bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma‐polymerized surfaces for culture of human keratinocytes and transfer of cells to an in vitro wound‐bed model
Authors: Haddow D. B. , Steele D. A. , Short R. D. , Dawson R. A. , Macneil S.
Published: December 2002

The aim of this study was to develop plasma‐polymerized surfaces suitable for the attachment and culture of human keratinocytes and that would allow their subsequent transfer to a wound‐bed model. Keratinocyte attachment has been assessed on a carrier polymer, either untreated or treated with a hydrocarbon plasma polymer, collagen I, or carboxylic‐acid‐containing plasma copolymers. Cell attachment was poor on the “bare” carrier polymer and hydrocarbon plasma polymer (PP) surfaces. Cell attachment was good and comparable on collagen I‐coated carrier polymer and carrier polymer plasma coated with carboxylic acid functionalities. After 24 h of cell culture, surfaces were inverted so that cells were adjacent to a de‐epidermalized dermis (DED) for 4 days. After 4 days in contact with DED, the surfaces were removed and the level of residual cells and cells transferred to DED were assessed using a cell viability assay. Cell transfer from the collagen I‐coated surface was on the order of 90%. Transfer from the carrier polymer surface and the hydrocarbon‐coated surface was poor while cells cultured on acid‐containing surfaces showed high levels of transfer. Cell transfer was greatest from those surfaces containing the highest level of acid functionality (ca. 21%). Cell transfer was not significantly affected by the choice of carrier polymer material although some sample‐to‐sample variation was seen. To determine that plasma‐polymerized surfaces could be used clinically, selected samples were sterilized with ethylene oxide. Subsequent analysis and cell culture indicated that the surface chemistry and cell‐transfer capability of these plasma‐polymerized surfaces were unaffected by the sterilization procedure. Plasma‐polymerized carboxylic‐acid‐containing surfaces show great promise in the field of wound healing, encouraging keratinocyte attachment and permitting keratinocyte transfer to a wound bed. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 80–87, 2003
Theoretical analysis of adsorption thermodynamics for charged peptide residues on SAM surfaces of varying functionality
Authors: Basalyga Dina M. , Latour Robert A.
Published: December 2002

Cellular response to an implant is largely controlled by protein adsorption because cells directly interact with the adsorbed protein rather than the implant surface. Protein adsorption will occur when the change in Gibbs free energy (ΔG) of the system decreases during the adsorption process. Electrostatic interactions between charged peptide residues presented by a protein's surface and surface functional groups greatly contribute to the ΔG of protein adsorption. In this study, semiempirical molecular orbital calculations were used to theoretically determine the adsorption enthalpy between charged peptide residues [aspartic acid (−1), glutamic acid (−1), and arginine (+1)] and functionalized SAM surfaces [methyl, hydroxyl, amine (+1), and carboxylic acid (−1)]. Additional enthalpic and entropic contributions attributed to water restructuring effects were then approximated based on literature values for functional group solvation and considered along with the calculated enthalpy values to estimate the change in ΔG for each residue/surface system as a function of surface separation distance. The results predict long‐range attraction and repulsion to the opposite and same‐charge residue/surface systems, respectively, followed by strong short‐range repulsion caused by functional group dehydration. Short‐range repulsion alone was predicted for the charged residues on the methyl and hydroxyl surfaces. These results provide a theoretical quantitative description of fundamental mechanisms governing protein adsorption behavior and provide a basis for the development of a knowledge‐based surface design approach to control biological response. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 120–130, 2003
Comparison of failure characteristics of a range of cancellous bone–bone cement composites
Authors: Lucksanasombool P. , Higgs W. A. J. , Ignat M. , Higgs R. J. E. D. , Swain M. V.
Published: December 2002

Over the past decade, orthopedic surgery has embraced an increase in the depth of cement penetration into the adjacent cancellous bone structure. The resultant interdigitation transforms this zone into a thick layer of continuous interpenetrating composite material. The failure behavior of the composite formed with a number of potential bone cements with different bonding ability was investigated. The cancellous bone–cement composites exhibit considerable resistance to crack extension, and in situ optical observation indicates that the contribution of the cancellous bone is analogous to that of a typical fiber bridging process. The critical stress intensity factor and the work of fracture have been used to quantify the failure characteristics of the cancellous bone–cement composites. The nature of the crack propagation through these cement–bone composites was also captured via optical microscopy, and scanning electron microscopic images were taken of the failure surfaces. The R‐curve behavior, or crack extension characteristic, of the cancellous bone–cement composite was also determined. The interesting outcome is that the cancellous bone–PMMA (poly‐methylmethacrylate) composite, despite the absence of chemical bonding with bone, required the highest energy to fracture. In addition, the dimensional stability of the cement has a great effect on the interface. © 2002 Wiley Periodicals Inc. J Biomed Mater Res 64A: 93–104, 2003
Biomimetic PMMA‐based bone substitutes: A comparative in vitro evaluation of the effects of pulsed electromagnetic field exposure
Authors: Torricelli Paola , Fini M. , Giavaresi G. , Botter R. , Beruto D. , Giardino R.
Published: December 2002

