results indicate that neuronal activity in the frontal cortices may decrease with the disruption of the microstructures of the CC without corresponding gray matter atrophy. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Recurrent laryngeal cancer presenting as delayed hypoparathyroidism
Authors: Hsu Amy K , Tabaee Abtin , Kraus Dennis H.
Published: April 2007

Background.

Endocrine dysfunction following therapy for head and neck cancer has been previously described. Permanent hypoparathyroidism may result from the tumor, surgery, or radiation therapy. However, the incidence and significance of delayed hypoparathyroidism following treatment for laryngeal cancer remains unclear.

Methods and Results.

We report a patient who had stable serum calcium measurements on serial testing following concurrent chemoradiation and salvage laryngectomy for locally advanced laryngeal cancer. The patient subsequently presented 32 months following salvage laryngectomy with new onset, symptomatic hypocalcemia secondary to hypoparathyroidism. Subsequent evaluation revealed local recurrence.

Conclusion.

To our knowledge, this case represents the first report of delayed hypoparathyroidism as the presenting manifestation of recurrence following treatment for laryngeal cancer. Possible pathophysiologic mechanisms are discussed. © 2007 Wiley Periodicals, Inc. Head Neck, 2007
Inner cylinder diameter effects on free convection heat transfer in a stable stratified fluid
Authors: Himeno Nobuhiro , Masuda Chihiro
Published: April 2007

An experimental study was performed to identify the effects of the inner cylinder diameter on free convection heat transfer in a stable stratified fluid between coaxial cylinders. The stratified layer was formed using a sucrose aqueous solution, and was heated from the outer cylinder (70 mm I.D.) at a constant heat flux and cooled from the inner cylinder at a constant temperature. The experiment was conducted for an inner cylinder of 50.8 mm O.D. and the results were compared with those for an inner cylinder of 30 mm O.D., which were previously reported by the authors. The results show that the inner cylinder size affects the heat transfer in the early stage of heating: increasing the diameter of the inner cylinder decreased the distance between the heating and cooling surfaces. It consequently reduced both the duration of heat conduction prevailing and the resulting temperature increase of the heating surface during that period. Increasing the diameter of the inner cylinder also made the heat transfer characteristics similar to those between vertical plates. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(3): 172– 186, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20148
Numerical investigation of flow in a channel obstructed by an array of square rods (2nd report, Investigation of a criterion for judging the uniqueness and validity of numerical results)
Authors: Murata Hiroyuki , Sawada Ken‐Ichi , Suzuki Kenjiro
Published: April 2007

Two‐dimensional numerical computation is performed for unsteady laminar flow. Spatially periodic boundary conditions are adopted in the streamwise direction, and in particular, a criterion for judging the uniqueness of the numerical solution is studied. The following results were obtained. When the numerical result fluctuates with the computational domain size, various low‐frequency components are markedly observed in the streamwise velocity of the calculated result. Compared with the channel flow obstructed by a single rod of the same size, the intensities of velocity fluctuation in this study are relatively high, and their distribution throughout the flow field is rather uniform. The spatially averaged kinematic energy of the velocity fluctuation is adopted as a key parameter, and a discrimination map of the uniqueness of the numerical solution is presented using a timescale ratio between mean flow and velocity fluctuation, the rod pitch, and the blockage ratio. The timescale ratio is well correlated with a geometric parameter obtained from the flow configuration, and the discrimination map can be converted such that the geometric parameter and the channel Reynolds number describe it. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(3): 113–126, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20152
Family history of gallstones and the risk of biliary tract cancer and gallstones: A population‐based study in Shanghai, China
Authors: Hsing Ann W. , Bai Yan , Andreotti Gabriella , Rashid Asif , Deng Jie , Chen Jinbo , Goldstein Alisa M. , Han Tian‐Quan , Shen Ming‐Chang , Fraumeni Joseph F. , Gao Yu‐Tang
Published: April 2007

