A biocompatible biological component is provided comprising a membrane-mimetic surface film covering a substrate. Suitable substrates include hydrated substrates, e.g. hydrogels which may contain drugs for delivery to a patient through the membrane-mimetic film, or may be made up of cells, such as islet cells, for transplantation. The surface may present exposed bioactive molecules or moieties for binding to target molecules in vivo, for modulating host response when implanted into a patient (e.g. the surface may be antithrombogenic or antiinflammatory) and the surface may have pores of selected sizes to facilitate transport of substances therethrough. An optional hydrophilic cushion or spacer between the substrate and the membrane-mimetic surface allows transmembrane proteins to extend from the surface through the hydrophilic cushion, mimicking the structure of naturally-occurring cells. An alkylated layer directly beneath the membrane-mimetic surface facilates bonding of the surface to the remainder of the biological component. Alkyl chains may extend entirely through the hydrophilic cushion when present. To facilitate binding, the substrate may optionally be treated with a polyelectrolyte or alternating layers of oppositely-charged polyelectrolytes to facilitate charged binding of the membrane-mimetic film or alkylated layer beneath the membrane-mimetic film to the substrate. The membrane-mimetic film is preferably made by in situ polymerization of phospholipid vesicles.

Several approaches have been proposed for improving the biocompatibility of biomaterials useful in medical applications. For example, modifying the biomaterial surface to provide either low polarity or ionic charge or coating the surface with biological substances such as cells, proteins, enzymes, etc., has been used to prevent undesirable protein adhesion. Another approach involves the incorporation of an anticoagulant into the biomaterial, rendering the biomaterial antithrombogenic. A further approach involves the incorporation of various phospholipids into the biomaterial. An additional approach involves the binding of a heparin-quaternary amine complex, or other antithrombotic agent, to the biomaterial surface However, many of these methods have the disadvantage of being nonpermanent systems in that the surface coating is eventually stripped off or leached away. For example, heparin, which is complexed to the biomaterial surface, is not only gradually lost from the polymer surface into the surrounding medium but also has limited bioactivity due to catabolism and its inherent instability under physiological conditions.
Membranes, as self-organizing noncovalent aggregates, offer a model for molecular engineering in which the constituent members can be controlled, modified, precisely defined, and easily assembled. During the past decade, phospholipids differing in chemical composition, saturation, and size have been utilized as building blocks in the design of a variety of structures of complex geometry. Lipid-based cylinders, cubes, and spheres have found applications in both drug delivery and as templates for composite molecularly engineered structures. Surface-coupled bilayers for biosensor applications have also been produced by assembling a layer of closely packed hydrocarbon chains onto an underlying substrate followed by exposure to either a dilute solution of emulsified lipids or unilamellar lipid vesicles (Spinke et al. [1992] Biophys. J. 63:1667-1671; Seifert et al. [1993] Biophys. J. 64:384-393; and Florin et al. [1993] Biophys. J. 64:375-383). In addition, Langmuir-Blodgett techniques have been used as an alternate strategy to construct supported bilayers via a process of controlled dipping of a substrate through an organic amphiphilic monolayer (Ulman, A. [1991] "An Introduction to Ultrathin Organic Films from Langmuir-Blodgett to Self-assembly," New York, Academic Press). Remarkably, these noncovalent molecular assemblies exhibit a high degree of stability. A force of 26 kT is required to remove a double chained C-16 phosphatidylcholine molecule from a bilayer into water (Cecv, G. and Marsh, D. [1987] "Phospholipid Bilayers," New York, Wiley; and Helm et al. [1991] Proc. Natl. Acad. Sci. USA 88:8169-8173). This nearly approximates the biotin-streptavidin bond energy of 35 kT and is several orders of magnitude greater than the strength of typical monoclonal antibody-antigen interactions. Thus, the significance of the methodologies of the present invention lies in the ability to engineer relatively robust materials with an unparalleled level of reproducibility and molecular control over surface order and chemistry.
In order to create robust surface structures, most membrane-mimetic systems for blood-contacting applications have been designed as copolymers containing the phosphorylcholine functional group in either side chains or, less frequently, the polymer backbone (Kojima et al. [1991] Biomaterials 12:121; Ueda, T. et al., [1992]Polym. J. 24:1259; Ishihara, K. et al. [1995] Biomaterials 16:873; Campbell et al. [1994] ASAIO J. 40(3):M853; Chen et al. [1996] J. Appl. Polym. Sci. 60:455; and Yamada et al. [1995] JMS Pure Appl. Chem. A32:1723). While these materials have improved stability and promising blood-contacting properties have been reported, a number of limitations exist. In particular, the ability to engineer surface properties on a molecular level, by taking advantage of the principal of self-organization intrinsic to amphiphilic molecules, is lost. In addition, the ability to early incorporate diverse biomolecular functional groups into the membrane-mimetic surface is also lost.
A significant limitation in the widespread use of supported biomembranes is their limited stability for most applications outside of a laboratory environment. In order to generate more robust systems, strategies have been developed to tether membranes to an underlying substrate, such as gold or glass with or without an intervening flexible spacer or polymer cushion (Spinke, J. Y. et al. (1992) Biophys. J. 63:1667-1671; Florin, E.-L. and Gaub, H. E. (1993) Biophys. J 64:375-383; Meuse, C. W. et al, (1998) Biophys J 74:1388-1398; Seitz, M. et al. (1998) Thin Solid Films 329:767-771; Beyer, D. et al. (1996) Thin Solid Films 285, 825-828; Shen, W. W. et al. (2001) Biomacromolecules 2:70-79). While membrane fluidity is critical for many of the functional responses of biological membranes, certain applications lend themselves to compromise in which a substantial increase in membrane stability may be achieved by in situ polymerization of the planar lipid assembly. The capacity to design surfaces with a high degree of molecular control over the assembly of diverse lipid and other membrane-associated constituents is retained. In this regard, applicants and colleagues have previously reported the in situ polymerization of phospholipids on self-assembled monolayers of octadecyl mercaptan bound to gold (Marra, K. G., et al. (1997) Langmuir 13: 5697-5701.), octadecyl trichlorosilane on glass (Marra, K. G., et al. (1997) Macromolecules 30:6483-6488; Orban, J. M. et al. (2000) Macromolecules 33:4205-4212.), and on an amphiphilic polymer cushion (Chon, I. H. et al. (1999) J. Biomat. Sci. Polymer Ed. 10:95-108).
Recently, polyelectrolyte multilayers (PEM) have been studied as bioinert films to reduce cell and protein adhesion (Elbert, D. L. et al. [1999] Langmuir 15:5355-5362) and as coatings to modulate interfacial molecular transport in drug delivery and immunoisolation systems (Moya, S. et al. [2000)] Macromolecules 33:4538-4544; Shi, X. and -Caruso, F. [2001] Langmuir 17:2036-2042). Other potential applications for these materials include their use as ultrafiltration membranes (van Ackern, F. et al. [998] Thin Solid Films 329:762-766) and in the assembly of optoelectronic devices (Cheung, J. H. et al. (1994) Thin Solid Films 244:985).
Membrane-mimetic systems have also had a direct impact on efforts aimed at understanding the mechanisms of blood coagulation at sites of vascular wall injury and on artificial surfaces. One of the most intriguing developments in the past decade has been the recognition that membrane mimetic systems having a phosphorylcholine component limit the induction of surface-associated blood clot formation. This biological property has been attributed to the large amount of surface bound water due to the zwitterion structure of the phosphorylcholine head group. It has also been suggested that specific plasma proteins which inhibit the blood clotting process are selectively adsorbed to this head group (Chapman [1993] Langmuir 9:39).
In a series of investigations using planar membrane models, Thompson and colleagues (Pearce et al. [1993] J. Biol. Chem. 268:22984-22991; and Tendian et al. [1991] Biochemistry 30:10991-10999) have characterized the molecular requirements for prothrombin binding to phospholipid membranes. It has been observed that the phosphorylcholine head group appears to limit the induction of blood clot formation on synthetic surfaces (Ishihara et al. [1994] J. Biomed. Mater. Res. 28:225-232; Hayward et al. [1984] Biomaterials 5:135-142; and Hall et al. [1989] Biomaterials 10[4]:219-224). It has been proposed that this biological property is related to the large amount of water bound to this zwitterionic head group, or conceivably, the selective adsorption to phosphorylcholine of specific plasma protein(s) that inhibit the blood clotting process (Chapman, D. [1993] Langmuir 9:39-45).
