bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of thin hydroxyapatite layers formed on anodic titanium oxide films containing Ca and P by hydrothermal treatment
Authors: Ishizawa Hitoshi , Ogino Makoto
Published: December 2004

An anodic titanium oxide film containing Ca and P (AOFCP) was formed on commercially pure titanium which was anodized in an electrolytic solution of dissolved β‐glycerophosphate (β‐GP) and calcium acetate (CA). Hydroxyapatite (HA) crystals were precipitated by hydrothermally heating the AOFCP at 300°C. After hydrothermal treatment, the film was characterized by scanning electron microscopy (SEM), energy‐dispersive X‐ray microanalysis (EDX), and tensile tests. The morphology, composition, and amount of HA crystals precipitated were significantly affected by the composition of the electrolytes. Nearstoichiometric HA crystals with high crystallinity were precipitated completely covering the AOFCP surface at specific electrolyte concentrations. The HA layers were thin at 1–2 μm in thickness. The adhesive strength of the film increased with decreasing electrolyte concentration and the maximum value was about 40 MPa. In vitro tests for 300 days suggested that the stability of the film was high. The high adhesive strength may result from the AOFCP existing as an intermediate layer between the HA layer and a titanium substrate. The intervention of the AOFCP may have prevented abrupt changes in Ca and P content at an HA coating‐titanium interface as seen in a plasma‐sprayed one. The porous TiO2 matrix of the AOFCP may be suitable for nucleation sites of HA crystals, as well as SiO2 matrix of silicate bioactive glasses or glass ceramics. © 1995 John Wiley & Sons, Inc.
Cellular responses to chemical and morphologic aspects of biomaterial surfaces. II. The biosynthetic and migratory response of bone cell populations
Authors: Chesmel K. D. , Clark C. C. , Brighton C. T. , Black J.
Published: December 2004

The biosynthetic and migratory response of bone cells to changes in both surface composition and morphology of polystyrene (PS) substrates was examined. A system was devised wherein micromachined silicon wafers were used as templates to solvent‐cast PS replicas [using 0, 1, or 2 wt % styrene (S) monomer additions] with either 0.5‐ or 5.0‐ μm‐deep surface grooves. Smooth replicas (0% S) served as the control surfaces. The chemical and morphologic characteristics of the nine unique model biomaterial surfaces (MBSs) produced using this system were documented and were found to be distinct. For the biosynthetic studies, bone cells isolated from neonatal rat calvaria were plated onto the MBSs and labeled at postconfluence with [14C]proline for 24 h. Total DNA per surface, total newly synthesized collagenous (CP), and noncollagenous protein (NCP) (cell associated and secreted) were determined. Cell‐associated CP was found to increase significantly for the bone cells cultured on the substrates with 0.5‐μm grooves and 2% S (P < .05). Cell‐associated NCP was found to be elevated for all 2% S substrates and for the 0.5‐μm grooves substrates with 1% S. For the migration studies, bone cells were plated first onto 5‐mm nitrocellulose disks that were attached to standard Petri dishes using a plasma clot. At confluence, the disks were removed aseptically and placed on the replicas. The cellular area occupied as a result of the outward migration of the bone cells was measured after 4 days of culture using an image analysis system. An average velocity for the leading edge of bone cell populations on each of the nine MBSs was calculated: Cells on surfaces with either 1% S or 5.0‐μm grooves displayed significantly higher velocities than did the control cultures. A significant interaction effect between chemistry and morphology was observed. The biosynthetic and migratory responses of in vitro cultures of bone cells were not predictable from the observations of the cellular responses to the individual features, but appeared to depend on cellular responses to more than one substrate factor. © 1995 John Wiley & Sons, Inc.
Study of aging of silicone rubber biomaterials with NMR
Authors: Pfleiderer Bettina , Xu Ping , Ackerman Jerome L. , Garrido Leoncio
Published: December 2004

Multinuclear nuclear magnetic resonance (NMR) spectroscopy (29Si, 13C, 1H) is used to characterize the aging process of silicone rubber‐based biomaterials in a rat model. 1H NMR relaxation measurements (spin‐lattice, T1, and spinspin, T2, relaxation times) were performed to better understand the molecular dynamics of polysiloxane chains in implants. After 1 year of implantation in animals, changes in the 1H T2 relaxation times and the NMR spectra were observed in polydimethylsiloxane, Silastic® sheets and chin implants, while these measurements remain unchanged in finger joints. Very small amounts of fat were detected in all types of silicone rubber implants at the end of the implantation period. This work shows that free silicone migrates from the implants to adjacent tissues and distant sites, such as spleen or liver, and is chemically modified. © 1995 John Wiley & Sons, Inc.
Dictyostelium Chemotactic Response to Spatial and Temporal Gradients. Theories of the Limits of Chemotactic Sensitivity and of Pseudochemotaxis
Authors: Futrelle R.P.
Published: December 2004

Four aspects of ameboid cell chemotaxis are discussed: 1) Ameboid cells (Dictyostelium discoideum, leukocytes) might orient to chemotaxin gradients by sensing a spatial gradient or a temporal change in the concentration. Using a moving micropipette source of cAMP, we show the D discoideum cells can orient toward a gradient in which the concentration is everywhere decreasing with time–implying a spatial mechanism. 2) The number of molecules N that must be released by a source to orient a cell is limited by the natural concentration “noise” due to diffusion. N is shown to be simply related to the cell size and the distance from the source. 3) We show that previous diffusion equations for cell population movement have not taken the speed variations (klinokinesis) into account properly, and we present a new result that does. 4) We briefly discuss reaction‐diffusion models of cell orientation.
Monoclonal Antibodies Which Alter the Morphology of Cultured Chick Myogenic Cells
Authors: Greve Jeffrey M. , Gottlieb David I.
Published: December 2004