Cancers of the biliary tract arise from the gallbladder, extrahepatic bile ducts and ampulla of Vater. Although relatively uncommon, the incidence of biliary tract cancer rose more than 100% in Shanghai, China between 1972 and 1994. Gallstones are the predominant risk factor for biliary tract cancers, with over 60% of the cancer cases having gallstones. A familial tendency to gallstones has been reported and may elevate the risk of gallbladder cancer further. As part of a large population‐based case–control study of biliary tract cancers in Shanghai, China, we examined the association between a family history of gallstones and biliary tract cancers as well as biliary stones. A total of 627 biliary tract cancers (368 gallbladder, 191 bile duct, 68 ampulla of Vater), 1,037 biliary stone cases (774 gallbladder, 263 bile duct) and 959 healthy subjects randomly selected from the population were included in this study. Information on family history of gallstones among first‐degree relatives (i.e., parents, siblings, offspring) was obtained through a self‐reported history during in‐person interviews. A family history of gallstones was associated with increased risks of biliary stones [odds ratio (OR) = 2.8, 95% confidence interval (CI) = 2.1–3.8], gallbladder cancer (OR = 2.1, 95% CI = 1.4–3.3) and bile duct cancer (OR = 1.5, 95% CI = 0.9–2.5), after adjustment for age, gender, marital status, education, smoking, alcohol drinking and body mass index. For gallbladder cancer, subjects with gallstones but without a family history of gallstones had a 21‐fold risk (95% CI 14.8–30.1), while those with both gallstones and a positive family history had a 57‐fold risk (95% CI 32.0–110.5). Significant risks for gallbladder cancer persisted after additional adjustment for gallstones, and when the analysis was restricted to subjects with first‐degree relatives whose gallstones were treated with cholecystectomy. The significant associations with a family history of gallstones were seen for all first‐degree relatives, including parents, siblings and offspring, but not spouses. This large population‐based study not only supports the role of gallstones in biliary carcinogenesis but also suggests that the underlying genetic or lifestyle determinants of stones within families contribute to the risk of biliary tract cancer. © 2007 Wiley‐Liss, Inc.
Protein C inhibitor inhibits breast cancer cell growth, metastasis and angiogenesis independently of its protease inhibitory activity
Authors: Asanuma Kunihiro , Yoshikawa Tomoaki , Hayashi Tatsuya , Akita Nobuyuki , Nakagawa Norimi , Hamada Yasuhiko , Nishioka Junji , Kamada Haruhiko , Gabazza Esteban C. , Ido Masaru , Uchida Atsumasa , Suzuki Koji
Published: April 2007

Protein C inhibitor (PCI) regulates the anticoagulant protein C pathway and also inhibits urinary plasminogen activator (uPA), a mediator of tumor cell invasion. In the present study, we evaluated the effect of human PCI and its inactive derivatives on tumor growth and metastasis of human breast cancer (MDA‐231) cells, and on angiogenesis in vivo. The invasiveness of MDA‐231 cells was inhibited by recombinant intact PCI, but not by reactive site‐modified PCI (R354APCI) or by the N‐terminal fragment of protease‐cleaved PCI (NTPCI). The in vitro invasiveness of MDA‐231 cells expressing intact PCI (MDA‐PCI) was significantly decreased as compared to MDA‐231 cells expressing R354APCI (MDA‐R354APCI) or NTPCI (MDA‐NTPCI). Further, in vivo growth and metastatic potential of MDA‐PCI, MDA‐R354APCI and MDA‐NTPCI cells in severe combined immunodeficient (SCID) mice were significantly decreased as compared to MDA‐Mock cells. Angiogenesis was also significantly decreased in Matrigel implant containing MDA‐PCI, MDA‐R354APCI or MDA‐NTPCI cells as compared to that containing MDA‐Mock cells. In vivo angiogenesis in rat cornea and in vitro tube formation were also inhibited by recombinant intact PCI, R354APCI and NTPCI. Furthermore, the anti‐angiogenic activity of PCI was strong as cleaved antithrombin (AT), and slightly stronger than that of plasminogen activator inhibitor (PAI)‐1 and pigment epithelium‐derived factor (PEDF). Overall, this study showed that, in addition to a reactive site‐dependent mechanism, PCI may also regulate tumor growth and metastasis independently of its protease inhibitory activity by inhibiting angiogenesis. © 2007 Wiley‐Liss, Inc.
A gene expression signature associated with metastatic cells in effusions of breast carcinoma patients
Authors: Dupont Virginie N. , Gentien David , Oberkampf Marine , De Rycke Yann , Blin Nathalie
Published: April 2007