Several investigators have described the direct immobilization of thrombomodulin onto polymeric surfaces in order to generate thromboresistant materials for blood contacting applications. Kishida et al. (1994) Biomaterials 15(10):848-852; Kishida et al. (1994) Biomaterials 15(14):1170-1174; and Kishida et al. (1994) ASAIO Journal 40(3):M840-845 have conjugated TM to both aminated and carboxylated surfaces, including poly(vinyl amine) and poly(acrylic acid) surface-grafted polyethylene and a surface-hydrolyzed poly(ether urethaneurea). Vasilets et al. (1997) Biomaterials 18(17):1139-1145, have reported the immobilization of TM onto poly(acrylic acid) surface-grafted PORE. In all cases, the conjugation scheme utilized a carbodiimide based coupling reaction to link TM to the substrate via freely available amino or carboxyl functionalities on the protein surface. In vitro studies demonstrated that both clotting time and protein C activation were enhanced, and this activity appeared to be directly proportional to TM surface density, as determined by a ninhydrin assay. However, the ability to control TM surface concentration was substrate dependent, with reported TM densities ranging between 0.15 and 0.45 μg/cm2, and TM bioactivity was significantly reduced after surface coupling, as evident by protein C activation rates which were increased only 5 to 10-fold as compared with an observed 20,000-fold enhancement when TM is evaluated as a component of either lipid vesicles or the endothelial cell surface. The loss of cofactor activity is believed attributable to the protein immobilization procedure, which is driven by random-site reactions to any accessible functional group on the TM surface, including those within the thrombin binding site. The impact of local flow conditions on the effectiveness of this strategy was not reported.
Although these studies confirm that substrate-bound thrombomodulin has the potential to limit thrombus formation on synthetic surfaces that are otherwise thrombogenic, the observed reduction in thrombomodulin bioactivity emphasizes that thrombomodulin's biological properties are intimately tied to a variety of structural features which can be lost upon direct covalent coupling to a biomaterial surface. For example, thrombomodulin's ability accelerate the thrombin-dependent activation of protein C requires three tandemly repeated EGF-like domains that serve as a thrombin binding site; a serine/threonine-rich 65 A spacer between the EFT-like domains and the transmembrane domain which optimally align thrombin's active site with the critical scissile bond in protein C; and a covalently associated chondroitin supine moiety that increases the affinity of thrombin binding to thrombomodulin by 10- to 20-fold and catalyzes ATIII inactivation of thrombin (Sadler, J. E. [1997] Thromb. Haemostasis 78[1]:392-395; and Esmon, C. T. [1995] FASEB Journal 9[10]:946-955). While some activity is retained even after the solubilization of thrombomodulin with detergents, membrane association significantly accelerates protein C activation by thrombomodulin. This is mediated, in part, by the ability of the membrane to locally concentrate and coordinate the approximate alignment of reacting cofactors and substrates with thrombomodulin (Galvin et al. [1987] J. Biol. Chem. 262[5]:2199-2205). For example, protein C has a C-terminal 4-carboxyglutamic acid (Gla) domain which binds to the cell membrane and presumably increases its local concentration by confining it to the two-dimensional plane of the lipid bilayer (Esmon et al. [1983] J. Biol. Chem. 258:[9]:5548-5553; Mann et al. [1988] Ann. Rev. Biochemistry 57:915-956; Kalafatis et al. [1996] Critical Reviews in Eukaryotic Gene Expression 6[1]:87-101). In addition, the binding of protein C to the plasma membrane may also induce conformational changes that help align the protein C cleavage site with thrombin's proteolytically active domain. Both electrostatic and hydrophobic interactions may be involved in the association of protein C with the cell membrane. In this regard, recent studies suggest that protein C prefers to bind to and function on membranes that contain both phosphatidylcholine and phosphatidylethanolamine lipids. Protein C may also directly interact with fatty acid side chains within the membrane bilayer (Smirnov et al. [1999] Biochemistry 38[12]:3591-3598). It is surprising that the nature of the phospholipid headgroup may contribute to the subsequent catalytic and binding efficiency of activated protein C. For example, Smirnov et al. (1999 supra); and Smirnov et al. (1994) J. Biol. Chem. 269(2):816-819, have demonstrated that both the PE headgroup and phospholipid polyunsaturation contribute to factor Va inactivation by the activated protein C complex Thus, the lipid bilayer serves as an essential 'cofactor,' that in concert with thrombomodulin, accelerates protein C activation and subsequently optimizes APC anticoagulant activity.
Atherosclerosis remains a serious source of morbidity and death despite advances in preventive measures and pharmacological therapeutics. Nearly 700,000 vascular surgical procedures are performed annually in the United States along with several hundred thousand peripheral and coronary angioplasties (1). Prosthetic bypass grafts and, more recently, arterial stents and other endovascular prostheses have been utilized in association with these reconstructive procedures. Although large diameter vascular grafts (6 mm internal diameter) have been successfully developed from polymers such as polytetrafluoroethylene (PTFE) and polyethylene terephthalate, the fabrication of a durable small diameter prosthesis (<6 mm internal diameter) remains unsolved. Furthermore, while prosthetic bypass grafting performed in the infra inguinal position with reasonable short-term success, within 5 years 30% to 60% of these grafts will fail (Winger T. M. et al. (1996), "Lipopeptide conjugates: Biomolecular building blocks for receptor activating membrane-mimetic structures. Biomaterials 17:443-449). Likewise, restenosis and/or occlusion occur in as many as 50% of all patients within 6 months of stent placement depending upon the site and the extent of the disease (Winger T. M. et al. [(1997]), "Behavior of lipid-modified peptides in membrane-mimetic monolayers at the air/water interface," Langmuir 13:3256-3259).
It is recognized that the adverse events leading to the failure of many vascular prostheses are related to maladaptive biological reactions at the blood-material and tissue-material interface. In response to these problems, and particularly thrombosis of the small caliber prosthesis, grafts and stents have been coated with albumin, heparin, or prostacyclin analogues, which inhibit the clotting cascade and platelet reactivity, or with relatively inert materials, such as polyethylene oxide (Marra, K. G. et al. [(1997]), "In-Situ polymerization of phospholipids on an alkylated surface," Macromolecules 30:6483-6487). An alternate approach has been to design materials which support the in situ regeneration of an endothelial cell lining in order to create a functional arterial substitute with a durable thromboresistant interface (Marra, K. G. et al. [1997], "Stabilized phosphatidylcholine surfaces via in-situ polymerization at a solid-liquid interface," Polymer Preprints 38(2):682-683; Winger, T. M. and Chaikof, E. L. [1998] "Synthesis and characterization of supported bioactive lipid membranes. In: "Materials Science of the Cell," Eds. A. Plant and V. Vogel, MRS Publications, Pittsburgh, 1998.) However, strategies based upon the coating or derivation of a prosthetic surface with matrix proteins or integrin-selective peptide sequences that promote endothelial cell growth have been unable to overcome the capacity of these substrates to activate platelets and the coagulation cascade. Thus, in the period prior to complete endothelial regeneration, the surface of a small caliber prosthesis remains at increased risk for thrombus formation.
There is a need in the art for effective antithrombogenic treatments for blood-contacting implants and treatment devices.
Whole organ pancreatic allografts using current immunosuppressive protocols have an expected graft survival as high as 86% at one year and 74% at five years after transplantation. Despite these encouraging results, the risk of major perioperative morbidity, the associated complications of chronic immunosuppressive therapy and the persistent shortage of donor organ tissue remain significant limitations of this approach. As a consequence, in the 1990s pancreas transplantation continues to have a limited role in the management of diabetes. The utilization of xenogeneic organs should provide a solution to the chronic shortage of donor tissue. Nonetheless, the prevention of tissue rejection following cross-species transplantation remains unsolved. It has been postulated that cell based therapy, using xenogeneic islets or insulin producing cell lines in association with an immunoisolation barrier, provides a rational strategy to circumvent the vigorous humoral and cellular response of the host while increasing the supply of non-human donor tissue (Sun, Y. et al. [1996], "Normalization of diabetes in spontaneously diabetic cynomologus monkeys by xenografts of microencapsulated porcine islets without immunosuppression," J. Clin. Invest. 98:1417; Halle I., et al. [1993] "Protection of islets of Langerhans from antibodies by microencapsulation with alginate-poly-L-lysine membranes," Transplantation, 44:350-4; Colton, C. and Avgoustiniatos, E. [1991] "Bioengineering in the development of the hybrid artificial pancreas I" Biochem. Eng. 113:152-70; Colton, C. K. [1992], "The engineering of xenogeneic islet transplantation by immunoisolation," Diab. Nutr. Metabol. 5:145-9).
Cell based therapy, using xenogeneic islets or insulin-producing cell lines in association with an immunoisolation barrier is thus an important step in the successful treatment of insulin-dependent diabetes mellitus (DDM). A critical component of this approach is the maintenance of long-term graft survival by protecting or isolating donor cells from immunological processes in the recipient which lead to islet cell construction. Enhanced control of both transport properties and surface physiochemical characteristics is required for providing the effective immunoisolation barrier crucial to the success of pancreatic islet cell transplantation.
