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/store/catalog/e-series/category/ESERIES_SU_SG_SHOPPUB/SG/en?navAction=pop&navCount=2> Philips Sonicare e-Series Standard sonic toothbrush heads
Philips Sonicare e-Series Standard sonic toothbrush heads
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e-Series Standard sonic toothbrush headsPhilips Sonicare E-Series is recommended for those with a focus on effective plaque removal every day.
Designed to optimize performance
Our classic brush headThis Philips Sonicare toothbrush head features a contoured profile to naturally fit the shape of your teeth for a thorough clean.
Engineered to maximize sonic motionPhilips Sonicare brush heads are vital to our core technology of high-frequency, high-amplitude brush movements performing over 31,000 brush strokes per minute. Our unparalleled sonic technology fully extends the power from the handle all the way to the tip of the brush head. This sonic motion creates a dynamic fluid action that drives fluid deep between teeth and along the gum line for superior, yet gentle, cleaning every time.
Reminder bristles ensure your most effective cleanAt first glance it may not be obvious, but brush heads lose stiffness and gradually wear down over months of normal use. Our blue reminder bristles fade to white and help you recognize when it's time for a replacement. For optimal results, replace your brush head every three months.
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Part of a better oral healthcare routineLike all authentic Philips Sonicare branded brush heads, this brush head is safe on teeth and gums. Each brush head has been quality tested for exceptional performance and durability.
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Screw-on system design for Essence, Elite, Xtreme, AdvanceThe Philips Sonicare E-Series brush heads screws-on and off your brush handle for a secure fit and easy maintenance and cleaning.
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Stermer, artist who redesigned Olympic medal, diesDugald Stermer, illustrator, artist who redesigned Olympic medals, dies at 74
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|Publication number
|Publication type
|Application number
|Publication date
|Jul 26, 1988
|Filing date
|Jun 23, 1986
|Priority date
|Apr 23, 1986
|Fee status
|Publication number
|John S. Sundsmo, George A. Ksander, John M. McPherson
|Original Assignee
|Collagen Corporation
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (9), Non-Patent Citations (4), Referenced by (108), Classifications (13), Legal Events (7)
|External Links: USPTO, USPTO Assignment, Espacenet
This application is a continuation-in-part of copending application Ser. No. 855,508, filed Apr. 23, 1986 and now abandoned.
1. Technical Field
The invention is in the fields of medicine, surgery, and biochemistry. More particularly, it concerns wound healing compositions comprising fibrillar collagen, heparin, and platelets or platelet releasate.
2. Background
The process of wound healing consists of a chronological sequence of events characterized by the various cellular infiltrates that appear within the wound. Immediately after wounding, the process of coagulation involves both the humoral aspects of coagulation and the cellular response. The principal cellular response concerns the interaction of platelets with coagulation proteins, thrombin and collagen. Once the coagulation process is completed, various types of leukocytes appear in the wound in an orderly and reproducible sequence. Fibroblasts, endothelial cells, and capillaries appear in the wound slightly later than leukocytes. The fibroblasts are responsible for the formation of the connective tissue components, specifically, collagen and the glycosaminoglycans, and, at a much later stage, for the formation of elastic fibers.
Wound healing is thus a complex process at the cellular level involving primarily fibroblasts and epithelial cells with additional effects being exerted by platelets, macrophages, neutrophils, endothelial cells, myofibroblasts, and perhaps other unidentified cell types. At a biochemical level the processes involved in wound healing are poorly understood, although it is clear that growth factors such as transforming growth factor (TGF), platelet-derived growth factor (PDCF), and epidermal growth factor exert effects on these cells in vitro. It is known that the platelets contain growth factors but it has not been determined whether these factors are normally released at wound sites. Collagen is known to induce platelet aggregation and degranulation reactions in vitro, but again it is not clear whether these reactions also occur in vivo at local wound sites. In sum, a comprehensive biochemical analysis of wound healing has not been accomplished, although it is presumed that the in vitro biological activities of platelets are operative in vivo.
Several prior patent publications have suggested using combinations of collagen and glycosaminoglycans to promote wound healing. Yannas et al have issued a series of U.S. patents describing laminated composites that may be used as synthetic skin. The first of the series, U.S. Pat. No. 4,060,081 describes a composite in which the bottom (skin side) layer is collagen cross-linked with a glycosaminoglycan. The glycosaminoglycan is added to solubilized collagen to form a precipitate, the precipitate is homogenized and then cross-linked with glutaraldehyde. U.S. Pat. No. 4,350,629 describes a variation of this process in which the glutaraldehyde is added before the glycosaminoglycan is added to the collagen. U.S. Pat No. 4,418,691 describes yet another variation in which the collagen-glycosaminoglycan lattice is impregnated with viable epithelial, mesenchymal, or fibroblast cells.