Malignant effusion in invasive breast carcinoma is associated with poor prognosis. To decipher molecular events leading to metastasis and to identify reliable markers for targeted therapies are of crucial need. Therefore, we have used cDNA microarrays to delineate molecular signatures associated with metastasis and relapse in breast carcinoma effusions. Taking advantage of an immunomagnetic method, we have purified to homogeneity EpCAM‐positive cells from 34 malignant effusions. Immunopurified cells represented as much as 10% of the whole cell fraction and their epithelial and carcinoma features were confirmed by immunofluorescence labeling. Gene expression profiles of 19 immunopurified effusion samples, were analyzed using human pan‐genomic microarrays, and compared with those of 4 corresponding primary tumors, 8 breast carcinoma effusion‐derived cell lines, and 4 healthy mammary tissues. Principal component and multiple clustering analyses of microarray data, clearly identified distinctive molecular portraits corresponding to the 4 categories of specimens. Of uppermost interest, effusion samples were arranged in 2 subsets on the basis of their gene expression patterns. The first subset partly shares a gene expression signature with the different cell lines, and overexpresses CD24, CD44 and epithelial cytokeratins 8,18,19. The second subset overexpresses markers related to aggressive invasive carcinoma (uPA receptor, S100A4, vimentin, CXCR4). These findings demonstrate the importance of using pure cell fractions to accurately decipher in silico gene expression of clinical specimens. Further studies will lead to the identification of genes of oustanding importance to diagnose malignant effusion, predict survival and tailor appropriate therapies to the metastatic effusion disease in breast carcinoma patients. © 2007 Wiley‐Liss, Inc.
Coffee consumption and risk of colorectal cancer in a population‐based prospective cohort of Japanese men and women
Authors: Lee Kyung‐Jae , Inoue Manami , Otani Tetsuya , Iwasaki Motoki , Sasazuki Shizuka , Tsugane Shoichiro ,   for the JPHC Study Group
Published: April 2007

We prospectively examined the association between coffee consumption and the risk of developing colorectal cancer in a large population‐based cohort study (the JPHC Study) of Japanese men and women. Data were analyzed from a population‐based cohort of 96,162 subjects (46,023 men and 50,139 women). A total of 1,163 incident colorectal cancers were identified during the follow‐up period, including 763 cases of colon cancer and 400 of rectal cancer. We observed a significant inverse association between coffee consumption and the risk of developing invasive colon cancer among women. Compared with those who almost never consumed coffee, women who regularly consumed 3 or more cups of coffee per day had a RR of 0.44 (95% CI = 0.19–1.04; p for trend = 0.04) after adjustment for potential confounding factors. However, no significant association was found for rectal cancer in women. In men, no significant decrease was observed in any colorectal cancer site. Further, additional analyses on the association of green tea consumption with colorectal cancer risk found no significant association in men or women. These findings suggest that coffee consumption may lower the risk of colon cancer among Japanese women. © 2007 Wiley‐Liss, Inc.
Chondrocyte‐alginate bioconstructs: An nuclear magnetic resonance relaxation study
Authors: Fantazzini Paola , Garavaglia Carla , Gomez Santiago , Toffanin Renato , Vittur Franco
Published: April 2007

