bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized comparison of cladribine alone or in combination with cyclophosphamide, and cyclophosphamide, vincristine and prednisone in previously untreated low‐grade B‐cell non‐Hodgkin lymphoma patients
Authors: Kalinka‐Warzocha Ewa , Wajs Jaroslaw , Lech‐Maranda Ewa , Ceglarek Bernadetta , Holowiecki Jerzy , Federowicz Irena , Walewski Jan , Czyz Jaroslaw , Robak Tadeusz , Warzocha Krzysztof ,   the Polish Lymphoma Research Group
Published: May 2008

BACKGROUND.

The objective of this study was to compare the efficacy of 3 regimens, cladribine alone, cladribine and cyclophosphamide combination, or cyclophosphamide, vincristine, and prednisone combination in previously untreated patients with low‐grade B‐cell non‐Hodgkin lymphoma (LGNHL).

METHODS.

For this 3‐arm, phase 3 study, 197 patients were randomly allocated to receive 6 monthly courses of cladribine alone, cladribine and cyclophosphamide combination, or cyclophosphamide, vincristine, and prednisone combination. Patients for whom all clinical data were available and 162 patients who completed scheduled chemotherapy were analyzed for the endpoints of this study.

RESULTS.

Compared with cyclophosphamide, vincristine, and prednisone combination regimen, cladribine alone or cladribine and cyclophosphamide combination induced higher probability of overall response (odds ratio [OR] = 4.0; 95% confidence interval [CI], 1.7–9,3; P = .002, and OR = 8.5; 95% CI, 3.2–22.7; P < .0001, respectively), complete remission (OR = 5.8; 95% CI, 1.8–18.5; P = .003; and OR = 14; 95% CI, 4.4–44; P < .0001, respectively), progression‐free survival (log‐rank test P < .0001), but not overall survival. After incorporating the International Prognostic Index in multivariate analysis, treatment with cladribine‐containing regimens remained an independent prognostic factor for progression‐free survival (χ2 = 35.94; hazard ratio = 2.38; P < .0002). Incidences of infections were similar in the randomized groups, whereas cladribine and cyclophosphamide combination, but not cladribine alone, induced more frequent neutropenia, anemia, and thrombocytopenia compared with cyclophosphamide, vincristine, and prednisone combination (P < .05 for each). This resulted in a higher frequency of prolongation of intervals between cladribine and cyclophosphamide combination and cyclophosphamide, vincristine, and prednisone combination cycles (P < .05), but dose reductions due to hematological or other toxicity did not differ significantly in cladribine alone, cladribine and cyclophosphamide combination, and cyclophosphamide, vincristine, and prednisone combination groups.

CONCLUSIONS.

For patients with LGNHL, first‐line cladribine alone or cladribine and cyclophosphamide combination regimens both provided similar treatment responses, acceptable toxicity, and better response rates than cyclophosphamide, vincristine, and prednisone combination. Cancer 2008. © 2008 American Cancer Society.
Fast multidimensional nearest neighbor search algorithm using priority queue
Authors: Ajioka Shiro , Tsuge Satoru , Shishibori Masami , Kita Kenji
Published: May 2008

Nearest neighbor search in high‐dimensional spaces is an interesting and important problem which is relevant for a wide variety of applications, including multimedia information retrieval, data mining, and pattern recognition. For such applications, the curse of high dimensionality tends to be a major obstacle in the development of efficient search methods. This paper addresses the problem of designing an efficient algorithm for high‐dimensional nearest neighbor search using a priority queue. The proposed algorithm is based on a simple linear search algorithm and eliminates unnecessary arithmetic operations from distance computations between multidimensional vectors. Moreover, we propose two techniques, a dimensional sorting method and a PCA‐based method, to accelerate multidimensional search. Experimental results indicate that our scheme scales well even for a very large number of dimensions. © 2008 Wiley Periodicals, Inc. Electr Eng Jpn, 164(3): 69–77, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20502
Location of partial discharge in air by detecting phase difference of electromagnetic waves
Authors: Kumazawa Takao , Hoshino Toshihiro , Fujii Shigeo , Maekawa Hiroshi
Published: May 2008

Electromagnetic interference (EMI) due to partial discharges (PDs), which occur at the rubber coatings or the strain insulators of outdoor distribution systems, might cause poor television reception in neighboring housing. It is difficult to identify the EMI with a visual check because the PDs rarely generate light and sound.

We investigate fundamental characteristics such as identifying the direction of a PD source using the time difference between two antennas, and an analog hardware system for calculating the direction from that time difference. The analog system is composed of IC devices such as a filter and a mixer, and also uses signal processing of intermediate frequency transforming. We confirm the validity of the relationship between the direction of a PD source and the time difference between two antennas, and also confirm the application of a surface acoustic wave (SAW) filter in the analog hardware system. We measure the pulse response of multiple devices, and estimate the linearity between the direction of a PD source and the outputs of multiple devices. © 2008 Wiley Periodicals, Inc. Electr Eng Jpn, 164(3): 27–34, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20540
Influence of high‐speed repetition of pulsed streamer discharge produced by polarity‐reversed traveling wave on NO oxidation
Authors: Matsuda Eiji , Kadowaki Kazunori , Nishimoto Sakae , Kitani Isamu
Published: May 2008