European Patent Application No. 85301127 (published Sept. 11, 1985 under No. 154447) describes a wound healing composition that consists of a suspension of collagen and a glycosaminoglycan such as heparin or heparan sulfate that induces chemotaxis. Of the previously described wound healing compositions, this composition is the most closely related to the present invention. As shown hereinafter, however, in vivo testing of collagen-glycosaminoglycan suspensions failed to cause any major change in the rate or extent of wound healing in experimental animals.
Soft and Hard Tissue Repair (Hunt, T. K. et al, eds) Praeger Publishers, New York (1984), pp. 381-394 describes the role of platelets and platelet constituents in wound repair.
The present invention provides a wound healing composition whose biological activity is vastly superior to the suspensions described in the mentioned European Patent Application. This new composition promotes re-epithelialization, fibroplasia, granulation tissue deposition, vascularization and new host collagen synthesis at wound sites. The granulation tissue is highly organized, even at early time points after initiation of treatment, which contributes to an overall appearance of increased wound strength at early times, and the appearance of a greater extent of wound healing at any given time. The composition also decreases the total time required for wound healing and wound repair, apparently by promoting the rate of wound healing. The composition is self-limiting, being active only at wound sites, eliminating the adverse possibility of disseminated subcutaneous growth effects.
The present invention is a soft tissue wound healing composition comprising an aqueous mixture of:
(a) fibrillar collagen at a concentration in the range of about 1 to about 70 mg/ml;
(b) about 0.1% to about 10% by weight based on collagen of heparin, a heparin-like glycosaminoglycan, or mixtures thereof; and
(c) about 0.01% to about 10% by volume based on collagen of undegranulated platelets or an equivalent amount of platelet releasate.
Wound dressings comprising the above composition carried on a solid carrier and methods of promoting wound healing by applying the above composition or dressing topically to wounds are other aspects of the invention.
In the drawings:
FIG. 1 is a set of bar graphs of results of the histological examinations reported infra showing the fibroplasia evident in histological sections of wound sites treated with various test compositions.
FIG. 2 is a set of bar graphs of results of the histological examination reported infra showing the vascularization evident in histological sections of wound sites treated with various test compositions.
FIG. 3 is a set of bar graphs of results of the histological examination reported infra showing the re-epithelialization evident in histological sections of wound sites treated with various test compositions.
FIG. 4 is a set of bar graphs of results of the histological examination reported infra showing total epithelial length (in ocular micrometer units) evident in histological sections of wound sites treated with various test compositions.
The composition of the invention is useful for treating soft tissue wounds such as cutaneous, dermal, mucosal or epithelial wounds in vertebrates. It is especially useful for treating cutaneous wounds in mammals including man, domestic and farm animals, sports animals, and pets. It may be used to treat any type of full or partial thickness cutaneous wounds including traumatic wounds, surgical wounds, thermal or chemical wounds (burns), radiation wounds and chronic ulcers such as decubiti, and cutaneous ulcers caused by vascular, hematologic and metabolic diseases, infections, or neoplasms.
The collagen that is used in the invention is fibrillar and is capable of binding heparin or heparin-like glycosaminoglycans. Type I or Type III collagen, or mixtures thereof, are preferred because of their heparin binding capacity. The collagen may be of genetically dissimilar origin (e.g., allogeneic or xenogeneic) than the individual to which it is applied. If the collagen is xenogeneic it is preferred that it be purified to lessen or reduce the likelihood of immunogenicity. The collagen fibers may be native or reconstituted and may be cross-linked or uncross-linked. Bovine dermal fibrillar collagen suitable for use in the composition is available commercially under the trademark ZYDERM� from the assignee of this application. The fibrillar collagen is in the form of an aqueous suspension or gel in which the concentration of collagen is in the range of about 1 to 70 mg/ml. A collagen concentration range of 15 to 35 mg/ml is preferred for handling purposes. Depending upon the concentration of collagen the consistency of the final mixture will range from a translucent gel to a runny syrup.
