bluuebunny/crossref_metadata_2025 huggingface dataset:
Using a piecewise linear bottom to fit the bed variation in a laterally averaged, z‐co‐ordinate hydrodynamic model
Authors: Chen XinJian
Published: March 2004

In developing a 3D or laterally averaged 2D model for free‐surface flows using the finite difference method, the water depth is generally discretized either with the z‐co‐ordinate (z‐levels) or a transformed co‐ordinate (e.g. the so‐called σ‐co‐ordinate or σ‐levels). In a z‐level model, the water depth is discretized without any transformation, while in a σ‐level model, the water depth is discretized after a so‐called σ‐transformation that converts the water column to a unit, so that the free surface will be 0 (or 1) and the bottom will be ‐1 (or 0) in the stretched co‐ordinate system. Both discretization methods have their own advantages and drawbacks. It is generally not conclusive that one discretization method always works better than the other. The biggest problem for the z‐level model normally stems from the fact that it cannot fit the topography properly, while a σ‐level model does not have this kind of a topography‐fitting problem.

To solve the topography‐fitting problem in a laterally averaged, 2D model using z‐levels, a piecewise linear bottom is proposed in this paper. Since the resulting computational cells are not necessarily rectangular looking at the x–z plane, flux‐based finite difference equations are used in the model to solve the governing equations. In addition to the piecewise linear bottom, the model can also be run with full cells or partial cells (both full cell and partial cell options yield a staircase bottom that does not fit the real bottom topography). Two frictionless wave cases were chosen to evaluate the responses of the model to different treatments of the topography. One wave case is a boundary value problem, while the other is an initial value problem. To verify that the piecewise linear bottom does not cause increased diffusions for areas with steep bottom slopes, a barotropic case in a symmetric triangular basin was tested. The model was also applied to a real estuary using various topography treatments. The model results demonstrate that fitting the topography is important for the initial value problem. For the boundary value problem, topography‐fitting may not be very critical if the vertical spacing is appropriate. Copyright © 2004 John Wiley & Sons, Ltd.
Development and testing of a simple 2D finite volume model of sub‐critical shallow water flow
Authors: Horritt Matthew
Published: March 2004

Many environmental applications of shallow water flow modelling can be characterized as only slowly varying and everywhere sub‐critical. A simplified finite volume model is therefore developed that is capable of describing pertinent shallow water flow processes more efficiently than the usual Godunov/ Riemann characteristics approaches. The model is tested against a number of analytical and numerical solutions to the governing equations. The model reproduces accurately flow round a circular bend, flow over topography, flow up an initially dry beach and floodwave propagation down a meandering river reach, with mass conservative solutions. Copyright © 2004 John Wiley & Sons, Ltd.
Hybrid genetic algorithms and artificial neural networks for complex design optimization in CFD
Authors: Duvigneau R. , Visonneau M.
Published: March 2004

The present paper is devoted to the study of design optimization strategies in the particular framework of complex computational fluid dynamics. Genetic algorithms are chosen as the optimization strategy, thanks to their robustness and flexibility. Two ways are explored to improve the behaviour of genetic algorithms in order to increase the efficiency of the search. First, approximated pre‐evaluations based on artificial neural networks are used to benefit from the knowledge acquired from the problem and to reduce the number of expensive evaluations by the flow solver required at each generation. Then, a hybridization technique is proposed for the final local search, which is performed by a deterministic method. These approaches are validated and applied on two‐ and three‐dimensional problems, involving Reynolds‐averaged Navier–Stokes computations with near‐wall turbulence modeling. Copyright © 2004 John Wiley & Sons, Ltd.
Multigrid simulations of detached shock waves
Authors: Gerlinger P. , Aigner M.
Published: March 2004

The use of multigrid convergence acceleration techniques is investigated for supersonic and hypersonic flows over blunt bodies. In these cases detached shock waves occur that usually complicate convergence for multigrid methods. It is shown that a simple damping of the restricted residual error enables convergence without the application of expensive upwind restriction or prolongation operators. The achieved reduction in CPU time increases with increasing free stream Mach number. A similar technique may be used for reactive flows where the restricted residual error is damped in regions of high chemical activity. A spherical nose projectile moving at Mach 6.46 in a stochiometric hydrogen–air mixture serves as a test case to demonstrate the efficiency of this approach in case of combustion. Copyright© 2004 John Wiley & Sons, Ltd.
Functional consequences of ATM sequence variants for chromosomal radiosensitivity
Authors: Gutiérrez‐Enríquez Sara , Fernet Marie , Dörk Thilo , Bremer Michael , Lauge Anthony , Stoppa‐Lyonnet Dominique , Moullan Norman , Angèle Sandra , Hall Janet
Published: March 2004