Two monoclonal antibodies that cause changes in the morphology of cultured myogenic cells are described. Antibody JG9 causes myoblasts to round up and causes myotubes to become thin, cable‐like structures with multiple round swellings. Antibody JG22 causes both myoblasts and myotubes to become round refractile cells poorly attached to the substratum. The effects of both antibodies are reversible. Fab fragments of JG22 can cause the morphological change. A tentative identification of the antigen recognized by JG22 is made.
Mitogenicity of Brain Axolemma Membranes and Soluble Factors for Dorsal Root Ganglion Schwann Cells
Authors: Cassel Dan , Wood Patrick M. , Bunge Richard P. , Glaser Luis
Published: December 2004

Previous studies in this laboratory have shown that membranes derived from dorsal root ganglia (DRG) neurites are mitogenic for cultured Schwann cells derived from the same source [Salzer et al (1980): J Cell Biol 84:767–778]. Improved procedures are described for preparing Schwann cells derived from dorsal root ganglia that are highly responsive to various mitogens. Under these conditions, the cells respond not only to the neurite mitogen but also to pituitary extracts, dibutyryl cyclic AMP, and cholera toxin that have been shown previously to be good mitogens for Schwannn cells derived from sciatic nerve [Raff et al (1978): Cell 15:813–822], thus reconciling discrepancies in the response of these different Schwann cell preparations to mitogens. Searching for a source of membranes more suitable for biochemical characterization of the neurite mitogen, we found that bovine brain axolemma, prepared by the method of DeVries et al [(1977): Brain Res 147:339–352] is highly mitogenic for Schwann cells. The milotic index of Schwann cells was increased by the addition of axolemma from 0.5%–2% to 30%–50% during 24‐h incubation with [3H]thymidine. Half maximal effect was obtained at about 0.4 μg axolemma protein per microwell containing 2–4 × 10 3 cells. The axolemma mitogen appears to be an integral membrane protein that remains bound to the membrane under various ionic conditions but can be extracted in a partially active form with deoxycholate. Like the DRG neurite mitogen, the mitogenic activity of axolemma was abolished by trypsin treatment. Unlike the neurite preparation, however, the mitogenic activity of axolemma was only partially inactivated by heat treatment (60%–70% inactivation). A significant difference between the mitogenic activity of axolemma membranes and neurite membranes is the fact that axolemma membranes fail to stimulate Schwann cell proliferation in a defined, serum‐free medium (N‐2), whereas neurites show significant mitogenic activity in this medium. These findings indicate a possible difference between DRG neurites and brain axolemma either in the mitogen itself or surface components responsible for recognition between the membranes and the cells.
Calcium‐Dependent and Calcium‐Independent Adhesive Mechanisms Are Present During Initial Binding Events of Neural Retina Cells
Authors: McClay David R. , Marchase Richard B.
Published: December 2004

The hypothesis that intercellular adhesion can be subdivided into two separable phenomena, an initial recognition event and a subsequent stabilization, is supported by the use of a new cell binding assay that provides a quantitative measure of intercellular binding strengths. Radioactive single cells are brought into contact with cell monolayers at 4°C in sealed compartments. The compartments are inverted and a centrifugal force is then applied tending to dislodge the probe cells from the monolayers. By varying the speed of centrifugation, the force maintaining associations between embryonic chick neural retina cells was determined to be on the order of 10−5 dynes after incubation at 4°C. Brief incubations at 37°C resulted in significant strengthening of the intercellular bond. Using this cell binding assay, neural retina cells were shown to exhibit both a Ca++‐independent and a Ca++‐dependent mechanism in their initial binding to one another.
Effect of phalloidin on liver actin distribution, content, and turnover
Authors: Low Robert B. , Low Elizabeth S. , Chaponnier Christine , Mitchell Janet W. , Gabbiani Giulio
Published: December 2004

Phalloidin increases F‐actin microfilament content and actin‐directed immunofluorescence in hepatocytes in vivo and also increases actin polymerization and the stability of F‐actin in vitro. We studied the sensitivity of immunofluorescent staining of actin to an actin depolymerizing factor (ADF) as well as actin content, degree of polymerization, and turnover in livers of in vivo phalloidin‐treated rats. Pretreatment with ADF abolished anti‐actin antibody (AAA) staining of normal liver but did not modify staining of livers from phalloidin‐treated animals. Plani‐metric analyses of SDS‐polyacrylamide gels snowed the percent actin of total protein was increased by approximately 40% and the absolute amount of actin by approximately 43%, ten days after daily phalloidin treatment (50 μg/100 gm body weight). Similar but smaller changes could be seen after one day of treatment. Ultracentrifugational analyses of liver extracts indicated no change in the amount or proportion of G‐actin but a 194% increase in the proportion of F‐actin in ten‐day treated animals, changes also apparent in one day animals. Neither the relative fractional rate of actin synthesis nor its synthesis as a percent of total protein synthesis was altered either at one‐day or ten‐day post‐phalloidin treatment. Dual‐isotope experiments indicated that the rate of actin degradation was decreased selectively in the one‐ to three‐day period ‐following drug treatment. Thus, phalloidin appears to stabilize actin against the depolymerizing actions of ADF, increases the proportion of F‐actin without altering the size of the G‐actin pool, and causes accumulation of actin by decreasing its relative rate of degradation.
Ultrastructural studies on the intracellular fate of 125I‐nerve growth factor in cultured rat sympathetic neurons
Authors: Claude Philippa , Hawrot Edward , Parada Isabel
Published: December 2004

