bluuebunny/crossref_metadata_2025 huggingface dataset:
Non‐Innocent Behaviour of Imido Ligands in the Reactions of Silanes with Half‐Sandwich Imido Complexes of Nb and V: A Silane/Imido Coupling Route to Compounds with Nonclassical SiH Interactions
Authors: Ignatov Stanislav K. , Rees Nicholas H. , Merkoulov Alexei A. , Dubberley Stuart R. , Razuvaev Alexei G. , Mountford Philip , Nikonov Georgii I.
Published: September 2007

Reactions of imido complexes [M(Cp)(NR′)(PR′′3)2] (M=V, Nb) with silanes afford a plethora of products, depending on the nature of the metal, substitution at silicon and nitrogen and the steric properties of the phosphine. The main products are [M(Cp)(NR′)(PR3)(H)(SiRnCl3−n)] (M=V, Nb; R′=2,6‐diisopropylphenyl (Ar), 2,6‐dimethylphenyl (Ar′)), [Nb(Cp)(NR′)(PR′′3)(H)(SiPhR2)] (R2=MeH, H2), [Nb(Cp)(NR′)(PR′′3)(Cl)(SiHRnCl2−n)] and [Nb(Cp)(η3‐N(R)SiR2H⋅⋅⋅)(PR′′3)(Cl)]. Complexes with the smaller Ar′ substituent at nitrogen react faster, as do more acidic silanes. Bulkier groups at silicon and phosphorus slow down the reaction substantially. Kinetic NMR experiments supported by DFT calculations reveal an associative mechanism going via an intermediate N‐silane adduct [Nb(Cp){N(→SiHClR2)R′}(PR′′3)2] bearing a penta‐coordinate silicon centre, which then rearranges into the final products through a SiH or SiCl bond activation process. DFT calculations show that this imido‐silane adduct is additionally stabilized by a SiH⋅⋅⋅M agostic interaction. SiH activation is kinetically preferred even when SiCl activation affords thermodynamically more stable products. The niobium complexes [NbCp(NAr)(PMe3)(H)(SiR2Cl)] (R=Ph, Cl) are classical according to X‐ray studies, but DFT calculations suggest the presence of interligand hypervalent interactions (IHI) in the model complex [Nb(Cp) (NMe)(PMe3)(H)(SiMe2Cl)]. The extent of SiH activation in the β‐SiH⋅⋅⋅M agostic complexes [Cp{η3‐N(R′)SiR2H⋅⋅⋅}M(PR′′3)(Cl)] (R′′=PMe3, PMe2Ph) primarily depends on the identity of the ligand trans to the SiH bond. A trans phosphine leads to a stronger SiH bond, manifested by a larger J(SiH) coupling constant. The SiH activation diminishes slightly when a less basic phosphine is employed, consistent with decreased back‐donation from the metal.
Expression of receptor tyrosine kinases and apoptotic molecules in rhabdomyosarcoma
Authors: Armistead Paul M. , Salganick Jason , Roh Jae S. , Steinert Dejka M. , Patel Shreyaskumar , Munsell Mark , El‐Naggar Adel K. , Benjamin Robert S. , Zhang Wei , Trent Jonathan C.
Published: September 2007

BACKGROUND.

Rhabdomyosarcoma (RMS) is a rare mesenchymal tumor with few treatment options after the failure of first‐line therapy. Understanding the expression of kinases and apoptotic molecules in RMS tumors may lead to elucidation of mechanisms of resistance to chemotherapy and development of new therapies.

METHODS.

Paraffin‐embedded tissue samples were collected from 105 RMS patients treated at the M. D. Anderson Cancer Center and examined for the immunohistochemical expression of kinases and apoptotic molecules deemed potential therapeutic targets. Clinicopathologic information was collected on all patients and analyzed for correlation with overall survival (OS).

RESULTS.

Of the 105 patients, 44 (42%) were female and 89 (85%) were older than 10 years of age. The 5‐year OS for this cohort was 24.7%, with inferior median OS in patients with genitourinary primary tumors and those with invasion through the deep fascial plane. Immunohistochemistry revealed Kit and c‐erb‐b2 to be present on < 10% of tumors but EGFR, PDGFR‐α, PDGFR‐β, Bcl‐2, and Bax were present in > 40% of tumors. Patients whose tumors expressed PDGFR‐α were found to have a shorter median OS by multivariate analysis (26 vs 266 months,P= .076). Conversely, patients whose tumors expressed Bax were found to have a longer OS (31 vs 19 months,P= .047).

CONCLUSIONS.

EGFR, PDGFR‐α, PDGFR‐β, Bcl‐2, and Bax are frequently expressed in human RMS tissue and may represent new therapeutic targets. Absence of PDGFR‐α and the presence of Bax are associated with a longer median OS in patients with RMS. Targeting these molecules may be a successful therapeutic strategy. Cancer 2007. © 2007 American Cancer Society.
Obesity and hypertension among children after treatment for acute lymphoblastic leukemia
Authors: Chow Eric J. , Pihoker Catherine , Hunt Kathryn , Wilkinson Karen , Friedman Debra L.
Published: September 2007

BACKGROUND.

The purpose was to determine the prevalence and treatment‐related risk factors for obesity and hypertension among childhood acute lymphoblastic leukemia (ALL) survivors treated with contemporary therapy.

METHODS.

In a single‐center longitudinal study, serial body mass indices (BMI) and blood pressure (BP) measurements of children ages 2–20 at time of ALL diagnosis and enrolled on pediatric cooperative group trials from 1993–2003 were abstracted from medical records and converted to population‐referenced z‐scores.

RESULTS.