This paper describes experimental results of NO removal from a simulated exhausted gas using a barrier‐type plasma reactor subjected to reciprocal traveling wave voltage pulses. A pulse‐forming cable was charged and then grounded at one end without any resistance, so that a traveling wave reciprocated along the cable with a change in its polarity because the traveling wave was negatively reflected at the grounded end. Transient discharge light between point‐plane electrodes with a glass barrier was observed using a gated image‐intensifier. Photographs of the transient discharge light indicated that many streamer channels extended widely in the gap at the initial stage of voltage oscillation, while only an intense discharge channel was observed at the latter stage. NO removal tests were performed using the reciprocal pulse generator and a coaxial plasma reactor with a cylindrical glass barrier. The results indicated that the discharges at the first and second polarity reversals contributed greatly to the oxidation reaction from NO into NO2, whereas the contribution of the subsequent discharges in the latter stage to NO removal was small. © 2008 Wiley Periodicals, Inc. Electr Eng Jpn, 164(3): 19–26, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20634
Preparation and characterization of electrodeposited in‐doped CdTe semiconductor films
Authors: Nishio Tomoari , Takahashi Makoto , Wada Shinpei , Miyauchi Toshiyuki , Wakita Koichi , Goto Hideo , Sato Shoji , Sakurada Osamu
Published: May 2008

In‐doped n‐CdTe thin films have been electrodeposited at −0.35 V versus Ag/AgCl from a nitric acid solution of pH 1 containing 0.05 mol/dm3(M)Cd(NO3)2, 0.5 mM TeO2, and various concentrations of In(NO3)3. Deposited films were annealed at 350°C under N2 flow. The films were characterized with X‐ray diffraction, energy‐dispersive X‐ray spectroscopy, scanning electron microscopy, and a reflectance meter. The conductivity and the carrier concentration of the films were measured using the van der Pauw method and Hall effect measurement at room temperature. This is the first study to investigate the effect of the In(NO3)3 concentration on the composition, the crystallinity, and the electric properties of In‐doped CdTe films prepared by electrodeposition. The conductivity of the CdTe films linearly increases from 9.3 to 27.4 S/cm and the electron concentration [log(n/cm3)] increases from 3.9×1018 to 2.8×1019cm−3 as the In(NO3)3 concentration rises from 1×10−2 to 1×10−1M. © 2008 Wiley Periodicals, Inc. Electr Eng Jpn, 164(3): 12– 18, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20673
Titanium Phthalocyanines with Axial Phenylenevinylenes
Authors: Lyubimtsev Alexey , Misir Miraç N. , Calvete Mario , Hanack Michael
Published: May 2008

The synthesis of soluble titanium(IV) phthalocyanines, axially substituted with phenylenevinylenes (PVs) (RxPcTiX), is described. The reaction of peripherally tetra‐ and octasubstituted (phthalocyaninato)titanium oxides (RxPcTiO) 1–3 with chelating PV‐diols 4a–4c leads to the formation of axially substituted RxPcTiX 5–7. All compounds were characterized by IR, UV/Vis, MS, and 1H NMR spectroscopy. Pcs 5–7 dissolved in dichloromethane are stable in the dark. The stability of solutions of 5–7 in sunlight depends on the nature of the peripheral substituents in the Pc ring and the chain length of the axial PV substituents.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Titanium‐Salan‐Catalyzed Asymmetric Oxidation of Sulfides and Kinetic Resolution of Sulfoxides with H2O2 as the Oxidant
Authors: Bryliakov Konstantin P. , Talsi Evgenii P.
Published: May 2008

Asymmetric oxidation of sufides to sulfoxides by aqueous hydrogen peroxide with catalysis by titanium‐salan complexes is presented. Optically active sulfoxides have been obtained with good to high enantioselectivities (up to 97 % ee) by a tandem enantioselective oxidation and kinetic resolution procedure, the catalyst performing over 500 turnovers with no loss of enantioselectivity.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Estimation of anthropogenic pollution using a Bayesian contamination model: an application to fractured bedrock groundwater from Han River Watershed, South Korea
Authors: Joo Yongsung , Kim Dalho , Lee Keunbaik , Yun Seong‐Taek , Kim Kyoung‐Ho , Mercante Donald
Published: May 2008

It is well known that groundwater is a valuable but vulnerable natural resource. To set forth a proper strategy for conservation and sustainable use of groundwater resources, we need precise evaluations of the human impact on groundwater quality. In this paper, we develop a Bayesian contamination model that clusters the sampling locations of groundwater into polluted and unpolluted groups and simultaneously estimates the average amount of human impact. Among major dissolved ions in groundwater, NO3−, Ca2+, SO42−, Cl−, and Na+were documented as useful variables describing the hydrochemical characteristics of anthropogenically polluted groundwater. Increased concentrations of these ions indicate that overused agrochemicals (particularly nitrogen fertilizers) and domestic sewage are the most important causes of groundwater pollution to considerable depths in the studied region. Our proposed model can be used to identify effective measures for groundwater quality management such as source control. Copyright © 2008 John Wiley & Sons, Ltd.
Process studies for development of adsorption technology for furfural recovery from waste water
Authors: Nanoti A. , Gupta P. , Dasgupta S. , Garg M.O. , Goswami A.N.
Published: May 2008