Heparin or a heparin-like glycosaminoglycan is mixed with the fibrillar collagen in amounts ranging between about 0.1% to about 10% by weight, based on collagen, preferably about 0.3% to 3%, and most preferably about 1%. Heparin is a staple product of commerce. Fragments and derivatives of heparin are known which possess chemical similarity to heparin. As used herein the term "heparin-like glycosaminoglycan" is intended to include such fragments and derivatives, provided they are functionally equivalent to heparin in the composition (i.e., combine with collagen and platelets to provide efficacious wound healing).
The platelets that are used in the invention are isolated from vertebrate blood, preferably mammalian blood, under conditions which prevent degranulation. Such conditions are well known and typically involve mixing the blood with an anticoagulant solution and centrifuging the platelets from the mixture. The mammalian species of the platelets are diluted in buffer and then added to the fibrillar collagen-heparin mixture. The final volume dilution of platelets, expressed in terms of volume of packed platelets, is in the range of about 1:10 to 1:10,000, preferably 1:50 to 1:100. Expressed in terms of volume % based on collagen, the packed platelets are added to the mixture at levels in the range of 0.01% to 10%, preferably 2% to 10%.
Platelet releasate may be used as an alternative to whole platelets. The releasate comprises granule constituents that are released after aggregation and that possess angiogenic activity, chemotactic activity, mitogenic activity, connective tissue deposition activity, or epidermal cell proliferation activity. It may be prepared by sonicating platelets or treating a platelet suspension with agents that cause the platelets to aggregate and release granule constituents. Examples of such agents are thrombin, collagen, ADP and immune complexes. After such treatment solids (e.g., cellular debris, aggregated platelets) are separated, such as by centrifugation. The releasate may be purified by affinity chromatography using a heparin-Sepharose column. The amount of releasate used in the mixture is that which is equivalent to 0.01% to 10% by volume, preferably 2% to 10%, based on collagen of packed platelets. In other words, one uses that amount of releasate that is derived from such an amount of packed platelets.
In addition to the fibrillar collagen, heparin, and platelets/platelet releasate, the composition will typically contain buffers and salts that maintain the aqueous mixture at approximately physiological pH and ionic strength (i.e., pH 6.8 to 7.4; ionic strength (r/2) 0.1 to 0.2). Minor amounts of other additives such as local anesthetics (e.g., lidocaine) bacteriostats, antibiotics, serum or plasma proteins, culture supernatants, cell extracts, gelling agents, and purified monocytes may be included in the wound healing composition.
A preferred storage temperature for the individual components of the composition and the final composition is 2� C. to 6� C.
The mixture of fibrillar collagen, heparin, and platelets/platelet releasate is applied topically to the wound site. The composition may be applied per se or in the form of an occlusive dressing. When applied per se the composition is applied as an ointment, gel, lotion or spray, depending upon its consistency. If the wound is depressed, the composition is packed into the wound. The composition is applied in conjunction with means for keeping the composition at the wound site and, in the case of open wounds, for maintaining the composition hydrated. For cutaneous wounds such means are exemplified by dressings, such as Opsite wound dressing, having a suitable water vapor transmission rate, or perhaps skin grafts or flaps that are placed over the composition.
When applied in the form of an occlusive dressing the composition is impregnated, coated, adsorbed or otherwise applied to a synthetic or natural solid support, such as a fibrous or nonfibrous backing or sponge, and the composite is applied to the wound site.
The following experiments further illustrate the invention and its relationship to the prior art. These experiments are not intended to limit the invention in any manner.
Test wound healing compositions were prepared in a stepwise manner. First, fibrillar collagen/heparin (FC-H) was prepared by mixing 10 ml of commercially available bovine dermal fibrillar collagen (FC; 35 mg/ml) with 1 ml of 3.3 mg/ml heparin (H)(Sigma, St. Louis, Mo.). Second, platelets were isolated and purified from 30 ml of blood obtained from Hartley strain guinea pigs by differential centrifugation using standard methods. The final packed undegranulated platelet cell pellet was resuspended in 3 ml of Tyrodes buffered saline (TBS). Third, composites were prepared containing three different dilutions of platelets by: (a) mixing 1 ml of platelets with 2 ml of FC-H giving a final platelet dilution of 1/12 (FC-H/PL-12); (b) diluting platelets 1/10 with TBS and then mixing 1 ml of platelets with 2 ml FC-H (FC-H/PL-120); or, (c) diluting platelets 1/1000 with TBS and then mixing 1 ml of platelets with 2 ml of FC-H (FC-H/PL-1200). Control materials were also prepared containing 1 ml of platelets mixed with 2 ml of FC (rather than FC-H).