Among 165 study participants, BMI z‐scores increased significantly between diagnosis (median age 4.8 years) and therapy completion. At the end of therapy, 17.0% of survivors were overweight (BMI of 25–29, or 85–94% for age), 21.2% were obese (BMI ≥30, or ≥95% for age), and 15.3% had BP meeting stage 1+ hypertension thresholds (systolic or diastolic BP ≥140/90 mm Hg, or 95% for age and height plus 5 mm Hg). These proportions were found to be unchanged 2‐3 years later. In multivariate analysis, the highest level of corticosteroid exposure was associated with both obesity (odds ratio [OR] 6.0; 95% confidence interval [95% CI], 1.2–28.5) as well as stage 1+ hypertension (OR 2.4; 95% CI, 1.2–5.1) compared with the lowest level. Females also were more likely to have increased BMI and elevated BP compared with males. Treatment intensity and cranial radiotherapy were not found to be associated with BMI or BP changes.

CONCLUSIONS.

Despite reductions in the use of cranial radiotherapy, contemporary childhood survivors of ALL remain at an increased risk of obesity and hypertension at least several years after the completion of treatment, with those exposed to higher doses of corticosteroids at greater risk. Cancer 2007. © 2007 American Cancer Society.
Positron emission tomography imaging in nonsmall‐cell lung cancer
Authors: Erasmus Jeremy J. , Macapinlac Homer A. , Swisher Stephen G.
Published: September 2007

Positron emission tomography (PET) using 18F‐2‐deoxy‐D‐glucose, a D‐glucose analog labeled with fluorine‐18, complements conventional radiologic assessment in the evaluation of patients with nonsmall‐cell lung cancer (NSCLC). PET is being routinely used to improve the detection of nodal and extrathoracic metastases. PET is also currently being evaluated in the assessment of prognosis and therapeutic response and by potentially allowing an earlier assessment of response may prove invaluable in the oncologic management of patients. The article discusses the diagnosis, staging, and assessment of treatment response and prognosis with an emphasis on the appropriate clinical use of PET in management. Cancer 2007. © 2007 American Cancer Society.
DQ‐based simulation of weakly nonlinear heat conduction processes
Authors: Tomasiello S.
Published: September 2007

In this paper, an explicit form for the numerical solution of problems in the space–time domain by using quadrature rules is proposed. The compact form of the shape functions recently proposed by the author is useful to the scope. Numerical solutions for the time‐dependent one‐dimensional nonlinear heat conduction problem are calculated by means of the iterative differential quadrature method, a method proposed by the author and based on quadrature rules. The accuracy of the solution and stability analysis show good performance of the approach. Copyright © 2007 John Wiley & Sons, Ltd.
Electrochemically Induced Growth of Zinc Oxide
Authors: Palms Dennis , Norwig Jochen , Wegner Gerhard
Published: September 2007

The electrolytically induced precipitation of zinc oxide from zinc nitrate solution on gold surfaces in the presence of water‐soluble polymers was examined for reaction times between 0.5 and 600 seconds. Regardless of the additive, polycrystalline films of zinc oxide have formed after 30 seconds, but polymeric additives dramatically change the morphology of the ZnO films. Amperometric analysis and fitting the diffusion reduced the current density‐time curve according to Avrami kinetics and it reveals that polymers bearing methacrylic acid groups result in spherical growth whereas such with sulfonic acid groups lead to a platelike growth of crystallites. Without additive prisms grow predominantly in one dimension. These findings are confirmed also by scanning electron microscopy (SEM) and X‐ray diffraction (XRD) analysis.
Inhibitory effects and target genes of bone morphogenetic protein 6 in Jurkat TAg cells
Authors: Sivertsen Einar A. , Huse Kanutte , Hystad Marit E. , Kersten Christian , Smeland Erlend B. , Myklebust June H.
Published: September 2007

Bone morphogenetic proteins (BMP) are multifunctional cytokines that belong to the TGF‐β superfamily. BMP have been shown to regulate haematopoietic stem cells, B lymphopoiesis and early thymocyte differentiation. In the present study we explored the role of BMP‐6 in Jurkat TAg cells. BMP‐6 rapidly induced phosphorylation of Smad1/5/8, p38 and ERK1/2, followed by a potent up‐regulation of ID1, ID2 and ID3. ID1 and ID3 were also induced at the protein level. Genome‐wide expression profiling of cells treated with BMP‐6 compared to medium confirmed that ID1–ID3 were target genes of BMP‐6 together with Noggin and Smad6. Furthermore, several genes involved in transcriptional regulation were also identified, including NFKBIA, HEY1, DLX2, KLF10 and early growth response 1. Stimulation with BMP‐6 exerted an antiproliferative effect that was counteracted by inhibitor of DNA binding (Id)1 siRNA, indicating that Id1 is an important downstream mediator in Jurkat TAg cells. A subset of CD4+ T cells were found to express the BMP receptors Alk‐2 and Alk‐3 (type I), in addition to BMPRII (type II). BMP‐6 also induced phosphorylation of Smad1/5/8, followed by transcriptional increase in ID1–ID3 mRNA expression. However, we did not observe significant changes in Id protein expression in CD4+ T cells. Altogether, the data indicate a role for BMP‐6 in human T lineage cells.
Immune modulation of human dendritic cells by complement
Authors: Castellano Giuseppe , Woltman Andrea M. , Schlagwein Nicole , Xu Wei , Schena Francesco P. , Daha Mohamed R. , van Kooten Cees
Published: September 2007