Current approaches for microencapsulation tailor transport properties by controlling the distribution of pore sizes generated by thermodynamically driven physical processes. Typically, semipermeable membranes for cell encapsulation can be formulated by one of three physical processes. The most common methodology is based upon the principle of phase inversion whereby polymer precipitation time, polymer-diluent compatibility, and diluent concentration influence phase separation, and as a consequence, membrane porosity (Crooks, C. A., Douglas, I. A, Broughton, R. L., Sefton, M. V., "Microencapsulation of mammalian cells in a HEMAMMA copolymer: Effects on capsule morphology and permeability," J. Biomed. Mater. Res. [1990] 24:1241-1262; Sefton, M. V. [1989], Can. I. Chem. Eng. 67:705; Uludag, H. and Sefton, M. V. [1993], "Metabolic activity and proliferation of CEO cells in hydroxymethyl methacrylate methyl methacrylate (KEA-M.A.)," Cell Transplantation 2:175-82; Roberts, I. et al. [1996], "Dopamine secretion by PC12 cells microencapsulated in a hydroxymethyl methacrylate-methyl methacrylate copolymer," Biomaterials 17:267-75). Using phase inversion techniques, the outer membrane surface morphology can range in pore size from nanometers to microns. As a second approach, barriers can be created by a polyelectrolyte coacervation reaction and molecular weight cutoff (MWCO) modulated by osmotic conditions, diluents, and the molecular weight distribution of the polycationic species (Matthew, H. W. et al [1993] "Complex coacervate microcapsules for mammalian cell culture and artificial organ development," Biotechnol. Prog. 9:510-519; Yoshioko, T. et al [1990], "Encapsulation of mammalian cell with chitosan-CMC capsule," Biotechol. Bioeng. 35:66-72; Dautzenberg, H. et al. [1996], Polym. Sci. 101:149). The utilization of multicomponent polycationic polymer blends and the diffusion time of oligocationic species through precast blends of polyanionic polymers have also been shown to be important variables in the control of MWCO when membranes are produced in this fashion. Alginate-calcium chloride systems represent a third technique for generating semipermeable capsules and have been used to produce monodisperse, spherical, transparent beads at a high production rate (Lim, F. and Sun, A. M. [1980], "Microencapsulated islets as a bioartificial endocrine pancreas, Science 210:908; King, G. A. et al [1987], "Alginate-polylysine microcapsules of controlled membrane molecular weight cutoff for mammalian cell culture engineering," Biotech Progress 3:231-240; Goosen, M. F. A. [1985], "Optimization of microencapsulation parameters: semipermeable microcapsules as a bioartificial pancreas, Biotech Bioeng 27:146-150). As a cell-compatible polysaccharide, alginate is an appealing polymer and, in addition, facilitates cryopreservation of the encapsulated cell (Rajotte, R. et al. [1995], "Adult islet cryopreservation. In: Ricordi, C., ed. "Methods in Cell Transplantation," Austin: R. Landes, 17-24). Control of transport properties, however, requires post-coating of the alginate with a poly(amino acid), typically, poly-L-lysine or a derivative thereof. In all of these strategies, membrane strength may be increased by altering the composition, structure, and dimensions of the membrane. This often has a secondary effect on diffusive transport. Therefore, in most systems, membrane strength and mass transport properties are interdependent membrane characteristics. It is also significant that the criteria for molecular exclusion is determined, in all of these systems, by the relatively broad distribution of pore sizes and/or dimensional characteristics of non-uniform pores. The inability to precisely control the transport characteristics of currently available encapsulation barriers has lead to their inevitable failure regardless of the chosen membrane formulation.
Recent data suggests that the rejection of pancreatic islet xenografts occurs by an immunological pathway which is distinct from that associated with either the autoimmune destruction of isogeneic islets or rejection of allogeneic grafts. In the latter two cases, islet damage appears to be mediated by a primary "Th1" immune response in which the dominant effector cell is a cytotoxic CD8 T cell (Peterson, I. D., and Haskins, K. [1996], "Transfer of diabetes in the NOD-scid mouse by CD4 T-cell clones: differential requirement for CD8 T-cells," Diabetes 45:328-36; Haskins, K. and McDuffe, M. [1990], "Acceleration of diabetes in young NOD mice with CD4+ islet-specific T cell clone," Science 249:1433-6; Jarpe, A. et al. [1990], "Flow cytometric enumeration of mononuclear cell populations infiltrating the islets of Langerhans in prediabetic NOD mice: Development of model of autoimmune insulinitis for Type I diabetes," Regional Immunology 3:305-17; Miller, B. et al. [1988], "Both the Lyt-2+ and L3T4+ T cell subsets are required for the transfer of diabetes in nonobese diabetic mice I" Immunol. 140:52-8). In contrast, the rejection of islet xenografts is characterized by a 'Th2' response in which CD4 helper T cells, but not CD8 cells, play a major role (Weber, C. et al. [1990], "Microencapsulated dog and rat islet xenografts into streptozotocin diabetic and NOD mice," Horm. Metab. Res. 35:219-226; Akita, K. et al. [1994], "Effect of FK506 and anti-CD4 therapy on fetal pig pancreas xenografts and host lymphoid cells in NOD/Lt, CBA, and BALB/c mice, Cell Transplantation 3:61-73; Gill, R. et al. [1994], "CD4+ T cells are both necessary and sufficient for islet xenograft rejection," Transplantation Proceedings 26:1203-4; Loudovaris, T. et al. (1992), "The role of T cells in the destruction of xenografts within cell impermeable membranes," Transplantation Proceedings 24:2938-9; Pierson, R. et al. [1989], "CD-4 positive lymphocytes play a dominant role in murine xenogeneic responses," Transplantation Proceedings 21:519-21; Parker, W. et al. [1996], "Transplantation of discordant xenografts: a challenge revisited," Immunology Today 17:373-8). That is, there is considerable evidence that xeno-recognition, unlike allorecognition or autoimmune destruction, primarily occurs via an "indirect" antigen presentation pathway in which host antigen presenting cells (APCs) display peptides scavenged from donor proteins to host helper T cells (Takeuchi, T. et al. [1992], "Heart allografts in murine systems," Transplantation 53:1281-94; Moses, R. et al. [1990], "Xenogeneic proliferation and lymphokine production are dependent upon CD4+ helper T cells and self antigen-presenting cells in the mouse. I," Exp. Med. 172:567-75; Lenschow, D. et al. [1992], "Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig," Science 257:789-95). Presumably, xenogenic antigens are either released by the occasional broken capsule or diffuse across an intact capsule membrane after having been shed from the cell surface or liberated from necrotic or apoptotic cells. APCs process these antigenic cellular constituents and activate CD4+ T cells which develop into Th2 cells. In turn, Th2 cells stimulate the matron of B cells, which uniquely express the processed foreign peptide, into plasma cells that secrete xenoantigen specific antibodies. Investigators now suspect that it is the generation of immune complexes either by the binding of newly-formed antibodies to xenoantigens or preexisting autoantibodies to islet antigens that leads to inevitable islet cell destruction even in the presence of a barrier which directly excludes their entry. (Weber, C. I. et al. [1998], "Long-term survival of poly-L-lysine-alginate microencapsulated rat, rabbit, and pig islet xenografts in spontaneously diabetic NOD mice," In: Lanza R, Chick, W., ed. "Handbook of Cell Encapsulation Technology and Therapeutics" [New York: Springer-Verlag]). Antigen-antibody complexes efficiently bind to Fc receptors expressed on the surface of macrophages which leads to their activation and the subsequent secretion of a variety of low molecular weight cytotoxic mediators including cytokines and free radicals, such as interleukin-1 and nitric oxide, respectively (Ke, Y. et al. [1995], "Ovalbumin injected with complete Freund's adjuvant stimulates cytolytic responses," Eur. J. Immunol. 1995:549-53). It is also likely that activation of the complement cascade by generated antigen-antibody complexes is a significant factor in potentiating islet destruction (Müller-Eberhard, H. I. [1988], "Molecular organization and function of the complement system," Ann Rev Biochem 57:321-47). The production and association of C3b with circulating immune complexes could enhance the binding of these complexes to macrophages via the cell surface C3b receptor (Krych, M. et al. [1992], Complement receptors," Curr. Opin. Immunol. 4:8-13). In addition, concomitant release of C3a induces a local neutrophil response with the release of soluble factors, thereby, further potentiating the activation and recruitment of macrophages (Frank, M. [1991], "The role of complement in inflammation and phagocytosis," Immunol. Today 12:322-6). Notably, at the time of islet rejection an intense pericapsular cellular response is observed which is dominated by the presence of macrophages and B cells (Weber, C. et al. [1994], "NOD mouse peritoneal cellular response to poly-L-lysine-alginate microencapsulated rat islets," Transplantation Proceedings 26: 1116-1119; Weber, C. I. et al. [1990], "The role of CD4+ helper T cells in destruction of microencapsulated islet xenografts in NOD mice," Transplantation 49:396-404).
Prior work by inventors hereof includes U.S. patent application Ser. No. 09/149,098 filed Sep. 8, 1998, provisional application No. 60/058,194 filed Sep. 8, 1997, provisional application Nos. 60/091,399 and 60/101,252 filed Jun. 30, 1998 and Sep. 21, 1998, respectively, provisional application No. 60/197,072 filed Apr. 13, 2000, provisional application 60/221,618 filed Jul. 28, 2000, provisional application No. 60/198,792 filed Apr. 20, 2000 and 60/221,828 filed Jul. 28, 2000, PCT application US01/12094 filed Apr. 13, 2001, and PCT application No. US01/12918 filed Apr. 20, 2001, PCT application 97/16080 filed Apr. 11, 1997, application Ser. No. 08/729,928 filed Oct. 15, 1996, Ser. No. 09/342,922 filed Jun. 30, 1999, Ser. No. 09/149,098 filed Sep. 8, 1998, U.S. Pat. No. 6,171,614 issued Jan. 9, 2001, U.S. Pat. No. 6,071,532 issued Jun. 6, 2000, U.S. Pat. No. 5,741,325 issued Apr. 21, 1998, and U.S. Pat. No. 4,906,465 issued Mar. 6, 1990.
All publications referred to herein are incorporated by reference to the extent not inconsistent herewith.