Lube refineries in India are facing pollution problems associated with the occasional loss of furfural from their solvent recovery column bottoms in the extraction plant, which constitute both an economic loss and an environmental hazard. Although earlier studies on furfural removal by adsorption on polymeric resins concentrated on equilibrium and kinetic/breakthrough measurements in small diameter columns in the adsorption, the regeneration of the loaded resin adsorbent has not been given adequate attention. This paper focuses on these issues and also includes studies on larger diameter columns with a view to provide data for design of a pilot scale plant for furfural recovery to be set up in a lube complex. The experimental data from adsorption cycle studies indicate that the resin bed is able to treat 28 bed volumes of furfural laden water bringing down the furfural concentration from 500 ppm to less than 10 ppm. The regeneration data indicate the recovery scheme produces an aqueous stream which contains 3% furfural which has to be taken back to the solvent recovery column in the extraction complex. Adsorption and regeneration data have been simulated respectively by the LDF and diffuse wave model. © 2008 American Institute of Chemical Engineers Environ Prog, 2008
Tumor progression of culture‐adapted human embryonic stem cells during long‐term culture
Authors: Yang Sheng , Lin Ge , Tan Yue‐Qiu , Zhou Di , Deng Lei‐Yu , Cheng De‐Hua , Luo Shu‐Wei , Liu Tian‐Cheng , Zhou Xiao‐Ying , Sun Zheng , Xiang Yang , Chen Tian‐Ji , Wen Ji‐Fang , Lu Guang‐Xiu
Published: May 2008

Human embryonic stem cells (hESCs) during long‐term culture acquire chromosomal changes similar to those occurring in tumorigenesis. This was raised concerns about the progression from hESCs to malignant cells. This study aimed to investigate the changes in chromosomes, cell phenotype, and genes in culture‐adapted hESCs to ascertain whether tumorigenic transformation occurred. By cytogenetic analysis we found progressive karyotypic changes from simple to complex in chHES‐3, one of the hESC lines established in our laboratory, during a long‐term suboptimal culture. We further compared chHES‐3 cells at different karyotypic stages in cell surface markers, in vivo differentiation, cell cycle, apoptosis, and gene expression profiles. We found that the karyotypically aberrant chHES‐3 had higher S‐phase fraction in cell cycle distributions and antiapoptosis ability. In vivo differentiation of karyotypically normal chHES‐3 resulted in relatively mature teratoma, whereas karyotypically aberrant chHES‐3 formed immature teratoma (grade III), in which more primary neural epithelium was revealed by pathological analysis. The microarray analysis and real‐time PCR results showed that some oncogenes were upregulated in karyotypically aberrant chHES‐3 cells, whereas the genes related to differentiation were downregulated, and that Wnt signal pathway was activated. In conclusion, chHES‐3 cells underwent deregulation of self‐renewal and dysfunction of related genes in long‐term culture adaptation, leading to malignant transformation. © 2008 Wiley‐Liss, Inc.
Preliminary results of ultrasonic snow depth sensor testing for National Weather Service (NWS) snow measurements in the US
Authors: Ryan Wendy A. , Doesken Nolan J. , Fassnacht Steven R.
Published: May 2008

During the 2006–2007 winter season, 17 sites across the US including Alaska tested an automated snow measurement system. This article aims to describe successes and failures of this system and provide insight into data collected this season. The system was designed in collaboration with both Environment Canada and Snow Sensor Study participants during the summer of 2006. This system included three Campbell Scientific SR‐50 sensors oriented 120° from one another and a temperature probe centred in the plot. Data collection efforts were successful with minimal amounts of data missing because of system or sensor failures. The system integrated automated retrieval of data from dataloggers, as well as automated file transfer protocol (FTP) to the study website for data archival and graphical display.

Overall, the sensors and installation worked well with only a few problems noted. The sensors compared well with both manual observations taken adjacent to each sensor as well as traditional total snow depth (TSD) on ground measurements. The comparison to depths, taken adjacent to the sensors, allows for investigation of frost heave and indicates periods where the sensors were not functioning properly. The comparison to TSD on ground reveal problems with siting at some locations that are recommended to be remedied by re‐installation or re‐location of those sites prior to the 2007–2008 snow season. These results are preliminary and research will be ongoing for signal processing, snowfall algorithm development and optimal installation in preparation for the 2007–2008 snow season. This research has potential to return important snow observations to national weather service(NWS) observing networks that were discontinued when automation began as well as provide continuous snowpack monitoring to data users. Copyright © 2008 John Wiley & Sons, Ltd.
Cancer of the mouth and pharynx, occupation and exposure to chemical agents in Finland [in 1971–95]
Authors: Tarvainen Laura , Kyyrönen Pentti , Kauppinen Timo , Pukkala Eero
Published: May 2008

The objective of this article was to find associations between cancer of the mouth and pharynx, occupation and chemical exposure. A cohort of Finns born between 1906 and 1945 was followed‐up for 46.8 (21.5 in males and 25.3 in females) million person‐years during 1971–95. Incident cases of cancer of the mouth and pharynx (n = 2,708) were identified in a record linkage with the Finnish Cancer Registry. The Census occupations in 1970 were converted to chemical exposures with a job‐exposure matrix (FINJEM). Cumulative exposure (CE) was calculated as the product of prevalence, level and duration of the exposure. Standardized incidence ratio (SIR) was calculated for each of the 393 occupations, and for CE categories of the 43 chemical agents, using total Finnish population as reference. Relative risks (RR) comparing various CE‐categories with unexposed ones were defined for selected agents by Poisson regression analysis. Elevated SIRs were observed among lawyers, authors, journalists, performing artists, musicians, electronics and telefitters, painters (building), building hands, dockers, unskilled labourers and hotel porters in males and private secretaries, dressmakers, shoemakers and cobblers, waiters, pursers and stewardesses in females. The multivariate analyses showed high RRs for high exposure to aliphatic and alicyclic hydrocarbons, pesticides and alcohol. In conclusion, occupations with high SIRs were mostly the ones with high consumption of alcohol. Exposure to solvents and possibly to pesticides, engine exhaust, textile dust and leather dust may increase the risk of cancer of mouth and pharynx. © 2008 Wiley‐Liss, Inc.
Dairy products, polymorphisms in the vitamin D receptor gene and colorectal adenoma recurrence
Authors: Hubner Richard A. , Muir Kenneth R. , Liu Jo‐Fen , Logan Richard F.A. , Grainge Matthew J. , Houlston Richard S. ,   and Members of the UKCAP Consortium
Published: May 2008