Deficiency in complement proteins such as C1q is associated with the development of systemic lupus erythematosus (SLE). Here, we show that the differentiation of dendritic cells (DC) in the presence of C1q (C1qDC) gives rise to CD1a+/DC‐SIGN+ cells with high phagocytic capacity and low expression of CD80, CD83 and CD86. Further, when C1qDC were exposed to LPS, a significant reduction in the production of IL‐6, TNF‐α and IL‐10 occurred with a limited up‐regulation of CD80, CD83 and CD86. In addition, C1qDC were less responsive to activation by CD40L in terms of IL‐12p70 secretion and CD86 expression. C1qDC showed an impaired ability to stimulate alloreactive T cells, with a reduced production of IFN‐γ. In conclusion, we have shown that C1q is a potent modulator of DC, resulting in cells characterized by an impaired capacity of cytokine production and an impaired up‐regulation of costimulatory molecules, leading to a limited T cell response. Therefore, we hypothesize that, next to a pivotal role in the safe clearance of apoptotic cells, C1q regulates the threshold of DC activation and thereby prevents hyperactivation of the overall immune response.
Calcium dependence of T cell proliferation following focal stimulation
Authors: Schwarz Eva C. , Kummerow Carsten , Wenning Anna S. , Wagner Kerstin , Sappok Anne , Waggershauser Katherina , Griesemer Désirée , Strauß Bettina , Wolfs Melodie‐Jo , Quintana Ariel , Hoth Markus
Published: September 2007

Clonal T cell expansion through proliferation is a central process of the adaptive immune response. Apoptosis of activated T cells is required to avoid chronic inflammation. T cell proliferation and apoptosis are often analyzed with stimuli that do not induce formation of a functional immunological synapse. Here we analyze the Ca2+ dependence of proliferation and apoptosis in primary human CD4+ T cells following stimulation with anti‐CD3/anti‐CD28‐coated beads, which induce a tight interaction similar to the immunological synapse. We found this focal stimulation to be much more efficient for stimulating IL‐2 production and proliferation than non‐focal TCR stimuli. Surprising little Ca2+ entry through Ca2+ channels was required for T cell proliferation. Transient free intracellular calcium concentration ([Ca2+]i) elevations of up to 220 nM from a baseline level of around 40 nM were sufficient for maximal proliferation in primary human CD4+ T cells. We also show that proliferation was very Ca2+ sensitive in the range 90–120 nM, whereas apoptosis was basically constant for [Ca2+]i levels of 90–120 nM. We conclude that very small changes in [Ca2+]i can dramatically change the ratio between proliferation and apoptosis, thus keeping the balance between overshooting and inefficient immune responses.
Specific TLR ligands regulate APRIL secretion by dendritic cells in a PKR‐dependent manner
Authors: Hardenberg Gijs , Planelles Lourdes , Schwarte Carla M. , van Bostelen Liesbeth , Le Huong Tran , Hahne Michael , Medema Jan Paul
Published: September 2007

A proliferation inducing ligand (APRIL) and B cell activating factor belonging to the TNF family (BAFF/BLyS) have been implicated in IgA class switch recombination in thymus‐independent (TI) B cell responses. Dendritic cells (DC) are thought to regulate Ig class switching in TI B cell responses by providing B cells with cytokines, including APRIL and BAFF. We therefore set out to analyze the regulation of APRIL and BAFF expression by human monocyte‐derived DC (moDC). We observed that moDC produce and secrete APRIL, but could not detect expression of BAFF. Importantly, stimulation with the Toll‐like receptor ligands CpG and poly I:C specifically induced APRIL production, while other Toll‐like receptor ligands were ineffective. The increase in APRIL was dependent on translation, but surprisingly not transcription. Instead, enhanced APRIL production and secretion resulted from activation of protein kinase receptor (PKR), as it was completely inhibited by the specific inhibitor of PKR, 2‐aminopurine. This suggests that the specific induction of APRIL by CpG and poly I:C, and the signal integration by PKR, are regulated by translational modification and hint at a role for APRIL in the TI B cell response to viral infections.
Functional role of phosphatidylcholine‐specific phospholipase C in regulating CD16 membrane expression in natural killer cells
Authors: Cecchetti Serena , Spadaro Francesca , Lugini Luana , Podo Franca , Ramoni Carlo
Published: September 2007

CD16, the low‐affinity FcIgG receptor (FcγRIIIA), is predominantly expressed in human NK cells. Our recent findings indicate that CD16 expression on the outer membrane surface of NK cells is correlated with the membrane expression of phosphatidylcholine‐specific phospholipase C (PC‐PLC). In the present study we analyzed the trafficking of CD16 from the plasma membrane to cytoplasmic regions, after stimulation with specific mAb. The CD16 receptor is internalized, likely degraded and newly synthesized; its endocytosis is independent of ATP, but requires an integral and functional actin cytoskeleton. Antibody‐mediated CD16 cross‐linking results in an approximately twofold increase in PC‐PLC enzymatic activity within 10 min. Analysis of PC‐PLC and CD16 distribution in NK cell plasma membrane demonstrates that the proteins are physically associated and partially accumulated in lipid rafts. Pre‐incubation of NK cells with a PC‐PLC inhibitor, D609, causes a dramatic decrease both in CD16 receptor and PC‐PLC enzyme expression on the plasma membrane. Interestingly, among phenotype PBL markers, only CD16 is strongly down‐modulated by D609 treatment. CD16‐mediated cytotoxicity is also reduced after D609 incubation. Taken together, these data suggest that the PC‐PLC enzyme could play an important role in regulating CD16 membrane expression, the CD16‐mediated cytolytic mechanism and CD16‐triggered signal transduction.
Endoglycosidase treatment abrogates IgG arthritogenicity: Importance of IgG glycosylation in arthritis
Authors: Nandakumar Kutty Selva , Collin Mattias , Olsén Arne , Nimmerjahn Falk , Blom Anna M. , Ravetch Jeffrey V. , Holmdahl Rikard
Published: September 2007