Primary cell cultures of sympathetic neurons from rat were exposed to 125I‐nerve growth factor (NGF) and the fate of the NGF in the cell was followed using electron microscopic autoradiography. The intracellular localization of NGF was determined in the cell bodies and in the proximal neurites of neurons that had been grown in three‐chamber dishes, following 5 or 24 hr of retrograde transport of NGF from the distal portions of the neurites. Label in the proximal neurites was predominantly associated with lysosomes and multivesicular bodies (MVBs), and at 5 hr elongated tubular elements were especially heavily labeled. Most of the label in the cell bodies was concentrated in lysosomes and MVBs. Lysosomes accounted for the largest fraction (45–60%) of the grains in the cell body, with a labeling density (LD = % grains/% area) of 3–5, while MVBs accounted for 5–10% of the grains with an LD of 5–20. We observed no evidence of nuclear labeling after 5 or 24 hr of retrograde transport. Mass cultures of neurons were incubated for 22 hr with NGF in the presence of the lysosomal inhibitors chloroquine (CQ, 0.05 mM) or methylamine (MA, 10 mM). In both agents the lysosomes were swollen with membranous material but still sequestered NGF, especially in CQ where the lysosomes were associated with almost 65% of the grains and had an LD of 6. CQ and MA had different effects on the morphology of the MVBs: in CQ they were few in number and compact while in MA they were numerous and appeared swollen and vacuolated. We observed no evidence for the nuclear accumulation of NGF even in the presence of the lysosomotropic agents.
Involvement of multiple subcellular compartments in intracellular processing of epidermal growth factor
Authors: Miskimins W. Keith , Shimizu Nobuyoshi
Published: December 2004

The intracellular translocation and processing of epidermal growth factor (EOF) in 3T3 cells has been studied utilizing Percoll density gradients. EGF is internalized and rapidly becomes associated with two types of intracellular compartments. The extent to which EGF is delivered to these two compartments is apparently regulated depending upon the cell's physiological condition. In growth medium, an increased proportion of EGF is taken up into a Golgi‐like element. Uptake through this pathway correlates with a decrease in degradation of the ligand. In the absence of scrum and amino acids, an increased proportion of EGF is taken up into a component which has a density of 1.05. Uptake through this pathway correlates with increased degradation of the ligand. The ligand taken up through both pathways is transferred to dense vesicles which comigrate with lysosomes. In the presence of growth medium, however, dense vesicles containing EGF can be shown to be lysosomal enzyme‐deficient upon further fractionation. In addition, in the presence of serum, a portion of the internalized EGF is apparently released from the cells, intact, and then re‐bound. The processes described may be important in the production of a mitogenic response and the ability of cells to self‐regulate their responsiveness to the growth factor.
Ligand/receptor internalization: a spectroscopic analysis and a comparison of ligand binding, cellular response, and internalization by human neutrophils
Authors: Sklar Larry A. , Jesaitis Algirdas J. , Painter Richard G. , Cochrane Charles G.
Published: December 2004

We have compared the kinetics of the responses of neutrophils to the kinetics of ligand‐receptor interaction and internalization, using as a model ligand the fluorcsceinated hexapeptide N‐CHO‐Nle‐Leu‐Phe‐Nle‐Tyr‐Lys‐Fluorescein (Nle, norleucine). Cellular responses, ie, membrane depolarization, enzyme (elastase) secretion, and superoxide anion (O) generation, are all initiated within 10 sec of the exposure of cells to stimulus. In the cases of membrane depolarization and secretion (in cytochalasin B‐treated cells), full responses are elicited by binding which occurs within 15 sec of peptide addition. Ligand binding and internalization have been analyzed over the same time frame with new spectroscopic techniques. The association of ligand and receptor is monitored using an antibody to fluorcscein. The antibody to fluorescein specifically quenches the ligand which is in solution, but receptor‐bound ligand is inaccessible to the antibody. The internalization of the receptor‐bound ligand is monitored by the accessibility of the fluoresceinated peptide to quenching by an external pH change (7.4 → 4.0). Ligand which is either outside or on the cell surface is instantaneously quenched while intracellular peptide (or intracellular fluorescein derived from fluorescein diacetate) is only slowly quenched. No internalization is observed until 1 min after binding begins and internalization proceeds at a rate of up to 5,000 receptors/min/cell following a near optimal stimulatory ligand concentration (∼ 1 nM) while the occupied receptors are being cleared from the surface. A comparison of the kinetics of internalization and the cellular responses suggests that internalization of the ligand is too slow to be involved in the triggering of the cellular responses.
Characterization of growth factors in human cartilage
Authors: Bekoff Marjorie C. , Klagsbrun Michael
Published: December 2004

