Abstract: Improvements are made to a novel media that replace the requirement for all protein growth factors by the addition to the medium of physiological concentrations of retinyl acetate. The media are serum-free, companion cell or feeder layer-free and organotypic, matrix free solutions for the cultivation of clonally competent basal keratinocytes. The media and methods are useful in the production of epidermal epithelial tissue that is suitable for skin grafting.
Abstract: Highly purified hepatic stem cells are trans-differentiated into pancreatic endocrine hormone-producing cells by culturing them in vitro in a medium containing high levels of glucose. These trans-differentiated cells express insulin, glucagon, and pancreatic polypeptide, but not hepatocyte protein Hep-par. When stimulated with glucose, these cells synthesize and secrete insulin, a response enhanced by nicotinamide. Transplantation of these trans-differentiated cells into a hyperglycemic animal normalizes blood sugar levels in the animal.
Type:
Grant
Filed:
February 24, 2003
Date of Patent:
April 18, 2006
Assignee:
University of Florida Research Foundation, Inc.
Abstract: A method of separating the epithelium and the stroma of a cornea includes providing a solution that includes a detaching agent diluted in a culture medium and applying the solution to the surface of the cornea.
Abstract: A culture medium for avian embryonic cells and an avian cell culture medium is disclosed. The culture medium is characterized in that it has elements complementary to avian embryonic cells. The complementary elements include insulin-like growth factors and stem cell growth factors. The medium is substantially free of active retinoic acid. A method of culturing avian embryonic cells and the resulting products are disclosed.
Type:
Grant
Filed:
March 15, 2002
Date of Patent:
February 14, 2006
Assignees:
Institute National de la Recherche Agronomique, Centre National de la Recherche Scientifique (CNRS), Ecole Normale Superieur de Lyon
Abstract: A method for detecting a microorganism by coloration is provided that includes adding and reacting, in a liquid culture medium, an alkaline sensitizing solution and a coloring reagent containing a redox dye, the liquid culture medium having been inoculated with a test sample, thereby detecting the microorganism by coloration in the reaction. There is also provided a method for testing drug susceptibility of a microorganism using above-mentioned method. Furthermore, kits used in these methods are provided. The invention is useful to assess readily and objectively the growth of microorganism when carrying out e.g. a detection of microorganism in foods and a test such as a drug susceptibility test.
Abstract: The present invention provides a process for identifying substances that modulate the activity of hyperpolarization-activated cation channels, and the use of this process.
Type:
Grant
Filed:
February 7, 2002
Date of Patent:
December 27, 2005
Assignee:
Aventis Pharma Deutschland GmbH
Inventors:
Hans-Willi Jansen, Andrea Brüggemann, Holger Heitsch, Heinz Gögelein
Abstract: Compositions and methods are provided for culturing in vitro potentially regenerative cells (PRCs) from which functional tissue-organs are regenerated. In one aspect of the invention, a tissue culture medium is provided which comprises at least 50% of water and a sterol compound that is dissolved in a fatty acid-containing oil at a concentration at least 0.1% by weight based on the weight of the oil and added to the water. The culture medium can be used to culture PRCs that are isolated from the body of a mammal to generate functional tissue-organs in vitro with substantially the same physiological structure and function as the corresponding ones existing in vivo and in situ. The cultured PRCs, tissues, and tissue-organs can serve as valuable models for scientific investigation in life sciences, nutraceutical discovery, drug screening, pharmacokinetic studies, medical devices and tissue/organ transplantation.
Abstract: The present invention provides cell culture media and methods useful for determining levels of intracellular function of glutathione or cysteine and for providing biochemical analysis of antioxidant function in human lymphocytes.
Abstract: A novel cell culture medium suitable for primary culture of insect cells, an insect-derived water-soluble chitin, and a process of preparing an insect culture cell line in a short period of time by using the insect primary culture medium and the insect-derived water-soluble chitin. The insect cell primary culture medium comprises lactalbumin hydrolysate, yeastolate, and tryptose phosphate broth as protein extracts, and polyvinylpyrrolidone as a viscosity-supplementing agent. The insect-derived water-soluble chitin is subjected to deacetylation as the sole chemical modification.
