bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone response to 3D periodic hydroxyapatite scaffolds with and without tailored microporosity to deliver bone morphogenetic protein 2
Authors: Dellinger Jennifer G. , Eurell Jo Ann C. , Jamison Russell D.
Published: November 2005

Three types of model hydroxyapatite (HA) scaffolds were implanted in the metacarpal and metatarsal bones of goats. Scaffolds, consisting of a latticed pattern of rods, were fabricated with a solid freeform fabrication (SFF) technique. All scaffolds contained macropores; some were also fabricated with micropores (5.2 ± 2.0 μm). Recombinant human bone morphogenetic protein‐2 (rhBMP‐2) was added to some microporous scaffolds. rhBMP‐2 caused increased percent filled with bone tissue compared to microporous scaffolds without rhBMP‐2. Lamellar bone in the scaffolds was aligned perpendicular to the long axis of the bone near the junctions of the rods that make up the scaffold but was more random away from the junctions of rods. Microporous scaffolds stained beneath areas of contact with new bone. This staining might indicate either extracellular matrix (ECM) in the rods, byproducts of ECM production, or reaction of cellular products with the scaffold. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Plasma‐immersion ion‐implanted nitinol surface with depressed nickel concentration for implants in blood
Authors: Maitz Manfred F. , Shevchenko Natalia
Published: November 2005

Ion implantation into nitinol had been shown previously to decrease the surface nickel concentration of this alloy and produce a titanium oxide layer. Nothing is known yet about the blood compatibility of this surface and the suitability for implants in the blood vessels, like vascular stents. Nickel depletion of superelastic nitinol was obtained by oxygen or helium plasma‐immersion ion implantation. The latter leads to the formation of a nickel‐poor titanium‐oxide surface with a nanoporous structure, which was used for comparison. Fibrinogen adsorption and conformation changes, blood platelet adhesion, and contact activation of the blood clotting cascade have been checked as in vitro parameters of blood compatibility; metabolic activity and release of cytokines IL‐6 and IL‐8 from cultured endothelial cells on these surfaces give information about the reaction of the blood vessel wall. The oxygen‐ion‐implanted nitinol surface adsorbed less fibrinogen on its surface and activated the contact system less than the untreated nitinol surface, but conformation changes of fibrinogen were higher on the oxygen‐implanted nitinol. No difference between initial and oxygen‐implanted nitinol was found for the platelet adherence, endothelial cell activity, or cytokine release. The nanoporous, helium‐implanted nitinol behaved worse than the initial one in most aspects. Oxygen‐ion implantation is seen as a useful method to decrease the nickel concentration in the surface of nitinol for cardiovascular applications. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
A long‐term in vitro biocompatibility study of a biodegradable polyurethane and its degradation products
Authors: van Minnen B. , Stegenga B. , van Leeuwen M. B. M. , van Kooten T. G. , Bos R. R. M.
Published: November 2005

The biological safety of degradation products from degradable biomaterials is very important. In this study a new method is proposed to test the cytotoxicity of these degradation products with the aim to save time, laboratory animals, and research funds. A biodegradable polyurethane (PU) foam was subjected to this test method. The PU had soft segments of DL‐lactide/ϵ‐caprolactone and hard segments synthesized from butanediol and 1,4‐butanediiosocyanate. Copolymer foams without urethane segments, consisting of DL‐lactide/ϵ‐caprolactone, were tested as well. Accumulated degradation products were collected by degrading the foams in distilled water at 60°C up to 52 weeks. Cell‐culture medium was prepared from powder medium with this water. In different tests the cytotoxicity of this medium was established. The first signs of cytotoxicity were observed after 3–5 weeks of degradation. This accounts for both materials and reestablishes the good short‐term biocompatibility of these materials. The PU showed more toxicity toward the end stages of degradation in comparison with the copolymer. This is probably related to the accumulation of degradation products of the urethane segments. In the in vivo situation the degradation of the PU and the metabolism and excretion of degradation products may differ. Therefore, long‐term in vivo studies will have to establish whether these in vitro results are representative for the in vivo behavior of the degrading PU. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Testing the utility of rationally engineered recombinant collagen‐like proteins for applications in tissue engineering
Authors: Ito Hidetoshi , Steplewski Andrzej , Alabyeva Tatiana , Fertala Andrzej
Published: November 2005

Collagens are attractive proteins as materials for tissue engineering. Over the last decade, significant progress has been made in developing technologies for large‐scale production of native‐like human recombinant collagens. Yet, the rational design of customized collagen‐like proteins for smart biomaterials to enhance the quality of engineered tissues has not been explored. We mapped the D4 domain of human collagen II as most critical for supporting migration of chondrocytes and used this information to genetically engineer a collagen‐like protein consisting of tandem repeats of the D4 domain (mD4 collagen). This novel collagen has been utilized to fabricate a scaffold for support of chondrocytes. We determined superior qualities of cartilaginous constructs created by chondrocytes cultured in scaffolds containing the mD4 collagen in comparison to those formed by chondrocytes cultured in bare scaffolds or those coated with wild‐type collagen II. Our results are a first attempt to rationally engineer collagen‐like proteins with characteristics tailored for specific needs of cartilage engineering and provide a basis for rational engineering of similar proteins for a variety of biomedical applications. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Effect of cast molded rifampicin/silicone on staphylococcus epidermidis biofilm formation
Authors: Liang Xuemei , Wang Anfeng , Cao Ting , Tang Haiying , McAllister James P. , Salley Steven O. , Ng K. Y. Simon
Published: November 2005