The ATM [for ataxia‐telangiectasia (A‐T) mutated] protein plays a key role in the detection and cellular response to DNA double‐strand breaks. Several single‐nucleotide polymorphisms (SNPs) have been described in the ATM gene; however, their association with cancer risk or radiosensitivity remains to be fully established. In this study, the functional consequences of specific ATM SNPs on in vitro radiosensitivity, as assessed by micronuclei (MN) formation, were measured in lymphoblastoid cell lines established from 10 breast cancer (BC) patients carrying different ATM missense SNPs, six A‐T patients, six A‐T heterozygotes (A‐T het), and six normal individuals. The BC, A‐T het, and A‐T cell line groups showed significantly higher mean levels of MN formation after exposure to ionizing radiation (IR) than did the group containing normal cell lines, with similar levels in the BC and A‐T het groups. Within the BC lines studied, the group composed of the six carrying the linked 2572T>C (858F>L) and 3161C>G (1054P>R) variants had a higher level of MN after IR exposure compared to that observed in the remaining four BC or in the normal cell lines. This increase was not related to the constitutive ATM mRNA level, which was similar in these BC and the normal cell lines. Our results indicate that alterations in the ATM gene, including the presence of heterozygous mutations and the 2572C and 3161G variant alleles, are associated with increased in vitro chromosomal radiosensitivity, perhaps by interfering with ATM function in a dominant‐negative manner. © 2004 Wiley‐Liss, Inc.
A fluorescence in situ hybridization study of ETV6‐NTRK3 fusion gene in secretory breast carcinoma
Authors: Makretsov Nikita , He May , Hayes Malcolm , Chia Stephen , Horsman Doug E. , Sorensen Poul H. B. , Huntsman David G.
Published: March 2004

The translocation t(12;15)(p13;q25), in which the ETV6 gene from chromosome 12 is rearranged with the NTRK3 gene from chromosome 15, has recently been identified in secretory breast carcinoma (SBC). This fusion gene was initially described in congenital fibrosarcoma and congenital mesoblastic nephroma. The biological consequence of this translocation is the expression of a chimeric protein tyrosine kinase with potent transforming activity. To assess the frequency of t(12;15)(p13;q25) in breast cancer, we developed complementary probe sets (fusion and split‐apart probes) for the detection of this translocation by fluorescence in situ hybridization (FISH) in paraffin‐embedded, formalin‐fixed tissue sections. We tested four histologically confirmed cases of SBC for the presence of the ETV6‐NTRK3 gene fusion and then applied the FISH assay to tissue microarrays (TMAs) in order to screen 481 cases of formalin‐fixed, paraffin‐embedded invasive breast carcinomas of various histologic subtypes. Three of the four cases of SBC revealed fusion signals. Of the 481 cases in the TMAs, 202 gave signals of sufficient quality for screening by FISH, and only one case showed fusion signals in most or all of the tumor cells. On review of the histology of this case, SBC was confirmed. On the other hand, none of the fusion‐negative breast cancers revealed SBC histology. In all cases, the results from the fusion and split‐apart FISH assays for the ETV6‐NTRK3 fusion genes were concordant. Our data suggest that the ETV6‐NTRK3 fusion gene is a specific genetic alteration in SBC. © 2004 Wiley‐Liss, Inc.
Protective effect of alpha‐tocopherol in head and neck cancer radiation‐induced mucositis: A double‐blind randomized trial
Authors: Ferreira Paulo Renato , Fleck James Freitas , Diehl Ada , Barletta Daniela , Braga‐Filho Aroldo , Barletta Antonio , Ilha Ligia
Published: March 2004

Background.

the study was designed to test whether vitamin E (VE) provides oral mucosal protection in patients with irradiated cancers of the head and neck.

Methods.

Fifty‐four patients with cancer of the oral cavity and oropharynx were randomly assigned to rinse the oral cavity in an oil solution containing either VE or placebo before every conventional fraction of 2 Gy and again 8 to 12 hours later during the 5 to 7 weeks of radiotherapy (RT).

Results.

Thirty‐six events/167 patient‐weeks (21.6%) and 54 events/161 patient‐weeks (33.5%) of symptomatic mucositis were observed in VE and placebo groups, respectively (p= .038). VE reduced the risk by 36%. Subjective data at the end of the treatment revealed that VE decreased pain grades 2 to 3 during RT (3 of 28 patients vs 14 of 26 patients,p= .0001). No significant influence was detected in survival.

Conclusion.

VE decreased the incidence of symptomatic oral radio‐induced mucositis in patients with cancer of the oropharynx and oral cavity. © 2004 Wiley Periodicals, Inc.Head Neck26:XXX–XXX, 2004
Loss of expression of ZAC/LOT1 in squamous cell carcinomas of head and neck
Authors: Koy Susanne , Hauses Martin , Appelt Hella , Friedrich Katrin , Schackert Hans K. , Eckelt Uwe
Published: March 2004

Background.

ZAC/Lot1 is a previously identified candidate tumor suppressor gene. The gene maps to the human chromosome 6q24‐q25, a region frequently deleted in squamous cell carcinomas of the head and neck and other solid tumors.

Methods.

We have used a model of head and neck squamous cell carcinoma (HNSCC) and cell lines to analyze the role of the candidate tumor suppressor gene ZAC/Lot1 in oral carcinogenesis. We analyzed the expression in 11 cell lines, and we performed loss of heterozygosity (LOH)‐ and sequence analyses in 51 primary tumors.

Results.

Three (27.3%) of 11 cell lines showed a distinctly reduced expression of ZAC/Lot1 compared with expression levels of the gene in the normal oral mucosa. In addition, we analyzed 51 primary squamous cell carcinomas of the head and neck for LOH with seven microsatellite markers flanking ZAC/Lot1. We detected an average LOH rate of 31.4% in the region of interest. Sequence analysis revealed no mutations for the ZAC/Lot1 coding exons, including the exon/intron boundaries.

Conclusions.