Type:
Grant
Filed:
March 6, 2002
Date of Patent:
September 13, 2005
Assignee:
National Institute of Agrobiological Sciences
Inventors:
Shigeo Imanishi, Atsunobu Haga, Jun Mitsuhashi
Abstract: Ligands for flt3 receptors capable of transducing self-renewal signals to regulate the growth, proliferation or differentiation of progenitor cells and stem cells are disclosed. The invention is directed to flt3-L as an isolated protein, the DNA encoding the flt3-L, host cells transfected with cDNAs encoding flt3-L, compositions comprising flt3-L, methods of improving gene transfer to a mammal using flt3-L, and methods of improving transplantations using flt3-L. Flt3 -L finds use in treating patients with anemia, AIDS and various cancers.
Abstract: A cultured skin and a grafting cultured skin sheet are provided, each of which is a cultured reconstructive skin with a high take rate using cells collectable from cells originated from tissue included in an umbilical cord such as tissue included in an umbilical cord originated from a human fetus. The grafting cultured skin stratified sheet is prepared by placing an epithelium sheet on the top surface of a cultured dermis. The cultured dermis includes as components a cultured skin containing cells originated from a tissue included in an umbilical cord, such as umbilical cells, more concretely, umbilical fibroblast cells, being separated and cultured, preferably in a collagen nonwoven fabric. On the other hand, the epithelium sheet is prepared by culturing and stratifying the umbilical cord epithelium cells.
Abstract: The present invention relates to methods and compositions for chemically defined media for growth of mammalian cells for production of commercially useful amounts of expressed proteins.
Type:
Grant
Filed:
February 5, 2002
Date of Patent:
May 31, 2005
Assignee:
Centocor, Inc.
Inventors:
ChiChang Lee, Celia Ly, Gordon Moore, Robert Perkinson
Abstract: A new human chitinase having an amino acid sequence as shown in FIG. 1 or FIG. 2. Modified forms of it having a similar chitin-hydrolyzing activity, and antigenic peptides representing one of its epitopes. Recombinant production of the human chitinase by genetically engineered hosts or host cells. Recombinant nucleic acid encoding it, and human chitinase-specific oligonucleotides. Use for therapeutic or prophylactic treatment of humans against infection by chitin-containing pathogens, or for decomposing chitin, e.g. from chitin-based articles. Antibodies binding to the human chitinase. Diagnostic test kits comprising the human chitinase, its antigenic peptides, human chitinase antibodies, recombinant nucleic acid or oligonucleotides.
Type:
Grant
Filed:
October 15, 2001
Date of Patent:
May 24, 2005
Assignee:
Universiteit va Amsterdam
Inventor:
Johannes Maria Franciscus Gerardus Aerts
Abstract: Nitric oxide adversely affects survival and development of cells such as oocytes and embryos in vitro, particularly in a co-culture system. The addition of a nitric oxide inhibitor such as hemoglobin to such systems eliminates this toxic effect, and promotes mammalian oocytes, embryos, or other cells in vitro.
Type:
Grant
Filed:
June 14, 2002
Date of Patent:
March 8, 2005
Assignee:
Board of Supervisors of Louisiana State University and Agricultural and Mechanical College
Abstract: A process of using a fish plasma component as a nutrient medium component for tissue culture includes obtaining blood from a fish that is a progeny of domesticated broodstock that are reared under consistent and reproducible conditions, separating plasma from the blood, and extracting one or more specific components of the plasma. The tissue is cultured using the extracted plasma components, and none of any remainder of the plasma, in a nutrient medium. The tissue cultured using the extracted plasma component is other than fish tissue, such as mammalian tissue or insect tissue.
Type:
Grant
Filed:
April 17, 2003
Date of Patent:
March 1, 2005
Assignee:
Sea Run Holdings, Inc.
Inventors:
Evelyn S. Sawyer, Paul A. Janmey, Lisa A. Flanagan
Abstract: The present invention provides low serum or serum free liquid culture media for human or animal cells, and the present invention relates to culture media containing antithrombin III and optionally heparin for the low-serum or serum-free culture of human or animal cells to suppress cell death. The antithrombin III is purified from human, bovine, or other animal serum, or antithrombin III derived from recombinant bacteria or cells containing the full length of the antithrombin III gene.