Vitamin D receptor (VDR) activation inhibits proliferation and angiogenesis in the colorectal epithelium, and inhibits metastasis of colorectal tumors. Polymorphisms in the VDR gene alter receptor cellular levels and functioning, and may confer altered susceptibility to colorectal neoplasia. We aimed to investigate the influence of VDR polymorphisms and dietary factors impacting on vitamin D metabolism on colorectal adenoma (CRA) recurrence. Data on dietary intakes of calcium, vitamin D and dairy products were collected from 853 participants in the United Kingdom Colorectal Adenoma Prevention trial, a randomized trial of aspirin and folate for CRA recurrence prevention. The VDR Cdx2, FokI, BsmI, ApaI and TaqI polymorphisms were genotyped in 546 participants with available DNA, and gene–diet interaction analyses performed in 480. Dairy product intake was inversely related to CRA recurrence risk independent of calcium and vitamin D [relative risk (RR) = 0.64; 95% confidence intervals (CIs): 0.47–0.88, for subjects in the highest compared to lowest intake tertile, ptrend = 0.005]. Milk accounted for 60% of dairy product intake, and on analysis of milk and nonmilk dairy products separately recurrence risk in individuals in the highest tertile of milk intake was half that of lowest tertile individuals (RR = 0.52; 95% CI: 0.38–0.72, ptrend = 3.2 × 10−5), whereas nonmilk dairy products did not influence recurrence. VDR polymorphism genotypes and haplotypes did not directly alter recurrence risk, but the reduction in risk associated with high dairy product intake was confined to individuals with ApaI aA/AA genotype (pinteraction = 0.02). These findings indicate dairy products, and in particular milk, have chemopreventive activity against CRA recurrence. © 2008 Wiley‐Liss, Inc.
Downregulation of osteopontin contributes to metastasis suppression by breast cancer metastasis suppressor 1
Authors: Hedley Benjamin D. , Welch Danny R. , Allan Alison L. , Al‐Katib Waleed , Dales David W. , Postenka Carl O. , Casey Graham , MacDonald Ian C. , Chambers Ann F.
Published: May 2008

Breast cancer metastasis suppressor 1 (BRMS1) inhibits the ability of multiple human and murine cancer cell lines to metastasize to lymph nodes, bones and lungs. Comparison of mRNA expression in metastatic MDA‐MB‐435 human carcinoma cells (435) and metastasis‐suppressed BRMS1 transfectants (435/BRMS1) showed a marked (>90%) reduction of osteopontin (OPN) mRNA and protein expression in BRMS1‐overexpressing cells. OPN expression is associated with disease progression in patients, with higher levels of OPN produced by cancer cells associated with poorer patient survival. Furthermore, OPN has been suggested to promote survival of cancer cells in response to stress, although the mechanisms by which this may occur remain poorly understood. This study tested the hypothesis that re‐expression of OPN in metastasis‐suppressed 435/BRMS1 cells would reverse metastasis suppression and confer protection from stress‐induced apoptosis. A stable pooled population of OPN overexpressing 435/BRMS1 cells was created (435/BRMS1/OPN). OPN re‐expression did not affect in vitro cell growth rates; however, increased anchorage independent growth/survival and protection from hypoxia‐induced apoptosis was observed (p < 0.05). In vivo, OPN re‐expression in BRMS1 transfected cells did not affect in vivo primary tumor growth but did increase the incidence of spontaneous metastasis to lymph nodes and lungs in mice. These novel findings suggest that OPN downregulation by BRMS1 may be responsible, at least in part, for BRMS1‐mediated metastasis suppression by sensitizing cancer cells to stress induced apoptosis. These studies clarify one mechanism by which BRMS1 can suppress metastasis. © 2008 Wiley‐Liss, Inc.
Reduced tumor growth in a mouse model of schizophrenia, lacking the dopamine transporter
Authors: Asada Masanori , Ebihara Satoru , Numachi Yohtaro , Okazaki Tatsuma , Yamanda Shinsuke , Ikeda Kazutaka , Yasuda Hiroyasu , Sora Ichiro , Arai Hiroyuki
Published: May 2008

The incidence of cancer in patients with schizophrenia has been reported to be lower that in the general population. On the other hand, it is well established that patients with schizophrenia have a hyper‐dopaminergic system and dopamine has the ability to inhibit tumor angiogenesis. Therefore, in order to investigate the molecular mechanisms responsible for the lower cancer risk in schizophrenic patients, we used a mouse model of schizophrenia, which shows hyper‐dopaminergic transmission in the nerve terminals of dopaminergic neurons. Here, we hypothesized that tumor growth was reduced in a mouse model of schizophrenia, lacking the dopamine transporter (DAT), and investigated tumor growth and angiogenesis in DAT knockout mice. The subcutaneous tumor in mice inoculated with cancer cells was smaller in DAT−/− mice than in the wild type (p < 0.05); however, the level of plasma dopamine in DAT−/− mice was lower than that of control littermates. Using human umbilical vascular endothelial cells (HUVEC), we examined dopamine signaling through dopamine D1 receptor (D1R) and D2R. Dopamine stimulation slightly decreased the surface expression of vascular endothelial growth factor receptor‐2 (VEGF‐R2) but induced the phosphorylation of VEGF‐R2 through Src in HUVEC. In addition, DAT−/− mice had less D1R. Both pharmacological and genetic interruption of D1R showed inhibited tumor growth. These results suggest that modulation of the dopaminergic system may contribute to cancer therapy. © 2008 Wiley‐Liss, Inc.
Nm23‐H1 modulates the activity of the guanine exchange factor Dbl‐1
Authors: Murakami Masanao , Meneses Patricio I. , Knight Jason S. , Lan Ke , Kaul Rajeev , Verma Subhash C. , Robertson Erle S.
Published: May 2008