These data could suggest a minimal role for ZAC/Lot1 in a subgroup of HNSCC tumors. © 2004 Wiley Periodicals, Inc. Head Neck 26: 338–344, 2004
Parathyroid hormone–related peptide as a cause of hypercalcemia in squamous cell carcinoma of the head and neck: A case presentation and subject review
Authors: Brawner J. Travis , Zitsch Robert P.
Published: March 2004

Background.

Serum levels of parathyroid hormone–related peptide (PTHrP) can be elevated with malignancy and cause hypercalcemia, which has been associated with a poor prognosis.

Methods.

We present a case of supraglottic squamous cell carcinoma with elevated serum PTHrP and hypercalcemia. The patient was acutely managed with intravenous fluids, furosemide, and zoledronic acid and then underwent a total laryngectomy and modified radical neck dissection.

Results.

The patient remains disease free and normocalcemic.

Conclusion.

Curative treatment for patients with head and neck cancer should not be withheld solely on the basis of humoral hypecalcemia of malignancy. © 2004 Wiley Periodicals, Inc. Head Neck 26: 382–384, 2004
Different ties for different needs: Recruitment practices of entrepreneurial firms at different developmental phases
Authors: Leung Aegean
Published: March 2004

Entrepreneurial firms face significant challenges in attracting and acquiring needed human resources. That is,
in addition to difficulties associated with resource constraints and organization legitimacy, the requirements for
“person‐organization fit” change substantially as these firms transit from start‐up to
growth phase. This study examines how entrepreneurial firms tap evolving social network ties in order to address
“needs‐and‐fits” issues across different developmental stages of the firm. The findings
go beyond what “strength of weak ties” and “structural hole” theories would suggest, and
highlight the persistent use of strong and direct ties across developmental phases. © 2004
Wiley Periodicals, Inc.
Radiation dose, chemotherapy and risk of soft tissue sarcoma after solid tumours during childhood
Authors: Menu‐Branthomme Axelle , Rubino Carole , Shamsaldin Akhtar , Hawkins Michael M. , Grimaud Emmanuel , Dondon Marie‐Gabrielle , Hardiman Claire , Vassal Gilles , Campbell Sarah , Panis Xavier , Daly‐Schveitzer Nicolas , Lagrange Jean‐Leon , Zucker Jean‐Michel , Chavaudra Jean , Hartman Olivier , de Vathaire Florent
Published: March 2004

Soft tissue sarcoma (STS) is one of the most frequent second primary cancer that occurs during the first 20 years following treatment for a solid cancer in childhood. Our aim was to quantify the risk of STS as a second malignant neoplasm and to investigate its relationship with radiotherapy and chemotherapy. A cohort study of 4,400 3‐year survivors of a first solid cancer diagnosed during childhood in France or the United Kingdom, between 1942 and 1985, was followed 15 years on average. In a partially nested case‐control study, we matched 25 cases of STS and 121 controls for sex, type of first cancer, age at first cancer and duration of follow‐up. Sixteen STS occurred in the cohort, as compared to 0.3 expected from the general population (Standardized Incidence Radio, SIR = 54 (95%CI: 34–89)). The SIR was 113 (95% CI: 62–185) after chemotherapy plus radiotherapy (13 STS), whereas it was 28 (95%CI: 2–125) after chemotherapy alone (1 STS) and 19 (95%CI: 3–60) after radiotherapy alone (2 STS). After adjustment for treatment, there was no evidence of variation in the annual excess of incidence or in the SIR with either age at first cancer or time since 1st cancer. In the case‐control study, the risk of a STS was increased with the square of the dose of radiation to the site of STS development and with the administration of Procarbazine. The increased risk of soft tissue sarcoma that occurred after childhood cancer is independently related to exposure to radiotherapy and Procarbazine. A closer surveillance of children treated with this treatment combination is strongly recommended. © 2004 Wiley‐Liss, Inc.
Identification of five chromosomal regions involved in predisposition to melanoma by genome‐wide scan in the MeLiM swine model
Authors: Geffrotin Claudine , Crechet Françoise , Le Roy Pascale , Le Chalony Catherine , Leplat Jean‐Jacques , Iannuccelli Nathalie , Barbosa Angela , Renard Christine , Gruand Joseph , Milan Denis , Horak Vratislav , Tricaud Yves , Bouet Stéphan , Franck Michel , Frelat Gérard , Vincent‐Naulleau Silvia
Published: March 2004

In human familial melanoma, 3 risk susceptibility genes are already known, CDKN2A, CDK4 and MC1R. However, various observations suggest that other melanoma susceptibility genes have not yet been identified. To search for new susceptibility loci, we used the MeLiM swine as an animal model of hereditary melanoma to perform a genome scan for linkage to melanoma. Founders of the affected MeLiM stock were crossed with each other and with healthy Duroc pigs, generating MeLiM, F1 and backcross families. As we had previously excluded the MeLiM CDKN2A gene, we paid special attention to CDK4 and MC1R, as well as to other candidates such as BRAF and the SLA complex, mapping them on the swine radiation hybrid map and/or isolating close microsatellite markers to introduce them into the genome scan. The results revealed, first, that swine melanoma was inherited as an autosomal dominant trait with incomplete penetrance, preferably in black animals. Second, 4 chromosomal regions potentially involved in melanoma susceptibility were identified on Sus Scrofa chromosomes (SSC) 1, 2, 7 and 8, respectively, in intervals 44–103, 1.9–18, 59–73 and 47–62 cM. A fifth region close to MC1R was revealed on SSC 6 by analyzing an individual marker located at position 7.5 cM. Lastly, CDK4 and BRAF were unlikely to be melanoma susceptibility genes in the MeLiM swine model. The 3 regions on SSC 1, 6 and 7, respectively, have counterparts on human chromosomes (HSA) 9p, 16q and 6p, harboring melanoma candidate loci. The 2 others, on SSC 2 and 8, have counterparts on HSA 11 and 4, which might therefore be of interest for human studies. © 2004 Wiley‐Liss, Inc.
Vaccination with a synthetic nonapeptide expressed in human tumors prevents colorectal cancer liver metastases in syngeneic rats
Authors: Vallebona Paola Sinibaldi , Rasi Guido , Pierimarchi Pasquale , Bernard Paola , Guarino Enrico , Guadagni Fiorella , Garaci Enrico
Published: March 2004