The glycosylation status of IgG has been implicated in the pathology of rheumatoid arthritis. Earlier, we reported the identification of a novel secreted endo‐β‐N‐acetylglucosaminidase (EndoS), secreted by Streptococcus pyogenes that specifically hydrolyzes the β‐1,4‐di‐N‐acetylchitobiose core of the asparagine‐linked glycan of human IgG. Here, we analyzed the arthritogenicity of EndoS‐treated collagen type II (CII)‐specific mouse mAb in vivo. Endoglycosidase treatment of the antibodies inhibited the induction of arthritis in (BALB/c × B10.Q) F1 mice and induced a milder arthritis in B10.RIII mice as compared with the severe arthritis induced by non‐treated antibodies. Furthermore, EndoS treatment did not affect the binding of IgG to CII and their ability to activate complement, but it resulted in reduced IgG binding to FcγR and disturbed the formation of stable immune complexes. Hence, the asparagine‐linked glycan on IgG plays a crucial role in the development of arthritis.
Programmed cell death 1 (PD‐1) and its ligand PD‐L1 are required for allograft tolerance
Authors: Wang Liqing , Han Rongxiang , Hancock Wayne W.
Published: September 2007

Programmed cell death‐1 (PD‐1, CD279) and its widely expressed, inducible ligand, PD‐L1 (CD274), together dampen T cell activation, but whether they are essential for allograft tolerance is unknown. We show, using gene‐deficient mice and blocking mAbs in wild‐type mice, that costimulation blockade is ineffectual in PD‐1–/– or PD‐L1–/– allograft recipients, or in wild‐type allograft recipients treated with anti‐PD‐1 or anti‐PD‐L1 mAb. Alloreactive PD‐1–/– CD4 and CD8 T cells had enhanced proliferation and cytokine production compared to wild‐type controls, and anergy could not be induced in PD‐1‐deficient CD4 T cells. We conclude that without inhibitory signals from PD‐1 ligation, alloantigen‐induced T cell proliferation and expansion cannot be regulated by costimulation blockade, and peripheral tolerance induction cannot occur.
Cover Picture: TLR agonists induce the differentiation of human bone marrow CD34+ progenitors into CD11c+ CD80/86+ DC capable of inducing a Th1‐type response – Eur. J. Immunol. 10/2007
Authors: Sioud Mouldy , Fløisand Yngvar
Published: September 2007

It has recently been shown that TLR are capable of regulating the differentiation of haematopoietic progenitor cells. Specifically, R848 (resquimod, a specific TLR7/8 agonist) is capable of stimulating the differentiation of human bone marrow CD34+ progenitors into myeloid DC. Sioud and Fløisand (pp. 2834–2846) investigate the differentiation induced by other TLR agonists (loxoribine (TLR7) and Pam3CSK4 (TLR2)), as well as further investigating the effects of R848. The cover image (a composite, artificially coloured figure) is based on May‐Grünwald‐Giesma staining of the CD11c– CD14– (green section of the image), CD11c+ CD14+ (yellow section) and CD11c+ CD14– (red section) cell subsets induced following stimulation of CD34+ progenitors with R848 for seven days. Importantly, around 30% of cells of the CD11c+ CD14– subset display DC morphology (multiple fine dendrites) and, furthermore, this CD11c+ CD14– subset is shown to be capable of activating allogeneic T cells.
[Bis(catechol)salen]MnIII Coordination Polymers as Support‐Free Heterogeneous Asymmetric Catalysts for Epoxidation
Authors: Cho So‐Hye , Gadzikwa Tendai , Afshari Mitra , Nguyen SonBinh T. , Hupp Joseph T.
Published: September 2007

The formation of coordination polymers by the reaction of [bis(catechol)salen]MnIII with several di‐ and trivalent metal ions is reported. These polymers are insoluble in a wide range of organic solvents and water but can be dissolved upon addition of excess pyrocatechol. They function as enantioselective heterogeneous epoxidation catalysts and exhibit catalytic activity comparable to that of the homogeneous[bis(catechol)salen]MnIII building block alone when used for the enantioselective epoxidation of 2,2‐dimethyl‐2H‐chromene. After catalysis, catalyst isolation from the reaction mixture can be readily achieved by centrifugation and decantation. Under practical oxidant concentrations, the catalyst can be recycled up to ten times with little loss of activity and no loss of enantioselectivity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Substitution, Addition, and Recombination Reactions of Precursor Complexes with Ferrocenyl Carboxylate Units
Authors: Wang Xia , Li Linke , Hou Hongwei , Wu Jie , Fan Yaoting
Published: September 2007

With the use of sodium β‐ferrocenylacrylate and sodium p‐ferrocenylbenzoate as functional ligands, we synthesized mononuclear precursor complexes containing facile leaving groups or coordinatively unsaturated metal ions: [Cd(η2‐OOCCH=CHFc)2(C2H5OH)2] (1), {[Cd(η2‐OOCC6H4Fc)2(dmf)2(H2O)]} (2), {[Cd(η2‐OOCC6H4Fc)2 (phen)(H2O)](CH3OH)} (3), and {[Zn(OOCC6H4Fc)2(phen)](H2O)} (4) (phen = 1,10‐phenanthroline). Investigation of the fourprecursor ferrocenyl carboxylate complexes as building blocks resulted in ten complexes. The complexes{[Cd(η2‐OOCCH=CHFc)2(bbbm)](H2O)}n (1a), {[Cd2(η2‐OOCCH=CHFc)4 (pbbm)2](CH3OH)6(H2O)4} (1b), {[Cd(η2‐OOCC6H4Fc)2(py)3] (CH3OH)4} (2a), {[Cd2(η2‐OOCC6H4Fc)4(btx)2](thf)3(CH3OH)2} (2b), {[Cd2(η2‐OOCC6H4Fc)2(OOCC6H4Fc)2(phen)2(bbbm)] (CH3OH)4(thf)2} (3a), and [Zn(OOCC6H4Fc)2(phen)(H2O)] (4a) were obtained by the substitution or addition reactions of the precursor complexes under moderate conditions. As anticipated, the structural integrity of the precursor complexes can be maintained from the precursors to these complexes. We designed the structures of the complexes by controlling the number of leaving groups in the precursor complexes. In addition, a recombination may have taken place in the reactions of the precursor complexes with organic ligands under severe conditions. The “recombinant” complexes {[Cd2(η2‐OOCCH=CHFc)2(μ2‐η2‐OOCCH=CHFc)2(L)2](CH3OH)4}n [L = 1,4‐bis(imidazol‐1‐ylmethyl)benzene (bix), 1c; L = btx, 1d], {[Cd(η2‐OOCC6H4Fc)2(pbbm)(H2O)](H2O)}n (3b) and {[Zn(OOCC6H4Fc)2(bbbm)](CH3OH)3}n (4b) were also obtained under reflux conditions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Pressure‐assisted field‐amplified sample injection with reverse migrating micelles for analyzing trace steroids in MEKC
Authors: Fang Huaifang , Yang Fangxing , Sun Junling , Zeng Zhaorui , Xu Ying
Published: September 2007