Infection is one of the most common catheter‐related complications, especially in shunt systems used to treat hydrocephalus. Staphylococcus epidermidis is directly related to biomaterial infections owing to its ability to form a biofilm on implanted materials. In this study, scanning electron microscopy (SEM) and atomic force microscopy (AFM) were employed to investigate the effect of the antibiotic rifampicin on the colonization and growth of S. epidermidis 35984 on the surface of silicone. A cast molding method was used to load rifampicin into the silicone precursor before it was cured. Bacteria with a diameter of 800–1000 nm and height of 200–500 nm were found to be embedded in the biofilm. Compact multilayer biofilm structures were found on silicone surfaces upon incubation for 4 and 24 h. On the other hand, sparser biofilm structures were observed on rifampicin‐loaded surfaces after incubation for the same duration. Deformation of bacteria was observed by AFM. Moreover, different bacterial colony structures on the surfaces of silicone and rifampicin‐loaded silicone were observed by AFM and SEM. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Biological effects of calcium sulfate as a bone graft substitute in ovine metaphyseal defects
Authors: Peters Christopher L. , Hines Jerod L. , Bachus Kent N. , Craig Marcis A. , Bloebaum Roy D.
Published: November 2005

Calcium sulfate has been used as a bone graft substitute in many fields, from dentistry to orthopedics. However, the results of many studies have yielded inconclusive results. In the present study, a sheep model was used with tibial and femoral metaphyseal defects to determine whether calcium sulfate was as effective as autograft and allograft in promoting new bone formation in a critical size defect. Medical‐grade calcium sulfate pellets, autograft bone, allograft bone, or nothing was used to fill the metaphyseal defects. The sheep were allowed to heal for 12 weeks. Sagittal sections from the bones were analyzed with high‐resolution contact radiographs, backscattered electron microscopy, and light microscopy. The volume fractions of bone within the defect perimeter were determined, and the histologic quality of the bone was observed. The volume fraction of new bone in the autograft, calcium sulfate, and allograft were not statistically different, but all were significantly different than the untreated control. The majority of the calcium sulfate had been resorbed at 12 weeks, and the histologic quality of the bone appeared similar to the autograft‐treated bone. Calcium sulfate appears to be a useful biocompatible bone graft substitute that yields results similar to autograft bone in sheep metaphyseal defects. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
In vivo biocompatibility of bacterial cellulose
Authors: Helenius Gisela , Bäckdahl Henrik , Bodin Aase , Nannmark Ulf , Gatenholm Paul , Risberg Bo
Published: November 2005

The biocompatibility of a scaffold for tissue engineered constructs is essential for the outcome. Bacterial cellulose (BC) consists of completely pure cellulose nanofibrils synthesized by Acetobacter xylinum. BC has high mechanical strength and can be shaped into three‐dimensional structures. Cellulose‐based materials induce negligible foreign body and inflammatory responses and are considered as biocompatible. The in vivo biocompatibility of BC has never been evaluated systematically. Thus, in the development of tissue engineered constructs with a BC scaffold, it is necessary to evaluate the in vivo biocompatibility. BC was implanted subcutaneously in rats for 1, 4, and 12 weeks. The implants were evaluated in aspects of chronic inflammation, foreign body responses, cell ingrowth, and angiogenesis, using histology, immunohistochemistry, and electron microscopy. There were no macroscopic signs of inflammation around the implants. There were no microscopic signs of inflammation either (i.e., a high number of small cells around the implants or the blood vessels). No fibrotic capsule or giant cells were present. Fibroblasts infiltrated BC, which was well integrated into the host tissue, and did not elicit any chronic inflammatory reactions. The biocompatibility of BC is good and the material has potential to be used as a scaffold in tissue engineering. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Improvement in hydrophilicity of PHBV films by plasma treatment
Authors: Wang Yingjun , Lu Ling , Zheng Yudong , Chen Xiaofeng
Published: November 2005

Poly(3‐hydroxybutyrate‐co‐hydroxyvalerate) (PHBV) films were prepared by the solvent cast method. Oxygen and nitrogen plasma treatment were used to improve the hydrophilicity of the surface of PHBV films. The surface properties were characterized by contact angle measurement and X‐ray photoelectron spectroscopy (XPS). The water contact angle of PHBV films decreased after plasma treatment, which suggested that the surfaces became more hydrophilic. The effects of exposure time, plasma generating power, and chamber pressure on water contact angle were investigated. Although the decrease of contact angle with both plasma treatments was similar, the change of PHBV surface structure was different. XPS analysis showed that the oxygen content and the ratio of O/C increased markedly after oxygen plasma treatment, while after nitrogen plasma treatment, the surface was enriched with nitrogen atoms. Furthermore, it was found that CO and CC bonds were broken with both plasma treatment, while different new bonds were formed, that is, COOH (for oxygen plasma), and CN, CN, and amide bonds (for nitrogen plasma) have been generated after plasma irradiation. Dog bone marrow stromal cell culture studies showed that cells grew better on the plasma treated surface. These results demonstrate potentiality of this method for grafting useful component in future tissue‐engineering applications. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Strontium‐containing hydroxyapatite (Sr‐HA) bioactive cement for primary hip replacement: An in vivo study
Authors: Ni G. X. , Lu W. W. , Chiu K. Y. , Li Z. Y. , Fong D. Y. T. , Luk K. D. K.
Published: November 2005