Growth factor activity has been identified in the chondrocytes and extracellular matrix (ECM) fractions of human costal cartilage. There was about five times more growth factor activity in the ECM than was found to be associated with the chondrocytes. The growth factor activity in chondrocytes was found to be associated with chromatin. Both the chromatin‐associated growth factor (CAGF) activity and extracellular matrix growth factor (EMGF) activity were characterized for molecular weight, charge, and the effect of reduction by sulfhydryl reducing reagents. Biorex cation exchange chromatography showed that both CAGF and EMGF were cationic. CAGF and EMGF have molecular weights between 15,000 and 18,000 as determined by size exclusion chromatography on HPLC TSK 3000 columns equilibrated with guanidine‐HCl and dithiothreitol.
Intracellular processing of 125I‐epidermal growth factor in rat embryo fibroblasts
Authors: Magun Bruce E. , Planck Stephen R. , Wagner Herbert N.
Published: December 2004

The intracellular fate of endocytosed 125I‐epidermal growth factor was examined in Rat‐1 fibroblasts. Cells were pulse‐labeled for 5 min in 125I‐EGF and chased for 3 hr with an excess of unlabeled EGF. At various times after application of the cold chase, cells were harvested and processed for isopycnic gradient centrifugation on Percoll gradients. Within the period of the 125I‐EGF pulse, about 50% of the 125I activity appeared in an organelle containing peak in the gradients. By 20 min after application of the cold chase, 125I activity in the organelle peak began to decrease, and the decrease continued over the next few hours. The 125I activity which exited from its organelle‐associated location appeared to be present in the cytosol and was apparently not confined within organelles. Lysosomotropic amines inhibited the egress of 125I activity from the organelle compartment. The 125I activity from both organelle and nonorganelle compartments reacted as completely as authentic 125I‐EGF with anti‐EGF antibodies and was similar in size to authentic 125I‐EGF. Little or no intracellular low molecular weight 125I‐containing compounds were detected, although they accumulated in the culture medium. Analytical isoelectric focusing revealed that the organelle‐bound form of endocytosed 125I‐EGF was more acidic than authentic 125I‐EGF and, upon exiting from the organelle compartment, was processed to an even more acidic form. It was the second macromolecular form of processed 125I‐EGF that was ultimately degraded to low molecular weight compounds which were then externalized from the cells.
Repair of O6‐methyl‐guanine residues in DNA takes place by a similar mechanism in extracts from hela cells, human liver, and rat liver
Authors: Myrnes Bjørnar , Giercksky Karl Erik , Krokan Hans
Published: December 2004

Extracts from HeLa S3 cells, human liver, and rat liver were found to contain an activity that transfers the methyl group from O6‐methyl‐guanine residues in DNA to a cysteine residue of an acceptor protein. The molecular weights of the acceptor proteins in HeLA cells and human liver are 24,000 ± 1,000 and 23,000 ± 1,000. respectively. Assuming that each acceptor molecule is used only once, the average number of acceptor molecules in HeLa cells was calculated to be about 50,000. The extracts also contained 3‐methyl‐adenine‐DNA glycosylase activity and 7‐methyl‐guanine‐DNA glycosylase activity, although the latter activity was not detected in extracts from human liver in our assay system. Thus, the three major alkylation products resulting from the effect of methylating agents, such as N‐methyl‐N‐nitroso urea, can all be repaired in animal cells. Pretreatment of HeLa cells with N‐methyl‐N′‐nitro‐N‐nitrosoguanidinc (0.1 μg/ml) strongly reduced the capacity of HeLa cell extracts to repair O6‐methyl‐guanine residues, while the activity of three DNA‐N‐glycosylases was essentially unaltered. This inactivation was not caused by a direct methylation of the enzyme by the carcinogen. The results demonstrate that the mechanism of repair of O6‐methyl‐guaninc residues, in DNA is strikingly similar in E coli and animal cells, including humans.
Inhibition of heme synthesis in bone marrow cells by succinylacetone: Effect on globin synthesis
Authors: Beru Nega , Sahr Kenneth , Goldwasser Eugene
Published: December 2004

The effects of 4,6‐dioxoheptanoic acid (succinylacetone, SA), an inhibitor of δ‐aminolevulinic acid dehydratase, on total iron uptake, heme synthesis, and globin synthesis were studied in rat marrow cells in culture in order to examine the coordination of heme and globin synthesis. SA inhibited heme synthesis in both control and erythropoietin‐stimulated cells in a dose‐dependent fashion; at 10−3 M, inhibition was complete, whereas at 10−7 M, there was no significant effect. Inhibition of total iron uptake was also dose‐dependent although, at 10−3 M, it was not complete. The inhibition of heme synthesis by SA was partially overcome by addition of 10−4 M porphobilinogen or protoporphyrin IX. SA caused an almost complete suppression of globin formation in both erythropoietin‐stimulated and unstimulated cells as early as five hours after the addition of the inhibitor. When inhibition of heme synthesis was incomplete, globin synthesis was partially inhibited. These results indicate that heme synthesis is required for erythropoietin‐mediated induction of globin synthesis in cultured bone marrow cells.
The uptake of swainsonine, a specific inhibitor of α‐D‐mannosidase, into normal human fibroblasts in culture
Authors: Chotai Kokila , Jennings Christine , Winchester Bryan , Dorling Peter
Published: December 2004