This paper describes a novel method that applies pressure‐assisted field‐amplified sample injection with reverse migrating micelles (PA‐FASI‐RMM) for the online concentration of neutral analytes in MEKC with a low‐pH BGE. After injection of a plug of water into the separation capillary, negative voltage and positive pressure were simultaneously applied to initialize PA‐FASI‐RMM injection. The hydrodynamic flow generated by the positive pressure compensated the reverse EOF in the water plug and allowed the water plug to remain in the capillary during FASI with reverse migrating micelles (FASI‐RMM) to obtain a much longer injection time than usual, which improved stacking efficiency greatly. Equations describing this injection mode were introduced and were supported by experimental results. For a 450‐s online PA‐FASI‐RMM injection, three orders of magnitude sample enhancement in terms of peak area could be observed for the steroids and an achievement of detection limits was between 1 and 10 ng/mL.
Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust
Authors: Hashimoto Akiko H. , Amanuma Kimiko , Hiyoshi Kyoko , Sugawara Yoshiki , Goto Sataro , Yanagisawa Rie , Takano Hirohisa , Masumura Ken‐ichi , Nohmi Takehiko , Aoki Yasunobu
Published: September 2007

Diesel exhaust (DE) is a major airborne pollutant of urban areas. It contains various polycyclic aromatic hydrocarbons (PAH) and nitrated PAHs. In this study, gpt delta mice were treated with inhalation of 1 or 3 mg m−3 DE, or a single intratracheal instillation of diesel exhaust particles (DEP) or DEP extract. In the lungs of mice treated with inhalation of 3 mg m−3 DE for 12 weeks, the mutant frequency (MF) was 3.2‐fold higher than that of the control group (1.90 × 10−5 and 0.59 × 10−5, respectively). An instillation of DEP and DEP extract resulted in a significant dose‐dependent linear increase in MF. In mice treated with 0.5 mg DEP and 0.2 mg DEP extract, the MFs were 3.0‐ and 2.7‐fold higher than that of the control group, respectively. The mutagenic potency (MF mg−1) of DEP extract (5.6 × 10−5) was double that of DEP (2.7 × 10−5), suggesting that the mutagenicity of the latter is derived primarily from compounds in the extract, which itself is responsible for ca. 50% of the weight of DEP. G:C→A:T transitions were the predominant gpt mutation induced by all three treatments and G:C→T:A transversions were induced by DEP and DEP extract. Guanine bases centered in nucleotide sequences such as GGA, TGA, CGG, and CGT were the major mutation targets of all three treatments. Thus, our results suggest that the mutagens contained in DEP such as PAH and nitrated PAHs induce mutations and may be responsible for carcinogenesis caused by inhalation of DE. Environ. Mol. Mutagen., 2007. © 2007 Wiley‐Liss, Inc.
Enhanced mutagenesis of Salmonella tester strains due to deletion of genes other than uvrB
Authors: Swartz Carol D. , Parks Nick , Umbach David M. , Ward William O. , Schaaper Roel M. , DeMarini David M.
Published: September 2007

The standard Salmonella mutagenicity (Ames) tester strains are missing 15–119 genes due to the extended Δ(gal‐bio‐uvrB) mutations that render the strains excision‐repair deficient (ΔuvrB). We constructed strains of Salmonella that are homologous to tester strains TA98 and TA100 except that in place of the uvrB deletion, they contain single‐gene defects in either uvrB, moaA, moeA, or both uvrB and moeA. We then tested the following mutagens in these strains: 2‐acetylaminofluorene, Glu‐P‐1, 4‐aminobiphenyl, benzo[a]pyrene, MX, 1‐nitropyrene, 6‐hydroxylaminopurine (HAP), and 2‐amino‐6‐hydroxylaminopurine (AHAP). We confirmed in Salmonella a previous finding in Escherichia coli that the enhanced mutagenicity of the purine analogues HAP and AHAP is not due to the deletion of the uvrB gene but due to the deletion of moeA and/or moaA, which are involved in molybdenum cofactor biosynthesis. The spontaneous mutant frequency and induced mutagenic potency of mutagens due to the extended ΔuvrB mutation are due largely to the deletion of uvrB and to some extent of moeA/moaA at the frameshift hisD3052 allele of TA98 but involve other genes in addition to uvrB and moeA/moaA at the base‐substitution hisG46 allele of TA100. The extended ΔuvrB mutation does not prevent the detection of mutagens that would have been detected in a strain containing a single uvrB defect. Because of the deletion of moeA/moaA, the extended uvrB deletion generally enhanced spontaneous and induced mutagenicity, especially at the base‐substitution allele. This enhanced sensitivity may underlay the severe health effects in humans who have mutations in molybdenum cofactor biosynthesis genes. Environ. Mol. Mutagen., 2007. © 2007 Wiley‐Liss, Inc.
Different behavior of SCE‐eliciting lesions induced by low and high doses of busulfan
Authors: Morales‐Ramírez Pedro , González‐Beltrán Francisco
Published: September 2007