Cytoskeleton rearrangement is necessary for tumor invasion and metastasis. Cellular molecules whose role is to regulate components of the cytoskeletal structure can dictate changes in cellular morphology. One of these molecules is the suppressor of tumor metastasis Nm23‐H1. The level of Nm23‐H1 expression has been linked to the invasiveness and metastatic potential of human cancers including melanoma and breast cancer. In this report, we demonstrate an interaction between the suppressor of tumor metastasis Nm23‐H1, and Dbl‐1, an oncoprotein which is associated with guanine exchange and belongs to a family of Guanine Exchange Factors (GEF). Nm23‐H1 also was shown to bind pDbl which is the proto‐oncoprotein of Dbl. Interestingly, the interaction between Nm23‐H1 and Dbl‐1 rescues the suppression of the cell motility activity Nm23‐H1. Moreover, this interaction results in loss of the ability of the Dbl‐1 oncoprotein to function as a GEF for the critical Rho‐GTPase family member Cdc42. The loss of GTP loading onto Cdc42 resulted in a dramatic reduction in adhesion stimulated ruffles and suggests that Nm23‐H1 can negatively regulate cell migration and tumor metastasis by modulating the activity of Cdc42 through direct interaction with Dbl‐1. © 2008 Wiley‐Liss, Inc.
Flow‐induced shear stresses increase the number of cell–cell contacts within extracellular matrix
Authors: Kong Qingjun , Vazquez Maribel
Published: May 2008

The formation of cell–cell contacts within extracellular matrix (ECM) is essential to maintain tissue homeostasis and metabolism, as well as critical toward the cell–ECM mechanotransduction that can affect intracellular organization and intercellular communication to enable cell response to external stimuli. This work illustrates the effects of shear stresses on cell–cell contacts within pre‐stressed collagen ECM that were loaded in two separate conditions of constant flow (CF) and constant elution time (CET). The numbers of cell–cell contacts and cytoplasmic processes in both media and 3D ECM gels were analyzed in order to examine the shear effects of different magnitudes and time periods on 3D cell–ECM formation. The sheared collagen ECM microstructures were imaged and studied via scanning electron microscopy (SEM) to illustrate greater distances between constituent cells when larger shear stresses were applied. And the gap junction Connexin 43 expressed between networked cells that were sheared in short time period using CF loading exhibited more than those using CET loading. Notably, the number of cell–cell contacts increased when larger shear stresses were applied, suggesting these stresses may be used to increase intercellular communication within 3D matrixes. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Alginate/poly (lactic‐co‐glycolic acid)/calcium phosphate cement scaffold with oriented pore structure for bone tissue engineering
Authors: Qi Xiaopeng , Ye Jiandong , Wang Yingjun
Published: May 2008

In this study, the alginate/calcium phosphate cement (CPC) scaffolds with oriented pore structure were fabricated by unidirectional freeze casting and poly (lactic‐co‐glycolic acid) (PLGA) was used to infiltrate into the macropores to strengthen the scaffolds. By modifying the liquid to powder ratio, the porosity and pore size of the alginate/CPC scaffold could be controlled. At the liquid to powder (L/P) ratio of 3.25, scaffolds possessing open directional macropores and a total porosity of 89.24% could be achieved. The size of the tubule‐like macropores could reach 100–200 μm in their radial dimension and more than 1000 μm in the axial one, with macropores well‐regulated arrayed. Increasing the L/P ratio would significantly decrease the mechanical strength of alginate/CPC scaffolds. The compressive strength and toughness of scaffolds could be greatly improved via PLGA reinforcement. Three mechanisms of PLGA reinforcement ran as follows: participating in the external load, strengthening the matrix, and patching the defects of CPC pores wall. Alginate/PLGA/CPC scaffold preserved the open directional macropores and might be a potential scaffold for bone tissue engineering. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Cohesive properties of CeN and LaN from first principles
Authors: Voloshina Elena , Paulus Beate
Published: May 2008

The effect of electron‐correlation on the ground‐state properties of CeN and LaN is studied by ab initio quantum‐chemical methods. The approach which is used combines two separate steps: (1) the ground‐state Hartree‐Fock calculations for the crystal; (2) application of the method of increments to the studied system, which allows an expansion of bulk properties using the information from quantum‐chemical calculations performed for finite clusters. As can be expected, for CeN correlation plays a significant role: with Hartree‐Fock method only 49% of the experimental cohesive energy has been recovered, whereas after correlation corrections (coupled‐cluster approach) the ground‐state properties were found to be in good agreement with the experimental data found in literature. Thus, we obtained about 90% of the expected cohesive energy; the computed lattice constants and bulk moduli also agree well with the experimental values. For comparison, the equivalent treatment has been performed for LaN, where no f orbital is occupied. There the HF contribution to the ground‐state properties is larger and hence the correlation effects weaker. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
Improved pKa prediction: Combining empirical and semimicroscopic methods
Authors: Kieseritzky Gernot , Knapp E. W.
Published: May 2008