Type:
Grant
Filed:
August 8, 2002
Date of Patent:
February 22, 2005
Assignee:
Agency of Industrial Science and Technology
Abstract: A process is provided for expanding the population of endothelial cells obtained from peripheral blood which can be transformed with a vector comprising a DNA sequence encoding a preselected bioactive polypeptide. The resulting transgenic endothelial cells are useful to biocompatibilize implantable medical devices or can be used directly, as for gene therapy.
Type:
Grant
Filed:
May 24, 2001
Date of Patent:
February 8, 2005
Assignee:
Regents of the University of Minnesota Emory University
Inventors:
Robert P. Hebbel, Yi Lin, John S. Lollar
Abstract: Disclosed are compositions for mammalian, avian or piscian reproductive cells and methods for the collection, holding, processing, in vitro fertilization, sexing culturing, or storing (including long-term cryopreservation) of mammalian, avian, or piscian reproductive sperm cells. The compositions comprise a suitable reproductive cell media and a transforming growth factor, an insulin-like growth factor, or zinc, and, optionally, inositol, transferrin, or fructose, or combinations thereof.
Abstract: A method for expressing a recombinant protein from bone marrow-derived cells comprises the steps of treating the bone marrow-derived cells in vitro with a TGF?1 protein, which selects a population of the cells for further treatment. The selected cells can then be expanded, after which a gene encoding a therapeutic protein can be inserted into the expanded cells and thereafter express the therapeutic protein. The transduced cells can then be introduced into a mammal to produce a therapeutic result.
Type:
Grant
Filed:
February 15, 2002
Date of Patent:
January 18, 2005
Assignee:
University of Southern California
Inventors:
Erlinda Maria Gordon, Frederick L. Hall, W. French Anderson
Abstract: The invention relates to a culture medium for culturing cells, in particular human cells in a process for tissue engineering bone. The medium comprises glucose, a mineral, a vitamin, a growth factor and L-glutamine, wherein the L-glutamine is present in a concentration of at least 300 mg/L.
Type:
Grant
Filed:
June 21, 2002
Date of Patent:
January 4, 2005
Assignee:
IsoTis N.V.
Inventors:
Joost Dick de Bruijn, Gerhardus Johannes M. Tibbe, Sandra Claudia da Silva Madureira Mendes
Abstract: Instead of immersing human reproductive cells in a single culture medium throughout the various procedures used in IVF, a process is provided by which the reproductive cells may be moved through a sequence of distinct culture media as the various IVF procedures are carried out. In one implementation, the culture media specifically formulated to provide a physical environment similar to that found within the female reproductive tract and conducive to growth and development of human reproductive cells during the various stages of the IVF process. In this regard, specifically formulated culture media can be applied to support the reproductive cells in one or more of the following procedures: oocyte retrieval and handling; oocyte maturation; ordinary fertilization; oocyte, zygote and embryo examination and biopsy; embryonic development to the eight-cell stage; embryonic development to the blastocyst stage; embryo transfer; and cryopreservation.
Abstract: The present invention relates to a method for designing a cell culture medium adapted to support a cell line in a pre-defined manner. The method includes generating an expression profile of a cell line, identifying from the expression profile a set of biomolecules to evaluate for their effect on an end-point assay using the cell line, testing each biomolecule in the set for its effect in the endpoint assay, wherein each biomolecule that is determined to have a measurable effect in the end-point assay relative to a control, not containing the biomolecule, is considered a positive biomolecule and formulating a cell culture medium for the cell line by adding a positive biomolecule to a basal medium to form a modified medium, and determining whether the modified medium is sufficient to support the cell line in the pre-defined manner.
Type:
Application
Filed:
May 10, 2004
Publication date:
December 30, 2004
Applicant:
Sigma-Aldrich Co.
Inventors:
Laurel M. Donahue, Daniel W. Allison, Terrell K. Johnson, Kathryn A. Aboytes, Danny Fong
Abstract: A solid culture medium which is intended, in particular, for micro-organisms and eukaryotic cells. The medium includes, by way of a gelling base, a polysaccharide having a reproduction unit including a side chain and six neutral sugars, including glucose and galactose, and an acid sugar, pyruvate substituents and acetates being present. A solution in water or a saline solution having a concentration of the polysaccharide which is greater than or equal to 2 g/l forms an elastic transparent gel.