In previous studies, the antigen CSH‐275 (RTNKEASIC) was found expressed in tissue specimens from colorectal cancer but not in normal colonic mucosa. It was also naturally expressed in the DHD‐K12 experimental colorectal cancer in BDIX rats. In this study, we describe the effect of vaccination with the synthetic nonapeptide CSH‐275 in preventing tumor growth in a model closely mimicking the clinical situation of liver metastases, after surgical resection of primary colorectal cancer. A vaccination protocol using CSH‐275, conjugated with complete or incomplete Freund's adjuvant, was carried out to determine the effect in preventing the progression of liver metastases induced by DHD‐K12 cells injected in the splenic vein (preventive vaccine). An additional vaccination procedure was carried out to determine the effect on s.c. tumor growth (therapeutic vaccine). A significant improvement in survival along with the prevention of liver metastases formation and reduced growth of s.c. tumor were observed. CSH‐275 vaccination resulted in a significant increase in CTL activity against autologous DHD‐K12 cells in DHD‐K12 tumor‐bearing rats and the generation of a CTL response against DHD‐K12 cells in DHD‐K12 naive rats. Vaccination also induced massive infiltration of CD8+ cells in tumor. These results demonstrate that CSH‐275 is a new molecular target for colorectal cancer immunotherapy; it is also an excellent candidate for preclinical studies because it is naturally expressed on tumors in a fully competent syngeneic animal, which reproduces the clinical pattern of cancer progression. © 2004 Wiley‐Liss, Inc.
Inhaled particles and lung cancer, part B: Paradigms and risk assessment
Authors: Borm Paul J.A. , Schins Roel P.F. , Albrecht Catrin
Published: March 2004

Poorly soluble particles of low toxicity (PSP), such as CB, TiO2and coal mine dust, have been demonstrated to cause lung cancer in rodents, being most pronounced in rats. Adequate epidemiologic studies do not clearly indicate increased lung cancer rates in humans exposed to such particles. This has caused controversial positions in regulatory decisions on PSP on different levels. The present review discusses the current paradigms in rodent particle carcinogenicity, i.e., (i) role of particle overload and of persistent inflammation and (ii) fibrosis as an intermediate step in particle‐induced lung cancer with regard to human risk assessment. Fibrosis, which is usually considered a precursor of lung cancer in humans, was not related to lung tumors in an animal study using 6 different particles, each at 3 dosages. Lung tumors after both inhalation and intratracheal instillation of PSP are related to particle surface dose, which forwards hazard assessment at surface‐based nonoverload concentrations and a standard setting using surface as an exposure metric. The scarce data available on humans do not support the overload concept but suggest a role for persistent lung inflammation. Differences in antioxidant protection between different rodent species correlate with susceptibility to PSP‐induced carcinogenicity and support the need for detailed studies on antioxidant response in humans. Apart from such bridging studies, further focus is also needed on surface chemistry and modifications in relation to their adverse biologic effects. © 2004 Wiley‐Liss, Inc.
Improving efficacy of interleukin‐12‐transfected dendritic cells injected into murine colon cancer with anti‐CD137 monoclonal antibodies and alloantigens
Authors: Tirapu Iñigo , Arina Ainhoa , Mazzolini Guillermo , Duarte Marina , Alfaro Carlos , Feijoo Esperanza , Qian Cheng , Chen Lieping , Prieto Jesus , Melero Ignacio
Published: March 2004

Intralesional administration of cultured dendritic cells (DCs) engineered to produce IL‐12 by in vitro infection with recombinant adenovirus frequently displays eradicating efficacy against established subcutaneous tumors derived from the CT26 murine colon carcinoma cell line. The elicited response is mainly mediated by cytolitic T lymphocytes. In order to search for strategies that would enhance the efficacy of the therapeutic procedure against less immunogenic tumors, we moved onto malignancies derived from the inoculation of MC38 colon cancer cells that are less prone to undergo complete regression upon a single intratumoral injection of IL‐12‐secreting DCs. In this model, we found that repeated injections of such DCs, as opposed to a single injection, achieved better efficacy against both the injected and a distantly implanted tumor; that the use of semiallogeneic DCs that are mismatched in one MHC haplotype with the tumor host showed slightly better efficacy; and that the combination of this treatment with systemic injections of immunostimulatory anti‐CD137 (4‐1BB) monoclonal antibody achieved potent combined effects that correlated with the antitumor immune response measured in IFN‐γ ELISPOT assays. The elicited systemic immune response eradicates concomitant untreated lesions in most cases. Curative efficacy was also found against some tumors established for 2 weeks when these strategies were used in combination. These are preclinical pieces of evidence to be considered in order to enhance the therapeutic benefit of a strategy that is currently being tested in clinical trials. Supplementary Material for this aricle can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html. © 2004 Wiley‐Liss, Inc.
Highly efficient DNA incorporation of intratumourally injected [125I]iododeoxyuridine under thymidine synthesis blocking in human glioblastoma xenografts
Authors: Buchegger Franz , Adamer Florence , Schaffland Andreas Oliver , Kosinski Marek , Grannavel Carine , Dupertuis Yves Marc , de Tribolet Nicolas , Mach Jean‐Pierre , Delaloye Angelika Bischof
Published: March 2004