Platelets were isolated by differential centrifugation using standard methods. The final washed platelet cell pellet was resuspended in 25 ml of 20 mM Tris buffer, pH 7.5, containing 0.14 M NaCl, 15 mM KCl, 5 mM glucose, and 2 mM CaCl . Thrombin (7 units/ml platelets) was added to induce aggregation and release. After 10 min at room temperature the aggregated platelets were removed by centrifugation at 22610�g for 20 min at 4� C. The concentration of the platelet proteins in the releasate was determined to be 642 μg/ml by Lowry analysis. Platelet releasate was stored frozen at -70� C. until use. This releasate was tested in vitro and found to stimulate human skin fibroplast proliferation.
A portion of the platelet releasate was purified by heparin-Sepharose column chromatography as follows: five ml of platelet releasate was applied to a column (0.7�9 cm) of heparin-Sepharose CL-6B (Pharmacia, Piscatawny, N.J.) which was previously equilibrated in 20 mM Tris buffer, pH 7.6, containing 0.15 M NaCl and 1 mM CaCl2. After applying the sample, the column was washed with this same buffer until all the absorbance at 278 nm had reached a background level. Protein bound on the column was eluted with 20 mM Tris, pH 7.6, containing 2.0 M NaCl and 1 mM CaCl2. The resultant flow-through fraction (non-bound fraction) and 2 M NaCl eluate (bound fraction) were collected, pooled, dialyzed to 0.1 M ammonium bicarbonate, pH 8, and lyophilized. Lyophilized samples were resuspended in 20 mM Tris, pH 7.6, containing 1 mM CaCl2 and the insoluble residue was removed by centrifugation. Protein concentration was determined by Lowry analysis.
Releasate or chromatographed releasate is mixed with fibrillar collagen and heparin in proportions equivalent to the packed volumes of platelets used.
Wounds were created in the dermis of Hartley guinea pigs using a 6 mm biopsy punch. These wounds were filled with FC, FC-H, FC-H/PL-12, FC-H/PL-120, or FC-H/PL-1200 composites and the sites were then covered with an occlusive dermal dressing. Wound sites were surgically removed after 5 or 11 days, fixed, embedded, sectioned, and stained for histological examination using hematoxylin-eosin (H&E) or Gomori trichrome stain to visualize collagen.
The following criteria were used to provide numerical evaluation of histological parameters.
The relative number of cells in the wound or subcutaneous implant sites (e.g., fibroblasts, macrophages, eosinophils, lymphocytes, plasma cells, polymorphonuclear neutrophils (PMN), macrophage giant cells, or adipocytes (fat cells) was graded on a scale of 0 to 3+, where 0 corresponded to no cells visible; 1+ was a few scattered cells; 2+ was many scattered cells; 3+ was concentrated masses containing large numbers of cells.
Vascularity of the wound and implant sites was graded on a scale of 0 to 3+, where 0 was no vessels visible; 1+ was several small vessels; 2+ was many small and a few large vessels; and 3+ was many large vessels.
The amount of new host collagen was graded on a scale of 0 to 3+, where new collagen (defined as lightly staining microfibrillar in architecture) filling up to 1/3 of the wound area was graded 1+; new collagen filling 1/3 to 2/3 of the wound area was graded 2+; and new collagen filling more than 2/3 of the wound area was graded 3+.
Epithelial maturation was also graded on a scale of 0 to 3+, where thin epithelium composed of flat cells was rated 1+; thicker epithelium with less flattened basal cells and a slight development of the stratum granulosum was graded 2+; and thick epithelium with rounded basal cells, a well developed granulosum, and extensive cornification was graded 3+. An ocular micrometer was used at an objective magnification of 4� to measure the length of the epithelium and the width of wounds. These data are reported in ocular micrometer units where 0.23 mm=1 ocular unit.
Table 1 summarizes the cellular response observed in the wound sites. The data presented in Table 1 are presented graphically in FIGS. 1 through 4.