This patent is subject to a terminal disclaimer.

Biological component comprising artificial membrane


Provided is an apparatus capable of easily splicing ACF tapes that are thin and are hard to handle. The tape splicing apparatus splices two ACF tapes (210) each having an ACF (212), and includes: a first holding unit that holds one of the ACF tapes (210); a second holding unit that holds the other one of the ACF tapes (210); a positioning unit (115) that positions the ACF tapes (210) to be overlapped in a thickness direction; and a pressing unit (116) that presses the overlapped ACF tapes (210) in the thickness direction.

1. Technical Field
The present invention relates to a splicing apparatus that splices tapes, such as ACF tapes. Furthermore, the present invention relates to an attaching apparatus that includes the splicing apparatus for splicing the tapes and that attaches an adhesive material on a board, such as a glass panel. More particularly, the present invention relates to an attaching apparatus that attaches an Anisotropic Conductive Film (ACF) on a terminal portion of the glass panel.
2. Background Art
ACFs have been attached on terminal portions of glass panels for use in liquid crystal displays or plasma displays, and electronic components for image formation have been mounted on the attached ACFs in order to ensure electrical continuity between the terminal portions.
These ACFs have been provided on one side of long resin tapes referred to as base tapes, and have been supplied as the ACF tapes. The ACFs can be attached on the glass panels by pressing the ACF tapes to the glass panels as they are and peeling off only the base tapes.
These ACFs have been automatically attached on the glass panels using ACF attaching apparatuses industrially, and the ACF tapes that are being wound onto reels and that provide the ACFs have been supplied to the ACF attaching apparatuses.
The ACFs required for a glass panel are being lengthened due to upsizing of displays in recent years. Thus, even when the ACF tapes being wound onto the reels are sufficiently long, they may be used up for a short period of time, and replacement frequency of the reels tends to be increased.
Operations of the ACF attaching apparatuses have been suspended when replacing reels with new reels conventionally. After the replacement, an ACF tape has been forwarded from the reel manually, and set through complicated paths for passing the tapes in the ACF attaching apparatus.
However, in the aforementioned method, it takes considerable time to set the ACF tapes. Thus, as illustrated in FIG. 1, a method to be applied to an ACF tape has been suggested. In the method, an additional ACF tape is spliced to an ACF tape that has been used so as to increase the number of turns of the ACF tape per reel (for example, Patent Reference 1). According to this method, the additional ACF tape is spliced to the used ACF tape having an established tape path. As the used ACF tape is taken up, the additional ACF tape passes the tape path. Therefore, a new ACF tape does not have to be set through the tape path.
Patent Reference 1: Japanese Unexamined Patent Application Publication No. 2004-202738
Although Patent Reference 1 discloses a method for splicing ACF tapes, it fails to specifically describe which kind of apparatus splices the tapes.
Furthermore, the ACF tape only measures 1 to 2 mm wide by 50 μm thick approximately, which is ultra thin. Thus, it is supposedly very difficult to splice the tapes manually, and such operation takes a very long time.
Furthermore, when the ACF attaching apparatus is used for splicing these ACF tapes, operations of the ACF attaching apparatus have to be suspended for a long time, and thus little improvement in operation rates of the ACF attaching apparatus can be expected.
In addition, when the ACF tapes are butt-spliced in a straight line as described above, a displacement between the ACF tapes in a width direction frequently occurs, and further it is very difficult to maintain the straight line of the spliced ACF tapes.
Furthermore, when splicing of ACF tapes causes any displacement or distortion, in particular, when a displacement between the spliced ACF tapes in a width direction occurs, there may be a possibility of dropping of the spliced ACF tapes from rollers included in a tape path in the case where the tapes pass through the tape path. Thus, when the ACF tapes are out of the tape path, the tape path needs to be set again manually. Thus, there is no point in splicing the ACF tapes, reducing the operation rates of the ACF attaching apparatus.
The present invention is to solve the aforementioned problems, and a first object is to provide a tape splicing apparatus that can prevent a displacement when splicing tapes together as much as possible and that can mechanically splice tapes for supplying an additional tape while maintaining a straight line of the spliced tapes.
Furthermore, a second object is to provide an attaching apparatus that can precisely splice an additional ACF tape to a tape that is being used and that can promote automation of replacing ACF tapes without suspending operations of the ACF attaching apparatus.
Furthermore, a third object is to provide an attaching apparatus that can continue to stably operate for a long period of time by holding the ACF tapes in volume and through automation of replacing the ACF tapes.

Tape splicing apparatus and attaching apparatus


An apparatus for providing support along the length of a catheter is described. The present invention consists of a mandrel fabricated from a non-metal. The mandrel extends through the lumen of a dilatation catheter to provide added support and stiffness to the catheter shaft. The stiffness along the length of the non-metal mandrel may easily be varied by making dimensional or morphological changes to the polymeric mandrel.

1. Field of the Invention
The present invention relates generally to catheters. More particularly, the present invention relates to a non-metal reinforcing mandrel for use with such catheters.
2. Description of Related Art
In percutaneous transluminal coronary angioplasty (PTCA), catheters are inserted into the cardiovascular system via the femoral artery under local anesthesia. A pre-shaped guiding catheter is positioned in the coronary artery, and a dilatation catheter having a distensible balloon portion is advanced through the guiding catheter into the branches of the coronary artery until the balloon portion traverses or crosses a stenotic lesion. The balloon portion is then inflated with a fluid to compress the atherosclerosis in a direction generally perpendicular to the wall of the artery, thereby dilating the lumen of the artery. After the last dilation, the balloon is deflated so that the dilatation catheter can be removed from the dilated stenosis and blood flow can resume through the dilated artery.
Ongoing development work of the dilatation catheters has reduced the transverse dimensions of the catheters for angioplasty procedures both as to their outer diameters as well as to the wall thickness of the catheter's tubular components. This reduction has led to difficulties in designing dilatation catheters having small transverse dimensions while still maintaining adequate pushability for advancement of the dilatation catheter through the guiding catheter into the patient's coronary artery and across tight stenoses. The marginal or inadequate pushability has been particularly noticeable with over-the-wire catheters that have been adapted for use with guidewires having diameters not more than about 0.014 inch (0.356 mm).
One solution to this dilemma has been the use of a reinforcing mandrel 24, such as the one shown in FIGS. 1A and 1B. The catheter 10 typically has an inner tubular member 12 with an inner lumen 14 adapted to receive a guidewire with a maximum OD of less than about 0.014 inch. An outer tubular member 16 is generally disposed about the inner tubular member 12 such that the inner tubular member 12 extends through the outer tubular member 16 and an outer lumen 18 is defined therebetween. The inflatable member (e.g., a balloon) 20 has a proximal end 21 which is secured to the distal end of the outer tubular member 16 and a distal end 23 secured to the distal end of the inner tubular member 12 so as to seal off the outer lumen 18 and the interior of the inflatable member 20.
The reinforcing mandrel 24 is within the outer lumen 18 between the inner 12 and outer 16 tubular members and extends from the proximal end of the catheter 10 into the distal portion of the catheter 10 but typically ends short of the inflatable member 20. The mandrel 24 is usually a cylindrical, often tapered axle inserted onto a device such as a catheter 10 to provide support along the length of the given device. The mandrel 24 is typically secured at the proximal end of the mandrel 24 within the adapter (not shown) mounted at the proximal end of the catheter 10.
Although difficult to achieve during processing, it is often desirable to vary the diameter of the mandrel 24 to establish a predetermined amount of flexibility. For example, since it is generally desirable for the proximal section of the catheter 10 to be more stiff to assist in the catheter's pushability, the proximal section of the mandrel 24 is designed/fabricated to have a larger diameter than the diameter of the mandrel 24 in a more distal section of the catheter 10. The smaller diameter portion of the mandrel 24 extending into the distal section of the catheter shaft 10 preferably has a transverse dimension of at least 20% less than the transverse dimension of the proximal section of the mandrel 24. This variation in the diameter of the mandrel 24 provides flexibility in the distal portion of the catheter 10 and allows the catheter 10 to track over the guidewire while still maintaining excellent pushability.
The mandrel 24 of the prior art is fabricated from a metal or metal alloy (hereinafter metal) rod. The metal mandrels 24 known in the prior art, however, have several inherent limitations. First, metal rods are generally too stiff for angioplasty procedures, and a too stiff rod reduces a catheter's trackability over a guidewire or other medical device. Not only is the rod often too stiff, but a metal rod is also more difficult to process. For example, the metal rod must be ground to the desired diameter for the various (i.e., proximal and/or distal) section and often still retains sharp edges along its length that can damage the interior of the catheter shaft. Further, the dimensions of a metal mandrel are fixed during fabrication.
It would be advantageous to replace the metal mandrels of the prior art with a non-metal mandrel that has more easily varied dimensions and stiffness characteristics along the length of the mandrel. The ability to easily vary the dimensions and stiffness characteristics of a mandrel will also allow more freedom in the choice of materials for the catheter shaft itself. In other words, because the stiffness of the mandrel can be easily varied during processing, the proximal section of the mandrel can be made stiff enough to provide the desired pushability for the catheter. A mandrel having a stiff proximal section reduces the need for a stiff proximal section of the catheter shaft itself. Thus, the material for the proximal shaft of the catheter will no longer be limited to a stiff polymer. By allowing the use of a less stiff polymer in the proximal section, the non-metal mandrel will also substantially reduce the likelihood of kinking. In this manner, a mandrel having a stiffer proximal section will provide the desired pushability without having to sacrifice the flexibility of the distal shaft of the catheter.


A semiconductor device includes an insulating film formed on a semiconductor substrate, a contact wiring formed in the insulating film, a protective film formed on the contact wiring and the insulating film, an opening portion formed in the protective film, the contact wiring being exposed through the opening portion, and an electrode pad formed in the opening portion, the electrode pad being electrically connected to the contact wiring. A region where the contact wiring is not provided is present below the opening portion.

The present disclosure relates to an electrode pad structure for semiconductor devices.
In recent years, there is a demand for a reduction in height of a chip including a wiring layer of a CCD (charge coupled device) or an imaging sensor in view of a relationship between the height and an optical characteristic thereof, in addition to improvements in function and scale of integration of a semiconductor device. Therefore, it is necessary to reduce the thickness of the wiring layer as well in the future. Wirings may be made of Cu in a state-of-the-art process. In this case, a Cu film is formed by plating before removal by Chemical Mechanical Polishing (CMP).
FIG. 7 is a cross-sectional view of a conventional semiconductor device having an electrode pad structure disclosed in Japanese Unexamined Patent Application Publication No. 2007-123546. As shown in FIG. 7, a first insulating film 102 is formed on a semiconductor substrate 101, and a second insulating film 103 and a first layer Cu wiring 104 are formed on the first insulating film 102. A third insulating film 105, and Cu connection vias 106 contacting the first layer Cu wiring 104 are formed on the second insulating film 103 and the first layer Cu wiring 104. A fourth insulating film 107, and a second layer Cu wiring 108 contacting the Cu connection vias 106 are formed on the third insulating film 105 and the Cu connection vias 106. A fifth insulating film 109, and Cu connection vias 110 contacting the second layer Cu wiring 108 are formed on the fourth insulating film 107 and the second layer Cu wiring 108. A sixth insulating film 111, and an uppermost layer Cu pad 112 contacting the Cu connection vias 110 are formed on the fifth insulating film 109 and the Cu connection vias 110. A passivation film 113 is formed on the sixth insulating film 111 and the uppermost layer Cu pad 112. An opening 114 through which a center portion of the uppermost layer Cu pad 112 is exposed is formed in the passivation film 113. An Al pad 116 is formed on the uppermost layer Cu pad 112 exposed in the opening 114 and the passivation film 113 around the opening 114 with a barrier film 115 being interposed therebetween. A tip of a bonding wire (not shown) is connected to the Al pad 116.


The present invention has an object to facilitate investigation of access status in internet.