Intratumoural (i.t.) injection of radio‐iododeoxyuridine (IdUrd), a thymidine (dThd) analogue, is envisaged for targeted Auger electron‐ or beta‐radiation therapy of glioblastoma. Here, biodistribution of [125I]IdUrd was evaluated 5 hr after i.t. injection in subcutaneous human glioblastoma xenografts LN229 after different intravenous (i.v.) pretreatments with fluorodeoxyuridine (FdUrd). FdUrd is known to block de novo dThd synthesis, thus favouring DNA incorporation of radio‐IdUrd. Results showed that pretreatment with 2 mg/kg FdUrd i.v. in 2 fractions 0.5 hr and 1 hr before injection of radio‐IdUrd resulted in a mean tumour uptake of 19.8% of injected dose (% ID), representing 65.3% ID/g for tumours of approx. 0.35 g. Tumour uptake of radio‐IdUrd in non‐pretreated mice was only 4.1% ID. Very low uptake was observed in normal nondividing and dividing tissues with a maximum concentration of 2.9% ID/g measured in spleen. Pretreatment with a higher dose of FdUrd of 10 mg/kg prolonged the increased tumour uptake of radio‐IdUrd up to 5 hr. A competition experiment was performed in FdUrd pretreated mice using i.t. co‐injection of excess dThd that resulted in very low tumour retention of [125I]IdUrd. DNA isolation experiments showed that in the mean >95% of tumour 125I activity was incorporated in DNA. In conclusion, these results show that close to 20% ID of radio‐IdUrd injected i.t. was incorporated in tumour DNA after i.v. pretreatment with clinically relevant doses of FdUrd and that this approach may be further exploited for diffusion and therapy studies with Auger electron‐ and/or beta‐radiation‐emitting radio‐IdUrd. © 2004 Wiley‐Liss, Inc.
Synergistic improvements in cell and axonal migration across sciatic nerve lesion gaps using bioresorbable filaments and heregulin‐β1
Authors: Cai Jie , Peng Xuejun , Nelson Kevin D. , Eberhart Robert , Smith George M.
Published: March 2004

The success of entubulation for peripheral nerve regeneration is still limited, especially with long lesion gaps. In this study, we examined if regeneration could be enhanced by constructing implants to both align axonal growth and promote Schwann cell proliferation and migration. Silicone implants were used to bridge a 1.4‐cm gap in the rat sciatic nerve. Adult female Sprague–Dawley rats were divided into four groups of tubes containing either 1) Matrigel; 2) Matrigel and heregulin; 3) Matrigel and poly(L‐lactic acid) (PLLA) microfilaments; or 4) Matrigel, PLLA microfilaments, and heregulin. Ten weeks postimplantation, the number of axons and Schwann cells were measured at the distal end of implants. Implants with microfilaments displayed better tissue cable formation, increased Schwann cell migration, and regeneration of anti‐calcitonin gene‐related peptide‐positive axons, but not RMDO95‐positive axons compared with nonfilament‐containing groups. Heregulin treatment caused an increase in Schwann cell number, but it demonstrated no significant improvement in either tissue cable formation or axon number. Extensive regeneration was observed through implants containing Matrigel, microfilaments, and heregulin, which induced significant improvements in the number and longitudinal organization of both Schwann cells and axons. These results indicate that physical guidance of microfilaments and the Schwann cell growth factor, heregulin, act synergistically to improve nerve regeneration across long lesion gaps. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 247–258, 2004
In vivo behavior and mechanical stability of surface‐modified titanium implants by plasma spray coating and chemical treatments
Authors: Lee Baek‐Hee , Kim Jung Kyu , Kim Young Do , Choi Kuiwon , Lee Kyu Hwan
Published: March 2004

The geometric design and chemical compositions of an implant surface may have an important part in affecting early implant stabilization and influencing tissue healing. In this study, in vivo behavior and mechanical stability in implants of three surface designs, which were smooth surface (SS), rough titanium (Ti) surface by plasma spray coating (PSC), and alkali‐ and heat‐treated (AHT) Ti surface after plasma spray coating, were compared by histological and mechanical analyses. Surface morphologies of the implants were observed by optical microscopy and scanning electron microscopy. Chemical compositional surface changes were investigated by energy dispersive spectroscopy. The implants were inserted transversely in a dog thighbone and evaluated at 4 weeks of healing. At 4 weeks of healing after implantation in bone, the healing tissue was more extensively integrated with an AHT implant than with the implants of smooth (SS) and/or rough Ti surfaces (PSC). The bone bonding strength (pull‐out force) between living bone and implant was observed by a universal testing machine. At 4 weeks' healing after implant placement in bone, the pull‐out forces of the SS, PSC, and AHT implants were 235 (±34.25), 710 (±142.25), and 823 (±152.22) N, respectively. Histological and mechanical data demonstrate that appropriate surface design selection can improve early bone growth and induce an acceleration of the healing response, thereby improving the potential for implant osseointegration. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 279–285, 2004
Quantification of inflammatory cellular responses using real‐time polymerase chain reaction
Authors: Bailey LeeAnn O. , Washburn Newell R. , Simon Carl G. , Chan Edward S. , Wang Francis W.
Published: March 2004