TABLE 1__________________________________________________________________________Histological and Morphometric Analysis ofCellularity of Decmal Wounds: Mean Score FC-H/PL FC/PLCharacteristic Days 1/12 1/120 1/1200 None 1/12 1/120 1/1200 None__________________________________________________________________________Fibrosis 5 2.7 2 1.3 1 2 1 1 1Vascularity 5 2.3 2.3 1.7 2.7 2.3 2 2 1Epidermal Length 5 8.0 7.8 9.5 4.5 4.7 8.5 6.4 2.7(X +/- SE) +/- 1.0 0.6 1.0 1.6 1.9 0.5 -- 1Mid-decmal Wound Width 5 9.5 9.0 9.2 7.9 9.3 9.8 9.8 6.0(X +/- SE) +/- 1.2 0.8 0.5 0.8 0.8 0.3 1.8 0Percentage Epidermis* 5 45 43 62 34 22 43 45 35(X +/- SE) +/- 7 4 8 20 4 4 -- 18Fibrosis 11 3 2.7 3 2.7 2.7 2.5 2 2Vascularity 11 2.3 2.3 1.7 1.3 2 2 2 2Percentage 11 100 100 100 100 100 100 100 100Epidermis*Epithelial Quality 11 2.7 2.3 2 1.7 2.7 3 1.7 1.7(X +/- SE) +/- 0.3 0.7 0.6 0.3 0 0.3 0.3Mid-decmis Wound Width 11 10.5 7 6.7 7.8 9.5 9.8 11.3 8.8(X +/- SE) +/- 0.5 0.3 0.2 0.6 1.3 1.3 1 1.3__________________________________________________________________________ *Percentage Epidermis epidermal length/wound width at the surface X 100%
a. Fibrillar Collagen with Heparin and Platelets (FC-H/PL): Day 5
Granulation tissue deposition, fibrosis, new host collagen, and neo-vascularization of wounds was increased at higher doses of platelets (Table 1, FIGS. 1-2). Morphometric measurements presented in Table 1 and FIGS. 3 and 4 show the percentage of the wound covered by new epithelium and the total length of newly formed epithelium on day 5. Wounds treated with FC-H/PL had greater amounts of new epithelium than wounds without platelets. This difference was statistically significant (P=0.02). The measured difference of the platelet-treated wound sites was also greater than that of the non-platelet treated wounds at the wound surface and at the level of the mid-dermis. It is important that while relatively small percentage differences in re-epithelialization were observed in the FC-H/PL treated wound sites (FIG. 3) the actual length of new epithelium was 1.7-2.1 times greater than control FC-H treated sites and 2.9-3.5 times greater than FC treated wound sites. The reason for this apparent disparity in measurements almost certainly lies within the finding of greater mid-dermis measurements in platelet/FC-H treated wounds (Table 1), a finding which suggests less wound contracture in these treated sites and hence a much longer expanse of wound surface which must be covered by new epithelium. Treatment of wound sites with FC-H resulted in granulation tissue deposition which appeared more extensive than that in wound sites treated with FC alone, however, this was not confirmed in morphometric analyses (Table 1, FIG. 1). At higher doses of platelets (i.e., 1/12), composite material visible in the tissue sections was broken up into smaller, less dense islands of material through infiltration of fibroblasts.
Inflammation of sites with PMN and lymphocytes was minimal with all composites and the extent of inflammation did not appear related to the dosage of platelets in the wound sites. Giant cells were occasionally observed, however, these were not associated with the implant material, nor were giant cells more prevalent in implant materials formulated with platelets. No eosinophils, plasma cells, or fat cells were observed.
b. Fibrillar Collagen with Platelets (FC/PL): Day 5
The results also presented in Table 1 summarize the histological findings at wound sites filled with FC with and without platelets. Wounds with higher concentrations of platelets had greater fibroplasia (FIG. 1) and more small blood vessels (FIG. 2) than controls receiving FC or FC-H alone. Epithelialization was incomplete but the length of new epithelial surface was greater in the platelet containing wounds than in control FC wounds (Table 1, FIGS. 3-4); FC/PL containing wounds showed greater re-epithelialization than FC-H wounds lacking platelets, but less than FC-H/PL. The FC composite was visible as large, dense and homogeneous masses of collagen with a fine fibrillar substructure. A few clefts or irregular spaces were visible within the composite. The inclusion of platelets in the composite resulted in a separation of the composite into smaller islands of material separated by infiltrating fibroblasts and new collagen. Small numbers of lymphocytes, PMN, or giant cells were seen within the composite (Table 2). There were no eosinophils, plasma cells, or fat cells visible.