Type:
Application
Filed:
July 29, 2004
Publication date:
December 30, 2004
Inventors:
Abdelkader Belardi, Regis De Baynast, Anthony Bresin
Abstract: The present invention provides compositions for the repair of mammalian skin. The compositions contain cell growth enhancers to increase the growth rate of skin cells, stimulators of cell growth enhancers, nutrients to support log phase growth of skin cells, cell protectors to protect growing cells and enhanced cellular activity, antioxidants to protect rejuvenated cells, extracellular matrix proteins, stimulators of extracellular matrix proteins, and penetration enhancers. The compositions of the present invention are effective for repairing and rejuvenating mammalian skin, such that aging skin treated with the compositions has a significant reduction in the number of fine lines and wrinkles in the skin. The compositions are also effective for promoting the healing of skin that has suffered a wound, such as a sunburn or abrasion, and for promoting the growth of hair on the scalp.
Abstract: A cosmetic composition contains an aqueous complex nutritive base comprising a plurality of amino acids, at least one vitamin, a plurality of assimilable organic components, and at least one inorganic salt. The cosmetic composition does not contain a biological extract of animal or cellular origin, or a living nourishing substrate. A cosmetic method comprises contacting human skin with the cosmetic composition.
Abstract: Cell culture media containing a sterol such as cholesterol stabilized by surfactant rather than serum products or phospholspid micelles and containing soluble carboxylic acids as fatty acid precursors to satisfy lipid requirements are further enhanced by the presence of alcohols promoting cell growth.
Abstract: A cell culture medium comprising glycerol or glucose, an ammonium salt, sodium polyphosphate, a magnesium salt, a potassium salt and trace elements, and having a pH between 5.5 and 8.0. The medium is particularly suitable for culturing E.coli for the expression of heterologous proteins (e.g., NAP from H.pylori).
Abstract: This disclosure provides an improved system for culturing human pluripotent stem cells. Traditionally, pluripotent stem cells are cultured on a layer of feeder cells (such as mouse embryonic fibroblasts) to prevent them from differentiating. In the system described here, the role of feeder cells is replaced by components added to the culture environment that support rapid proliferation without differentiation. Effective features are a suitable support structure for the cells, and an effective medium that can be added fresh to the culture without being preconditioned by another cell type. Culturing human embryonic stem cells in fresh medium according to this invention causes the cells to expand surprisingly rapidly, while retaining the ability to differentiate into cells representing all three embryonic germ layers. This new culture system allows for bulk proliferation of pPS cells for commercial production of important products for use in drug screening and human therapy.
Abstract: The invention relates to a method of manufacturing a culture medium on which plants can be grown. The method comprises mixing organic and/or inorganic particulate base materials with a thermoplastic, biologically degradable, binding agent, heating the mixture to make it at least semi-fluid, and then cooling the mixture to solidify it.
Abstract: A complex nutrient medium containing compounds that are biocompatible, biomimetic and bioavailable in the skin, but no biological extract of animal or cellular origin, for preparing a topical composition. Said complex nutrient medium has a suitable composition enabling viable in vitro culture of a human epidermal keratinocyte inoculum, with at least one clonal proliferation thereof during the first stage, and without the use of a live nutritive layer. The composition may be used as the active principle, particularly in a cosmetic preparation or a galenic base, and as a carrier capable of potentiating the activity of specific active principles.
Abstract: A culture medium, which is capable of sustaining long-term cultures of hepatocytes and liver cells. In this medium, mammalian primary hepatocytes retain highly replicative capacity and hepatic gene expression activity. The liver cells from genetically defined sources may be reproducibly immortalized without the delivery of foreign genes, such as viral oncogenes. The immortalized hepatocytes are non-tumorigenic, making them suitable for clinical and therapeutic purposes.
Type:
Application
Filed:
May 14, 2003
Publication date:
November 18, 2004
Applicant:
Board of Regents University of Texas System
Abstract: A method for in vitro cultivation of cells, which grow on a culture surface, wherein the cells are sown on culture surfaces (1) and are cultivated in a culture medium, whereby the culture surface is continually or periodically expanded, without being removed from the culture medium. To expand the culture surface, the cells are not detached from the culture surface and the culture surface between the cells is expanded. However, at least part of the cells can be detached and the culture surface can be expanded by the flooding of additional culture surface areas. The culture surface of an example device for cell cultivation consists of one side of an expanding membrane (6), which is expanded by modifying the pressure on the other side. The cell cultivation can be carried out without manual passaging. The cells are subjected to less stress than in known cell cultivation methods and the method can be automated more easily.