The introduction of tissue engineering strategies for the repair and replacement of human body components extends the application and importance of biomaterials. Implanted biomaterials frequently evoke inflammatory responses that are complex and not well understood at present. The goals of this work were to develop improved measurement methods for the quantification of cellular inflammatory responses to biomaterials and obtain data that lead to an enhanced understanding of the ways in which the body responds to the introduction of biomaterials. To evaluate the biocompatibility of materials, we established a system that allows for the analysis and quantitation of cellular inflammatory responses in vitro. In this study, the inflammatory responses of murine macrophages (RAW 264.7) were analyzed. The cells were incubated with polymethylmethacrylate (PMMA) microspheres in the presence and absence of lipopolysaccharide (LPS) at 8 and 18 h. The analysis of the genetic material obtained from the cells was quantitated using real‐time reverse transcription polymerase chain reaction (RT‐PCR). The cell populations treated with LPS or PMMA microspheres singly resulted in an elevation of cytokine levels compared to the untreated control. LPS resulted in a 258‐fold increase, while PMMA resulted in an 87.9‐fold increase at 8 h. RAW 264.7 cells incubated with LPS and PMMA particles demonstrated a synergistic effect by producing a marked increase in the level of cytokine expression, 336‐fold greater than that of the untreated control at 8 h. Fluorescence microscopy studies that assessed cellular viability were also performed and are consistent with the RT‐PCR results. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 305–313, 2004
The influence of resin chemistry on a dental composite's biodegradation
Authors: Finer Y. , Santerre J. P.
Published: March 2004

Previous work reported that commercial dental composite resins containing a urethane‐modified bisGMA (bisphenylglycidyl dimethacrylate)/TEGDMA (triethylene glycol dimethacrylate) (ubis) based monomer system showed a 10‐fold reduction in the release of a bisGMA‐derived product, bishydroxypropoxyphenyl propane (bisHPPP), as compared with that found for bisGMA/TEGDMA (bis) based composites after incubation with cholesterol esterase (CE). Unfortunately, these materials also differed substantially in filler type and content, making it impossible to directly relate any specific parameter to the differences in biodegradation levels. By controlling for filler content and type, the current study will seek to probe the biomolecular interactions between composite resin chemistry and esterase activity in order to help explain the observed differences in biodegradation levels between the ubis and bis resin systems. After 32 days of incubation, buffer and CE solutions were analyzed for degradation products using high‐performance liquid chromatography, UV spectroscopy, and mass spectrometry. Both materials were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and X‐ray photoelectron spectroscopy. In the CE groups, the ubis system showed a 2.6‐ to 86‐fold reduction (dependent on the product) in the amount of isolated products relative to the bis system (p < 0.01). Scanning electron microscopy data also demonstrated the relative stability of the ubis system and X‐ray photoelectron spectroscopy analysis showed a higher content of the ester bond at the surface of the bis samples. Fourier transform infrared data showed that both resins had similar conversions. Because both systems were identical except for their monomer systems, it was concluded that changes in biostability were associated with chemistry. Crosslinking, hydrophobicity, and solubility all relate to ubis's pro‐stability. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 233–246, 2004
Cell responses to BMP‐2 and IGF‐I released with different time‐dependent profiles
Authors: Raiche A. T. , Puleo D. A.
Published: March 2004

During wound healing, growth factors are expressed in time‐dependent amounts. Constant delivery of biomolecules, however, is often used to influence cell and tissue behavior. In the present studies, a crosslinked gelatin‐coating system was used to deliver bone morphogenetic protein 2 (BMP‐2) or insulin‐like growth factor (IGF‐I) to three types of mesenchymal cells with three temporally varying release profiles. The “early” delivery profile released most of the growth factor within the first 2 days. The “pseudo‐zero‐order” profile approximated constant rate of delivery for about 5 days. The “late” delivery profile released most of the growth factor after about 5 days. Early delivery of IGF‐I had the greatest effect on mitogenesis of SaOS‐2 human osteosarcoma cells with a secondary effect noted nearly 5 days after delivery was completed. Late delivery of BMP‐2 resulted in greatest alkaline phosphatase (AP) activity in mouse pluripotent C3H10T1/2 cells. Rat bone marrow stromal cells (BMCs) responded to all delivery profiles of BMP‐2, with the duration of elevated AP activity increasing as the amount of BMP‐2 delivered increased. In addition to an early increase in AP activity, late release also stimulated BMCs over a longer portion of the culture period. BMCs responded similarly to SaOS‐2 cells when seeded on early IGF‐I delivery coatings, increasing AP activity after delivery had ended. Overall, these studies further show the importance of delivery profile, specifically the characteristics of time and concentration, on cell and tissue responses. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 342–350, 2004
In vitro behavior of osteoblastic cells cultured in the presence of pseudowollastonite ceramic
Authors: Sarmento Carlos , Luklinska Zofia B. , Brown Lindsey , Anseau Michel , De Aza Piedad N. , De Aza Salvador , Hughes Francis J. , McKay Ian J.
Published: March 2004