The purpose of this study was to evaluate the strontium‐containing hydroxyapatite (Sr‐HA) cement in primary hip replacement, using a rabbit model, and to investigate the histological findings at the cement–implant and bone–cement interfaces under weight‐bearing conditions. Unilateral hip replacement was performed with Sr‐HA cement or polymethylmethacrylate (PMMA) cement in rabbits and observations were made after 6 months. Good fixation between the Sr‐HA cement and implant was observed. Osseointegration of the Sr‐HA cement with cancellous bone was widespread. Many multinucleus cells covered the surface of the cement, and resorbed the superficial layer of the cement. By scanning electron microscopy (SEM) and energy‐dispersive X‐ray (EDX) analysis, high calcium and phosphorus levels were detected at the interface with a thickness of about 10 μm. Intimate contact was also observed between the Sr‐HA cement and cortical bone without fibrous layer intervening. The overall affinity index of bone on Sr‐HA cement was (85.06 ± 5.40)%, which is significantly higher than that on PMMA cement (2.77%± 0.49%). On the contrary, a fibrous layer was consistently observed between PMMA cement and bone, and PMMA cement evoked an inflammatory response and foreign body reaction in the surrounding bony tissues. Results suggested good bioactivity and bone‐bonding ability of the Sr‐HA cement under weight‐bearing conditions. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Fabrication of polycaprolactone scaffolds using a sacrificial compression‐molding process
Authors: Yao Donggang , Smith Aaron , Nagarajan Pratapkumar , Vasquez Adrian , Dang Loan , Chaudhry G. Rasul
Published: November 2005

A method of compression‐molding fine‐powder blends of polycaprolactone (PCL) and poly(ethylene oxide) (PEO) and subsequently dissolving the PEO phase was investigated to prepare porous PCL scaffolds. Different mixing ratios of the two polymers from 20 to 70% PCL were used to study the effect of the mixing ratio on the morphology formation of the scaffold. The mixing ratio was found to play an important role in affecting the porosity of the scaffold and the size of pores. Murine embryonic stem cell derived osteogenic cells were utilized to test the suitability of these scaffolds in tissue engineering applications. The seeded cells were able to colonize and grow in these scaffolds. Based on the overall consideration of morphology, mechanical performance, and ability for cell attachment and proliferation, the scaffolds with approximately 30–40% PCL appear to be an appropriate choice for tissue engineering. These findings suggest that sacrificial compression‐molding of PCL–PEO powder blends can be used in the generation of biocompatible scaffolds with controllable porosity and pore size and may be used for in vitro tissue engineering applications. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Role of fluid dynamics on the healing of an in vivo tissue engineered vascular graft
Authors: Lyman Donald J. , Stewart Sandy F.C. , Murray‐Wijelath Jacqueline , Wijelath Errol
Published: November 2005

A polyester (PET) reinforced fibrin‐FN‐VEGF‐TGFβ vascular graft, formed by a four‐step preclotting technique of a porous PET arterial graft, shows the overlapping inflammation, proliferation, and remodeling steps of normal wound healing when implanted in the descending thoracic aorta (DTA) position in the dog, forming a surface layer of endothelial cells. While the DTA grafts readily healed (i.e., endothelialized), similar grafts implanted in the carotid–femoral artery position did not fully heal. Since the initial phases of healing were shown to be dependent upon the transport of blood‐borne constituents to the graft surface, the extent of healing appears to be dependent on the fluid dynamics present in the artery–graft–artery construct. The length of the noncompliant graft, the construction of the anastomoses, bends in the construct, graft diameter, and graft compliance can affect the fluid dynamics in the implant, and thus the healing of the graft. This has clinical relevance for the testing and development of new vascular graft materials. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Nanoindentation of dental composites
Authors: Drummond James L.
Published: November 2005

The intent of this project was to evaluate the elastic modulus and hardness of four composites with different fillers, a microfill, a hybrid, a dental resin cement, and a fiber filler, using nanoindentation. An indentation load of 0.001 N was used and 100 indents per specimen were taken. The elastic modulus measured for the Choice composite was 30.2–30.3 GPa, 15.9–16.0 GPa for Micronew, 24.6–27.1 GPa for Renew, and 36.4–47.1 GPa for Restolux. The statistical analysis indicated a significant difference in the elastic modulus for all four composites. Micronew had the lowest hardness (1.2–1.3 GPa) followed by Renew (1.6–1.8 GPa), Choice (2.6–2.8 GPa), and Restolux (2.7–4.0 GPa). The statistical analysis indicated a significant difference between Choice and Restolux from Micronew and Renew, with Renew and Micronew not being significantly different from each other. Nanoindentation of dental composites, using a 10 × 10 matrix of indentations, resulted in a wide range of measured values for the elastic modulus and hardness because of the size of the filler particle, the location of the indenter within the filler particle, the composition of the filler particles, and the location of the indenter within the filler/resin matrix. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
A novel method to obtain microtensile specimens minimizing cut flaws
Authors: Sadek Fernanda Tranchesi , Monticelli Francesca , Muench Antonio , Ferrari Marco , Cardoso Paulo Eduardo Capel
Published: November 2005