Pulsed electromagnetic fields (PEMFs) are known to be effective in the stimulation of cultured osteoblasts and in vivo healing of delayed and nonunion fractures. In the present in vitro study the effects of PEMFs on osteoblastic cell cultures (MG63 human osteoblast‐like cells) grown in the presence of poly‐methylmethacrylate (PMMA) and of a biomimetic bone substitute made of a PMMA matrix added with alfa‐tricalcium phosphate (PMMA+α‐TCP) were evaluated, to assess the biological response at the cell‐biomaterial interaction. Cultures were stimulated with PEMFs (75 Hz, 2.3 mT, 1.3‐ms pulse duration) 12 h/day for 3 days and evaluations (MTT, ALP, OC, PICP, TGFβ‐1, IL‐6) were performed at 3 and 6 days. PMMA had a negative effect on osteoblasts, whereas PMMA+α‐TCP enhanced production of ALP, PICP, OC and TGFβ‐1, and reduced IL‐6 levels. Cells responded positively to PEMF stimulation even when cultured with a poorly biocompatible material, such as PMMA. This effect was more evident in the presence of PMMA+α‐TCP (further improvement in proliferation and synthetic activity) both at 3 and at 6 days. The properties of PMMA+α‐TCP look promising, and the present results support the use of PEMFs to improve tissue response to biomaterials implanted as bone substitutes. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 182–188, 2003
Differentiation of human bone‐derived cells grown on GRGDSP‐peptide bound titanium surfaces
Authors: Zreiqat H. , Akin F. Ahu , Howlett C. R. , Markovic B. , Haynes D. , Lateef S. , Hanley L.
Published: December 2002

Various surface modifications have been applied to titanium alloy (Ti‐6Al‐4V) implants, in an attempt to enhance osseointegration; crucial for ideal prosthetic fixation. Despite the numerous studies demonstrating that peptide‐modified surfaces influence in vitro cellular behavior, there is relatively little data reporting their effects on bone remodeling. The objective of this article was to examine the effects of chemically modifying Ti‐6Al‐4V surfaces with a common RGD sequence, a 15‐residue peptide containing GRGDSP (glycine‐arginine‐glycine‐aspartate‐serine‐proline), on the modulation of bone remodeling. The expression of proteins known to be associated with osseous matrix and bone resorption were studied during the growth of human bone‐derived cells (HBDC) on these peptide‐modified surfaces. HBDC grown for 7 days on RGD surfaces displayed significantly increased levels of osteocalcin, and pro‐collagen Iα1 mRNAs, compared with the production by HBDC grown on the native Ti‐6Al‐4V. A pattern that was also reflected at the protein levels for osteocalcin, type I collagen, and bone sialoprotein. Moreover, HBDC grown for 7 and 14 days on RGD‐modified Ti‐6Al‐4V expressed significantly higher level of osteoclast differentiation factors and lower levels of osteoprotegerin and IL‐6 proteins compared with other surfaces tested. These results suggest that different chemical treatments of implant material (Ti‐6Al‐4V) surface result in differential bone responses, not only their ability to form bone but also to stimulate osteoclastic formation. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 105–113, 2003
Low permeability biomedical polyurethane nanocomposites
Authors: Xu Ruijian , Manias Evangelos , Snyder Alan J. , Runt James
Published: December 2002

In this article we describe our continuing research on a novel nanocomposite approach for reducing gas permeability through biomedical polyurethane membranes. Nanocomposites were prepared using commercially available poly(urethane urea)s (PUU) and two organically modified layered silicates (OLS). Wide‐angle X‐ray diffraction experiments showed that the silicate layer spacing in the nanocomposites increased significantly compared with the neat OLS, signifying the formation of intercalated PUU/OLS structures. The nanocomposite materials exhibit increased modulus with increasing OLS content, while maintaining polymer strength and ductility. Water vapor permeability was reduced by about fivefold at the highest OLS contents, as a result of PUU/inorganic composite formation. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 114–119, 2003
Calcium and phosphate adsorption as initial steps of apatite nucleation on sol‐gel‐prepared titania surface
Authors: Coreño Juan , Martínez Antonia , Coreño Oscar , Bolarín Ana , Sánchez Félix
Published: December 2002

Titania powders have been prepared by the sol‐gel route from Ti (IV) ethoxide under acidic conditions. Adsorption experiments of calcium and phosphate ions on gel‐derived titania suspensions were performed to suggest a likely initial step of apatite growth on its surface. Experiments were performed as a function of time and pH at 37°C with and without NaCl present in the suspensions. Also, zeta (ζ) potential experiments were performed to determine the kind of calcium adsorption. Results suggest that, apparently, calcium and phosphate adsorption can act as two different initial steps for apatite growth. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 131–137, 2003
Effect of chitosan film containing basic fibroblast growth factor on wound healing in genetically diabetic mice
Authors: Mizuno Keisuke , Yamamura Keiko , Yano Kohji , Osada Takashi , Saeki Satomi , Takimoto Norio , Sakurai Tsunehisa , Nimura Yuji
Published: December 2002