Proton nuclear magnetic resonance (NMR) relaxometry can give informations about hydrogel scaffold properties. As these properties can be modified with culture time and conditions according to scaffold biodegradability and new tissue biosynthesis, the aim of this research was to test the efficiency of this noninvasive NMR technique in the follow‐up of 3D cultures for tissue engineering. The distributions of proton relaxation times T1 and T2 have been measured on cylindrical gel samples of different types of alginate, in the presence or absence of hyaluronate, in gels or bioconstructs with encapsulated chondrocytes cultured for 30 days in normal or reduced weight conditions. It was found that T2 increases with the mannuronate/guluronate ratio in alginate samples and with the presence of hyaluronate. The distributions of both T1 and T2 result wider for bioconstructs cultured in normal gravity than for those cultured in reduced weight conditions. Neither cell growing nor collagen production but only GAG neosynthesis have been demonstrated in our experimental conditions. In conclusion, T2 is sensitive to the gel properties (possibly to the rigidity of macromolecular components). The homogeneity of bioconstructs can be monitored by the distribution of T1 and T2. We propose that nonspatially resolved NMR relaxometry can efficiently be used in monitoring tissue development in a biodegradable scaffold for tissue engineering. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
Phenotype and gene expression pattern of osteoblast‐like cells cultured on polystyrene and hydroxyapatite with pre‐adsorbed type‐I collagen
Authors: Hanagata Nobutaka , Takemura Taro , Monkawa Akira , Ikoma Toshiyuki , Tanaka Junzo
Published: April 2007

Hydroxyapatite and type‐I collagen are major components of bone matrix. We compared phenotype and gene expression pattern of osteoblast‐like cells cultured on HAp and HAp with pre‐adsorbed type‐I collagen from neutral solutions (HAp/NCs) with those of tissue culture grade polystyrene (TCPS) and TCPS with the collagen (TCPS/NCs). In initial cell attachment, the cells tensely spread on TCPS, while loosely spread on TCPS/NCs, HAp, and HAp/NCs. The levels of expressed integrin α2 and α5 subunits were not significantly different among any surfaces. Although the cells on HAp/NCs directly attached with the same collagen molecules as TCPS/NCs, mineralization was observed in only TCPS/NCs. The basal substrates (TCPS and HAp) greatly influenced osteoblast maturation even in the surfaces with pre‐adsorbed collagen, since mineralization was induced by TCPS, but not by HAp. Gene expression pattern analyzed with DNA microarray also supported greater influence of basal substrates than pre‐adsorbed collagen. In addition, comprehensive gene expression analyses revealed that HAp and HAp/NCs specifically up‐regulated Ly6a and Tmem37 genes, while down‐regulated Ifitm5 gene. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
Impedimetric sensing of cells on polypyrrole‐based conducting polymers
Authors: Ateh D.D. , Waterworth A. , Walker D. , Brown B.H. , Navsaria H. , Vadgama P.
Published: April 2007

Polypyrrole (PPy) is a conducting polymer that may be electrochemically generated with the incorporation of any anionic species, including net‐negatively charged biological molecules such as proteins and polysaccharides. In this article, dermatan and chloride‐loaded PPy films were prepared on gold sputter‐coated coverslips and various skin derived cells were studied on them by electrochemical impedance spectroscopy. Impedance spectra in the frequency range 1–100 kHz were either determined at specific times or impedance was monitored continuously at specific frequencies. An equivalent impedance circuit was fitted to the recorded impedance spectra to obtain parameters whose contributions could be mapped to intracellular and intercellular current pathways, and the membrane properties of cells. Results show cell‐induced impedance changes were detected over PPy modified electrodes and were dependent on cell density and type, monitoring frequency, material composition, and treatment. Lower cell densities were detected on PPy when compared with bare gold. Keratinocyte confluence, as determined by impedimetric analysis, was reached more rapidly on PPy than on gold. This was consistent with previous, more cumbersome, biochemical assays. Electrical equivalent circuit analysis provided evidence that the technique may be extended to discriminate cell type because of the intracellular and intercellular resistance, and cell membrane capacitance being related to cell morphology. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
Quaternized chitosan/alginate nanoparticles for protein delivery
Authors: Li Tao , Shi Xiao‐Wen , Du Yu‐Min , Tang Yu‐Feng
Published: April 2007