a. Fibrillar Collagen with Heparin and Platelets: Day 11
Histological differences among wounds with different doses of platelets were less pronounced at day 11 than at day 5 (above). All wounds were completely covered by new epithelium and the quality of the epithelium appeared to be related to the number of platelets in the composite, with higher epithelial quality being associated with larger numbers of platelets (Table 1). In these cases the epidermis was thicker, with more rounded basal cells and there was increased differentiation with a more pronounced kerato-hyalin layer and increased cornification. In all wounds less composite was visible than at day 5, and the composite was well infiltrated by fibroblasts. Equivalent amounts of granulation tissue and new collagen were seen in the various groups (Table 1). Wounds treated with higher concentrations of platelets appeared more vascular, however, this was not confirmed in numerical analyses (Table 1). A minimal inflammatory profile was observed: namely, only a few lymphocytes, macrophages, giant cells, and pyknotic neutrophils were observed in these tissue sections.
b. Fibrillar Collagen with Platelets: Day 11
All wounds appeared to be completely re-epithelialized. The quality of the epithelium was notably better in wound sites treated with FC-platelet composites (Table 1). In these cases the epidermis was thicker, with more rounded basal cells, and there was notably greater differentiation of the epidermis with a more pronounced kerato-hyalin layer and increased cornification (Table 1). Fibroplasia and neo-vascularization did not appear to be more pronounced in wound sites treated with FC-platelets than in control wound sites. FC composites were more dispersed at the higher platelet dosages, apparently due to division of the composite by infiltrating fibroblasts. New host collagen synthesis was visible in sites. Small numbers of lymphocytes, giant cells, and pyknotic neutrophils were observed. No plasma cells were noted.
In addition to the histological evaluations, serological evaluations of the animals were made using blood taken at sacrifice and an ELISA for antibodies to the collagen or collagen-platelet composites. No animal developed antibodies to the collagen or the composites. Samples of the composites were also placed in subcutaneous tissue sites in the same animals immediately adjacent the wound sites. The implants were removed after 5 or 11 days. No significant fibroplasia, new collagen formation, inflammation or fibrous encapsulation of the implants were observed thus ruling out the possibility of uncontrolled growth.
In over two years of testing various biomaterials in the guinea pig model described above, the platelet-containing composites were the only materials that have exhibited a significant enhancement in rate of wound healing. The data also show that the composites enhance the extent of wound healing (platelet/FC-H composites inhibit wound contracture). If contracture is related to the formation of keloids or hypertrophic scars, then the composites may provide a mechanism for healing without scarring.
Modifications of the above-described modes for carrying out the invention that are obvious to those of skill in the fields of medicine, surgery, biochemistry, and related fields are intended to be within the scope of the following claims.
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|International Heart Institute Of Montana Foundation
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|Jun 15, 2004
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|Variable tip catheter
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|Scimed Life Systems, Inc.
|Catheter shaft assembly
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|Boston Scientific Scimed, Inc.
|Infusion devices and method
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|Boston Scientific Scimed, Inc.
|Methods for delivering a therapeutic implant to tissue
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|Mar 14, 2006
|Hemogenesis, Llc
|Separation of platelets from whole blood for use as a healant
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|Boston Scientific Scimed, Inc.
|Tortuous path injection device
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|Oct 10, 2006
|Neucoll, Inc.
|Methods and compositions for improved articular surgery using collagen
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|Nov 14, 2006
|Baxter International, Inc.
|Devices and methods for mixing and extruding medically useful compositions
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|May 1, 2007
|Boston Scientific Scimed, Inc.
|Elongated medical device with functional distal end
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|Jun 5, 2007
|Baxter International Inc.
|Element provided with a fibrin layer, preparation and use thereof
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|Jul 15, 2008
|Boston Scientific Scimed, Inc.
|Controlled depth injection device
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|Elongated medical device with functional distal end
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|Device for separating platelets from fluid suspensions
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|Incept, Llc
|Drug delivery through hydrogel plugs
|Feb 26, 2013
|Oct 22, 2013
|Incept, Llc
|Drug delivery through hydrogel plugs
|Sep 17, 2010
|Feb 24, 2015
|Incept, Llc
|Method for applying flowable hydrogels to a cornea
|Jul 9, 2007
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|Incept Llc
|Adhesive hydrogels for ophthalmic drug delivery
|Dec 5, 2012
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|Composite containing collagen and elastin as a dermal expander and tissue filler
|Aug 27, 2014
|Jun 21, 2016
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|Separation of platelets from whole blood for use as a healant
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|Oct 16, 2003
|Mickley Timothy J.