Basic fibroblast growth factor (bFGF) has been shown to stimulate wound healing. However, consistent delivery of bFGF has been problematic. We studied the stability of bFGF incorporated into a chitosan film as a delivery vehicle for providing sustained release of bFGF. The therapeutic effect of this system on wound healing in genetically diabetic mice was determined as a model for treating clinically impaired wound healing. A chitosan film was prepared by freeze‐drying hydroxypropylchitosan (a water‐soluble derivative of chitosan) acetate buffer solution. Growth factor was incorporated into films before drying by mixing bFGF solution with the hydroxypropylchitosan solution. bFGF activity remained stable for 21 days at 5°C, and 86.2% of activity remained with storage at 25°C. Full‐thickness wounds were created on the backs of diabetic mice, and chitosan film or bFGF‐chitosan film was applied to the wound. The wound was smaller in after 5 days in both groups, but the wound was smaller on day 20 only in the bFGF‐chitosan group. Proliferation of fibroblasts and an increase in the number of capillaries were observed in both groups, but granulation tissue was more abundant in the bFGF‐chitosan group. These results suggest that chitosan itself facilitates wound repair and that bFGF incorporated into chitosan film is a stabile delivery vehicle for accelerating wound healing. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A:177–181, 2003
Synergistic effect of high‐affinity binding and flow preconditioning on endothelial cell adhesion
Authors: Mathur Anshu B. , Truskey George A. , Reichert William M.
Published: December 2002

The current study examined whether the combined introduction of high‐affinity avidin–biotin bonds and fibronectin–integrin bonds (i.e., dual ligand treatment) would further augment the adhesion of flow‐preconditioned endothelial cells to model substrates via contributions to the actin cytoskeleton and the formation of focal contacts. Human umbilical vein endothelial cells (HUVEC) were grown under static conditions or exposed to a flow‐preconditioning regimen for 24 h. Cell retention was determined by exposure to 75 dynes/cm2. The combination of flow preconditioning and the dual ligand treatment yielded higher cell retention under flow compared to the cells adherent via fibronectin–integrin bonds only. This increase in adhesion strength correlated with a greater focal contact area. Elongation of the HUVEC occurred after exposure to flow preconditioning; however, orientation of dual ligand adherent cells was restricted due to the presence of the high‐affinity ligand. Flow‐preconditioned cells showed increased stress fiber formation compared to nonconditioned cells although the stress fibers per cell for flow‐preconditioned cells were the same on both the ligand systems employed. The results indicate that enhanced adhesion strength is due to a combination of increased focal contact area, stress fiber formation, and cell alignment. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 155–163, 2003
Structural dependence of apatite formation on titania gels in a simulated body fluid
Authors: Uchida Masaki , Kim Hyun‐Min , Kokubo Tadashi , Fujibayashi Shunsuke , Nakamura Takashi
Published: December 2002

The apatite‐forming ability of titania gels with different structures has been investigated in a simulated body fluid with ion concentrations nearly equal to those of human blood plasma. Titania gels with an amorphous structure or with an anatase or rutile structure were prepared by the sol‐gel process with a subsequent heat treatment at various temperatures. The titania gels with an amorphous structure did not induce apatite formation on their surfaces in the simulated body fluid , whereas gels with an anatase or rutile structure induced apatite formation on their surfaces. The deposition of apatite was more pronounced on the anatase gels than on the rutile gels. This indicates that a specific structure of titania is effective in inducing apatite formation in a body environment. Such a specific structure was assumed in this study to be the crystalline planar arrangement in the anatase structure, which facilitates epitaxy of the apatite crystal. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 164–170, 2003
Type I collagen production by osteoblast‐like cells cultured in contact with different bioactive glasses
Authors: Bosetti Michela , Zanardi Laura , Hench Larry , Cannas Mario
Published: December 2002

Bioactive glasses are silica‐based, surface‐active bone substitutes that have shown good biocompatibility both in bone and in soft tissue and are used in oral and maxillofacial bone augmentation. Previous in vitro studies showing that bioactive glasses support the growth and maturation of rat osteoblast‐like cells and promote the expression and maintenance of the osteoblastic phenotype have suggested that there is both a solution‐mediated and a surface‐controlled effect on cell activity. In this study, we investigated the behavior of human primary osteoblast‐like cells cultured in contact with three different bioactive glasses and compared them with amorphous silica (SiO2) used in the form of granules. The specific activity of alkaline phosphatase determined biochemically was significantly higher at 2 and 4 days on the bioactive glass with 46.1 mol % silica content (45S5 Bioglass®) cultures than in the control cultures and in the bioactive gel‐glass cultures, which had 60 mol % (58S) and 80 mol % (77S) silica content. Osteoblasts synthesize collagen type I, which is subsequently mineralized. Immunoblot and biochemical studies showed increased collagen release from osteoblast‐like cells cultured in contact with bioactive glasses over that of controls. Among the three bioactive glasses, 45S5 is the highest inducer of osteoblast‐like cell collagen release; moreover, mRNA for type I collagen was stimulated approximately three‐ to fivefold after 45S5 treatment. 77S bioactive glass similarly increased type I collagen synthesis even though alkaline phosphatase was not higher. These results suggest that 45S5 Bioglass® not only induces osteogenic differentiation of human primary osteoblast‐like cells, but can also increase collagen synthesis and release. The newly formulated bioactive gel‐glass 77S seems to have potential applications for tissue engineering, inducing increased collagen synthesis. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 189–195, 2003
Effect of the chemical composition of Ricinus communis polyurethane on rat bone marrow cell attachment, proliferation, and differentiation
Authors: Beloti Márcio M. , Hiraki Karen R. N. , Barros Valdemar M. R. , Rosa Adalberto L.
Published: December 2002