Quaternized chitosan (QCS)/alginate (AL) nanoparticles (QCS/AL) were successfully prepared in neutral condition for the oral delivery of protein. The physicochemical structure of the QCS/AL nanoparticles was characterized by IR spectroscopy and transmission electron microscopy. The diameter of the nanoparticles with a positive surface charge was about 200 nm. The load of bovine serum albumin (BSA) was affected by the concentration and the molecular parameters, i.e. degree of substitution (DS) and weight‐average molecular weight (Mw) of QCS, as well as the concentration of BSA. The release of BSA from nanoparticles was pH‐dependent. Quick release occurred in 0.1M phosphate buffer solution (PBS, pH = 7.4), while the release was slow in 0.1M HCl (pH = 1.2). The DS and Mw of QCS play important roles in the release of BSA in vitro. QCS with high Mw accelerated the release of BSA in acid, while high DS retarded the release of BSA in both 0.1M HCl and 0.1M PBS. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007
Structural, electronic, and optical properties of 9‐heterofluorenes: A quantum chemical study
Authors: Chen Run‐Feng , Zheng Chao , Fan Qu‐Li , Huang Wei
Published: April 2007

Density‐functional theory studies were applied to investigate the structural, electronic, and optical properties of 9‐heterofluorenes achieved by substituting the carbon at 9 position of fluorene with silicon, germanium, nitrogen, phosphor, oxygen, sulfur, selenium, or boron. These heterofluorenes and their oligomers up to pentamers are highly aromatic and electrooptically active. The alkyl and aryl substituents of the heteroatom have limited influence, but the oxidation of the atom has significant influence on their molecular structures and properties. The highest occupied molecular orbital (HOMO)‐lowest occupied molecular orbital (LUMO) interaction theory was successfully applied to analyze the energy levels and the frontier wave functions of these heterofluorenes. Most heterofluorenes belong to type B of interaction with low‐lying LUMO and have the second kind of wave function. Carbazole and selenafluorene have type C of interaction with high‐lying HOMO and the third kind of wave function. Types C and D of heterofluorenes, such as carbazole, oxygafluorene, sulfurafluorene, and selenafluorene also have high triplet state energies. The extrapolated HOMO and LUMO for polyheterofluorenes indicate that polyselenonafluorene has the lowest LUMO; polycarbazole has the highest HOMO; polyselenafluorene has the highest bandgap (Eg); and polyborafluorene has the lowest Eg. Heterofluorenes and their oligomers and polymers are of great experimental interests, especially those having extraordinary properties revealed in this study. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
A combined electronegativity equalization and electrostatic potential fit method for the determination of atomic point charges
Authors: Berente Imre , Czinki Eszter , Náray‐szabó Gábor
Published: April 2007

We report an approach for the determination of atomic monopoles of macromolecular systems using connectivity and geometry parameters alone. The method is appropriate also for the calculation of charge distributions based on the quantum mechanically determined wave function and does not suffer from the mathematical instability of other electrostatic potential fit methods. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
New six‐site acetonitrile model for simulations of liquid acetonitrile and its aqueous mixtures
Authors: Nikitin Alexei M. , Lyubartsev Alexander P.
Published: April 2007

A new six site flexible acetonitrile molecular model is developed. The AMBER force field was used for description of intramolecular parameters, the atomic charges were calculated from a high level ab initio theory and finally the Lennard–Jones parameters were tuned to fit the experimental density and evaporation heat. The obtained in this way model reproduces correctly densities of water–acetonitrile mixtures as well as provides qualitative description of the dielectric permittivity and self‐diffusion coefficients. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Algorithm to evaluate rate constants for polyatomic chemical reactions. I. Theory and computational details
Authors: González Javier , Giménez Xavier , Bofill Josep Maria
Published: April 2007