Swainsonine, an indolizidine alkaloid, found in plants of the genus Swainsona, has been shown to be a strong inhibitor in vitro of the α‐D‐mannosidase activity in normal human fibroblasts. Therefore, inhibition of α‐D‐mannosidase activity in extracts of harvested cells grown with swainsonine in the medium has been used to follow the association of the alkaloid with normal human fibroblasts in culture. Swainsonine that could not be removed by extensive washing became associated with the cells within 1 min, and it is concluded that the alkaloid is internalized rapidly by the cells. The amount of swainsonine taken up into the cells depended on the length of time in contact and the concentration of swainsonine in the medium, but at 37°C a plateau of internalized swainsonine occurred after 2 hr with extracellular concentrations of swainsonine of 100 μM or greater. At lower concentrations of swainsonine the rate of uptake was found to be temperature‐dependent, increasing greatly at 20°C. The rapidity and temperature sensitivity of the uptake, together with the observation that mannose or mannose‐6‐phosphate did not prevent the association, suggest that swainsonine enters the cells by permeation rather than by endocytosis. When swainsonine is withdrawn from the culture medium, there is a decrease with time of cell‐associated swainsonine. The kinetics of uptake and release of swainsonine and its slightly basic nature make it likely that swainsonine is concentrated initially in the lysosomes. This rapid, but reversible, concentration of swainsonine in lysosomes would be consistent with the observed effects of the toxin in vivo.
Biosynthesis and secretion of fibronectin in human melanoma cells
Authors: Bumol Thomas F. , Reisfeld Ralph A.
Published: December 2004

The biosynthesis and secretion of cellular fibronectin from human melanoma cells have been investigated by pluse‐chase/immunoprecipitation analysis. Melanoma cells synthesize endolglycosidase H (Endo H)‐sensitive glycoprotein precursors of fibronectin glycoproteins which chase to an Endo H‐resistant monomer with an apparent Mr of 240,000 (240 K). This molecule, which has a significantly higher molecular weight than normal plasma or cellular fibronectin, is rapidly secreted by melanoma cells, resulting in the secretion of 80% of newly synthesized fibronectin in 120 min, following a 10‐min biosynthetic pulse. This active secretory process can be inhibited by brief exposure of melanoma cells to sodium monensin (10−7 M), which also results in a modified fibronectin of lower apparent Mr. Monosaccharide‐incorporation studies of melanoma fibronectin reveal that monensin significantly inhibits galactose and fucose incorporation into this glycoprotein, correlating with reported effects of monensin on Golgi apparatus functions. These studies indicate that this tumor‐associated and biosynthetically altered cellular fibronectin is a rapidly secreted major N‐linked glycoprotein of metastatic human melanoma cells.
Interactions between insulin and the cyclic AMP system of Cloudman S91 mouse melanoma cells
Authors: Pawelek John , Emanuel Janet , Kahn Richard , Murray Marilyn , Fleischmann Robert
Published: December 2004

Insulin inhibits the proliferation of wild‐type Cloudman S91 mouse melanoma cells. The effects, which are mediated through specific, high‐affinity receptors for insulin, appear to involve interactions with the cAMP system. Our evidence is as follows: (1) Cloudman cells have a cAMP requirement for proliferation and pigmentation. Exposure of cells to insulin results in a lowering of intracellular cAMP levels and inhibition of both cell division and pigment formation. (2) The effects of insulin are reversed by agents which raise cAMP levels, or by the cAMP analogue dibutyryl cAMP. (3) A mutant cell line with a temperature‐dependent requirement for cAMP is most sensitive to the growth inhibitory effects of insulin when its requirements for cAMP are maximal. (4) Mutants selected only for alterations in their response to Insulin frequently have concomitant alterations in their cAMP systems. (5) The melanotropin‐responsive adenylate cyclase system is stimulated following prolonged exposure of cells in culture to insulin. Although we do not know the mechanism(s) for the interactions between the insulin and the cAMP system, our initial findings suggest that protein phosphorylation/dephosphorylation reactions are involved.
Trypanosoma cruzi: The immunological consequences of infection
Authors: Hudson Leslie
Published: December 2004

Trypanosoma cruzi, the causative agent of Chagas' disease, infects an estimated 12 million people in Latin America and may induce cardiopathy and megaformation of the oesophagus and colon. During the early, acute stage of the infection, parasite‐induced inflammatory infiltrates may cause transitory disease which terminates with the emergence of an immune response sufficient to reduce the parasite to insignificant levels. Even so, severe disease may develop many years after the original infection. It has been suggested that this might result from an autoimmune process triggered by the parasite and mediated either (1) by the adsorption of parasite antigens to host cells, thus rendering these cells susceptible to the host's own antiparasite immune response, or (2) via cross‐reactive antigens shared by the host and parasite. In common with many parasitic diseases, there is an urgent need for studies on the T‐cell response to T cruzi infection, as this might not only hold the key to the immunopathology but also serve as a means of clearing this lifelong infection which survives by sequestering into an intracellular site.
Graph theoretical characterization and computer generation of certain carcinogenic benzenoid hydrocarbons and identification of bay regions
Authors: Balasubramanian K. , Kaufman Joyce J. , Koski Walter S. , Balaban Alexandru T.
Published: January 2005