Alterations in the chemical composition of a polymer may be undertaken to improve its biological properties. The aim of this study was to investigate the in vitro biocompatibility of Ricinus communis polyurethane (RCP) with three different chemical compositions: RCPp (pure RCP), RCP+CaCO3, and RCP+Ca3(PO4)2. Rat bone marrow cells were cultivated under conditions that allowed osteoblastic differentiation and were evaluated for cell attachment, cell proliferation, cell morphology, total protein content, alkaline phosphatase (ALP) activity, and bonelike nodule formation. For the evaluation of attachment, cells were cultured for 4 h. After 3 days, cell morphology was evaluated. Cell proliferation was evaluated after 7 and 14 days. Total protein content and ALP activity were evaluated after 14 days. For bonelike nodule formation, cells were cultured for 21 days. Data were compared with an analysis of variance and Duncan's multiple range test when appropriate. Cell attachment and ALP activity were not affected by RCP chemical composition. Proliferation, total protein content, and bonelike nodule formation were all affected by RCP chemical composition. These results suggest that initial cell events are not affected by RCP chemical composition, whereas RCPs blended with calcium carbonate or, better yet, calcium phosphate, by favoring events that promote matrix mineralization, are more biocompatible materials. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 171–176, 2003
Maximal flow rates and sieving coefficients in different plasmafilters: Effects of increased membrane surfaces and effective length under standardized in vitro conditions
Authors: Unger J.K. , Haltern C. , Dohmen B. , Rossaint R.
Published: December 2002

In Europe, capillary membrane filters are the favored method for plasmapheresis and detoxification systems including a plasma separation unit. Using capillary membrane filters clearance depends on the filtration rate and the sieving coefficient (Qs) for the plasma substrates. We investigated whether the increase of the effective membrane surface of plasmafilters enables higher clearance rates than a small plasmafilter. Heparinized porcine blood (5 I.U./l) of healthy pigs was used for an in vitro circuit. Filter types used were from GAMBRO: n = 5 PF1000N (effective membrane surface: 0.15 m2), n = 4 PF2000N (0.35) and from ASAHI: n = 4 PLASMAFLO OP‐05W (L) (0.5). Spontaneous hemolysis was chosen to indicate the individual threshold limit for maximal flow rates. Sieving coefficient was determined for ten parameters at lowest and highest blood flow (Qb) and filtration rates (Qf). PF1000N enabled maximal flow rates as high as PF2000N and PLASMAFLO (Qb/Qf in ml/min: 200/40). Qs for most substrates were similar between the filter types and the flow rates. Compared to PLASMAFLO, the filter type with the largest membrane surface, the PF1000N provided significantly better Qs for triglycerides and albumin and a trend for a better elimination of cholesterol, GGT, and LDH. The sieving properties of the PF2000N ranged between PF1000N and PLASMAFLO. Under standardized in vitro conditions, the larger plasmafilters tested did not improve the overall performance of the plasmapheresis procedure. Thus, enlargement of the membrane surface such as provided by two commercially available and clinically well‐established plasmafilters could not be proven to enable higher clearance rates. J. Clin. Apheresis 17:190–198, 2002. © 2002 Wiley‐Liss, Inc.
A randomized comparison of plateletpheresis with the same donors using four blood separators at a single blood center
Authors: Tenorio Grace C. , Strauss Ronald G. , Wieland Martha J. , Behlke Timothy A. , Ludwig Gerald A.
Published: December 2002

At one blood center, each of 20 donors underwent plateletpheresis on four blood cell separators in random order. We compared the CS3000+, Amicus V 2.41, MCS Plus, and Spectra LRS V 7 Turbo regarding platelet (PLT) yield, pre‐ and post‐procedure PLT counts, percent fall in donor PLT count, process time, efficiency, PLT product and donor PLT volume (MPV). Using ≥ 150 × 109 PLTs/L pre‐donation counts, a goal was set of 4.5 × 1011 PLTs unit in up to 100 minutes processing time. Results were (mean values) PLT yields of Amicus, Spectra, CS3000+, and MCS Plus: 4.3, 4.6, 4.3, 4.0 × 1011 PLTS, respectively; percent donor PLT fall: 24, 32, 30, 29%, respectively; processing times: 50, 74, 87, 101 minutes, respectively; relative efficiency (RE): 2.2, 1.6, 1.2,1.0, respectively (based on the MCS Plus performance with RE of 1 = 4 × 109 PLTS/min); PLT product MPV: 6.7, 7.4, 6.8,7.1 fL, respectively; pre‐procedure donor MPV: 7.7, 7.3, 7.6 and 7.6 fL, respectively; and percent donor MPV change: −5.2, 0, −6.6, and −10%, respectively. Significant changes in the donor MPV were noted (P < 0.05) but could not be related to product MPV. Spectra seemed to collect larger PLTs (higher MPV); the significance remains unknown for both donors and recipients. Importantly, all four separators gave acceptable and comparable PLT yields (P < 0.05) with Spectra trending higher. The short process time and high RE together indicate highly efficient collections particularly by Amicus and Spectra. J. Clin. Apheresis 17:170–176, 2002. © 2002 Wiley‐Liss, Inc.
First two patients with ulcerative colitis who developed classical thrombotic thrombocytopenic purpura successfully treated with medical therapy and plasma exchange
Authors: Baron Beverly W. , Jeon Hye‐Ran , Glunz Catherine , Peterson Amy , Cohen Russell , Hanauer Stephen , Rubin David , Hart John , Baron Joseph M.
Published: December 2002