Cutting procedures conventionally used for microtensile specimens' preparation induce mechanical stress and attrition, leading to cracks in dental structure. Enamel is mainly affected due to its high module of elasticity and brittleness. As an alternative to the conventional diamond saw, a diamond wire was used for cutting. The two techniques were compared in efficacy in the preparation of two different sample shapes. Forty human molars, flattened in dentin or enamel, were used for sample preparation. After bonding procedures, resin block was built incrementally. Half of the teeth were cut using a diamond disc and the other half using a diamond wire, obtaining slabs and stick‐shaped specimens. Slabs were then shaped to obtain hourglass samples. Five samples from each subgroup were randomly selected for Scanning electron microscopy (SEM) analysis. Remaining samples underwent microtensile test and the results were analyzed, including/excluding premature failures (pf), with three‐way ANOVA and Tukey test, performed separately, by substrate. On dentin, only the exclusion of pf showed a significant higher bond strength values than when pf were included (p < 0.05); however, on enamel, all factors (equipment, shape and including/excluding pf) had a significant effect on bond strength (p<0.05). The most remarkable finding from SEM was the incidence of specimens' cracks and defects when diamond blade was used. Scratches and cracks in the hourglass‐shaped specimens were also detected. In both cases, enamel was more affected than dentin. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
UV‐embossed microchannel in biocompatible polymeric film: Application to control of cell shape and orientation of muscle cells
Authors: Shen Jin‐Ye , Chan‐Park Mary Bee‐Eng , Feng Zhi‐Qin , Chan Vincent , Feng Zhi‐Wei
Published: November 2005

This article shows that ultra violet (UV) micro‐embossing can be successfully used for fabricating biocompatible micropatterned films with microchannels separated by high aspect ratio microwalls. Eight series of micropatterns were investigated; the width of the microwall was either 10 or 25 μm and that of the microchannel either 40, 80, 120, or 160 μm. The material investigated was principally polyurethane diacrylate. The UV‐embossed micropattern was extracted with methanol, converting the micropatterns from cytotoxic to biocompatible. The typical UV embossing method was modified by using a marginally adhesive polyester substrate, which facilitates demolding but is removable before methanol extraction to avoid fragmentation of the embossed micropatterns. The effect of the micropatterns on A7r5 smooth muscle cells and C2C12 skeletal muscle cells was investigated. The dimensions of both channel and wall have significant effects on the elongation of both muscle cells. In the narrower 40‐μm channel, the C2C12 cells merged together to form myofibers. These results indicate that UV‐embossed micropatterns may present a useful scaffold for in vitro cell shape and orientation control needed in vascular and muscle tissue engineering. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Stair ascent kinematics affect UHMWPE wear and damage in total knee replacements
Authors: Cottrell Jocelyn M. , Babalola Omotunde , Furman Bridgette S. , Wright Timothy M.
Published: November 2005

Investigations were performed to characterize the wear patterns of tibial inserts in a load‐controlled knee simulator by incorporating both normal gait and clinically acquired stair climbing kinematics and load conditions. Two different tibial insert designs were evaluated: the NexGen Cruciate Retaining Augmentable and NexGen Legacy Posterior Stabilized inserts. Two test conditions were run: standard gait only, and gait with bouts of stair climbing at a ratio of 70:1. Gravimetric wear measurements, damage and contact area assessments, and kinematic evaluations were performed. The addition of stair climbing kinematics significantly affected the wear behavior. Regardless of design, wear rates for standard gait tests were significantly higher than those that included bouts of stair climbing. The damage modes seen in both test conditions were primarily burnishing with secondary scratching and pitting. At 2 Mc, the damage areas were not significantly different between the two designs, but the damage area with stair climbing was significantly larger than that with gait alone. The fact that even small bouts of an additional activity of daily living could markedly impact wear simulator results calls into question the usefulness of studies that rely solely on kinematics and load inputs assumed from level gait. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
In vitro wear of resin‐based materials—Simultaneous corrosive and abrasive wear
Authors: Correr Gisele Maria , Alonso Roberta Caroline Bruschi , Sobrinho Lourenço Correr , Puppin‐Rontani Regina Maria , Ferracane Jack Liborio
Published: November 2005

The aim of this study was to evaluate the wear of resin‐based materials caused by the association of abrasive and corrosive processes. Twenty specimens were prepared for each material, cast in epoxy in acrylic rings, polished, and profiled with an MTS 3D Profiler. Antagonists were made from deciduous molars. Specimens were distributed into eight groups (n = 10), according to the material (Filtek Supreme, Point 4, Dyract AP, and Fuji II LC) and the type of slurry (neutral and acidic), and then cycled 100,000 times in the OHSU oral wear simulator. The specimens were cleaned and reprofiled. Volume loss and maximum depth were determined. ANOVA and Tukey's test were used for data analysis (p < 0.05). The area of the wear facet on the antagonist was also measured. Composites displayed less wear than the compomer and the resin‐modified glass ionomer. Significant differences also were found for cusp wear, with a significant positive correlation shown between cusp and material wear. The acidic slurry significantly increased the wear of the materials compared to the neutral slurry. Exposure to acidic slurry accelerated the wear of resin‐based materials. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Advanced nanocomposite materials for orthopaedic applications. I. A long‐term in vitro wear study of zirconia‐toughened alumina
Authors: Affatato S. , Torrecillas R. , Taddei P. , Rocchi M. , Fagnano C. , Ciapetti G. , Toni A.
Published: November 2005