An algorithm is developed for generating and characterizing carcinogenic catacondensed benzenoid hydrocarbons. The bay regions in these structures are identified by a technique that we developed at Johns Hopkins. Using the three‐digit code proposed by Balaban, and the concept of ring adjacency matrix expounded here, we generate catacondensed benzenoid hydrocarbons in the computer and identify the number of potentially carcinogenic bay regions in each of them. The results of computer generation agree with the combinatorial enumeration of Harary and Read. All structures containing up to five rings and some with six rings and the number of bay regions in these are presented. Computer results for the structures and bay regions of all seven‐, eight‐, and nine‐membered unbranched catacondensed benzenoid hydrocarbons and the number of bays are available from the authors.
Transport Properties of Macromolecules by Brownian Dynamics Simulation: Vectorization of Brownian Dynamics on the Cyber‐205
Authors: Ganti Girija , Andrew McCammon J.
Published: January 2005

Time consuming portions in the computation of transport properties of rigid and flexible molecules are the evaluation of subunit hydrodynamic interaction tensors Q and σ, and the procedure for satisfying subunit‐subunit distance constraints. Vector algorithms to speed up these parts of the computation are given. Using these algorithms, a vector version of the Ermak‐McCammon Brownian dynamics code has been developed on a Cyber‐205. To demonstrate the order of speedups that can be achieved, the code was tested on a rigid “trimer” system comprising 24 spherical subunits with a fixed geometry. A speedup of about 14 times for the whole program, and of 45, 6, and 18 times for the computation of Q, σ, and for the procedure to enforce the constraints, respectively, were obtained.
A Comparison of the Rotational Potential Functions in Butane, Propylsilane, Ethylmethylsilane, and 1,2‐Disilylethane: Ab Initio and MM2 Results
Authors: Profeta Salvatore , Unwalla Rayomand J. , Nguyen Binh T. , Cartledge Frank K.
Published: January 2005

Ab initio calculations at several basis set levels were used to examine the rotational potential energy function around the CC bond of 1,2‐disilylethane, also known as disilabutane (DSB). The best basis set for this system was found to be the 3‐21G(*) basis, which was also used to verify the potential function around the CH2—SiH2 segment in ethylmethylsilane (EMS). The torsional parameters developed by Frierson and Allinger for the CSiCC fragments were shown to yield a potential in excellent agreement with those from the 3‐21G(*) basis. Full 3‐21G(*) geometry optimizations were performed on the 0°, gauche (60°), and 180° conformers of DSB and EMS. Data derived from the ab initio calculations on DSB were used to establish MM2 torsional and bond length parameters for the SiCCSi fragment. The MM2 and ab initio structures agree well. A detailed comparison of rotational potentials and the steric energy components is presented. We also report the torsional potential of propylsilane (PS) and compare the MM2 calculated structure with experiment. Our findings suggest that the similarity of the torsional potentials of butane and DSB and the dissimilarity between butane and EMS arise from the same phenomenon—van der Waals interactions that are attractive rather than repulsive dominant.
Implementation and applications of Gaussian 82 on a CDC Cyber 205
Authors: Rauk Arvi , Dutler Remo
Published: January 2005

The implementation of the GAUSSIAN 82 system of quantum chemistry codes on the CDC Cyber 205 supercomputer required approximately 1 1/2 man years of effort. Idiosyncracies of the Cyber 205 architecture, operating system, and compiler in so far as they affect the conversion and operation of large quantum chemistry codes on the machine are described. While advantage has not been taken of the powerful vector processor, the high intrinsic speed of the scalar processor and the large virtual storage capacity of the Cyber 205 make it a very powerful research tool for computational chemistry. The impact of the GAUSSIAN 82/Cyber 205 combination on computational chemistry research at the University of Calgary is illustrated by brief descriptions of a range of applications from highly accurate calculations on small systems to semiempirical studies of large molecular aggregates. Complete geometry optimizations and harmonic frequency analyses, for the most part, have become routine.
Generalized potential surfaces under inclusion of nuclear motion
Authors: Krüger Thomas , Jug Karl
Published: January 2005

A new method for the solution of the vibronic Schrödinger equation is presented. The proposed approach allows the preservation of the concept of potential surfaces under inclusion of nuclear motion. The dynamical interaction of electrons and nuclei is partially included in the equation determining the potential surfaces. The corresponding electronic wave functions can be used as a basis for a generalized representation. Since the variation principle is involved for the determination of the potential surfaces, the proposed representation may be considered as a generalization of the adiabatic one. As a consequence the vibrational wave equation and the calculation of radiationless transition probabilities is simplified.
Linear notations and molecular graph similarity
Authors: Herndon William C. , Bertz Steven H.
Published: January 2005

Two simple linear notation systems are suggested to encode molecular structure including stereochemical elements. Both systems give rise to a unique numbering of the molecular graph, and thus also lead to a unique linear notation. Both linear notation systems are extremely compact and require only standard chemical symbols. A string comparison technique is developed to measure the similarity of two molecular linear notations. This procedure allows one to define a molecular similarity index with values that range from zero to unity, the zero value characterizing complete dissimilarity and the value of unity denoting identity. The notation and similarity index procedures are applied to several small molecular structures.
Application of the MuMATH computer algebra system to sets of first order kinetic equations of significance in chemistry
Authors: Trindle Carl
Published: January 2005