|Controlled depth injection device
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|Nov 20, 2003
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|Tortuous path injection device and method
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|Apr 8, 2004
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|Devices and methods for mixing and extruding medically useful compositions
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|Oct 14, 2004
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|Catheter and method for the delivery of therapeutic agents to tissues
|May 13, 2004
|Oct 21, 2004
|Matthew Hawk
|Elongated medical device with functional distal end
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|Dec 2, 2004
|Penegor Stephen A.
|Hemostatic wound dressing
|Nov 3, 2004
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|Hydrogel polymeric compositions and methods
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|Allan Mishra
|Method of treating cancer using platelet releasate
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|Jun 15, 2000
|C. R. Bard, Inc.
|Collagen hemostatic foam
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|Nov 14, 2002
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|Separation of platelets from whole blood for use as a healant
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|U.S. Classification
|International Classification
|Cooperative Classification
|European Classification
|Jun 23, 1986
Owner name: COLLAGEN CORPORATION 2500 FABER PLACE, PALO ALTO,
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|May 23, 1988
Owner name: COLLAGEN CORPORATION, A CORP. OF DE
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:COLLAGEN CORPORATION, A CA CORP.;REEL/FRAME:004887/0276
Effective date: 19880510
|Apr 1, 1991
Owner name: CELTRIX LABORATORIES, INC., 2500 FABER PLACE, PALO
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:COLLAGEN CORPORATION, A CORP. OF DELAWARE;REEL/FRAME:005648/0715
Effective date: 19910130
|Sep 30, 1991
|Fee payment
Year of fee payment: 4
|Aug 21, 1995
Owner name: CELTRIX PHARMACEUTICALS, INC., DELAWARE
Free format text: CHANGE OF NAME;ASSIGNOR:CELTRIX LABORATORIES, INC.;REEL/FRAME:007596/0428
Effective date: 19911221
|Jan 16, 1996
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|Jan 3, 2000
|Fee payment
Year of fee payment: 12


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Each month, Rated People connects over 50,000 homeowners with quality tradesmen - simply enter your job details in the form above to get started.
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Blacksmith / Metal worker
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wrought iron hand rail about 1 metre long beside the 2 steps up to my front door. 2/3 upright...
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Hotel Guman Heritage
Call us 1800-300-2400-1 (Toll Free) and Get additional Discount upto 50% for this Hotel.
Per Room Per Night
Lowest Price Guarantee
You are getting lowest possible rate for this hotel
- About Hotel
- Reviews
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About Hotel Guman Heritage
Hotel Guman Heritage located in Jaipur provides the free internet access to their guests. The place is accessible from Durgapura bus stand, which is at a distance of 7 km and Shanteshwar Mahadev Mandir, which is at 1 km. Consisting of 20 rooms and suites it offers television, a tea/ coffee maker, bottled drinking water, hot and cold water supply, medical services and wardrobes too.
Checkin Time: 1200 pm
Checkout Time: 1200 pm
Hotel Information and Amenities
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Hotel Amenities
- Parking
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- 24-Hour Front Desk
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Blue Pearl Crayfish (Cherax albidus) - Tank-Raised!
Sold Out
* For the safety of our animals, we now ship Cherax crayfish exclusively via UPS Next Day Air. If your order contains this item, you will only see UPS Next Day Air as a shipping option during checkout *
The Blue Pearl Crayfish (Cherax albidus) is an electric blue variation of its species and is native to Australia. This crayfish is also commonly known as the Blue Pearl Freshwater Lobster, though true lobsters do not exist in freshwater. The entire body and appendages of this crayfish are electric blue. They actually look very similar to Electric Blue Crayfish, but they are a different species and feature solid blue appendages. The Blue Pearl Crayfish breeds easily in the aquarium, but the fry are extremely slow growing. In fact, many of our specimens have bred in our tanks at our facility!
This particular crayfish is relatively active and spends plenty of time exploring the floor of the aquarium in search of food. The Blue Pearl Crayfish is an omnivorous scavenger and will eat most any meaty or plant-based foods. This crayfish should not be kept with ornamental live plants as it will eat them at a surprising rate.