The association of ulcerative colitis (UC) and thrombotic thrombocytopenic purpura (TTP) is rare. Only one prior patient with these two syndromes has been reported in the literature. In that case, splenectomy and proctectomy were performed to control the symptoms of TTP. We present two patients with UC who developed TTP and were successfully treated with multiple plasma exchanges (PEXs) in conjunction with medical therapy without the necessity for surgical intervention. Acquired TTP may be another extraintestinal autoimmune feature of UC. TTP in association with UC may be refractory to high‐dose steroids and PEX, possibly requiring vincristine and splenectomy, as in the one previously reported case, to achieve remission. J. Clin. Apheresis 17:204–206, 2002. © 2002 Wiley‐Liss, Inc.
Extracorporeal photopheresis reduces the number of mononuclear cells that produce pro‐inflammatory cytokines, when tested ex‐vivo
Authors: Bladon John , Taylor Peter
Published: December 2002

Extracorporeal photopheresis (ECP) has been shown to be clinically effective in the treatment of many T cell–mediated conditions. ECP's mechanism of action includes the induction of apoptosis and the release of pro‐inflammatory cytokines. Recently, we have observed early lymphoid apoptosis, detectable immediately post ECP. We were interested to determine what influence ECP has on pro‐inflammatory cytokine secretion at this early pre‐infusion stage. Samples from 6 cutaneous T cell lymphoma (CTCL) and 5 graft versus host disease (GvHD) patients were taken pre ECP and immediately post ECP, prior to re‐infusion. Following separation, the PBMCs were added to a cell culture medium and stimulated with PMA, Ionomycin, and Brefeldin A for 6 hours. Using flow cytometry, intracellular cytokine expression of IFNγ and TNFα was determined in the T cell population. The monocytes were evaluated for IL6, IFNγ, IL12, and TNFα. For both patient groups, the number of IFNγ‐expressing T cells fell significantly at re‐infusion, whilst both T cell‐ and monocyte‐expressing TNFα levels were reduced at re‐infusion. All other cytokines tested showed no significant change post ECP. For GvHD, pro‐inflammatory cytokines have a pathological role. Their down‐regulation may have a direct clinical benefit. However, the reduction in the number of IFNγ‐ and TNFα‐expressing mononuclear cells means, at this early stage, it is unlikely that these cytokines assist in the removal of the malignant Th2 cells present in CTCL. J. Clin. Apheresis 17:177–182, 2002. © 2002 Wiley‐Liss, Inc.
MOPED: Method for optimizing physical energy parameters using decoys
Authors: Seok Chaok , Rosen J. B. , Chodera John D. , Dill Ken A.
Published: December 2002

We present a method called MOPED for optimizing energetic and structural parameters in computational models, including all‐atom energy functions, when native structures and decoys are given. The present method goes beyond previous approaches in treating energy functions that are nonlinear in the parameters and continuous in the degrees of freedom. We illustrate the method by improving solvation parameters in the energy function EEF1, which consists of the CHARMM19 polar hydrogen force field augmented by a Gaussian solvation term. Although the published parameters for EEF1 correctly discriminate the native from decoys in the decoy sets of Levitt et al., they fail on several of the more difficult decoy sets of Baker et al. MOPED successfully finds improved parameters that allow EEF1 to discriminate native from decoy structures on all protein structures that do not have metals or prosthetic groups. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 89–97, 2003
Fast approximate methods for calculating nucleic acid base pair interaction energies
Authors: Sherer Edward C. , York Darrin M. , Cramer Christopher J.
Published: December 2002

Interaction enthalpies for six base pairs have been computed at a variety of efficient levels of electronic structure theory and compared to experiment. In addition to previously defined levels of theory, modified Hamiltonians with adjusted parameters in hybrid Hartree–Fock/density functionals and semiempirical neglect‐of‐diatomic‐differential‐overlap models were examined. Of the pure and hybrid density functional levels, mPWPW91/MIDI! performed most satisfactorily, as judged by comparison not only to the available experimental data, but also to data from more robust electronic structure methods for 22 additional base pairs. The low computational cost of the mPWPW91/MIDI! model was further exploited in an investigation of various base trimers, tetramers, and one base pentamer. A carefully reparameterized semiempirical model, PM3BP, was able to achieve similar levels of accuracy at a still greater savings in terms of computational effort. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 57–67, 2003
Catalysis on the coastline: Theozyme, molecular dynamics, and free energy perturbation analysis of antibody 21D8 catalysis of the decarboxylation of 5‐nitro‐3‐carboxybenzisoxazole
Authors: Ujaque Gregori , Tantillo Dean J. , Hu Yunfeng , Houk K. N. , Hotta Kinya , Hilvert Donald
Published: December 2002