Analytical solutions to systems of first order differential equations have long been available; however, they become so involved that they are seldom used. Numerical simulations are preferred in practice, although they produce bulky output that is difficult to interpret. Even worse, they are occasionally seriously in error owing to “stiffness” in the equations, intrinsic instability, or other pathological behavior. Computer algebra systems can handle the complicated manipulations that make the analytical solutions of first order kinetic systems inconvenient and can serve as a check on numerical simulations. We show applications of the small MuMATH(R) computer algebra package to a variety of first‐order process, including relaxation kinetics and the analysis of stability of steady states in nonlinear kinetic systems.
On the SCF calculation of excited states: Singlet states in the two‐electron problem
Authors: McCourt Mary , McIver James W.
Published: January 2005

The problem of determining SCF wave functions for excited electronic states is examined for singlet states of two‐electron systems using a Lowdin natural orbital transformation of the full CI wave function. This analysis facilitates the comparison of various SCF methods with one another. The distribution of the full CI states among the natural orbital MCSCF states is obtained for the S states of helium using a modest Gaussian basis set. For SCF methods that are not equivalent to the full CI wave functions, it is shown that the Hartree‐Fock plus all single excitation wave functions are equivalent to that of Hartree‐Fock plus one single excitation. It is further shown that these wave functions are equivalent to the perfect pair or TCSCF wave functions in which the CI expansion coefficients are restricted to have opposite signs. The case of the natural orbital MCSCF wave function for two orbitals is examined in greater detail. It is shown that the first excited state must always be found on the lower natural orbital MCSCF CI root, thus precluding the use of the Hylleras‐Undeim‐MacDonald (HUM) theorem in locating this state. It is finally demonstrated that the solution obtained by applying the HUM theorem (minimizing the upper MCSCF CI root with respect to orbital mixing parameters) is an artifact of the MCSCF method and does not correspond to any of the full CI states.
Column design. 3. Theoretical studies of a chiral stationary phase used in column chromatography
Authors: Lipkowitz Kenny B. , Demeter David A. , Parish Carol A. , Landwer Jo M. , Darden Thomas
Published: January 2005

Conformational features of a chiral stationary phase used in column chromatography are discussed. The syn forms invoked in chiral recognition models are consistent with MNDO and MM2 calculations. It is speculated that the inherent flexibility of the syn form makes these phases effective templates for analyte binding.
Electrostatic interaction of a solute with a continuum. Improved description of the cavity and of the surface cavity bound charge distribution.
Authors: Pascual‐Ahuir J. L. , Silla E. , Tomasi J. , Bonaccorsi R.
Published: January 2005

Algorithms for a finer description of cavities in continuous media and for a more efficient selection of sampling points on the cavity surface are described. Applications to the evaluation of solute surface and volume and to the calculation of the solute‐solvent electrostatic interaction energy, as well as of the cavitation energy are shown as examples.
Theoretical studies on the acid hydrolysis of methyl carbamate
Authors: Lee Ikchoon , Kim Chang Kon , Lee Byung Choon
Published: January 2005

The mechanism of the A2 acid hydrolysis of methyl carbamate was investigated using MNDO method. The reaction was found to proceed in two steps: (1) the rate‐determining nucleophilic attack of water on the carbonyl carbon of the N‐protonated tautomer involving the tetrahedral TS; and (2) the fast subsequent proton abstraction by the leaving group, NH3, to form products. The mechanism is similar to that involved in the A2 hydrolysis of acetamide. Effects of substituents, R1, R2, and R3 in R1OCONR2R3, on rates can be predicted by the changes in electron densities on alkoxy oxygen and N, in complete agreement with the experimental results. We concluded that there is no need for invoking two different mechanisms for amides and carbamates since a common mechanism can easily accommodate all the experimental results.
Molecular mechanics study of myelin basic protein
Authors: Gilliom Richard D. , Stoner Gerald L.
Published: January 2005

Myelin basic protein (MBP) is the major extrinsic protein of the myelin sheath in the central nervous system. We have examined the predicted structure of segments of MBP using the molecular mechanics program ECEPP83 developed by Scheraga and coworkers as modified by Chuman, Momany, and Schafer. We have focused upon segments containing the Pro‐Pro‐Pro sequence (residues 100‐102), which have been predicted from standard algorithms to exist in a hairpin loop connecting anti‐parallel beta‐strands. Both the shorter (98‐105, 99‐105, and 100‐105) and longer segments (87‐109, 87‐118, and 87‐120) have been examined. These results indicate potential for a chain reversal in this region. The shorter segments have been studied by others using NMR techniques and the results are compared.
Combined bond‐polarization basis sets for accurate determination of dissociation energies. II. Basis set superposition error as a function of the parent basis set
Authors: Martin J. M. L. , François J. P. , Gijbels R.
Published: January 2005

The effect of the parent basis set on the basis set superposition error caused by bond functions is investigated systematically. An important difference between BSSE at the SCF and correlated levels is pointed out. Three new basis sets are defined, denoted 6‐311 + G(d,p)B, 6‐311 + G(2d,p)B, and 6‐311 + G(2df,p)B. BSSE for the first‐row hydrides seems to increase uniformly with increasing atomic number of the central atom. Expansion of the valence part of the basis set from 6‐31G to 6‐311G, as well as adding f functions, has a significant effect on the BSSE. Additional BSSEs incurred by bond functions are less than or equal to 1 kcal/mol for the 6‐311 + G(2df,p)B basis set. For the dissociation energies of the first‐row hydride species, agreement with experiment within only a few kcal/mol can be obtained even without resorting to isogyric reaction cycles. For high‐quality calculations, adding bond functions seems to have definite advantages over expanding the polarization space beyond the [2d1f] level.
Long‐Range proton‐proton coupling constants. I. Propanic coupling involving a methyl group 4JMeH
Authors: Esteban Angel L. , Galache Maria P. , Mora Francisco , Diez Ernesto , Fabian Jesus San
Published: January 2005