WWW (World Wide Web) services provided by many HTTP (Hyper Text Transfer Protocol) servers connected to internet can easily be utilized by operating HTTP perusal software such as a Web browser executed on a user terminal connected to internet.
Operation of a Web browser has been facilitated by introduction of GUI (Graphical User Interface). The number of HTTP servers in use connected to internet is rapidly increasing. This tendency makes it easy for users to obtain many pieces of information, and WWW services have rapidly become popular.
Recently, commercial transactions have been made through WWW services. Because of the possibility to easily investigate access status of the user as compared with ordinary commerce, it has been now used also for marketing activity.
For carrying out such an investigation, the following methods are known:
(1) Storing identity information intrinsic to the each user using HTTP perusal software such as a so-called Web browser, such as Cookie or the like on the user terminal, an HTTP server acquiring this identity information when the user makes an access to the HTTP server, and recording and analyzing user's accesses to the information provided by the HTTP server;
(2) Analyzing a transmission packet from the user terminal connected to an internet service provider (hereinafter simply referred to as an ISP (Internet Service Provider)), and recording and analyzing user's accesses to the information provided by the HTTP server; and
(3) Recording and analyzing user's accesses, separately from information provided by the HTTP server and access log of the HTTP server, by an application independent of the HTTP server such as access analyzing software and the like.
To put it specifically, there is a method of recording information corresponding to user access in a file by use of the Java (trademark) applet adopted, for example, in http;//www.snippet.com/home.htm or the like.
However, in the aforementioned method (1), there has been room for improvement in terms of certainty, for example, in that Cookie cannot be used for some set conditions of the HTTP perusal software executed at the user terminal.
Because issuance and management of Cookie are accomplished for each HTTP server, it is impossible to carry out an investigation of access status in cooperation with the other HTTP server. In order to investigate access status of the user to a plurality of HTTP servers, therefore, it is necessary to unify access status data for the individual HTTP servers, and a larger number of servers makes it difficult to conduct such an investigation.
In the aforementioned method (2), when investigating access status to an external HTTP server managed outside the ISP used for the user to connect to internet, objects of investigation increase because of a very large number of HTTP servers connected to internet, thus making it very difficult to accomplish investigation.
In the aforementioned method (3), it is necessary to operate an application for carrying out the investigation and to analyze logs, separately from management of information and logs provided by the HTTP server, and also to conduct complicated operations such as specification of an HTTP server to be investigated, thus preventing easy accomplishment of the investigation.
The present invention was made in view of the problems mentioned above, and has an object to provide an information providing system permitting relatively easy investigation of the status of user access.

Information providing system and identification information adding device

Abstract: To achieve this object, when the HTTP server (203) transmits prescribed image data, identity information meeting the access from the terminal unit (30) is generated in the identity information adding process (205), and added to prescribed image data. The corresponding relationship between the identity information and the image data containing the added identity information is recorded in the database (206).


A MOS device having reduced recesses under a gate spacer and a method for forming the same are provided. The MOS device includes a gate structure overlying the substrate, a sidewall spacer on a sidewall of the gate structure, a recessed region having a recess depth of substantially less than about 30 Å underlying the sidewall spacer, and a silicon alloy region having at least a portion in the substrate and adjacent the recessed region. The silicon alloy region has a thickness of substantially greater than about 30 nm. A shallow recess region is achieved by protecting the substrate when a hard mask on the gate structure is removed. The MOS device is preferably a pMOS device.

The scaling of VLSI circuits is a constant effort. With circuits become smaller and faster, improvement of device driving current becomes more important. Metal-oxide-semiconductor (MOS) transistor current is closely related to gate length, gate capacitance, and carrier mobility in the channel region. Shortening poly-gate length, increasing gate capacitance and increasing carrier mobility can improve the device currents of MOS devices. Gate length reduction is an ongoing effort in order to shrink circuit size. Increasing gate capacitance has also been achieved by efforts such as reducing the gate dielectric thickness, increasing the gate dielectric constant, and the like. In order to further improve device current, enhancing carrier mobility has also been explored.
Among efforts made to enhance carrier mobility, forming a stressed channel region is a known practice. Stress, sometimes referred to as strain, can enhance electron and hole mobility. The performance of a MOS device can be enhanced through a stressed-surface channel. This technique allows performance to be improved at a constant gate length, without adding complexity to circuit fabrication or design. Research has revealed that a tensile stress in the channel length direction can improve nMOS performance, and a compressive stress in the channel length direction can improve pMOS device performance.
A commonly used structure for applying compressive stress to the channel region of a pMOS device is shown in FIG. 1. A gate stack including a gate dielectric 4 and a gate electrode 6 is formed on a silicon substrate 1. SiGe regions 2 are formed in the substrate 1 with a channel region 8 therebetween. Typically, the formation of the SiGe regions 2 includes forming recesses in the silicon substrate 1 and epitaxially growing SiGe (with desired impurities) in the recesses. Since SiGe has a greater lattice constant then silicon, SiGe regions 2 press on the channel region 8, so that a compressive stress is developed in the channel region 8.
FIGS. 2 and 3 illustrate intermediate stages in the fabrication of the gate stack shown in FIG. 1. Typically, to form the gate stack, stacked layers, which include a gate dielectric layer, a gate electrode layer and a hard mask layer, are formed on the substrate 1. The stacked layers are then patterned to form gate dielectric 4, gate electrode 6, and hard mask 10. Hard masks have been extensively used in the formation of pMOS devices having SiGe regions. The patterning step may cause recesses 12 to be formed on the surface of the silicon substrate 1. In subsequent steps, as shown in FIG. 3, SiGe regions 2 are formed and the hard mask 10 is removed. Typically, the hard mask 10 comprises silicon nitride and is preferably removed using H3PO4. H3PO4 attacks silicon substrate 1 and results in deepened recesses 12. In prior art pMOS devices, if the hard mask is removed by H3PO4 after epitaxially growing SiGe regions 2, the depth Dp of the recesses 12 is easily greater than about 30 Å, and even achieving a depth of only 30 Å is difficult.
When doped SiGe regions are formed in pMOS devices, the impurities in the SiGe are more prone to diffusion during subsequent thermal processes. Diffused impurities deepen junction depths and compensate for pocket regions, resulting in the reduction of junction abruptness. Therefore, the short channel effects are adversely affected. If deeper recesses are formed under the spacers, the junction depth will be further increased, and the performance of the pMOS devices will be affected more.
Therefore, there is the need for a method for forming MOS devices, particularly pMOS devices, with reduced recesses in substrate regions close to the gate structure.

MOS devices with reduced recess on substrate surface

Taiwan Semiconductor Manufacturing Company, Ltd.


System and method for providing control for switch-mode power supply. According to an embodiment, the present invention provides a system for regulating a power converter. The system comprises a signal processing component that is configured to receive a first voltage and a second voltage, to process information associated with the first voltage and the second voltage, to determine a signal based on at least information associated with the first voltage and the second voltage, and to send the signal to a switch for a power converter. The switch is regulated based on at least information associated with the signal. The signal processing component is further configured to determine the signal to be associated a first mode, if the first voltage is higher than a first threshold.

The present invention is related to integrated circuits. More specifically, the present invention can be applied to controllers used for switch mode power supply. According to various embodiments, the present invention provides various power control schemes to reduce standby power consumption and improves system efficiency. Merely by way of example, the present invention can be used in switch mode power conversion system including, among, other things, offline fly-back converters and forward converters. It is to be appreciated that the present invention has a broad range of applications.
Power converters are widely used in various applications, such as providing power to portable consumer electronics. The power converters can convert electric power from one form to another form. As an example, the electric power is transformed from alternate current (AC) to direct current (DC), from DC to AC, from AC to AC, or from DC to DC. Additionally, the power converters can convert electric power from one voltage level to another voltage level.
In the past various types of power converters have been developed. For example, linear regulators have traditionally been used for power converters. A linear regulator is a voltage regulator based on an active device (such as a bipolar junction transistor, field effect transistor or vacuum tube) operating in its "linear region" or passive devices like zener diodes operated in their breakdown region. The regulating device is made to act like a variable resistor. While linear regulators have been used for many years, their power efficiency is often inadequate for portable electronics. For example, due to low power efficiency, linear regulators often waste large amount of energy and generate excessive heat for portable devices.
With the advent of integrated circuits, switched-mode power supply has been invented and utilized for various applications. Switch mode power supplies are typically implemented with a switching regulator, which is an internal control circuit that switches the load current rapidly on and off in order to stabilize the output voltage. For certain applications, switch-mode power supply uses pulse-width-modulated (PWM) or pulse-frequency-modulated (PFM) mechanism. These mechanisms are usually implemented with a switch-mode-controller including various protection components.
In recent years, power systems are often required to comply with standards for energy consumption. For example, various international organizations have imposed energy saving standards such as "Energy Star", "Blue Angel", etc. For example, such standards impose requirements that, among other things, power supplies have low standby power consumption (i.e., high power efficiency under very light or zero load condition).
In the past various techniques have been developed to lower various forms of power consumption. For example, different types of standby power consumption schemes have been developed. Unfortunately, conventional techniques are often inadequate.
Therefore, it is desirable to have improved systems and methods for power systems.

On-Bright Electronics (Shanghai) Co., Ltd.


The present invention provides a calcified tissue facing preparation characterized by having a polymerizable resin, and an antimicrobial agent of formula (I) where R1 is a hydrocarbon radical having between 1 and 16 carbon atoms, n is an integer between 1 and 8 inclusive and X is a halogen atom selected from fluorine, chlorine or bromine. It is appreciated that R1 includes unsaturated hydrocarbon radicals, as well as heteroatom containing radicals. Preferably, the molecule of formula (I) is associated with an adduct species. A solvent and the complementary spectrum antimicrobial benzalkonium chloride are also optionally added. An antimicrobial oral rinse excluding the polymerizable resin contains at least 0.2% by weight of the antimicrobial agent.