Antibody 21D8 catalyzes the decarboxylation of 5‐nitro‐3‐carboxybenzisoxazole. The hapten used was designed to induce an antibody binding site with anion binders for the carboxylate, plus a nonpolar environment to accelerate decarboxylation. A recent X‐ray crystal structure of 21D8 has shown that the binding pocket contains an array of both polar and charged residues. Nevertheless, 21D8 is able to catalyze a reaction that involves a decrease in polarity from reactant to transition state. The origins of this phenomenon were explored using various computational strategies—quantum mechanics, theozyme models, docking, molecular dynamics, free energy perturbation, and linear interaction energy—the combination of which has produced a consistent picture of catalysis. By partially desolvating the charged carboxylate, 21D8 manages to effect “catalysis on the coastline,” without burying the carboxylate in a nonpolar region of the binding pocket. The results have implications for that broad class of enzyme and antibody catalyzed reactions that involve the conversion of a substrate with a relatively localized charge into a transition state with a highly dispersed charge. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 98–110, 2003
The intramolecular mechanism for the second proton transfer in triosephosphate isomerase (TIM): A QM/FE approach
Authors: Alagona Giuliano , Ghio Caterina , Kollman Peter A.
Published: December 2002

The intramolecular mechanism we earlier proposed [Alagona, G.; Desmeules, P.; Ghio, C.; Kollman, P. A. J Am Chem Soc 1984, 106, 3623] for the second proton transfer of the reaction catalyzed by triosephosphate isomerase (TIM) is examined ab initio at the HF and MP2/6‐31+G** levels in vacuo for two conformers of the enediolate phosphate (ENEP), with the ethereal oxygen of the phosphate group either syn (X), as in the crystal structure, or anti (Y) with respect to the enediolate carbonyl O. The barrier height for the intramolecular proton transfer occurring in enediolate is very sensitive to electron correlation corrections. The MP2 internal energy barrier is much lower than the HF one, while the free energy (FE) barrier is even more favorable, indicating that the enzyme presence is not requested to speed up that step. An investigation of the dynamical aspects of the mechanism, along the pathway from ENEP A (with H on O1) to TS and from TS to ENEP B (with H on O2), was, however, carried out in the presence of the enzyme field while using a neutral His‐95 with its proton on Nδ. To perform the FE simulations, it was necessary to parametrize in the AMBER force‐field the ENEP A, TS and B species, whose partial charges have been determined with the RESP procedure, with the X and Y arrangements of the phosphate head. Actually, the FE/QM approach produced a low barrier and a substantial balance between A and B, especially at the MP2 level. The trajectories, analyzed paying a particular attention to the positions assumed by His‐95 and by the other active site residues, put forward somewhat different H‐bond patterns around the X or Y enediolate phosphate. © 2002 Wiley Periodicals, Inc. J Comput Chem 1: 46–56, 2003
Transferability of fragmental contributions to the octanol/water partition coefficient: An NDDO‐based MST study
Authors: Curutchet C. , Salichs A. , Barril X. , Orozco Modesto , Javier Luque F.
Published: December 2002

This study examines the transferability of fragmental contributions to the octanol/water partition coefficient. As a previous step, we report the parameterization of the AM1 and PM3 versions of the MST model for n‐octanol. The final AM1 and PM3 MST models reproduce the experimental free energy of solvation and the octanol/water partition coefficient (log Pow) with a root‐mean‐square deviation of around 0.7 kcal/mol and 0.5 (in units of log P), respectively. Based on this parameterization, an NNDO‐based procedure is presented to dissect the free energy of transfer between octanol and water in contributions directly associated with specific atoms or functional groups. The application of this procedure to a set of representative molecular systems illustrates the dependence of the log Pow fragmental contribution due to electronic, hydrogen bonding, and steric effects, which cannot be easily accounted for in simple additive‐based empirical schemes. The results point out the potential use of theoretical methods to refine the fragmental contributions in empirical methods. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 32–45, 2003
Motifs in nucleic acids: Molecular mechanics restraints for base pairing and base stacking
Authors: Harvey Stephen C. , Wang Chunlin , Teletchea Stephane , Lavery Richard
Published: December 2002

In building and refining nucleic acid structures, it is often desirable to enforce particular base pairing and/or base stacking interactions. Energy‐based modeling programs with classical molecular mechanics force fields do not lend themselves to the easy imposition of penalty terms corresponding to such restraints, because the requirement that two bases lie in or near the same plane (pairing) or that they lie in parallel planes (stacking) cannot be easily expressed in terms of traditional interactions involving two atoms (bonds), three atoms (angles), or four atoms (torsions). Here we derive expressions that define a collection of pseudobonds and pseudoangles through which molecular mechanics restraints for base pairing and stacking can be imposed. We have implemented these restraints into the JUMNA package for modeling DNA and RNA structures. JUMNA scripts can specify base pairing with a variety of standard geometries (Watson–Crick, Hoogsteen, wobble, etc.), or with user‐defined geometries; they can also specify stacking arrangements. We have also implemented “soft‐core” functions to modify van der Waals and electrostatic interactions to avoid steric conflicts in particularly difficult refinements where two backbones need to pass through one another. Test cases are presented to show the utility of the method. The restraints could be adapted for implementation in other molecular mechanics packages. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 1–9, 2003
Molecular mechanics force‐field development for amino acid zwitterions
Authors: Kirschner K. N. , Lewin A. H. , Bowen J. P.
Published: December 2002