Type:
Application
Filed:
February 27, 2004
Publication date:
November 4, 2004
Inventors:
Heribert Frei, Pierre Mainil-Varlet, Werner Muller
Abstract: The present invention is directed generally to metal binding compounds which may be added to cell culture media to replace factors required for cultivation of the cells (e.g. transferrin) which are of animal or human origin. More specifically, the invention is directed to metal binding compounds or complexes thereof comprising one or more transition element cations (such as ferrous or ferric ions), which are added to cell and tissue culture medium compositions. The metal binding compounds may be added to the media alone or may be first complexed with a transition metal ion. The invention is also directed to methods of use of such compositions, including, for example, methods for the cultivation of eukaryotic cells, particularly animal cells, in vitro. The invention also relates to compositions comprising such culture media and one or more cells, and to kits comprising one or more of the above-described compositions.
Type:
Application
Filed:
May 26, 2004
Publication date:
October 28, 2004
Inventors:
David A. Epstein, Paul J. Battista, Dale F. Gruber, David A. Judd
Abstract: A UV-cross-linkable PVA-based polymer coating for cell culture that provides support for cell adhesion. The polymer coating may also contain bioaffecting molecules reversibly entrapped within the polymer coating that provides necessary nutrients to cell culture. Preferably, the UV-cross-linkable PVA-based polymer is PVA-SbQ.
Type:
Application
Filed:
April 18, 2003
Publication date:
October 21, 2004
Inventors:
Steven C. Keith, Mohammad A. Heidaran, John J. Hemperly, Christopher J. Knors
Abstract: Solid substrates for cell culture are UV-cross-linked PVA-based hydrogel polymer particles. The particles are biocompatible with living cells and support cell adherence. Bioaffecting molecules may be reversibly entrapped within the particles. The particles are capable of forming self-assembled aggregates with cultured cells in aqueous suspension. Preferably, the PVA-based polymer is PVA-SbQ.
Type:
Application
Filed:
April 18, 2003
Publication date:
October 21, 2004
Inventors:
John J. Hemperly, Chorng-Fure Robin Hwang, Steven C. Keith, Mohammad A. Heidaran
Abstract: This invention relates to a composite material that comprises a support member that has a plurality of pores extending through the support member and, located in the pores of the support member, and filling the pores of the support member, a macroporous cross-linked gel. The invention also relates to a process for preparing the composite material described above, and to its use. The composite material is suitable, for example, for separation of substances, for example by filtration or adsorption, including chromatography, for use as a support in synthesis or for use as a support for cell growth.
Type:
Application
Filed:
February 2, 2004
Publication date:
October 14, 2004
Inventors:
Ronald F. Childs, Carlos Filipe, Raja Ghosh, Alicja M. Mika, Jinsheng Zhou, Elena N. Komkova, Marcus Y. Kim, Tapan K. Dey
Abstract: A cell or tissue-culturing carrier which can effectively regenerate an intended a cell or tissue, while suppressing an excessive growth of fibroblasts, and a method of culturing a cell or tissue by using the above carrier, the cell or tissue-culturing carrier wherein fibroblasts showing substantially no growing property in a gel based on the hydrogel-forming polymer, is constituted by using a hydrogel-forming polymer; an aqueous solution of which shows a thermo-reversible sol-gel transition such that it assumes a sol state at a lower temperature and assumes a gel state at a higher temperature.
Type:
Application
Filed:
January 13, 2004
Publication date:
October 14, 2004
Inventors:
Hiroshi Yoshioka, Sunao Kubota, Yuichi Mori
Abstract: A cell culture preparation and methods are provided which are suitable for production in cells of a first protein in a class of proteins where the medium is deficient in a second protein in a related class, where the second protein is normally present in the serum and capable of interfering with the purification of the first compound.
Abstract: The present invention relates to a method for disrupting cultured cells that lack a cell wall, the method comprising passing the cells suspended in a suspension fluid through a nozzle at a low pressure, wherein the outflow of the nozzle does not impinge on the outflow of a second nozzle if multiple nozzles are present.