Our previous studies suggested a dose‐dependent transition in the types of DNA lesions induced by busulfan, as measured using the comet assay and by micronuclei analyses. The aim of the present study was to investigate the dose‐dependent induction of different sister‐chromatid exchange‐eliciting lesions; lesions were distinguished by their efficiency in producing sister‐chromatid exchange (SCE), and by their reparability during G1. Synchronously dividing murine salivary gland cells were assayed in vivo. Groups of mice were intraperitoneally injected with either 30 or 80 μmol busulfan/kg body weight solution at early or late G1. The rate of SCE/μmol busulfan/kg body weight obtained by exposure at late G1 with the high dose was twice that of the low dose. SCE induction during early G1 was higher than at late G1 with both doses; only the low‐dose response was statistically significant. The frequency distribution of SCEs per cell demonstrated that cells exposed at the late G1 phase showed typical profiles that closely fit a Gaussian curve. However, an irregular profile was obtained for cells treated during early G1, which showed some cells with high‐SCE frequency. Cells treated in early G1 have more time to repair lesions before DNA synthesis; therefore, the results suggest that instead of repair, secondary SCE‐eliciting lesions during G1 were produced, especially at the lower dose. The results obtained in this study indicate that there are dose‐dependent differences in the types of SCE‐eliciting lesions induced by busulfan. Environ. Mol. Mutagen., 2007. © 2007 Wiley‐Liss, Inc.
Collocated finite volume schemes for the simulation of natural convective flows on unstructured meshes
Authors: Chénier Eric , Eymard Robert , Herbin Raphaèle , Touazi Ouardia
Published: September 2007

We describe here a collocated finite volume scheme that was recently developed for the numerical simulation of the incompressible Navier–Stokes equations on unstructured meshes, in two or three space dimensions. We recall its convergence in the case of the linear Stokes equations, and we prove a convergence theorem for the case of the Navier–Stokes equations under the Boussinesq hypothesis. We then present several numerical studies. A comparison between a cluster‐type stabilization technique and the more classical Brezzi–Pitkäranta method is performed, the numerical convergence properties are presented on both analytical solutions and benchmark problems, and the scheme is finally applied to the study of the natural convection between two eccentric cylinders. Copyright © 2007 John Wiley & Sons, Ltd.
Parameter estimation for a three‐dimensional numerical barotropic tidal model with adjoint method
Authors: Zhang Jicai , Lu Xianqing
Published: September 2007

The parameters of a three‐dimensional (3‐D) barotropic tidal model are estimated using the adjoint method. The mode splitting technique is employed in both forward and adjoint models. In the external mode, the alternating direction implicit method is used to discretize the two‐dimensional depth‐averaged equations and a semi‐implicit scheme is used for the 3‐D internal mode computations. In this model the bottom friction is expressed in terms of bottom velocity which is different from the previous works. Besides, the bottom friction coefficients (BFCs) are supposed to be spatially varying, i.e. the BFC at some grid points are selected as the independent BFC, while the BFC at the other grid points can be obtained through linear interpolation with these independent BFCs. On the basis of the simulation of M2 tide in the Bohai and North Yellow Seas (BNYS), twin experiments are carried out to invert the prescribed distributions of model parameters. The parameters inverted are the
Fourier coefficients of open boundary conditions (OBCs), the BFC and the vertical eddy viscosity profiles. In these twin experiments, the real topography of BNYS is installed. The ‘observations’ are produced by the tidal model and recorded at the position of TOPEX/Poseidon altimeter data, tidal gauge data and current data. The experiments discuss the influence of initial guesses, model errors and data number. The inversion has obtained satisfactory results and the prescribed distributions have been successfully inverted. The results indicate that the inversion of BFC is more sensitive to data error than that of OBC and the vertical eddy viscosity profiles. Copyright © 2007 John Wiley & Sons, Ltd.
Influence of macromer molecular weight and chemistry on poly(β‐amino ester) network properties and initial cell interactions
Authors: Brey Darren M. , Erickson Isaac , Burdick Jason A.
Published: September 2007

A library of photocrosslinkable poly(β‐amino ester)s (PBAEs) was recently synthesized to expand the number of degradable polymers that can be screened and developed for a variety of biological applications. In this work, the influence of variations in macromer chemistry and macromer molecular weight (MMW) on network reaction behavior, overall bulk properties, and cell interactions were investigated. The MMW was controlled through alterations in the initial diacrylate to amine ratio (≥1) during synthesis and decreased with an increase in this ratio. Lower MMWs reacted more quickly and to higher double bond conversions than higher MMWs, potentially due to the higher concentration of reactive groups. Additionally, the lower MMWs led to networks with higher compressive and tensile moduli that degraded slower than networks formed from higher MMWs because of an increase in the crosslinking density and decrease in the number of degradable units per crosslink. The adhesion and spreading of osteoblast‐like cells on polymer films was found to be dependent on both the macromer chemistry and the MMW. In general, the number of cells was similar on networks formed from a range of MMWs, but the spreading was dramatically influenced by MMW (higher spreading with lower MMWs). These results illustrate further diversity in photocrosslinkable PBAE properties and that the chemistry and macromer structure must be carefully selected for the desired application. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Biodegradable microparticles and fiber fabrics for sustained delivery of cisplatin to treat C6 glioma in vitro
Authors: Xie Jingwei , Tan Ruo Shan , Wang Chi‐Hwa
Published: September 2007