Using three different methods we tried to compute 171 experimentally known pKa values of ionizable residues from 15 different proteins and compared the accuracies of computed pKa values in terms of the root mean square deviation (RMSD) from experiment. One method is based on a continuum electrostatic model of the protein including conformational flexibility (KBPLUS). The others are empirical approaches with PROPKA deploying physically motivated energy terms with adjustable parameters and PKAcal using an empirical function with no physical basis. PROPKA reproduced the pKa values with highest overall accuracy. Differentiating the data set into weakly and strongly shifted experimental pKa values, however, we found that PROPKA's accuracy is better if the pKa values are weakly shifted but on equal footing with that of KBPLUS for more strongly shifted values. On the other hand, PKAcal reproduces strongly shifted pKa values badly but weakly shifted values with the same accuracy as PROPKA. We tested different consensus approaches combining data from all three methods to find a general procedure for most accurate pKa predictions. In most of the cases we found that the consensus approach reproduced experimental data with better accuracy than any of the individual methods alone. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008
Prolonged gene silencing in hepatoma cells and primary hepatocytes after small interfering RNA delivery with biodegradable poly(β‐amino esters)
Authors: Vandenbroucke Roosmarijn E. , De Geest Bruno G. , Bonné Stefan , Vinken Mathieu , Van Haecke Tamara , Heimberg Harry , Wagner Ernst , Rogiers Vera , De Smedt Stefaan C. , Demeester Joseph , Sanders Niek N.
Published: May 2008

Background

Small interfering (si)RNA mediated inhibition of oncogenes or viral genes may offer great opportunities for the treatment of several diseases such as hepatocellular carcinoma and viral hepatitis. However, the development of siRNAs as therapeutic agents strongly depends on the availability of safe and effective intracellular delivery systems. Poly(β‐amino esters) (PbAEs) are, in contrast to many other cationic polymers evaluated in siRNA delivery, biodegradable into smaller, nontoxic molecules.

Methods and Results

We show for the first time that PbAE : siRNA complexes, containing 1,4‐butanediol (PbAE1) or 1,6‐hexanediol (PbAE2) diacrylate‐based polymers, induced efficient gene silencing in both hepatoma cells and primary hepatocytes without causing significant cytotoxicity. Furthermore, carriers that slowly release the siRNA into the cytoplasm and hence induce a prolonged gene silencing are of major clinical interest, especially in fast dividing tumour cells. Therefore, we also studied the duration of gene silencing in the hepatoma cells and found that it was maintained for at least 5 days after siRNA delivery with PbAE2, the polymer with the slowest degradation kinetics.

Conclusions

From the time‐dependent cellular distribution of these PbAE : siRNA complexes, we suggest that the slowly degrading PbAE2 causes a sustained endosomal release of siRNA during a much longer period than PbAE1. This may support the hypothesis that the endosomal release mechanism of PbAE : siRNA complexes is based on an increase of osmotic pressure in the endosomal vesicles after polymer hydrolysis. In conclusion, our results show that both PbAEs, and especially PbAE2, open up new perspectives for the development of efficient biodegradable siRNA carriers suitable for clinical applications. Copyright © 2008 John Wiley & Sons, Ltd.
The chemical oxidative polymerization of aniline in water: Raman spectroscopy
Authors: Ćirić‐Marjanović Gordana , Trchová Miroslava , Stejskal Jaroslav
Published: May 2008

The structural changes of aniline oligomers and polyaniline, associated with oxidation of aniline with ammonium peroxydisulfate in aqueous solutions without any added acid, were studied. The reaction was quenched at various times and the films deposited on silicon windows have been studied in detail by Raman spectroscopy, at excitation wavelengths 633 and 514 nm. The presence of substituted phenazine structural units, in addition to ordinary benzenoid, quinonoid, and semiquinonoid structures, has been proved by the appearance of characteristic Raman bands at 1645–1630, 1420–1400, 1380–1365, ∼575, and ∼415 cm−1. The remarkable differences of the Raman spectra of oligoanilines, precipitated in the first phase of oxidative polymerization, and polyaniline nanotubes and nanorods, formed in the second stage of reaction, are discussed. Copyright © 2008 John Wiley & Sons, Ltd.
Parahydrogen induced polarization of barbituric acid derivatives: 1H hyperpolarization studies
Authors: Roth Meike , Bargon Joachim , Spiess Hans Wolfgang , Koch Achim
Published: May 2008

Homogeneous hydrogenation of barbituric acid derivatives with parahydrogen yields a substantial increase of the 1H NMR signals of the reaction products. These physiologically relevant compounds were hydrogenated at both ambient and elevated temperatures and pressures using a standard cationic rhodium catalyst. The resulting nonthermal nuclear spin polarization (hyperpolarization) is limited by the spin–lattice relaxation time T1 of the corresponding nuclei in the products, being shorter than the time constant of the hydrogenation. The signal‐to‐noise ratio of the NMR spectra could be further increased upon signal averaging the antiphase PHIP signals of 25 successive scans following 30° pulse experiments and a delay of 10 s. Copyright © 2008 John Wiley & Sons, Ltd.
Microbial transformation of the diterpene mulin‐11,13‐dien‐20‐oic acid by Mucor plumbeus
Authors: Areche Carlos , Loyola Luis A. , Borquez Jorge , Rovirosa Juana , San‐Martin Aurelio
Published: May 2008