A classical reaction path, Liouville algorithm, as previously developed by the authors, has been reformulated in a more efficient form, based on the time‐dependent first integral method from the theory of partial differential equations. Both the theory and computational details are presented. The formulation is based on solving the complete rate constant problem, concerning both the density distribution as well as the reactive flux, by means of solving the classical Liouville equation. The numerical implementation is discussed in detail, including some specifics concerning the reaction path calculation. The formulation is tested with the well‐known Müller–Brown bidimensional potential energy surface. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Complete maps of molecular‐loop conformational spaces
Authors: Porta Josep M. , Ros Lluís , Thomas Federico , Corcho Francesc , Cantó Josep , Pérez Juan Jesús
Published: April 2007

This paper presents a numerical method to compute all possible conformations of distance‐constrained molecular loops, i.e., loops where some interatomic distances are held fixed, while others can vary. The method is general (it can be applied to single or multiple intermingled loops of arbitrary topology) and complete (it isolates all solutions, even if they form positive‐dimensional sets). Generality is achieved by reducing the problem to finding all embeddings of a set of points constrained by pairwise distances, which can be formulated as computing the roots of a system of Cayley–Menger determinants. Completeness is achieved by expressing these determinants in Bernstein form and using a numerical algorithm that exploits such form to bound all root locations at any desired precision. The method is readily parallelizable, and the current implementation can be run on single‐ or multiprocessor machines. Experiments are included that show the method's performance on rigid loops, mobile loops, and multiloop molecules. In all cases, complete maps including all possible conformations are obtained, thus allowing an exhaustive analysis and visualization of all pseudo‐rotation paths between different conformations satisfying loop closure. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Protein structure prediction aided by geometrical and probabilistic constraints
Authors: Porwal Gaurav , Jain Swapnil , Babu S. Dhilly , Singh Deepak , Nanavati Hemant , Noronha Santosh
Published: April 2007

Database‐assistedab initioprotein structure prediction methods have exhibited considerable promise in the recent past, with several implementations being successful in community‐wide experiments (CASP). We have employed combinatorial optimization techniques toward solving the protein structure prediction problem. A Monte Carlo minimization algorithm has been employed on a constrained search space to identify minimum energy configurations. The search space is constrained by using radius of gyration cutoffs, the loop backbone dihedral probability distributions, and various secondary structure packing conformations. Simulations have been carried out on several sequences and 1000 conformations have been initially generated. Of these, 50 best candidates have then been selected as probable conformations. The search for the optimum has been simplified by incorporating various geometrical constraints on secondary structural elements using distance restraint potential functions. The advantages of the reported methodology are its simplicity, and modifiability to include other geometric and probabilistic restraints. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Expression, localization and functions in acrosome reaction and sperm motility of CaV3.1 and CaV3.2 channels in sperm cells: An evaluation from CaV3.1 and CaV3.2 deficient mice
Authors: Escoffier Jessica , Boisseau Sylvie , Serres Catherine , Chen Chien‐Chang , Kim Daesoo , Stamboulian Séverine , Shin Hee‐Sup , Campbell Kevin P. , De Waard Michel , Arnoult Christophe
Published: April 2007

In spermatozoa, voltage‐dependent calcium channels (VDCC) have been involved in different cellular functions like acrosome reaction (AR) and sperm motility. Multiple types of VDCC are present and their relative contribution is still a matter of debate. Based mostly on pharmacological studies, low‐voltage‐activated calcium channels (LVA‐CC), responsible of the inward current in spermatocytes, were described as essential for AR in sperm. The development of CaV3.1 or CaV3.2 null mice provided the opportunity to evaluate the involvement of such LVA‐CC in AR and sperm motility, independently of pharmacological tools. The inward current was fully abolished in spermatogenic cells from CaV3.2 deficient mice. This current is thus only due to CaV3.2 channels. We showed that CaV3.2 channels were maintained in sperm by Western‐blot and immunohistochemistry experiments. Calcium imaging experiments revealed that calcium influx in response to KCl was reduced in CaV3.2 null sperm in comparison to control cells, demonstrating that CaV3.2 channels were functional. On the other hand, no difference was noticed in calcium signaling induced by zona pellucida. Moreover, neither biochemical nor functional experiments, suggested the presence of CaV3.1 channels in sperm. Despite the CaV3.2 channels contribution in KCl‐induced calcium influx, the reproduction parameters remained intact in CaV3.2 deficient mice. These data demonstrate that in sperm, besides CaV3.2 channels, other types of VDCC are activated during the voltage‐dependent calcium influx of AR, these channels likely belonging to high‐voltage activated Ca2+channels family. The conclusion is that voltage‐dependent calcium influx during AR is due to the opening of redundant families of calcium channels. J. Cell. Physiol. 212:753–763, 2007. © 2007 Wiley‐Liss, Inc.
No evidence for vasculogenesis regulation by angiostatin during mouse embryonic stem cell differentiation
Authors: Prandini Marie‐Hélène , Desroches‐Castan Agnès , Feraud Olivier , Vittet Daniel
Published: April 2007