The duration of cisplatin release from most of the drug delivery devices seemed to be shorter than 14 days except large microparticles. The objective of this study was to fabricate and characterize cisplatin‐loaded PLA microparticles, PLA/PLGA (30/70) composite microparticles, and fibers as formulations for long‐term sustained delivery of cisplatin to treat C6 glioma in vitro by electrospray and electrospinning techniques. Cisplatin‐loaded biodegradable microparticles with particle size of around 5 μm and fiber fabrics with diameter of 0.5–1.7 μm were obtained using electrospray and electrospinning techniques. Encapsulation efficiency and in vitro release of formulations were measured by ICP‐OES. The encapsulation efficiency for different samples of microparticles was approximately from 33% to 72% and the fiber fabrics had encapsulation efficiency greater than 90%. Cisplatin‐loaded microparticles showed typical characteristics of cisplatin release profile: a large initial burst followed by a sustained slow release of 35 days. The composite PLA/PLGA (30/70) microparticles could reduce the initial burst release of cisplatin because of their core–shell structures. In contrast, more than 75 days sustained release could be achieved by fiber fabric formulations without large initial burst. MTT assay was used to quantify the cytotoxicity of different formulations against C6 glioma cells. Microparticle formulations had slightly higher cytotoxicity than free drug. In contrast, the cytotoxicity of fiber fabrics formulation was around 4 times higher than of the free drug based on the actual amount of drug released. The microparticle and fiber fabric formulations presented may be promising for the sustained delivery of cisplatin to eliminate the undesired side effects caused by direct injection of cisplatin solution in systemic administration. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate)/poly(ϵ‐caprolactone) blends for tissue engineering applications in the form of hollow fibers
Authors: Chiono Valeria , Ciardelli Gianluca , Vozzi Giovanni , Sotgiu Maria Giulia , Vinci Bruna , Domenici Claudio , Giusti Paolo
Published: September 2007

In this work, hollow fibers to be used as guides for tissue engineering applications were produced by dry‐jet‐wet spinning of poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate)/poly(ϵ‐caprolactone) (PHBHV/PCL) solutions in chloroform with various weight ratios between the components (PHBHV/PCL 100/0; 80/20; 60/40; 50/50; 40/60; 20/80; 0/100 w/w). Fibers obtained from PHBHV/PCL blends had a low degree of surface and bulk porosity, depending on composition. Physicochemical characterization involving scanning electron microscopy and differential scanning calorimetry (DSC) showed that PHBHV/PCL blends are compatible. Interactions between blend components were studied by Fourier transform infrared total reflectance spectroscopy, DSC analysis, and polarized optical microscopy analysis. Homogeneity of blend composition was assessed by IR‐chemical imaging analysis. PHBHV/PCL samples were found to be weakly hydrophilic and their biocompatibility was proved by in vitro tests using mouse fibroblasts. Mechanical properties of PHBHV/PCL blends were investigated by stress–strain tests, showing an increasing ductility of blend samples with increasing PCL amount. Hollow fibers supported fibroblasts attachment and proliferation depending on composition and porosity degree. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Enhanced nerve regeneration through a bilayered chitosan tube: The effect of introduction of glycine spacer into the CYIGSR sequence
Authors: Wang Wei , Itoh Soichiro , Matsuda Atsushi , Aizawa Tomoyasu , Demura Makoto , Ichinose Shizuko , Shinomiya Kenichi , Tanaka Junzo
Published: September 2007

We have developed a novel bilayered chitosan tube that comprises an outer layer of chitosan film and an inner layer of chitosan nonwoven nano/microfiber mesh. The tube is fabricated with an electrospinning method. We characterized the microstructure and mechanical properties of this material. We introduced glycine spacers into the CYIGSR sequence, domain of laminin‐1 that enhances Schwann cells migration and attachment, as well as neural outgrowth, resulting in the amino acid sequences CGGYIGSR and CGGGGGGYIGSR. These peptides were covalently bound to the nano/microfiber mesh surface of the chitosan tube to examine the effects of peptide mobility on nerve regeneration. Scaffolds constructed from these bilayered chitosan tubes were grafted to bridge injured sciatic nerve. Isografting was performed as a control. These scaffolds were removed 5 and 10 weeks after implantation for histological analysis. Nerve regeneration into chitosan tubes, on which the CGGGGGGYIGSR peptide was immobilized, exhibited efficacy similar to that of the isograft and represent a promising candidate for promoting peripheral nerve repair. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Bone regeneration using a naturally grown HA/TCP carrier loaded with rh BMP‐2 is independent of barrier‐membrane effects
Authors: Schopper C. , Moser D. , Spassova E. , Goriwoda W. , Lagogiannis G. , Hoering B. , Ewers R. , Redl H.
Published: September 2007

The present study investigated whether bone regeneration and biomaterial replacement would be improved by loading of biogenous biphasic biomaterial scaffolds (HA/TCP ratio 30/70) with rhBMP‐2, and whether the placement of three barrier membranes differing in structure and porosity (prototyped SLA Ti specimens, GORE RESOLUT Adapt specimens, and titanized TiMESH light specimens) would have a synergistic effect. A rabbit calvarial model was used for the implantation studies. Histological specimens were obtained after 12 weeks and evaluated quantitatively for differences between the various material combinations. Loading of the biomaterials with rhBMP‐2 significantly enhanced the amount of regenerated bone and caused a pronounced biomaterial replacement. While BMP‐induced bone had formed uniformly over the surgical defects, bone regeneration in the absence of BMP depends on bone promotion from the margins of the defects toward the center. No positive effect on bone regeneration was seen for any of the placed barrier membranes. While the present study had shown that rhBMP‐2 loading significantly increases bone regeneration using the investigated biomaterial, barrier‐membrane placement may be useful in predetermining the final shape of the regenerative site but provides no additional beneficial impact on the amount and quality of the bone regeneration induced by rhBMP‐2. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Synthesis of partial‐stabilized cement (PSC) via sol–gel process
Authors: Wang Wen‐Hsi , Lee Yuan‐Ling , Lin Chun‐Pin , Lin Feng‐Huei
Published: September 2007