Understanding the conformational flexibility of amino acid zwitterions (ZWs) and their associated conformational energies is crucial for predicting their interactions in biological systems. Gas‐phase ab initio calculations of ZWs are intractable. Molecular mechanics (MM), on the other hand, is able to handle large systems but lacks the necessary force field parameters to model ZWs. To develop force field parameters that are able to correctly model ZW geometries and energetics we used a novel combinatorial approach: amino acid ZWs were broken down structurally into key functional components, which were parameterized separately. Møller–Plesset second‐order perturbation calculations on small carboxylates, on the glycine cation, and on novel hydrogen bonded systems, coupled with available experimental data, were used to generate MM3(2000) ZW parameters (Allinger N. L.; Yuh, Y. H.; Lii, J.‐H. J Am Chem Soc 1989, 111, 8551). The MM3 results from this combinatorial approach gave geometries that are in good agreement with neutron diffraction experiments, plus their frequencies and energies appear to be reasonably modeled. Current limitations and future development of MM force fields are discussed briefly. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 111–128, 2003
Conformational analysis by intersection: CONAN
Authors: Smellie Andrew , Stanton Robert , Henne Randy , Teig Steve
Published: December 2002

As high throughput techniques in chemical synthesis and screening improve, more demands are placed on computer assisted design and virtual screening. Many of these computational methods require one or more three‐dimensional conformations for molecules, creating a demand for a conformational analysis tool that can rapidly and robustly cover the low‐energy conformational spaces of small molecules. A new algorithm of intersection is presented here, which quickly generates (on average <0.5 seconds/stereoisomer) a complete description of the low energy conformational space of a small molecule. The molecule is first decomposed into nonoverlapping nodes N (usually rings) and overlapping paths P with conformations (N and P) generated in an offline process. In a second step the node and path data are combined to form distinct conformers of the molecule. Finally, heuristics are applied after intersection to generate a small representative collection of conformations that span the conformational space. In a study of ∼97,000 randomly selected molecules from the MDDR, results are presented that explore these conformations and their ability to cover low‐energy conformational space. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 10–20, 2003
Cool walking: A new Markov chain Monte Carlo sampling method
Authors: Brown Scott , Head‐Gordon Teresa
Published: December 2002

Effective relaxation processes for difficult systems like proteins or spin glasses require special simulation techniques that permit barrier crossing to ensure ergodic sampling. Numerous adaptations of the venerable Metropolis Monte Carlo (MMC) algorithm have been proposed to improve its sampling efficiency, including various hybrid Monte Carlo (HMC) schemes, and methods designed specifically for overcoming quasi‐ergodicity problems such as Jump Walking (J‐Walking), Smart Walking (S‐Walking), Smart Darting, and Parallel Tempering. We present an alternative to these approaches that we call Cool Walking, or C‐Walking. In C‐Walking two Markov chains are propagated in tandem, one at a high (ergodic) temperature and the other at a low temperature. Nonlocal trial moves for the low temperature walker are generated by first sampling from the high‐temperature distribution, then performing a statistical quenching process on the sampled configuration to generate a C‐Walking jump move. C‐Walking needs only one high‐temperature walker, satisfies detailed balance, and offers the important practical advantage that the high and low‐temperature walkers can be run in tandem with minimal degradation of sampling due to the presence of correlations. To make the C‐Walking approach more suitable to real problems we decrease the required number of cooling steps by attempting to jump at intermediate temperatures during cooling. We further reduce the number of cooling steps by utilizing “windows” of states when jumping, which improves acceptance ratios and lowers the average number of cooling steps. We present C‐Walking results with comparisons to J‐Walking, S‐Walking, Smart Darting, and Parallel Tempering on a one‐dimensional rugged potential energy surface in which the exact normalized probability distribution is known. C‐Walking shows superior sampling as judged by two ergodic measures. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 68–76, 2003
Using PC clusters to evaluate the transferability of molecular mechanics force fields for proteins
Authors: Okur Asim , Strockbine Bentley , Hornak Viktor , Simmerling Carlos
Published: December 2002

The transferability of molecular mechanics parameters derived for small model systems to larger biopolymers such as proteins can be difficult to assess. Even for small peptides, molecular dynamics simulations are typically too short to sample structures significantly different than initial conformations, making comparison to experimental data questionable. We employed a PC cluster to generate large numbers of native and non‐native conformations for peptides with experimentally measured structural data, one predominantly helical and the other forming a β‐hairpin. These atomic‐detail sets do not suffer from slow convergence, and can be used to rapidly evaluate important force field properties. In this case a suspected bias toward α‐helical conformations in the ff94 and ff99 force fields distributed with the AMBER package was verified. The sets provide critical feedback not only on force field transferability, but may also predict modifications for improvement. Such predictions were used to modify the ff99 parameter set, and the resulting force field was used to test stability and folding of model peptides. Structural behavior during molecular dynamics with the modified force field is found to be very similar to expectations, suggesting that these basis sets of conformations may themselves have significant transferability among force fields. We continue to improve and expand this data set and plan to make it publicly accessible. The calculations involved in this process are trivially parallel and can be performed using inexpensive personal computers with commodity components. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 21–31, 2003
Inherent speedup limitations in multiple time step/particle mesh Ewald algorithms
Authors: Barash Danny , Yang Linjing , Qian Xiaoliang , Schlick Tamar
Published: December 2002