This invention relates to compositions for sealing calcified tissue substrates to inhibit infection and promote subsequent restorative material bonding; in particular, the invention is tailored to dentinal tubules, in order to prevent dentinal hypersensitivity and further to promote effective bonding of subsequent restorative dental materials such as amalgams, composites, resins and cementitious materials.
Dental caries are a common disease of modern humankind. The treatment of dental caries involves the removal of the carious lesion by a number of means including mechanical drilling and light ablation. The ensuing removal of dentin brings the dental nerve endings contained within the pulp into proximity with the mouth. Filling the resulting cavity in order to isolate the nerve endings leaves the tooth susceptible to thermal hypersensitivity via thermal conduction through the filling as well as bacterial infection. Bacterial colonization of the filled cavity induces further caries formation and hypersensitivity.
Currently, polymeric resinous materials are widely used to fill cavities, as well as in cosmetic dentistry and corrective dental structures including brackets, braces, veneers, onlays, crowns, and the like. In adhering dental structures to tooth enamel, there are minor problems with thermal or bacterial hypersensitivity.
In contrast, when the dentin of a tooth is exposed as a result of cervical erosion or tooth decay, changes occur in the physical structure of the dentin. Whereas tooth enamel is a densified, nonporous substance, dentin is characterized by a porous structure containing thousands of dentinal tubules. The dentinal tubules extend outward from the tooth pulp and terminate at or before the tooth enamel. These tubules contain pressurized pulp fluid which seeps from the pulp when the ends of the tubules are exposed. Collagen fibers are also associated with the tubules.
Typically, neither cervical erosion nor drilling of dentin directly exposes the ends of the dental tubules. Cervical erosion surfaces are characterized by irregularities and hemispherical protrusions. The dentinal tubules are mostly filled with inorganic material although some maintain openings of various sizes. Drilling of dentin creates a debris field which is characterized by weakened and cracked dentin. Since the debris field is structurally unsound, adhering a restorative material thereto creates a weak filling.
The cleaning of dentin prior to bonding a material thereto is. thus highly advantageous. Typically, acid etching is used to decalcify the surface dentin and enlarge the openings of the tubules. Acid etching leaves behind the protruding collagen fibers that are associated with the dentinal tubes. These collagen fibers represent a substrate for bacterial colonization as well as a hydrophilic surface for the bonding of a polymeric resinous material. The acid etching solution is typically a 20-50% by weight solution of phosphoric acid, but also includes citric and nitric acids.
A number of facing preparations are currently in use to seal and disinfect a dentin surface following acid etching. These preparations typically include a monomeric resin capable of cross linking to the collagen fibers. Glutaraldehyde (GLUMA, Heraeus Kulzer, Inc.) and benzalkonium chloride (Healthdent, Inc.) are added as antimicrobials. These prior art antimicrobials are limited in their efficacy. Glutaraldehyde polymerizes in water and thereby the effective dosages decrease. Furthermore, glutaraldehyde is a known irritant as well as antiseptic and thereby may induce the dental hypersensitivity which the facing preparation is designed to prevent. Benzalkonium chloride is a potent antimicrobial yet is incompatible with anionic detergents such as soap, as well as with nitrates. While the benzalkonium cation is electrically attracted to dentin, stearic considerations prevent optimal interactions between the radical and dentinal tubules.
The present invention provides a facing preparation composition containing a polymerizable resin and an antimicrobial agent having the formula:
where R1 is a hydrocarbon having between 1 and 16 carbon atoms, n is an integer between 1 and 8 inclusive, R2 is selected from the group consisting of halophenyl and 2-ethylhexyl. Optionally, the antimicrobial agent is delivered in the form of an organic salt, with the anionic species selected from: acetate, gluconate, propionate, and acrylate. Optionally, a solvent is also provided to promote diffusion of the other composition components into a substrate. Solvents operative in the present invention illustratively include: methanol, water, acetone, methyl ethyl ketone, and isopropanol.
The present invention also provides for a facing preparation composition consisting essentially of: 28-55 weight percent polymerizable resin; 0.1-10 weight percent antimicrobial agent having the formula:
where R1 is a hydrocarbon having between 1 and 16 carbon atoms, n is an integer between 1 and 6 inclusive, R2 is selected from the group consisting of halophenyl and 2-ethylhexyl; 30-69.8% solvent and 0.1-10% benzalkonium chloride.
An antimicrobial oral rinse contains the antimicrobial agent present at greater than 0.2% by weight in a buccal cavity compatible solvent and excluding the polymerizable resin of the facing preparation composition.
The present invention pertains to compositions for facing and disinfecting a calcified tissue structure. The facing preparation of the present invention inhibits thermal and microbial hypersensitivity in proximal nerves of the organism. The facing preparation of the present invention also promotes bonding of a subsequent structural sealing layer to the calcified tissue. The term xe2x80x9ccalcified tissuexe2x80x9d as used herein is defined to mean periosteum, cortical bone, tooth enamel, cementum, dentin, and pulp. The present invention has particular utility in facing and disinfecting exposed dentin for subsequent bonding of additional restorative dental materials.
Optionally, calcified tissue substrates are etched by means conventional to the art, prior to application of a facing preparation of the instant invention. Acid etching generally involves application of mineral acids illustratively including phosphoric, nitric, citric and hydrofluoric acids. It is appreciated that mechanical etching using an abrasive grit is also operative herein. Following etching, extraneous acid and debris are removed from the substrate by irrigating the etched substrate with water. The substrate is then blotted or evaporatively dried by means illustratively including an air jet.
The facing preparation of the instant invention contains a polymerizable resin. The term xe2x80x9cpolymerizable resinxe2x80x9d as defined herein means either a hydrophilic polymerizable compound having at least one hydroxyl moiety therein, a hydrophobic polymerizable hydrocarbon, or a polymerizable compound having both a hydrophobic and a hydrophilic moiety therein. Polymerizable resins operative within the present invention illustratively include hydroxyalkyl methacrylates, hydroxyalkyl acrylates, alkyl methacrylates, alkyl acrylates, polyhydric alcohols, mixtures thereof, substituted derivatives thereof and the like. Specific polymerizable resins operative within the present invention illustratively include 2-hydroxymethyl methacrylate (HMMA), 2-hydroxyethyl methacrylate (HEMA), bisphenol-A-glycidyl methacrylate prepolymer (bis-GMA), N-phenylglycine/glycidyl methacrylate (NPG-GMA), bis(glycerol dimethacrylate) phosphate, glycerol methacrylate, methyl acrylate, triethylene glycol dimethacrylate and the like. Preferably, hydrophilic resins such as HMMA and HEMA are used in facing preparations of the present invention which are tailored to treatment of inherently moist substrates, such as dentin. The facing preparations of the present invention preferably include a polymerizable resin present in amounts ranging from about 10-90% by weight relative to the total facing preparation weight. More preferably, the polymerizable resin is included in the facing preparation in amounts from 20-60 weight percent relative to the total facing preparation weight. Most preferably, the polymerizable resin is included in the facing preparation in amounts from 30-50 weight percent relative to the total facing preparation weight.
The facing preparation of the present invention optionally further includes a solvent. The solvent promoting diffusion of the facing preparation into microscopic pores and crevices of the substrate. The solvent is chosen to impart solubility on the polymerizable resin used in a particular facing preparation. In those instances where the osteoporotic substrate is dentin, hydrophilic solvents are preferred. Solvents operative within a facing preparation of the present invention illustratively include: ethanol, water, acetone, methyl ethyl ketone, and isopropanol. The solvent is preferably present in the facing preparation in amounts ranging from 10-90% relative to the total facing preparation weight. More preferably, the solvent is included in the facing preparation in an amount ranging from 20-80% by weight relative to the total facing preparation weight. Most preferably, the solvent is included in the facing preparation in an amount ranging from 30-70% by weight relative to the total facing preparation weight. It is appreciated that a miscible mixture of solvents is also operative herein.
The facing preparation of the present invention also includes an antimicrobial agent of the formula:
where R1 is a hydrocarbon radical having between 1 and 16 carbon atoms, n is an integer between 1 and 8 inclusive and R2 is selected from halophenyl and 2-ethylhexyl. It is appreciated that R1 includes unsaturated hydrocarbon radicals, as well as heteroatom containing radicals. Preferably, the molecule of Formula (1) is associated with an adduct species. The adduct species being selected to promote solubility in the facing preparation. Adduct species operative in the present invention illustratively include: acetate, gluconate, propionate, and acrylate. Preferably, R1 is a saturated hydrocarbon. Preferably, R1 has between 1 and 6 carbon atoms. Preferably, the halophenyl is chlorophenyl. More preferably, the halophenyl is para-halophenyl. Specific antimicrobial agents of the present invention illustratively include: alexidine, chlorhexidine, alexidine gluconate, chlorhexidine gluconate, alexidine acetate, chlorhexidine acetate and chlorhexidine digluconate.
Both alexidine and chlorhexidine are effective antimicrobials against a wide range of vegative gram positive and gram negative organisms. The facing preparation of the present invention is preferably buffered to pHs ranging from about 5-9. More preferably, the present invention is buffered to pHs ranging from 6-9.
Optionally, a secondary biocide is introduced into the compositions of the present invention. Benzalkonium chloride is operative as an additive in the present invention compositions between 0.1 and 10% by weight of the total composition weights. It is appreciated that other additives, adjuvants, surfactants, stabilizers, dyes, and emulsifiers are also added optionally to the present invention. In particular, fluoride solution present to about 0.5% by weight is a well established wash effective against dental caries.
In another embodiment, solutions of the antimicrobial agent (I) are provided which lack the polymerizable resin. This solution has utility as an oral rinse to cleanse the buccal cavity and in particular tubules prior to application of conventional dental structures. While such rinses have previously been utilized having between about 0.12% to 0.20% chlorohexidine, considerably more effective antimicrobial formulations are disclosed herein. An antimicrobial rinse according to the present invention includes between 0.2 and 10% by weight of antimicrobial based on total solution weight. Preferably, the rinse contains 0.2 to 5% antimicrobial. More preferably, the rinse contains a solvent of water, acetone or ethanol or mixtures thereof.
It is appreciated that the facing preparation of the present invention may also include other conventional microbial agents which have a complementary antimicrobial spectrum to those of Formula I. The microbial agents of Formula I are particularly effective over time owing to charge interactions between the substrate and the agents of Formula I.

Calcified tissue facing preparation containing an antimicrobial agent


Interactions between users of a computer network are facilitated by transmitting a first user""s proposal for an activity to another user, with the proposal including one or more parameters descriptive of the proposed activity. A response received from the other user may include a counterproposal having one or more parameters descriptive of the proposed activity, with at least one of the parameters of the counterproposal differing from a corresponding parameter of the proposal. The users automatically engage in the proposed activity using the parameters included in the counterproposal upon acceptance of the counterproposal by the first user.