An equation is formulated on the basis of theoretical INDO/FPT calculations which describes the angular dependence of the propanic long‐range coupling constant 4JMeH in substituted HCCCH3 fragments. This equation is a truncated Fourier series in the torsion angle ϕ, HCCMe, which takes into account the dependence of the Fourier coefficients on the bond angle θ, CCMe. The substituent effects are assumed to be additive. Some parameters in the equation may be obtained from the 4JMeH couplings in propane and neopentane derivatives. The calculated effect upon 4JMeH of changes in the bond angle θ is significant and it seems to be in part the cause of some effects which have been attributed to conformational dependence.
On the evaluation of the characteristic polynomial of a chemical graph
Authors: Živković Tomislav P.
Published: January 2005

The evaluation of the characteristic polynomial of a chemical graph is considered. It is shown that the operation count of the Le Verrier–Faddeev–Frame method, which is presently considered to be the most efficient method for the calculation of the characteristic polynomial, is of the order n4. Here n is the order of the adjacency matrix A or equivalently, the number of vertices in the graph G. Two new algorithms are described which both have the operation count of the order n3. These algorithms are stable, fast, and efficient. A related problem of finding a characteristic polynomial from the known eigenvalues λi of the adjacency matrix is also considered. An algorithm is described which requires only n(n − 1)/2 operations for the solution of this problem.
Determining atom‐centered monopoles from molecular electrostatic potentials. The need for high sampling density in formamide conformational analysis
Authors: Breneman Curt M. , Wiberg Kenneth B.
Published: January 2005

An improved method for computing potential‐derived charges is described which is based upon the CHELP program available from QCPE.1 This approach (CHELPG) is shown to be considerably less dependent upon molecular orientation than the original CHELP program. In the second part of this work, the CHELPG point selection algorithm was used to analyze the changes in the potential‐derived charges in formamide during rotation about the CN bond. In order to achieve a level of rotational invariance less than 10% of the magnitude of the electronic effects studied, an equally‐spaced array of points 0.3 Å apart was required. Points found to be greater than 2.8 Å from any nucleus were eliminated, along with all points contained within the defined VDW distances from each of the atoms. The results are compared to those obtained by using CHELP. Even when large numbers of points (ca. 3000) were sampled using the CHELP selection routine, the results did not indicate a satisfactory level of rotatational invariance. On the basis of these results, the original CHELP program was found to be inadequate for analyzing internal rotations.
Efficient formulation of the large generator matrices required for computation of the higher moments, and mixed moments, of conformation‐dependent properties of chain molecules with independent bonds
Authors: Galiatsatos V. , Mattice Wayne L.
Published: January 2005

Dimensionless ratios of various moments of conformation‐dependent physical properties play an important role in the evaluation of the behavior of chain molecules. For example, the correlation coefficient, ρxy, between two conformation‐dependent physical properties, denoted here as x and y, is determined by the three dimensionless ratios 〈x2〉/〈x〉2, 〈y2〉/〈y〉2, and 〈xy〉/〈x〉〈y〉. Angle brackets denote the statistical mechanical average of the enclosed property. In the rotational isomeric state approximation, generator matrices of modest size can often be used for calculation of 〈x〉 and 〈y〉. The dimensions of the matrices grow rapidly upon going to higher moments or to mixed moments, such as 〈xy〉. Formulation of these large matrices, while straight‐forward, has been extremely tedious for chains with independent bonds, arbitrary rotational potentials, and arbitrary bond angles (which need not be fixed). Here we describe an approach that quickly and accurately solves this problem for all cases in which the generator matrices required for 〈x〉 and 〈y〉 are known. The algorithm is validitated by successful use for the computation of ρr2s2 for r2 and s2 for freely jointed chains of various n, a case for which an exact analytical result in closed form is available in the literature. Here r2 and s2 denote the squared end‐to‐end distance and squared radius of gyration for a specified conformation, and n denotes the number of bonds.
Atomic charges derived from semiempirical methods
Authors: Besler Brent H. , Merz Kenneth M. , Kollman Peter A.
Published: January 2005

It is demonstrated that semiempirical methods give electrostatic potential (ESP) derived atomic point charges that are in reasonable agreement with ab initio ESP charges. Furthermore, we find that MNDO ESP charges are superior to AM1 ESP charges in correlating with ESP charges derived from the 6‐31G* basis set. Thus, it is possible to obtain 6‐31G* quality point charges by simply scaling MNDO ESP charges. The charges are scaled in a linear (y = Mx) manner to conserve charge. In this way researchers desiring to carry out force field simulations or minimizations can obtain charges by using MNDO, which requires much less computer time than the corresponding 6‐31G* calculation.
On proper dissociation configurations of a molecule
Authors: Krishna M. V. Rama
Published: January 2005

An analytical procedure is presented for the determination of the proper dissociation configurations of a molecule. We illustrate this procedure by determining the proper dissociation configurations of many electronic states of the first‐row diatomic molecules and ozone. Finally, a few simple guidelines are provided to help in the identification of the important configurations needed for proper dissociation of a molecule.