The use of ceramic‐on‐ceramic (alumina‐ and zirconia‐based) couplings in hip joint prostheses has been reported to produce lower wear rates than other combinations (i.e., metal‐on‐polyethylene and ceramic‐on‐polyethylene). The addition of zirconia into an alumina matrix (zirconia‐toughened alumina, ZTA) has been reported to result in an enhancement of flexural strength, fracture toughness, and fatigue resistance. The development of new processing routes in nonaqueous media has allowed to obtain high‐density ZTA nanocomposites with a very homogeneous microstructure and a significantly smaller and narrower particle‐size distribution of zirconia than conventional powder mixing methods. The aim of the present study was to set up and validate a new ZTA nanocomposite by testing its biocompatibility and wear behavior in a hip‐joint simulator in comparison with commercial alumina and experimental alumina specimens. The primary osteoblast proliferation onto ZTA nanocomposite samples was found to be not significantly different from that onto commercial alumina samples. After 7 million cycles, no significant differences were observed between the wear behaviors of the three sets of cups. In this light, it can be affirmed that ZTA nanocomposite materials can offer the option of improving the lifetime and reliability of ceramic joint prostheses. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Characterization of functionally graded hydroxyapatite/titanium composite coatings plasma‐sprayed on Ti alloys
Authors: Chen Chun‐Cheng , Huang Tsui‐Hsien , Kao Chia‐Tze , Ding Shinn‐Jyh
Published: November 2005

Bioceramic coatings like hydroxyapatite (HA) have shown promising bioactive properties in load‐bearing implant applications. The aim of this work is to deposit functionally graded HA/Ti layers consisting of an underlying Ti bond coat, the alternating layer, and an HA top‐layer on Ti6Al4V substrates using plasma spray to improve the coating–substrate interface properties. The alternating layers were created by means of changing the feeding rate and input power of Ti and HA powders, which gradually decrease Ti content with increasing depth from the Ti bond‐coat. The major consideration is to examine the stability of the graded coatings. Experimental results indicated that surface chemistry and morphology of the graded coatings were similar to those of monolithic HA coatings. The bond strength values of the as‐sprayed graded coatings were much superior to those of monolithic HA coatings. The cyclic fatigue did have a statistically significant effect on bond strength of monolithic HA coatings, with a decrease of 23%. However, the graded coatings were able to survive 1 million cycles of loading in air without significantly reduced bond strength. The in vitro electrochemical measurement results also indicated that the graded coatings had a more beneficial and desired behavior than monolithic HA coatings after fatigue. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
A charge‐scaling implementation of the variational electrostatic projection method
Authors: Gregersen Brent A. , York Darrin M.
Published: November 2005

Two new charge‐scaling methods for efficient modeling of the solvated macromolecular environment in hybrid QM/MM calculations of biological reactions are presented. The methods are extensions of the variational electrostatic projection (VEP) method, and allows a subset of atomic charges in the external environment to be adjusted to mimic, in the active dynamical region, the electrostatic potential and field due to the large surrounding macromolecule and solvent. The method has the advantages that it offers improved accuracy, does not require the use of a three‐dimensional grid or auxiliary set of fitting points, and requires only minor molecular simulation code modifications. The VEP−cs and VEP‐RVM+cs methods are able to attain very high accuracy (relative force errors of 10−7 or better with appropriate choice of control parameters), and take advantage of a recently introduced set of high‐order discretization schemes and Gaussian exponents for boundary element solvation and VEP methods. The methods developed here serve as potentially powerful tools in the arsenal of computational techniques used in multiscale computational modeling problems. © 2005 Wiley Periodicals, Inc. J Comput Chem 27: 103–115, 2006
Cyclic m‐cycle systems with m ≤ 32 or m = 2q with q a prime power
Authors: Wu Shung‐Liang , Fu Hung‐Lin
Published: November 2005

In this paper, the necessary and sufficient conditions for the existence of cyclic 2q‐cycle and m‐cycle systems of the complete graph with q a prime power and 3 ≤ m ≤ 32 are given. © 2005 Wiley Periodicals, Inc. J Combin Designs
The number of triangles in 2‐factorizations
Authors: Sui Qidi , Du Beiliang
Published: November 2005

Given an arbitrary 2‐factorization ${\cal F} = {F_{1},F_{2}, \cdots , F_{v - 1/2}}$ of $K_{v}$, let δi be the number of triangles contained in Fi, and let δ = Σδi. Then $\cal F$ is said to be a 2‐factorization with δ triangles. Denote by Δ(v), the set of all δ such that there exists a 2‐factorization with δ triangles. Let

where

Dejter et al. 1 proved that when v ≡ 1 or 3 (mod 6), apart from some small exceptions, and some additional 11 possible exceptions, Δ(v) = PΔ (v). In this paper, we consider the remaining case v ≡ 5 (mod 6). We will prove that when v ≡ 5 (mod 6), apart from some small exceptions, and some additional 9 possible exceptions, Δ (v) = PΔ (v). © 2005 Wiley Periodicals, Inc. J Combin Designs 14: 277–289, 2006
Erratum to: Self‐dual codes and the (22,8,4) balanced incomplete block design
Authors: Bilous R. T. , van Rees G. H. J.
Published: November 2005

The original article to which this Erratum refers was published in Journal of Combinatorial Designs 13: 363–376, 2005.