Pseudowollastonite ceramic (psW) is a bioactive ceramic that binds to bone when implanted in vivo and may be useful for the treatment of skeletal defects. However, there have been no studies that examined the interaction between psW and osteoblastic cells in vitro. This study investigated the suitability of psW as a substratum for cell attachment and the ability of the material to effect osteoblasts at a distance from the material surface. Fetal rat calvarial cells were plated onto the ceramic and examined by scanning electron microscopy. The findings reported show that cells attached and proliferated on the surface to the ceramic. Attachment by cells to the material can be enhanced by preincubation of psW in serum or media containing fibronectin. The adhesion of cells can be inhibited by addition of GRGDS peptides suggesting that adhesion to psW is mediated by integrin binding to adsorbed proteins. To study the effects of psW at a distance, cells were cultured in the presence but not in direct contact with the material. Subsequent changes in proliferation, alkaline phosphatase expression, and bone nodule formation were assessed. Cells grown in wells containing psW demonstrated an increase in both the rate and total numbers of bone nodules formed, although there were no differences in proliferation or alkaline phosphatase expression. Overall, these results suggest that psW is biocompatible and osteoconductive. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 351–358, 2004
Influence of pores created by laser superfinishing on osseointegration of titanium alloy implants
Authors: Stangl R. , Pries A. , Loos B. , Müller M. , Erben R. G.
Published: March 2004

The aim of this study was to assess the osseointegration of copper vapor laser–superfinished titanium alloy (Ti6Al4V) implants with pore sizes of 25, 50, and 200 μm in a rabbit intramedullary model. Control implants were prepared by corundum blasting. Each animal received all four different implants in both femora and humeri. Using static and dynamic histomorphometry, the bone–implant interface and the peri‐implant bone tissue were examined 3, 6, and 12 weeks postimplantation. Among the laser‐superfinished implants, total bone–implant contact was smallest for the 25‐μm pores, and was similar for 50‐ and 200‐μm pore sizes at all time points. However, all laser‐superfinished surfaces were inferior to corundum‐blasted (CB) control implants in terms of bone–implant contact. Within the 12‐week study period, remodeling of woven bone initially formed within pores occurred only in the implants with 200‐μm pores. Implants with 25‐μm pores showed the highest amount of peri‐implant bone volume at all time points, indicating that the amount of peri‐implant bone was not correlated with the quality of the bone–implant interface. At 3 and 6 weeks postsurgery, we did not find any differences in mineral apposition rates or bone formation rates between the various implant surfaces. However, the peri‐implant bone formation rate at the end of the trial was 70 and 62% higher in implants with 50‐ and 200‐μm pores compared with CB implants, respectively. We conclude that, although laser‐superfinished implants were not superior to CB control implants in terms of osseointegration, our study has provided further insights into the mechanisms of bone remodeling within pores of various sizes, and may form a basis for future experiments to design optimal implant surfaces with the help of modern laser technology. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 444–453, 2004
Patterns of variation in the phalangeal formulae of land tortoises (Testudinidae): Developmental constraint, size, and phylogenetic history
Authors: Crumly C. R. , Sánchez‐Villagra M. R.
Published: March 2004

Documentation of variation in phalangeal formulae in land tortoises combined with ontogenetic information from turtles in general were used, in a phylogenetic context, to infer the potential effect of size and developmental constraints upon patterns of morphological variation. A sample of 201 specimens and published illustrations of 37 tortoise species were examined, representing all but one living genera and most species of the Testudinidae. Specimens were either articulated dry skeletons or preserved animals that were x‐rayed. The patterns of digital and phalangeal loss in tortoises were predicted from developmental studies of the manus and pes in other turtles. If a digit is lost, it is the first digit, which is the last one to develop. If a digit has a single phalanx, it is usually the fifth digit. The primitive phalangeal formula for land tortoises is probably 2–2–2–2–1, the most common pattern found in living testudinid species. The presence of a second phalanx in the fifth digit evolved independently many times and usually in large tortoises. Such additions were interpreted as instances of peramorphosis. Many small tortoises have a full complement of digits (five) and phalanges (two in each digit); nevertheless, phalangeal and digital loss is associated with small size. Small and medium size tortoises exhibit greater variation in phalangeal number than do large tortoises. We hypothesize that epigenetic processes, and not simply adaptation, played a major role in the evolution of the variation in phalangeal formulae in tortoises. J. Exp. Zool. (Mol. Dev. Evol.) 302B:134–146, 2004. © 2004 Wiley‐Liss, Inc.
Tyrosine hydroxylase and dopamine transporter expression following 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced neurodegeneration of the mouse nigrostriatal pathway
Authors: Jakowec Michael W. , Nixon Kerry , Hogg Elizabeth , McNeill Tom , Petzinger Giselle M.
Published: March 2004