Two new mulinane‐type derivatives: 16‐hydroxy mulin‐11,13‐dien‐20‐oic (2) acid and 7α,16‐dihydroxy mulin‐11,13‐dien‐20‐oic (3) acid were obtained by microbial transformation of mulin‐11,13‐dien‐20‐oic acid (1), along with tyrosol (4) using liquid cultures of Mucor plumbeus. The latter compound has not been previously identified in the genus Mucor. Structural elucidation of these metabolites was achieved using 1D‐ and 2D‐NMR spectroscopy. Copyright © 2008 John Wiley & Sons, Ltd.
Synthesis and NMR spectral assignments of novel nitrogen and sulfur heterocyclic compounds
Authors: Chandrashekhar N. , Thomas Bejoy , Gayathri V. , Ramanathan K. V. , Gowda N. M. Nanje
Published: May 2008

Synthesis and NMR spectral studies of multidentate N and S heterocycles, 1,3,5‐tris(N‐methylbenzimidazolyl)benzene, 1,3,5‐tris(benzimidazolyl)benzene,1,3,5‐tris(benzothiazolyl) benzene, 2,2′‐bipyridine 3,3′‐bis(benzothiazolyl)benzene and 1,2,4,5‐tetrakis(benzothiazolyl) benzene have been carried out. 2D 1H1H PFG‐COSY as well as 1H13C single and multiple bond correlated (2D GRASP‐HSQC and GRASP‐HMBC) experiments have been employed to characterize the compounds. 1D NOE experiments have been useful in understanding the structure of 1,3,5‐tris(N‐methylenzimidazolyl)benzene. Copyright © 2008 John Wiley & Sons, Ltd.
Macrophage physiological function after superparamagnetic iron oxide labeling
Authors: Hsiao Jong‐Kai , Chu Hung‐Hao , Wang Yu‐Hsiu , Lai Chih‐Wei , Chou Pi‐Tai , Hsieh Sung‐Tsang , Wang Jaw‐Lin , Liu Hon‐Man
Published: May 2008

Our goal was to analyze the changes in morphology and physiological function (phagocytosis, migratory capabilities, humoral and cellular response, and nitric oxide secretion) of murine macrophages after labeling with a clinically used superparamagnetic iron oxide (SPIO), ferucarbotran. In SPIO‐treated macrophages, nanoparticles were taken up in the cytoplasm and accumulated in a membrane‐bound organelle. Macrophage proliferation and viability were not modified after SPIO labeling. Phagocytic function decreased after labeling with only 10 µg Fe/mL SPIO, whereas other functions including migration and production of tumor necrosis factor‐α and nitric oxide increased at the highest SPIO concentration (100 µg Fe/mL). Copyright © 2008 John Wiley & Sons, Ltd.
Enabling novel premium service classes in DiffServ over MPLS‐enabled network
Authors: Alshaer Hamada , Elmirghani Jaafar M. H.
Published: May 2008

Network resources dimensioning and traffic engineering influence the quality in provisioned services required by the Expedited Forwarding (EF) traffic in production networks established through DiffServ over MPLS‐enabled network. By modeling EF traffic flows and the excess of network resources reserved for it, we derive the range of delay values which are required to support these flows at DiffServ nodes. This enables us to develop an end‐to‐end (e2e) delay budget‐partitioning mechanism and traffic‐engineering techniques within a framework for supporting new premium QoS levels, which are differentiated based on e2e delay, jitter and loss. This framework enables ingress routers to control EF traffic flow admission and select appropriate routing paths, with the goal of EF traffic balancing, avoiding traffic congestion and getting the most use out of the available network resources through traffic engineering. As a result, this framework should enable Internet service providers to provide three performance levels of EF service class to their customers provided that their network is DiffServ MPLS TE aware. Copyright © 2008 John Wiley & Sons, Ltd.
Intercalation degree in PP/organoclay nanocomposites: role of surfactant structure
Authors: Bellucci Federica , Terenzi Andrea , Leuteritz Andreas , Pospiech Doris , Frache Alberto , Traverso Giuliano , Camino Giovanni
Published: May 2008

The formation of exfoliated polymer–clay nanocomposites depends upon several factors such as the nature of the polymer, the nature of the clay, as well as the type, packing density, and size of the organic modifier on the silicate layers. The main aim of this work was focused on the role of the chemical structure of the organic modifier on the intercalation properties of the organo‐modified clay into non‐polar polymer matrices such as a polypropylene homopolymer. To achieve this purpose organo‐montmorillonites containing different loadings of organic modifier with increasing molar volume were prepared and used to produce PP based nanocomposites. Morphology studies performed on the composites pointed out that two distinct aspects have to be considered for organic modification of the clays: the interlayer distance and the degree of the inorganic surface coverage, which are the main driving forces for the intercalation process. It was found that an intercalated structure was reached when either a large non‐polar molecule, which ensures an optimal interlayer distance with a partial surface coverage or a mixture of small and large molecules leading to a slightly lower interlayer distance but to a higher surface coverage degree was used. Moreover, rheological, mechanical, and thermal studies indicated that the degree of dispersion and interaction between clay platelets and the polymer chains strongly depended on the interlayer spacing and clay surface coverage. Copyright © 2008 John Wiley & Sons, Ltd.
Linear pentablock quintopolymers (l‐SIDMV) with five incompatible blocks: Polystyrene, polyisoprene‐1,4, poly(dimethylsiloxane), poly(tert‐butyl methacrylate), and poly(2‐vinylpyridine)
Authors: Fragouli Panagiota , Iatrou Hermis , Lohse David J. , Hadjichristidis Nikos
Published: May 2008