No Abstract.
Physiology and pathology of notch signalling system
Authors: Bianchi Silvia , Dotti Maria Teresa , Federico Antonio
Published: November 2005

Notch proteins encode a family of transmembrane receptors that are part of a signalling transduction system known as Notch signalling, an extremely conserved and widely used mechanism regulating programs governing growth, apoptosis and differentiation in metazoans. Notch signalling begins when the Notch receptor binds ligands and ends when the Notch intracellular domain enters the nucleus and activates transcription of target genes. This core pathway is subjected to a wide array of regulatory influences and protein‐protein interactions and is correlated with other signalling pathway. This review will sumarize recent findings concerning the physiology and pathology of Notch signalling in vascular development and homeostasis. Moreover, the clinical phenotypes of Notch3 signalling system pathology will be described, with particular regard to CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) for which the most recent pathogenetic hypotheses are reported. J. Cell. Physiol. 207: 300–308, 2006. © 2005 Wiley‐Liss, Inc.
Four novel RUNX2 mutations including a splice donor site result in the cleidocranial dysplasia phenotype
Authors: Kim Hyo‐Jin , Nam Soon‐Hyeun , Kim Hyun‐Jung , Park Hyo‐Sang , Ryoo Hyun‐Mo , Kim Shin‐Yoon , Cho Tae‐Joon , Kim Seung‐Gon , Bae Suk‐Chul , Kim In‐San , Stein Janet L. , van Wijnen Andre J. , Stein Gary S. , Lian Jane B. , Choi Je‐Yong
Published: November 2005

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder caused by haploinsufficiency of the RUNX2 gene. In this study, we analyzed by direct sequencing RUNX2 mutations from eleven CCD patients. Four of seven mutations were novel: two nonsense mutations resulted in a translational stop at codon 50 (Q50X) and 112 (E112X); a missense mutation converted arginine to glycine at codon 131 (R131G); and an exon 1 splice donor site mutation (donor splice site GT/AT, IVS1 + 1G > A) at exon 1–intron junction resulted in the deletion of QA stretch contained in exon 1 of RUNX2. We focused on the functional analysis of the IVS1 + 1G > A mutation. A full‐length cDNA of this mutation was cloned (RUNX2Δe1) and expressed in Chinese hamster ovary (CHO) and HeLa cells. Functional analysis of RUNX2Δe1 was performed with respect to protein stability, nuclear localization, DNA binding, and transactivation activity of a downstream RUNX2 target gene. Protein stability of RUNX2Δe1 is similar to wild‐type RUNX2 as determined by Western blot analysis. Subcellular localization of RUNX2Δe1, assessed by in situ immunofluorescent staining, was observed with partial retention in both the nucleus and cytoplasm. This finding is in contrast to RUNX2 wild‐type, which is detected exclusively in the nucleus. DNA binding activity was also compromised by the RUNX2Δe1 in gel shift assay. Finally, RUNX2Δe1 blocked transactivation of the osteocalcin gene determined by transient transfection assay. Our findings demonstrate for the first time that the CCD phenotype can be caused by a splice site mutation, which results in the deletion of N‐terminus amino acids containing the QA stretch in RUNX2 that contains a previously unidentified second nuclear localization signal (NLS). We postulate that the QA sequence unique to RUNX2 contributes to a competent structure of RUNX2 that is required for nuclear localization, DNA binding, and transactivation function. J. Cell. Physiol. 207: 114–122, 2006. © 2005 Wiley‐Liss, Inc.
Dengue in the Dominican Republic: Epidemiology for 2004
Authors: Cabrera‐Batista Brinia , Skewes‐Ramm Ronald , Fermin Cesar D. , Garry Robert F.
Published: November 2005

The Dominican Republic (DR) has experienced tremendous increase in the number of cases of dengue virus (DENV) reported in the past few years. There are four serotypes of DENV (1–4), and each can cause classic dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS). DENV‐1–4 are currently circulating in the DR; however, the Department of Epidemiology of the Dominican Republic (DIEGPI) has been able to isolate only DENV‐2 and DENV‐4. In the DR, the development of DENV infection occurred primarily in the second semester of the year. Since the DR instituted a vigilant approach to dengue infections, there have been three major outbreaks detected: one in 1998, one in 2000, and one in 2002. DF is the clinical presentation most currently seen at clinics, accounting for about 75% of cases, while patients with DHF account for about 19% of cases seen. Currently, there are seven provinces in which the total number of dengue cases per 100,000 inhabitants is higher than 32. With a vigilant approach, the DR should continue to see success in controlling the DENV outbreak. Microsc. Res. Tech. 68:250–254, 2005. © 2005 Wiley‐Liss, Inc.
HCV‐hepatocellular carcinoma: New findings and hope for effective treatment
Authors: Dash Srikanta , Haque Salima , Joshi Virendra , Prabhu Ramesh , Hazari Sidhartha , Fermin Cesar , Garry Robert
Published: November 2005