Administration of the neurotoxicant 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) to C57BL/6 mice targets nigrostriatal dopaminergic neurons, leading to cell death and the depletion of striatal dopamine. After MPTP lesioning in young adult mice, surviving nigrostriatal dopaminergic neurons display robust and reproducible return of striatal dopamine weeks to months after injury. Thus, the mouse provides an excellent model with which to investigate the mechanisms underlying neuroplasticity of the nigrostriatal system following neurotoxic injury. The purpose of this study was to analyze proteins and mRNA transcripts of genes involved in dopamine biosynthesis (tyrosine hydroxylase; TH) and uptake (dopamine transporter; DAT) with regard to time course (7–90 days) after MPTP lesioning. Molecular analysis using immunohistochemistry and Western immunoblotting techniques demonstrated an increase in striatal TH by 30–60 days postlesioning that returned to near‐control (prelesioned) levels by 60–90 days. In situ hybridization histochemistry indicated that this increase in TH protein might be due in part to increased TH mRNA expression in surviving nigrostriatal dopaminergic neurons. Analysis of TH protein at 7, 30, 60, and 90 days postlesioning with two‐dimensional polyacrylamide gel electrophoresis in conjunction with Western immunoblotting revealed altered TH protein isoforms migrating at isoelectric points different from those of the native isoform. In contrast to TH protein, which returned to prelesioned levels by 60 days, DAT protein analysis showed that increased expression of striatal DAT protein did not return to near‐prelesion levels until 90 days postlesioning. These results suggest that TH and DAT may differ in their time course of expression in surviving dopaminergic neurons and may play a role in mediating the return of striatal dopamine. © 2004 Wiley‐Liss, Inc.
Effect of mating surface on the high temperature wear of 253 MA alloy
Authors: Roy M. , Pauschitz A. , Wernisch J. , Franek F.
Published: March 2004

The wear behaviour of metallic material is influenced by the friction force, which in turn, is governed by the hardness and oxidation kinetics of the mating surface. In view of this, present investigation is undertaken to find the influence of mating surface on the high temperature wear of 253 MA alloy. This alloy is developed for high temperature application. In this work 253 MA alloy is made to slide against two different types of counter face material, namely 100Cr6 steel and PM 1000 alloy, at five different temperatures. 100Cr6 steel gets soften with increase of temperature whereas PM 1000 alloy retains its strength even at high temperature. The friction coefficient and the thickness loss of 253 MA alloy is measured and compared against both variety of mating surfaces as function of temperatures. The morphology of the worn surfaces and the transverse section of the worn surfaces are examined under scanning electron microscope (SEM) to identify the material removal mechanisms. The results showed that the friction coefficient of test material against PM 1000 alloy is around 40% higher than the friction coefficient against 100Cr6 steel. The transverse section of the worn surface showed presence of a transfer layer, mechanically mixed layer and composite layer, which govern the wear behaviour particularly at elevated temperature. The chemical characteristics of these layers are dependent on the test temperature and the counter face material.
Voltammetric behaviour of an archeaological bronze alloy in aqueous chloride media
Authors: Souissi N. , Bousselmi L. , Khosrof S. , Triki E.
Published: March 2004

The interface archaeological bronze alloy‐chloride media was characterized by using linear sweep rate cyclic voltammetry. The electrochemical behaviour of the Cu‐Sn alloy being different from pure copper and pure tin. In fact, the voltammograms show an anodic peak and two cathodic peaks. Surface examination revealed a compact layer which spread over the ancient material. The influence of different parameters such as scan rate, chloride concentration and repetitive cycling on the voltammetric response of the archaeological bronze was also studied. The results indicate that patina layer formation is a spreading process over the electrode surface leaving only small pores. Diffusion of the halide controls the growing rate of this layer. Two other anodic peaks are evidences when potential cycling increases. The oxidation became more difficult as a result of a constant layer thickness.
An Error‐in‐Variables Method for Determining Reactivity Ratios by On‐Line Monitoring of Copolymerization Reactions
Authors: Sünbül Didem , Çatalgil‐Giz Huceste , Reed Wayne , Giz Ahmet
Published: March 2004

Summary: A new error‐in‐variables method was developed to estimate the reactivity ratios in copolymerization systems. It brings the power of automatic, continuous, on‐line monitoring of polymerization (ACOMP) to copolymerization calculations. In ACOMP systems, monomer and polymer concentrations are measured by the monitoring of two independent properties of the system. The reactivity ratios are found by taking into account errors in the monomer concentrations determined from measurements and from calibration of the instruments. All the error sources are taken into account according to the error‐in‐variables method, and their effects are reflected in determining the confidence intervals of the reactivity ratios by the usual error propagation technique.

Distribution of concentrations [a] and [b] for the simulated experiment I. Random errors are 1% of the initial value in both observed variables.

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Distribution of concentrations [a] and [b] for the simulated experiment I. Random errors are 1% of the initial value in both observed variables.
Development of a Coupled Viscosity‐Polymerization Model for the Synthesis of High Solids‐Low Viscosity Latexes
Authors: do Amaral Marcelo , van Es Steven , Asua José M.
Published: March 2004

Summary: The development of a model‐assisted methodology for the synthesis of high solids‐low viscosity latexes is presented. A simplified polymerization model for systems with a polydisperse particle size distribution, PSD, was developed. The polymerization model was then coupled with an equation for the computation of the viscosity. Their combination resulted in a powerful tool that helped to screen strategies for the synthesis of high solids‐low viscosity latexes. Furthermore, using the model‐assisted methodology it was possible to determine the workable viscosity boundary for a given formulation. The evolution of the viscosity with the volume fraction was calculated for different polymerization strategies.

Particle size distribution evolution of Simulation 1. Large particles (•) and small particles (□).

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Particle size distribution evolution of Simulation 1. Large particles (•) and small particles (□).