Multiple time step (MTS) algorithms present an effective integration approach to reduce the computational cost of dynamics simulations. By using force splitting to allow larger time steps for the more slowly varying force components, computational savings can be realized. The Particle‐Mesh‐Ewald (PME) method has been independently devised to provide an effective and efficient treatment of the long‐range electrostatics interactions. Here we examine the performance of a combined MTS/PME algorithm previously developed for AMBER on a large polymerase β/DNA complex containing 40,673 atoms. Our goal is to carefully combine the robust features of the Langevin/MTS (LN) methodology implemented in CHARMM—which uses position rather than velocity Verlet with stochasticity to make possible outer time steps of 150 fs—with the PME formulation. The developed MTS/PME integrator removes fast terms from the reciprocal‐space Ewald component by using switch functions. We analyze the advantages and limitations of the resulting scheme by comparing performance to the single time step leapfrog Verlet integrator currently used in AMBER by evaluating different time‐step protocols using three assessors for accuracy, speedup, and stability, all applied to long (i.e., nanosecond) simulations to ensure proper energy conservation. We also examine the performance of the algorithm on a parallel, distributed shared‐memory computer (SGI Origin 2000 with 8 300‐MHz R12000 processors). Good energy conservation and stability behavior can be demonstrated, for Newtonian protocols with outer time steps of up to 8 fs and Langevin protocols with outer time steps of up to 16 fs. Still, we emphasize the inherent limitations imposed by the incorporation of MTS methods into the PME formulation that may not be widely appreciated. Namely, the limiting factor on the largest outer time‐step size, and hence speedup, is an intramolecular cancellation error inherent to PME. This error stems from the excluded‐nonbonded correction term contained in the reciprocal‐space component. This cancellation error varies in time and introduces artificial frequencies to the governing dynamics motion. Unfortunately, we find that this numerical PME error cannot be easily eliminated by refining the PME parameters (grid resolution and/or order of interpolating polynomial). We suggest that methods other than PME for fast electrostatics may allow users to reap the full advantages from MTS algorithms. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 77–88, 2003
Qualitative analysis of social support and conflict among Mexican and Mexican‐American disaster survivors
Authors: Ibañez Gladys E. , Khatchikian Nadya , Buck Chad A. , Weisshaar Deborah L. , Abush‐Kirsh Tsila , Lavizzo Evelyn A. , Norris Fran H.
Published: December 2002

We describe in this study the various ways that survivors may experience social support and conflict after a disaster. Using unstructured interviews, 25 Mexicans/Mexican Americans (14 women, 11 men) were asked to recount the ways that they received support, as well as the ways they experienced conflict. Interviews occurred across three cities: Guadalajara, Jalisco (n = 9), Homestead, Florida (n = 6), and Puerto Angel, Oaxaca (n = 10). Recurrent themes were found for both support and conflict. Survivors reported more support from informal sources (family, neighbors) than formal sources (government) and far more tangible (food, shelter) than emotional or informational support. Conflict themes were different for each city. In Mexico, reports of conflict were more likely to involve abuses by government officials while in Homestead conflict involved abuses by residents. Theoretical and practical implications for future disaster research in developing countries are discussed. © 2003 Wiley Periodicals, Inc.
Paths to psychological empowerment in an urban community: Sense of community and citizen participation in substance abuse prevention activities
Authors: Peterson N. Andrew , Reid Robert J.
Published: December 2002

Empowerment represents a promising intervention target for substance abuse prevention activities. To date, however, there has been a paucity of research examining the role of empowerment processes engaged in by citizens within substance abuse prevention contexts. Addressing this concern, this study tested a path model that included perceptions of person, situation, and environment‐related predictors of empowerment. The hypothesized model was found to fit data from a sample of randomly selected urban residents (n = 661) who participated in an evaluation of a Center for Substance Abuse Prevention (CSAP) Community Partnership. Findings elucidate the need for developing substance abuse prevention initiatives that promote empowerment by increasing participation in substance abuse prevention activities, with particular emphasis on incorporating strategies designed to improve sense of community. Limitations of the study and directions for future research are discussed. © 2003 Wiley Periodicals, Inc.
Spousal relations and well‐being: A comparative analysis of Jewish and Arab dual‐earner families in Israel
Authors: Kulik Liat , Rayyan Faisal
Published: December 2002

The study examined differences in division of household tasks and spousal support among a sample of educated dual‐earner families from two national groups in Israel: Jews (n = 116), and Arabs (n = 163). The contribution of the spousal interaction variables (household roles and spousal support) toward explaining two dimensions of psychological well‐being (burnout and life satisfaction) was also examined. The research findings indicate that in general, the Arabs maintain a more traditional orientation toward gender roles than their Jewish counterparts. Arab men showed a greater tendency to perform outside tasks than their Jewish counterparts who participate more in domestic chores. By contrast, no differences were found between the two groups with regard to the mutual support provided by spouses. Gender role attitudes were found to be a key predictor of the two psychological well‐being dimensions in both national groups. Regarding sex differences, men of both nationalities were more likely than women to report that they perform all types of household tasks. Concomitantly, the women reported higher levels of burnout, while no differences between the sexes were found with respect to life satisfaction. © 2003 Wiley Periodicals, Inc.