We present here a comprehensive review of the current literature plus our own findings about in vivo and in vitro analysis of hepatitis C virus (HCV) infection, viral pathogenesis, mechanisms of interferon action, interferon resistance, and development of new therapeutics. Chronic HCV infection is a major risk factor for the development of human hepatocellular carcinoma. Standard therapy for chronic HCV infection is the combination of interferon alpha and ribavirin. A significant number of chronic HCV patients who cannot get rid of the virus infection by interferon therapy experience long‐term inflammation of the liver and scarring of liver tissue. Patients who develop cirrhosis usually have increased risk of developing liver cancer. The molecular details of why some patients do not respond to standard interferon therapy are not known. Availability of HCV cell culture model has increased our understanding on the antiviral action of interferon alpha and mechanisms of interferon resistance. Interferons alpha, beta, and gamma each inhibit replication of HCV, and the antiviral action of interferon is targeted to the highly conserved 5′UTR used by the virus to translate protein by internal ribosome entry site mechanism. Studies from different laboratories including ours suggest that HCV replication in selected clones of cells can escape interferon action. Both viral and host factors appear to be involved in the mechanisms of interferon resistance against HCV. Since interferon therapy is not effective in all chronic hepatitis C patients, alternative therapeutic strategies are needed to treat chronic hepatitis C patients not responding to interferon therapy. We also reviewed the recent development of new alternative therapeutic strategies for chronic hepatitis C, which may be available in clinical use within the next decade. There is hope that these new agents along with interferon will prevent the occurrence of hepatocellular carcinoma due to chronic persistent hepatitis C virus infection. This review is not inclusive of all important scientific publications due to space limitation. Microsc. Res. Tech. 68:130–148, 2005. © 2005 Wiley‐Liss, Inc.
Alterations of lymphocyte membranes during HIV‐1 infection via multiple and simultaneous entry strategies
Authors: Fermin Cesar , Garry Robert
Published: November 2005

Human immunodeficiency virus type 1 (HIV‐1) must bind to and enter lymphocytes to replicate and cause the acquired immunodeficiency syndrome. The association of viral particles with the lymphocyte plasma membrane may vary according to a multitude of unknown variables, including lymphocyte membrane receptor mobilization, lipid raft aggregation, clathrin, caveolin, endosomes, microendosome‐mediated penetration or penetration through a hole in the membrane. The time course of this delivery appears to be short. Fusion of the virion membrane and lymphocyte plasma membrane leads to destabilization of the lymphocyte membrane. Five morphological stages of membrane alteration were observed in the infected lymphocytes: (1) swelling, (2) splitting, (3) fusion, (4) breaking, and (5) thinning of the lipid bilayer. These plasma membrane alterations were not contributed by fixation artifacts, because the dimensions and distance between the subunits of the surface glycoprotein (SU, gp120) and the transmembrane glycoprotein (gp41) of the viral particles adjacent to the infected cells and processed at the same time remained unchanged. Destabilization of lipid raft patches in the lymphocyte plasma membrane by unknown variables may facilitate HIV‐1 penetration of lymphocyte, and other cell types. This a combined review of the pertinent literature with our data showing that HIV‐1 may take advantage of multiple penetration approaches simultaneously in the same cell type (H9) to overwhelm the infected cells. The ultrastructural details of H9 cultured cells infected in vitro with HIV‐1 contribute to our understanding of viral particle association with the plasma membrane of infected cells. Microsc. Res. Tech. 68: 149–167, 2005. © 2005 Wiley‐Liss, Inc.
Dystrophin expression in the mdx mouse after localised and systemic administration of a morpholino antisense oligonucleotide
Authors: Fletcher Susan , Honeyman Kaite , Fall Abbie M. , Harding Penny L. , Johnsen Russell D. , Wilton Steve D.
Published: November 2005

Background

Duchenne and Becker muscular dystrophies are allelic disorders arising from mutations in the dystrophin gene. Duchenne muscular dystrophy is characterised by an absence of functional protein, while Becker muscular dystrophy is usually caused by in‐frame deletions allowing synthesis of some functional protein. Treatment options are limited, and we are investigating the potential of transcript manipulation to overcome disease‐causing mutations. Antisense oligonucleotides have been used to induce specific exon removal during processing of the dystrophin primary transcript and thereby by‐pass protein‐truncating mutations. The antisense oligonucleotide chemistry most widely used to alter pre‐mRNA processing is 2′‐O‐methyl‐modified bases on a phosphorothioate backbone.

Methods

The present studies evaluate 2′‐O‐methylphosphorothioate, peptide nucleic acid and morpholino antisense oligonucleotides in the mdx mouse model of muscular dystrophy, which has a nonsense mutation in exon 23 of the dystrophin gene.

Results

We demonstrate dystrophin expression in mdx mouse tissues after localised and systemic delivery of a morpholino antisense oligonucleotide designed to target the dystrophin exon 23 donor splice site.

Conclusions

The stability of the morpholino structural type, and the fact that it can be delivered to muscle in the absence of a delivery reagent, render this compound eminently suitable for consideration for therapeutic exon skipping to address dystrophin mutations. Copyright © 2005 John Wiley & Sons, Ltd.
Combinatorial engineering of a gene therapy vector: directed evolution of adeno‐associated virus
Authors: Perabo Luca , Endell Jan , King Susan , Lux Kerstin , Goldnau Daniela , Hallek Michael , Büning Hildegard
Published: November 2005

Background

Viruses are being exploited as vectors to deliver therapeutic genetic information into target cells. The success of this approach will depend on the ability to overcome current limitations, especially in terms of safety and efficiency, through molecular engineering of the viral particles.