During embryogenesis, the formation of blood vessels proceeds by both vasculogenesis and angiogenesis. Both processes appear to be finely regulated. To date, factors and genes involved in the negative regulation of embryonic vasculogenesis remain largely unknown. Angiostatin is a proteolytic fragment of plasminogen that acts as an inhibitor of angiogenesis. In this study, we analyzed the potential role of angiostatin during early stages of embryonic stem (ES) cell endothelial in vitro differentiation, as a model of vasculogenesis. We found an early expression of the known angiostatin binding sites (angiomotin, αv integrin and c‐met oncogene) during ES cell differentiation. Nevertheless, we did not detect any significant effect of angiostatin on mesoderm induction and on differentiation commitment into cells of the endothelial lineage. In both control and angiostatin‐treated conditions, the temporal and extent of formation of the Flk1 positive and Flk‐1/CD31 (PECAM‐1) positive cell populations were not significantly different. Quantitative RT‐PCR experiments of endothelial gene expression (Flk‐1, PECAM‐1 and tie‐2) confirm a lack of interference with early steps of endothelial differentiation in embryoid bodies. No evidence for an angiostatin effect on endothelial cord‐like formation could be detected at later differentiation stages. On the other hand, angiostatin inhibits vascular endothelial growth factor‐induced endothelial sprouting from embryoid bodies cultured in three dimensional type I collagen gels. Taken together, these findings support a selective inhibitory effect on the sprouting angiogenesis response for angiostatin during embryonic vascular development. J. Cell. Physiol. 213: 27–35, 2007. © 2007 Wiley‐Liss, Inc.
Separase, securin and Rad21 in neural cell growth
Authors: Pemberton H.N. , Franklyn J.A. , Boelaert K. , Chan S.Y. , Kim D.S. , Kim C. , Cheng S.Y. , Kilby M.D. , McCabe C.J.
Published: April 2007

The key mitotic regulator securin is expressed at low levels in fetal brain compared with adult, and modulates the proliferation of human embryonic neuronal N‐Tera2 (NT2) cells. We now examine the function and expression of securin's interacting partner separase, along with Rad21, the functional component of cohesin, which is cleaved by separase following interaction with securin. In contrast to securin, the cleaved forms of separase and Rad21 were highly expressed in human fetal cerebral cortex compared with adult. In a murine model of absent securin expression – the PTTG knock‐out mouse – separase and Rad21 were over‐expressed in multiple brain regions. In addition, cDNA array analysis of other key mitotic regulators additionally identified cyclin C and sestrin 2 to be induced in the brains of securin‐null mice compared with wild type. Further, Rad21 mRNA expression was highly correlated with that of securin, separase, cyclin C and sestrin 2 in fetal brains. In embryonic neuronal NT2 cells, siRNA repression of separase failed to significantly alter cell turnover, whereas repression of securin expression resulted in increased levels of the activated forms of Rad21 and separase, and promoted cell proliferation. Our data suggest that the co‐ordinated expression of separase, securin and Rad21 is fundamental for the developing brain. J. Cell. Physiol. 213: 45–53, 2007. © 2007 Wiley‐Liss, Inc.