Three linear pentablock quintopolymers (l‐SIDMV), where S is polystyrene (PS), I polyisoprene‐1,4 (PI), D poly(dimethylsiloxane) (PDMS), M poly(tert‐butyl methacrylate) (PtBuM), and V poly(2‐vinylpyridine) (P2VP), were synthesized by anionic polymerization high vacuum techniques. The approach involves the following: (a) The synthesis of living triblock terpolymer PS‐b‐PI‐b‐PDMSLi and diblock copolymer P2VP‐b‐PtBuMK by sequential polymerizations of the corresponding monomers with sec‐BuLi and benzyl potassium, respectively; and (b) The selective linking of the living triblock terpolymer with the chlorosilane group of 2‐(chloromethylphenyl)ethyldimethylchlorosilane (CMPDMS), followed by linking of the living block copolymer with the remaining chloromethyl group of CMPDMS. Molecular characterization carried out by size exclusion chromatography, membrane osmometry, solution (in CDCl3 or d8‐toluene) and solid‐state 1H‐NMR spectroscopy indicated a high degree of molecular and compositional homogeneity. Differential scanning calorimetry results on the precursors and final polymers were discussed. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3938–3946, 2008
Synthesis and properties of sulfonated multiblock copoly(ether sulfone)s by a chain extender
Authors: Nakabayashi Kazuhiro , Matsumoto Kazuya , Ueda Mitsuru
Published: May 2008

A new series of sulfonated multiblock copoly(ether sulfone)s applicable to proton exchange membrane fuel cells was synthesized. The multiblock copolymers were synthesized by the nucleophilic aromatic substitution of hydroxyl‐terminated oligomers in the presence of highly reactive decafluorobiphenyl (DFB) as a chain extender. Because of the high reactivity of DFB, the ether–ether interchange reaction, which could lead to a randomized polymer architecture, was prevented, and multiblock copolymers with high molecular weights were easily produced. The multiblock copolymers gave tough, flexible, and transparent membranes by solution casting. The ion exchange capacity values could be easily controlled by changing the sulfonated block ratios in the copolymers. The resulting membranes demonstrated good oxidative and dimensional stability and significantly higher proton conductivity than sulfonated random poly(ether sulfone) copolymers. The morphologies of the membranes were investigated by tapping mode atomic force microscopy, which showed that the multiblock membranes had a clear hydrophilic/hydrophobic separated structure. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3947–3957, 2008
End‐group modification of poly(2,6‐dimethyl‐1,4‐phenylene ether) and in situ synthesis of poly(2,6‐dimethyl‐1,4‐phenylene ether)‐b‐poly(ethylene terephthalate) block copolymer
Authors: Jéol Stéphane , Fenouillot Françoise , Rousseau Alain , Monnet Christiane , Masenelli‐Varlot Karine , Briois Jean‐François
Published: May 2008

The preparation of poly(2,6‐dimethyl‐1,4‐phenylene ether)‐b‐poly(ethylene terephthalate) block copolymer was performed by the reaction of the 2‐hydroxyethyl modified poly(2,6‐dimethyl‐1,4‐phenylene ether) (PPE‐EtOH) with poly(ethylene terephthalate) (PET) by an in situ process, during the synthesis of the polyester. The yield of the reaction of the 2‐hydroxyethyl functionalized PPE‐EtOH with PET was close to 100%. A significant proportion of the PET‐b‐PPE‐EtOH block copolymer was found to have short PET block. Nevertheless, the copolymer structured in the shape of micelles (20 nm diameter) and very small domains with 50–200 nm diameter, whereas unmodified PPE formed much larger domains (1.5 μm) containing copolymer. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3985–3991, 2008
Synthesis of porphyrin‐embedded dendronized polymers by Suzuki polycondensation
Authors: Fei Zhuping , Han Yang , Bo Zhishan
Published: May 2008

Porphyrin‐embedded high molecular weight dendronized polymers up to fourth generation have been synthesized by Suzuki polycondensation of Fréchet‐type dendritic dibromo macromonomers and porphyrin diboronic pinacol ester. Higher generation lateral dendritic wedges not only endow the dendronized polymers with good solubility in commonly used organic solvents, but also prevent planar porphyrins and conjugated polymer backbones from aggregating by their “site isolation” effect. This type of porphyrin‐embedded dendronized polymers can be used as saturated red light‐emitting materials. With the increase of the generation of the lateral dendrons, the quantum yields of the dendronized polymers also gradually increased. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4030–4037, 2008
Computational evidence for the catalytic mechanism of glutaminyl cyclase. A DFT investigation
Authors: Calvaresi Matteo , Garavelli Marco , Bottoni Andrea
Published: May 2008

The results of a DFT theoretical investigation on the catalytic mechanism of the QC enzyme are presented. A rather large model‐system is used. It includes the most important residues that are believed to play a key‐role in the catalysis. The computational results show that the rate‐determining step of the catalytic process is not the nucleophilic attack leading to the cycle formation (a very easy and fast process with a negligible barrier of 0.8 kcal mol−1), but a proton transfer, which is assisted by the Glu201 residue acting as a proton shuttle (general base and general acid). A complex network of hydrogen bonds (involving Asp248 and other residues) contribute to lower the activation barrier for the proton shift which affords the formation of an ammonia molecule bonded to the substrate. The ammonia molecule is a good leaving group which is easily expelled from the substrate in the last step of the catalytic cycle, but remains anchored to the enzyme as a ligand of the zinc cation. The metal plays a key‐role in assisting the nucleophilic attack (electrostatic catalysis) since it polarizes the substrate γ‐amide carbonyl group (its electrophilic character increases). Also, the strength of the nucleophilic nitrogen (substrate α‐amino group) is enhanced by hydrogen bonds involving the Glu201 residue. The computations outline the important role of Trp329 in helping the substrate binding process and stabilizing the cyclization transition state. Proteins, 2008. © 2008 Wiley‐Liss, Inc.