This invention relates to managing communications between users of a computer network.
The rapid emergence of the Internet and the World Wide Web has created an environment in which anybody in the world who can connect to the Internet through a personal computer is generally able to access the universe of information that is available via Web sites. Electronic mail (a.k.a. e-mail) has also become ubiquitous due to its ease of use and its low cost. The emergence of these capabilities has been spurred by technological advances in various areas, including microprocessors (both computing speed and miniaturization), computer operating systems and interfaces (e.g., Windows, Macintosh, and Unix), and Internet browsers (e.g., Netscape Navigator). In turn, the rapidity of increase of the technology has had a direct positive impact upon productivity, and the world economy in general. Thus, there is an incentive for high-tech entities to create further improvements in the state of the art with respect to the Internet.
An online forum is a communications interchange in which people may communicate with others through successive electronic transmissions between respective computer systems. An online forum, or any other type of distributed computer services, may be implemented on a distributed computer system such as that shown in FIG. 1. Forum participants (equivalently, users of the computer services) typically are scattered across a large geographical area and communicate with one or more central server systems 100 through respective client systems 102 (e.g., a personal or laptop computer). In practice, the server system 100 typically will not be a single monolithic entity but rather will be a network of interconnected server computers, possibly physically dispersed from each other, each dedicated to its own set of duties and/or to a particular geographic region. In such a case, the individual servers are interconnected by a network of communication links, in known fashion. One such server system is xe2x80x9cAmerica Onlinexe2x80x9d from America Online Incorporated of Virginia (AOL).
Each client system 102 runs client software that allows it to communicate in a meaningful manner with corresponding software running on the server system 100. The client systems 102 communicate with the server system 100 through various channels, such as a modem 104 connected to a telephone line 106 or a direct Internet connection using a transfer protocol such as Transfer Control Protocol/Internet Protocol (TCP/IP). The server system 100 is responsible for receiving input from the client systems 102, manipulating the collective body of input information (and possibly information from other sources) into a useful format, and retransmitting the formatted information back to one or more clients 102 for presentation on an output device, such as a display screen.
A specific aspect of the Internet xe2x80x9cculturexe2x80x9d is the xe2x80x9cchat roomxe2x80x9d phenomenon. A chat room is a virtual space (i.e., an electronic channel) in which some specific communications activity is ongoing. In some cases, the activity is an application, such as a computer game. In many other cases, the activity is a simple conversation, or xe2x80x9cchat sessionxe2x80x9d, between the participants. Referring to FIG. 2, a chat room 200 is illustrated, in which the various participants 204 (e.g., xe2x80x9cAllens9xe2x80x9d, xe2x80x9cJOSHUAALEXxe2x80x9d, etc.) may enter text which appears in a scrolling text window 202 on each participant""s computer display screen. In the example in FIG. 2, the chat room 200 has 22 participants whose identities (or xe2x80x9cscreen namesxe2x80x9d) are listed in a scrolling window 210. A participant 204 may respond to the comment of another participant 204 by entering a line of text in an edit box 206 and activating (e.g., by clicking with a pointer device, such as a mouse) a SEND button 208. In response, the text in the scrolling text window 202 scrolls upwards and the newly entered line of text is displayed at the bottom of the scrolling text window 202. In the illustrated example, the last participant to enter a comment was JOSHUAALEX, who typed xe2x80x9cTEXASxe2x80x9d.
The chat room 200 shown in FIG. 2 is xe2x80x9cpublicxe2x80x9d, meaning that it is generally open to any user of the online service who accesses it, and it typically has multiple participants who were placed in the chat room by the computer-service provider and who most likely never have met or conversed with one another before. A comment by a participant in a public forum may be seen by all of the participants of the chat room. If a participant desires some privacy, that participant may open and enter a xe2x80x9cprivatexe2x80x9d chat room (for example, by clicking on a xe2x80x9cPrivate Roomxe2x80x9d button 212), and thereafter invite one or more other participants to enter the private chat room, which can be accessed exclusively by the originators and their invitees. Once in a private forum, participants may communicate with one another without fear that uninvited participants will be able to see their comments. It is also possible to have a semi-public chat room, which is open to a specified group of users.
AOL has created the AOL Instant Messenger (AIM(trademark)) system. The AIM system allows a user to create an electronic messaging medium known as a xe2x80x9cBuddy Listxe2x80x9d(trademark) of others (such as friends and family) with whom the user often interacts while online and send instant messages (IMs) to those users. The AIM system automatically informs the user whenever a member of that user""s buddy list is online. Thus, the two buddies can communicate directly (i.e., chat) because they both are online and are aware of each other""s presence.
Another development by AOL in this arena is the concept of xe2x80x9cEvilxe2x80x9d. This concept arose in recognition of the fact that users can and do abuse the privileges afforded them by the abilities to communicate instantly with others and to transmit large volumes of information. Such abuse may occur, for example, when a user sends messages having objectionable content, or when a user overuses the AIM system by sending excessive numbers of messages to other users. Another form of abuse occurs when a user sends files that contain large amounts of data to another user, so that when the recipient tries to open or download the files, or even perform other activities, the recipient""s computer system is slowed down due to the processing of the received files.
AOL""s creation of the Evil concept is an attempt to remedy this and other types of abuse. If a user perceives that another user is behaving badly (e.g., repeatedly sending unwanted IMs), the offended user can xe2x80x9cevilxe2x80x9d, or warn, the misbehaving user, thereby increasing the misbehaving user""s Evil level. The effect of eviling a user typically is small but cumulative. Over time, if a user has been eviled a sufficient number of times, that user""s ability to use system resources (e.g., send IMs) will be deliberately slowed as a punishment. If the abuse continues and even more eviling occurs, the abuser eventually can be involuntarily logged off the computer network. The underlying notion is to promote computer etiquette and basic courtesy in the online (and particularly chat room) environment. Giving users the power to xe2x80x9cevilxe2x80x9d one another gives them the ability to create a self-policing society, thus alleviating the Internet Service Provider (ISP) from having to perform the policing function. Further details on eviling techniques can be found in U.S. Ser. No. 09/076,483, filed May 13, 1998 now U.S. Pat. No. 6,336,133, entitled xe2x80x9cRegulating Users of Online Forumsxe2x80x9d, and U.S. Ser. No. 09/076,484, filed May 13, 1998 now U.S. Pat. No. 6,339,784 entitled xe2x80x9cSelf-Policing, Rate Limiting Online Forumsxe2x80x9d, both of which are incorporated by reference.
Although it is possible for a chat room to be completely free-form dialogue on any subject, it is common for chat rooms to be organized around a specific subject for discussion. The proliferation of the chat room phenomenon has created a need for a mechanism to optimally arrange a chat room environment to meet the needs of the users. For example, a given user might desire to have a private conversation with a specific group of three other users on a particular subject. Alternatively, the user might wish to play a particular computer game jointly with two friends, each located at a different remote site. Presently, if such a user wishes to engage in such activity, the user can either 1) find an existing chat room where the desired activity is ongoing and attempt to join in, but not necessarily having any control over the identities or number of other participants; or 2) send an IM or e-mail message to the other users with whom the user wishes to engage in the activity and invite them to do so. Typically, the inviting user will receive either no response at all (e.g., if the recipient ignores the invitation) or a binary response (i.e., yes or no) to the invitation.
In light of the foregoing, the present inventors have recognized the need for a powerful and flexible negotiation mechanism, whereby users desiring to communicate or otherwise interact with each other can xe2x80x9cbargainxe2x80x9d with one another in order to agree ultimately upon a mutually acceptable communication (e.g., chat room) or other interaction (e.g., multiple user computer game) context.
Implementations may include various combinations of the following features.
A protocol, referred to as the xe2x80x9cRendezvousxe2x80x9d protocol, is designed to facilitate interactions between users of a computer network by transmitting a first user""s proposal for an activity to another user. The proposal may include one or more parameters descriptive of the proposed activity. A response, such as an acceptance, a rejection, or a counterproposal, is received from the other user. Depending on the received response, the users may or may not selectively engage in the proposed activity.
One such activity could be an online xe2x80x9cchatxe2x80x9d session, and a typical set of parameters for a proposal to chat could include a proposed topic on which the chat session will be focused and a proposed channel in which the chat session will take place. Another typical activity could be an online computer game, and the specified parameters could identify proposed participants in the game.
An acceptance indicates agreement to all parameters of the proposal. A rejection indicates disagreement with at least one parameter of the proposal. A counterproposal indicates an offer to modify one or more of the proposal parameters. If a counterproposal is made, a further response to the counterproposal can be made, and this response also can be an acceptance, a rejection, or yet another counterproposal. This sequence may occur indefinitely until acceptance or rejection occurs.
A cancellation of a proposal or counterproposal may be issued by the user that originally made the proposal or counterproposal, so long as this occurs prior to the receipt of a response. Typically, such a cancellation should include a reason for the cancellation.
In issuing a rejection, a user may indicate that the proposal is being ignored, either explicitly or implicitly (by inaction).
The protocol allows users to transmit messages, referred to as xe2x80x9cEvilxe2x80x9d messages, registering displeasure with any proposal, counterproposal, or acceptance. An Evil message has a cumulative (and potentially exponential) effect upon a recipient""s ability to access the computer system""s resources.
One objective of the protocol is to help online users produce an optimal environment for an activity by enabling them to negotiate the parameters of the activity until agreement is reached. Typical activities include exchanging voice messages, playing an online game, finding a route from one client computer to another, transferring files, direct instant messaging, exchanging avatars, participating in a chat room, or engaging in collaborative project development.
Another potential online activity that can make use of the Rendezvous protocol is e-commerce. The protocol lends itself to a negotiation of a sale/purchase of goods or services, or intangible property. Parameters of such a negotiation might typically include price, model, style, color, delivery details, and warranty details.
A rejection message may indicate a reason for the rejection. Typical reasons include the following: the proposed activity is unsupported by a client computer associated with a recipient of the proposal; the proposed activity was denied by a recipient of the proposal; a recipient of the proposal explicitly ignored the proposal; the proposal timed out; or the proposal message could not be understood.
In one embodiment, the Rendezvous protocol is implemented as computer software potentially within a larger computer software application. The protocol software is tangibly embodied in a computer-readable medium or propagated carrier signal. The protocol software contains instructions to allow the computer system to conduct an online negotiation session.
The techniques and mechanisms described here may provide one or more of the following advantages. The Rendezvous protocol provides users with the ability to negotiate characteristics of an interactive online environment (chat session, online game, etc.). As a result, users can tailor and optimize their online environments so that they are mutually agreeable to all participants. This optimization typically occurs prior to inception of the environment undergoing negotiation. Consequently, users can engage in environments of their own choosing and according to their own desires, and without encountering unwanted or undesirable circumstances or participants.
Additional features and advantages will be apparent from the following description, including the figures and the claims.