Type:
Application
Filed:
March 25, 2004
Publication date:
September 30, 2004
Inventors:
Charbel Haber, Russel J. Lander, Jennifer Chen
Abstract: Neo-cartilage constructs for growth and surface coating for the de novo formation of a superficial cartilage layer. A method for generation of the neo-cartilage and the neo-cartilage construct. A method for repair and restoration of the injured, damaged, diseased or aged cartilage into its full functionality and for treatment of injured or diseased cartilage by implanting the neo-cartilage construct between two layers of biologically acceptable sealants.
Type:
Application
Filed:
July 22, 2003
Publication date:
September 30, 2004
Inventors:
Shuichi Mizuno, Akihiko Kusanagi, Laurence J. B. Tarrant, Toshimasa Tokuno, Robert Lane Smith
Abstract: The present invention provides a process for large scale in vitro production of amoebocytes of Indian Horseshoe Crab (Tachypleus gigas) (T. gigas) from dissected gill flaps of T. gigas, in Leibovitz L-15 culture medium concentration (2×), to provide enhanced generation of amoebocytes. The process comprises the steps of: dissecting gill flaps of T. gigas; washing the gill flaps with an antibiotic solution followed by alcohol; culturing the gill flaps in tissue culture plates of sterile saline on a Rocker platform; culturing further the gill flaps in Leibovitz L-15 culture medium (2×); purging the gill flaps with Tween 80 solution; and purging again the gill flaps with horseshoe crab serum, while keeping the gill flaps in the culture medium viable for 90 days by feeding with fresh medium at an interval of 10-15 days to enable the enhanced release of amoebocytes both within and outside the gill flaps.
Type:
Grant
Filed:
March 28, 2002
Date of Patent:
September 14, 2004
Assignees:
Council of Scientific and Industrial Research, National Center for Cell Sciences
Abstract: A method for the prevention of the adhesion of particles, in particular cells and cellular components in solution to surfaces, characterized in that to the solution is added at least one polyalcohol.
Abstract: The present invention provides serum-free cell culture media formulations which are capable of supporting the in vitro cultivation of animal cells. The media comprise at least one nutrient of non-animal derivation, such as at least one plant peptide and/or at least one non-animal or plant lipid and/or fatty acid. The media may further optionally comprise an enzymatic digest or extract of yeast cells. The present invention also provides methods of cultivating animal cells in vitro using these cell culture media formulations. In addition, the media of the present invention can be used for growth of animal cells for virus production.
Type:
Application
Filed:
January 26, 2004
Publication date:
September 2, 2004
Applicant:
Invitrogen Corporation
Inventors:
Paul Price, Steve Gorfien, Douglas Danner, Mark Plavsic
Abstract: Methods of treating and forming biocompatible microcapsules that contain living cells are provided, to improve the function of the microcapsules. In particular, methods of treating islet cells or microcapsules containing islet cells are provided. Culture of isolated islet cells prior to encapsulation, culture of encapsulated cells, and cryopreservation of islet cells prior to encapsulation, are described. Methods for harvesting viable islets that incorporates an anti-oxidant in the digestion medium are also disclosed.
Abstract: A chemically defined mammalian cell culture medium is provided that supports maintenance and long term clonal growth of mammalian hepatocytes and other cells.
Abstract: A carrier for cell culture comprising a water-containing polymer gel containing chitosan, wherein the water-containing polymer gel is coated with collagen and/or alginic acid, and a carrier for cell culture, which comprises a gel layer containing chitosan and an inorganic layer adjacently provided to the gel layer.
Abstract: The present invention is directed generally to metal binding compounds which may be added to cell culture media to replace factors required for cultivation of the cells (e.g. transferrin) which are of animal or human origin. More specifically, the invention is directed to metal binding compounds or complexes thereof comprising one or more transition element cations (such as ferrous or ferric ions), which are added to cell and tissue culture medium compositions. The metal binding compounds may be added to the media alone or may be first complexed with a transition metal ion. The invention is also directed to methods of use of such compositions, including, for example, methods for the cultivation of eukaryotic cells, particularly animal cells, in vitro. The invention also relates to compositions comprising such culture media and one or more cells, and to kits comprising one or more of the above-describcd compositions.
Type:
Grant
Filed:
August 28, 2000
Date of Patent:
July 27, 2004
Assignee:
Invitrogen Corporation
Inventors:
David A. Epstein, Paul J. Battista, Dale F. Gruber, David A. Judd