The traditional method of preparing partial‐stabilized cement (PSC), which is a kind of calcium silicate cement, is through power mixing method. Low reaction efficiency and initial strength limited the application of PSC as a dental root‐end filling material. This study provides a one‐step sol–gel process for the synthesis of PSC. A complexing ligand is used for tuning down the activity of aluminum sec‐butoxide (ASB) in order to avoid possible self‐polymerization. After the modification with complex ligand, there is no residue of reactant observed on the analysis of SDT, and bonding between metal atoms is observed in the FTIR spectrum. Each component of PSC is identified using XRD. The hydration product, which is called portlandite, of sol–gel‐synthesized PSC is observed after 1 day of hydration, and crystallinity of portlandite increases much faster than that of traditional PSC. The initial strength of sol–gel‐synthesized PSC achieves detectable level 24 h earlier than that of traditional PSC; microhardness value of sol–gel‐synthesized PSC at 7th day is 2.98 HV, which is much higher than that of traditional PSC (2.05 HV). PSC is successfully synthesized and the initial strength of PSC is improved by this modified sol–gel process. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
A novel system for water soluble protein encapsulation with high efficiency: “Micelles enhanced” polyelectrolyte capsules
Authors: Li Xiaodong , Li Xiaohui , Zhang Jianxiang , Zhao Shifang , Shen Jiacong
Published: September 2007

Novel “micelles enhanced” polyelectrolyte (PE) capsules based on functional templates of hybrid calcium carbonate were fabricated. Evidences suggested that the structure of capsule wall was different from that of conventional PE capsules, and the wall permeability of these PE capsules changed significantly. Lysozyme, a positively charged protein in neutral solution, was studied as a model protein to be encapsulated into the “micelles enhanced” PE capsules. Confocal laser scanning microscope was used to observe the entrapping process in real time, while UV‐Vis spectroscope and scanning force microscope measurements suggested the high efficiency of encapsulation. In addition, the fluorescence recovery after photobleaching technique was employed to determine the existence form of deposited molecules. Further studies showed even negatively charged water‐soluble peptides or proteins can be encapsulated into these hybrid capsules by modulating the pH value in bulk solution under its isoelectronic point as well. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Nonfouling biomaterials based on polyethylene oxide‐containing amphiphilic triblock copolymers as surface modifying additives: Solid state structure of PEO‐copolymer/polyurethane blends
Authors: Tan J. , Brash J. L.
Published: September 2007

Three novel polyethylene oxide‐containing amphiphilic triblock copolymers (PEO‐PU‐PEO) with PEO MWs 550, 2000, and 5000, were blended with a segmented polyurethane (PU). It was expected that the block copolymers would act as surface modifiers to produce surfaces rich in PEO. The solid state properties of the PEO‐copolymer/PU blends were studied by infrared spectroscopy, differential scanning calorimetry, and tensile stress–strain measurements. Infrared analysis showed no significant hydrogen bonding between the PEO blocks of the copolymers and the PU matrix. Differential scanning calorimetry data indicated that for copolymer content up to 5 wt % the microphase structure of the blends was indistinguishable from that of the unmodified PU matrix; for copolymer content of 10% or greater, the blends showed phase separated structures. Similarly the tensile stress–strain properties of the blends were essentially the same as those of the matrix up to 5 wt % copolymer. At higher copolymer content, however, the tensile strength decreased with increasing content of the copolymers; for a given copolymer content the change in tensile properties increased with increasing PEO MW. The structures of the 20% blends were also investigated after extraction with toluene (copolymers soluble, matrix insoluble). Bulk compositional change upon extraction was determined by nuclear magnetic resonance spectroscopy. Surface compositional change was studied by X‐ray photoelectron spectroscopy and water contact angles. Surface morphology was observed using scanning electron microscopy and atomic force microscopy. It was shown that the copolymers were removed from the blends by extraction and that the extent of removal increased with decreasing MW of the PEO block. After toluene extraction, the blend surfaces showed advancing water contact angle and surface elemental composition similar to those of the PU matrix. However in contrast to the relatively smooth matrix surface, the extracted blend surfaces were “decorated” with lacunae or pits. Consistent with the weight loss trends, the extent of pitting was greater for the copolymers having shorter PEO blocks, suggesting that surface enrichment of the copolymers increased with decreasing MW of the copolymers. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Nonfouling biomaterials based on polyethylene oxide‐containing amphiphilic triblock copolymers as surface modifying additives: Protein adsorption on PEO‐copolymer/polyurethane blends
Authors: Tan J. , McClung W. G. , Brash J. L.
Published: September 2007

Surface modification of a segmented polyurethane was achieved by blending with novel PEO‐containing amphiphilic triblock copolymers (PEO‐polyurethane‐PEO). Three copolymers having different PEO MW (550, 2000, 5000) were used as surface modification additives. The protein resistance of the blend surfaces was evaluated using radiolabeling methods. On the blends of copolymers with PEO blocks of MW 2000 and 5000, fibrinogen adsorption from physiologic buffer decreased with increasing copolymer content up to 20 wt%. On the blends with PEO blocks of MW 550, resistance to adsorption for a given copolymer content was much greater. For all three blend types at 20% copolymer content, reductions in adsorption compared to the unmodified PU matrix were greater than 95%. Reductions in adsorption were similar for the 20% blends and surfaces prepared by coating the copolymers directly on the matrix, suggesting that the 20% blend surfaces were completely covered by copolymer. At low copolymer content (≤10 wt %), fibrinogen adsorption decreased with decreasing PEO block length. This was probably due to increasing surface coverage of the copolymers with decreasing block length. It is therefore concluded that surface density of PEO is more important than PEO MW for the protein resistance of these surfaces. Lysozyme, a much smaller protein, showed adsorption trends similar to fibrinogen. The adsorption of fibrinogen and lysozyme from binary solutions to blends of the copolymer with PEO blocks of 2000 MW was investigated to probe the effects of protein size on adsorption resistance. Fibrinogen and lysozyme showed similar fractional decreases in adsorption relative to the PU matrix independent of the surface density of PEO. However lysozyme was enriched in the surface relative to the solution, that is, it was adsorbed preferentially to fibrinogen. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008