Managing negotiations between users of a computer network by automatically engaging in proposed activity using parameters of counterproposal of other user


A ghost removal apparatus to prevent visual emphasis of image noises when removing ghosts. A transparent characteristic of an image signal is changed with respect to frequency characteristics of ghost removing filters at a frequency of at least 4.2 MHz depending on amounts of noises included in the image signal, and an equalizing characteristic of the image signal is changed with respect to the frequency characteristics of the ghost removing filters at a frequency of at most 4.2 MHz depending on the amounts of the noises.

The present invention relates to an apparatus for removing ghosts of television signals with a data processing for controlling filters.
Description of the Related Art
In a television (TV) receiver, a TV radio wave transmitted from a broadcasting station is converted into electric signals at a receiving antenna and is then converted into TV signals by a tuner. A TV radio wave reaches an antenna via a plurality of paths by some shielding or reflecting in addition to its direct arrival.
The radio wave repeatedly reflected has suffered a delay in time and a change in intensity compared with the radio wave directly reached. When reproducing on a TV screen, this reflected radio wave may often produce ghosts. A plurality of conventional ghost removal apparatuses have been developed, as disclosed in Japanese Patent Laid-Open Publication Nos. 56-69974, 3-117273, and 3-132166.
In such conventional ghost removal apparatuses, the ghosts are removed using a ghost removal reference signal shown in FIG. 1. In that case, a TV signal having much more noise, as shown in FIG. 2, is received, after the ghost removal, the frequency characteristic of the TV signal is shown in FIG. 3. A hatching 18 in FIG. 2 and a hatching 19 in FIG. 3 show noise included in the TV signal received. A hatching 20 in FIG. 3 shows noise emphasized by removing the ghosts.
In the conventional ghost removal apparatuses, when the ghosts are removed, the frequency characteristic of the TV signal is made to be an ideal characteristic. Accordingly, the high frequency area of the image signal is emphasized and the noise is thus emphasized in a receiving area having a weak electric field intensity. Further, with a transparent band of a cutoff frequency equal to or less than 4 MHz, a color ghost cannot be removed.


A plurality of constraints are identified for a model of a software deployment in an integrated development environment. Each of the constraints are associated with one of a plurality of analysis levels. It is determined for each analysis level whether the corresponding associated constraints are met so that an identification indicating the same may be provided. Related techniques, apparatus, systems, and articles are described.

Large software deployments are increasingly being modeled prior to initiation of coding. Model checking ensures that model artifacts satisfy a set of criteria when models pass to the next level of maturity. Such criteria can include the correctness and plausibility of artifacts as well as infrastructure-related issues that take into consideration the underlying technical infrastructure (e.g., availability, adequateness of configuration, etc.). Constraints associated with a check define what criteria an artifact has to satisfy in order to pass a check. Constraints can be repeatedly applied to artifacts without changing the artifact as such. Given an identical context, constraints should return a predictable result. Conventional architectures for model checking require improvements in efficiency, error reporting, and troubleshooting assistance.

Integrated model checking and issue resolution framework


A communication method in a discontinuous reception mode of a mobile communication system and communication terminal having the discontinuous reception mode are disclosed in the present invention. The method comprises: performing, by a terminal, a contention based transmission; starting a first timer, wherein the terminal is kept active during the operation of the first timer; and stopping the first timer when a preset first condition is met.

In a mobile communication system, for saving power consumed by a mobile terminal, the terminal may stop receiving some signal from a base station serving the terminal, which is called as "discontinuous reception". If the terminal is in the discontinuous reception mode, a time period, during which the reception of the signal of the serving base station must be kept, is called "active time", the time period except for the active time is called "idle time". As shown in FIG. 1, the terminal does not receive some signal from the serving base station during the idle time. Of course, the terminal may perform other operations, such as measurement of a neighboring cell, during the idle time.

Communication method and communication terminal under discontinuous reception mode


The disk recording apparatus and method are arranged to specify a recording address and a recording position on an optical disk with a wobble PM (phase modulation) format through the use of a wobble reproduced signal and a track reproduced signal. The recording apparatus operates to detect address information and a synchronous signal on the optical disk that correspond with the wobble reproduced signal and the track reproduced signal sent from the optical disk respectively. Then, the address information required for specifying a disk recording track and the synchronizing timing required for specifying a linking position are selected from the detected states.

The present invention relates to a disk recording method and a disk recording apparatus, and more particularly to the disk recording method and apparatus which are required when information is linked or rewritten onto an optical recording disk.
As a typical large-volume disk-type recording medium, a DVD (Digital Versatile Disc) may be referred. Further, as an information-recordable medium, recently, a write-once-read-many DVD-R or DVD+R and a rewritable DVD-RW or DVD+RW have been developed. These kinds of disks include wobbles formed on the side of each recording track on the disk and pits (land pre-pits) marked on the disk surface. For the purpose of specifying a recording position (track) on the disk, the data composed of a synchronous signal, address information and additional information is modulated and recorded on those wobbles and pits.
As the method of modulating the synchronous signal, the address information and the additional information, as disclosed in JP-A-2001-110061, a LPP (Land Pre-Pit) format and a wobble PM (Phase Modulation) may be referred. The LPP format is used for the DVD-R and DVD-RW disk and the PM format is used for the DVD+R and DVD+RW.
Herein, the PM format will be described with reference to FIGS. 2A to 2C. FIGS. 2A to 2C illustrate one example of the PM format. FIG. 2A shows the wobble PM method. FIG. 2B shows an ADIP (Address In Pre-groove) word composition that is a component unit of the information to be wobble-phase-modulated, the relation between one ECC block period, which corresponds to the data recording unit of the DVD and the number of ADIP words included in the ECC block period, and a frame composition within one sector that is a component unit of the ECC block. FIG. 2C shows the block-by-block rewriting and linking methods, which are executed on the recording track.
In FIG. 2A, each wobble phase-modulated portion is inverted 180 degrees in phase. In a group of 93 wobbles, an ADIP synch that is located at the head of the ADIP word, a bit synch that is located at the head of each data bit, and a data bit are separated at appearing intervals of the phase-modulated portions. Concretely, the ADIP synch appears at each four-wobble interval, the bit synch appears at each one-wobble interval, and a data bit appears at each two-wobble interval. O data is separated from 1 data based on the difference of the appearing interval between the bit synch and the data bit.
In FIG. 2B, the ADIP word is composed of 52 bits, concretely, an ADIP address, an AUX (Auxiliary) data, and an error-correcting code. The ADIP address is composed of three bytes, that is, data 0 (=0 fixed) and data 1 to 23, the data 0 being matched to the head ADIP synch. The AUX data is composed of one byte, that is, data 24 to 31. The error-correcting code is composed of data 32 to 51, that is, 2.5 bytes, and is used for correcting an error contained in the restored ADIP word. On the other hand, the ECC block period, which corresponds to the disk recording unit, is composed to have four ADIP words, for securing the reliability of access to a target ECC block. Then, the composition of the ECC block will be described. The ECC block is composed of 16 sectors, which corresponds to the access unit in reproduction, a synchronous signal, which corresponds to the synchronous unit to a data volume of one sector in reproduction, and 26 frames each of which is composed of modulated data. One frame is composed of 1488T data volume (in which T is a channel bit that is the basic unit of the recording mark length on the disk, and T=26.16 MHz). The head frame of one sector includes a frame synchronous signal SY0 that indicates the sector head and a data portion ID located thereafter, the data portion ID being used for specifying the track position in reproducing the data from the disk.
In FIG. 2C, the linking method is executed to add dummy data of 8T before the ECC block including the recording information, start to record the dummy data from the linking position of the previous ECC block end 8T (that matches to the seventeenth wobble), and stop the recording at the linking position of the ECC block end 8T where the recording is to be ended (that matches to the seventeenth wobble), for executing the block-by-block rewrite and link recording. The linking position is specified by detecting the wobble-phase-modulated ADIP synch, data bit, the ADIP address information, and so forth.

Disk recording apparatus and disk recording method


Privacy evaluation in a mobile electronic device. Location data collected by one or more applications operating on the electronic device is evaluated to determine the precision with which a user's location and movements can be reconstructed based on the location data collected by one or more of the applications. Information relating to such precision may be presented to the user, suitably by a graphic display representing a circle or ellipse within which the user's movement cannot be determined or a set of streets within which the user's movement cannot be determined.

Electronic devices are becoming more and more capable and more and more indispensable. For some users, being without the instant communication provided by Internet-capable electronic devices is inconceivable. Such users make sure that their devices are always turned on and, if they are using devices that allow battery replacement, that they have at least one spare battery available.
Many other users, even those who are not constantly engaged with their devices usually have their devices turned on, and many applications run in the background whenever a device is turned on. Many background applications, and other applications, collect location data of users. Weather applications, for example, need to know a user's location within a broad radius to select weather reports relevant to the user. Map applications often need to know the user's precise location to provide location information and directions to the user. Applications identifying points of interest can operate more seamlessly for the user if they have updated location information for the user. Therefore, many applications periodically poll the user's device for location information. Depending on the components that the user has enabled, the location information may be more or less precise. For example, location information may be computed based on the proximity of a base station, such as an eNodeB (eNB) to a user device, which may be a user equipment (UE). Such information is often relatively imprecise. Under other circumstances, location information may be determined based on a device's global positioning system component, and this information is often relatively precise.

Methods and apparatus for reporting location privacy