Methods

Here we show that in vitro directed evolution can be successfully performed to randomize the viral capsid by error prone PCR and to obtain mutants with improved phenotype.

Results

To demonstrate the potential of this technology we selected several adeno‐associated virus (AAV) capsid variants that are less efficiently neutralized by human antibodies. These mutations can be used to generate novel vectors for the treatment of patients with pre‐existing immunity to AAV.

Conclusions

Our results demonstrate that combinatorial engineering overcomes the limitations of rational design approaches posed by incomplete understanding of the infectious process and at the same time offers a powerful tool to dissect basic viral biology by reverse genetics. Copyright © 2005 John Wiley & Sons, Ltd.
A note on the cover degeneracy of graphs
Authors: Zhang Li , Wu Baoyindureng
Published: November 2005

We give a 4‐chromatic planar graph, which admits a vertex partition into three parts such that the union of every two of them induces a forest. This solves a problem posed by Böhme. Also, by constructing an infinite sequence of graphs, we show that the cover degeneracy can be arbitrarily less than the chromatic number. © 2005 Wiley Periodicals, Inc. J Graph Theory
Brain and sensory organ morphology in Antarctic eelpouts (perciformes: Zoarcidae: Lycodinae)
Authors: Lannoo Michael J. , Eastman Joseph T.
Published: November 2005

Eelpouts of the family Zoarcidae comprise a monophyletic group of marine fishes with a worldwide distribution. Centers of high zoarcid diversity occur in the North Atlantic and North Pacific, with important radiations into the Arctic, along southern South America, and into the Southern Ocean around Antarctica. Along with snailfishes (Liparidae), zoarcids form an important component of the non‐notothenioid fauna in the subzero shelf waters of Antarctica. We document the anatomy and histology of the brains, cranial nerves, olfactory apparatus, cephalic lateral lines, taste buds, and retinas of three Antarctic zoarcid species, living at depths of 310–939 m, representing three of the nine genera from this region. The primary emphasis is on Ophthalmolycus amberensis, and we provide a detailed drawing of the brain and cranial nerves of this species. Although this brain reflects general perciform neural morphology, it exhibits a reduction of the (optic) tecta and the eminentia granulares and crista cerebellares of the lateral line system. Interspecific differences among the three species are slight. The olfactory rosette consists of three to four lamellae and the nasal sac, contrary to the claim of Fanta et al. ([2001] Antarct Rec, Natl Inst Polar Res, Tokyo 45:27–42), is not in communication with the cephalic lateral line system. Primary olfactory neurons are abundant and converge on branches of the olfactory nerve. Numerous taste buds are located in the lips. All three species lack an ocular choroid rete and have relatively thin retinas with a low cell density and a single bank of rods as the only type of photoreceptor. Neural diversification among Antarctic zoarcids has not involved the evolution of sensory specialists; brain and sensory organ morphologies do not approach the condition seen in primary deep‐sea fishes, or even that of some sympatric non‐perciform secondary deep‐sea fishes, including liparids and muraenolepidids (eel cods). There may be phylogenetic constraints on brain morphology in perciforms such that we do not see extreme specialization in sensory and neural systems for deep habitats. We suggest that the brains and sensory organs of Antarctic zoarcids reflect habitation of 500–2,000‐m depths and likely reflect morphologies seen in zoarcids living on continental slopes elsewhere in the world. This balance among the sensory modalities makes zoarcids relatively generalized among secondary deep‐sea fishes and may be one of the reasons this opportunistic and adaptable group has been successful in colonizing a variety of emergent and ephemeral habitats. J. Morphol. © 2005 Wiley‐Liss, Inc.
Magnetic susceptibility effects on the accuracy of MR temperature monitoring by the proton resonance frequency method
Authors: Boss Andreas , Graf Hansjörg , Müller‐Bierl Bernd , Clasen Stephan , Schmidt Diethard , Pereira Philippe L. , Schick Fritz
Published: November 2005

Purpose

To evaluate the error of MR temperature assessment based on the temperature‐dependent Larmor frequency shift of water protons, which can result from susceptibility effects caused by the radiofrequency (RF) applicator.

Materials and Methods

Local frequency shifts due to RF applicator displacements were simulated numerically by means of a three‐dimensional elementary dipole model. Experimental examinations using a water tank phantom equipped with a high‐precision screw thread were applied to examine temperature and movement effects for five commercially available, MR‐compatible RF applicators. Measurements were performed at 1.5 Tesla.

Results

For single‐needle electrodes perpendicular to the external field, a distortion of 0.1 ppm and 0.2 ppm was recorded at a distance of 17.5 mm and 12.5 mm, respectively, to the needle shaft. Cluster applicators and umbrella‐shaped applicators caused distortions of 0.1 ppm up to distances of 36 mm. Sinusoidal dependence on applicator orientation was found with the highest values for perpendicular orientation and the lowest values for orientation parallel to the magnetic field. With a single electrode oriented perpendicular to the field at a distance of 1.5 cm and 2.0 cm, a needle displacement of 5 mm led to an error in temperature measurement of 16.3°C and 7.5°C, respectively.

Conclusion

In MR temperature measurement, displacement of the RF applicator by patient movement or breathing leads to significant errors that have to be taken into account when PRF temperature maps are used to monitor tumor ablation in the presence of paramagnetic applicators. J. Magn. Reson. Imaging 2005. © 2005 Wiley‐Liss, Inc.