As it reaches adulthood, the Blue Pearl Crayfish will become relatively territorial, so it may behave aggressively towards other animals in the tank. It is important that ample hiding places such as rockwork, driftwood, or PVC pipes be provided. This is even more crucial when housing multiple crayfish in the same tank. Due to the size and waste production of this crayfish, a minimum 30-gallon, well-filtered aquarium is necessary for one adult. A larger aquarium of 55 gallon or larger aquarium can house multiple adults of similar size. This is a reasonably hardy animal, but regular water changes are vital to its optimal health. Other bottom-dwelling invertebrates and fish should not be kept with large crayfish. It is possible to keep mid- and upper-level, fast-swimming fish with the Blue Pearl Crayfish, but crayfish are opportunistic feeders and will generally eat whatever they can catch.
As with all of our crayfish, the coloration of the Blue Pearl Crayfish is EXTREMELY high quality - much higher quality than others on the market. This crayfish may TEMPORARILY change color and hide more than usual after molting, which may occur during shipping. If your crayfish is not blue and you find a molt in the bag or in your aquarium, do not worry; this is normal and the bright color will return in 2 weeks or less.
*IMPORTANT* Please "Choose a Variant" above before adding this crayfish to your cart. The variants we're currently offering are:
- 1 Blue Pearl Crayfish - 3 to 4 inch Young Adult (No sex specified. Most popular option)
- 1 B-Grade Blue Pearl Crayfish - 3 to 4 inch Young Adult (All of our "B-Grade" crayfish are simply specimens that are missing legs or claws. Loss of appendages is not permanent and happens commonly with crustaceans. They are completely healthy with excellent coloration and will completely regenerate lost appendages within 1 to 2 molts (about 2 to 3 months).
- 1 Juvenile Blue Pearl Crayfish - 1+ inch (A younger and smaller variant of Blue Pearl Crayfish at a lower price than our young adult specimens. This is a particularly fast-growing, hardy species and will usually grow well into adult size and coloration within 1 to 3 months. In the meantime, any customers who choose to go with a juvenile specimen can save some money and experience the excitement of watching their little crayfish grow!)
- Consistently excellent electric blue coloration
- Less aggressive than many other crayfish
- Easy to feed
- Excellent scavenger
- Temperature: 68° - 85° F (20° - 29° C)
- pH: 6.5 - 7.5
- KH: 6 - 15 dKH
- Minimum tank size: 30 gallons
- Diet: Omnivorous. High-quality sinking pellets, plants, and freeze-dried or frozen meaty foods will be readily accepted. Cuttlebone should be added to the aquarium to supplement calcium, which will aid in exoskeleton production
- Warning! Avoid any food product, medication, or plant fertilizer that contains Copper of any form. Copper is toxic to invertebrates. Many commercial fish foods, medications, and plant fertilizers contain copper or more commonly copper sulfate. Always look at the ingredient list for any product going into the aquarium to ensure they are copper free.
- Social behavior: Can be aggressive/territorial with other crayfish, but is much less so than Procambarus species such as the Electric Blue Crayfish
- Origin: Western Irian Jaya, Indonesia
- Average adult size: 5 - 6 inches (12.7 - 15.2 cm)
- Average purchase size: 1.5 inch (3.8 cm) or larger
- Recommended Aquatic Arts tankmates: Fast-moving fish (such as Celestial Pearl Danios, Rasboras, Guppies, etc.). While dwarf shrimp can be kept successfully with these crayfish, caution should be exercised, as the crayfish have been known to catch and eat slow, sick, or particularly small shrimp. Cichlids can be aggressive toward crayfish and should not be kept in the same tank. Bottom-dwelling tankmates should definitely be avoided.


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If you're an investor and would like to receive CMA's of potential REO and off market deals in Maryland and D.C., send me you email address and contact number and I'll add you to my list of investors.
Ron Howell.
Posted 10/24/15 -
Updated 11 months ago
Columbia Md
1 result(s) found for term "columbia-md" in Discussions


text:
Have a unique travel experience with Flying Squirrel Holidays. Managed by an experienced
team of people who has a strong passion in travelling, plan your dream trip
with flying squirrel holidays best travel agent in Kolkata . Be it exclusive
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text:
Master STAGES™ emulsion corrosion inhibitors are built for spray or immersion applied rust prevention. Emulsion corrosion inhibitors provide great in-process or pre packaging protection for three to six months.
Number of products in category is 1
Master STAGES™ NOCOR® E6 is a super-concentrated, barium-free, water-based emulsion rust inhibitor that will protect steel, cast iron, and other ferrous parts from in-plant corrosion for up to six months. Parts coated with NOCOR E6 have a soft, almost invisible film that is easily removed using mild cleaners.


text:
Most Helpful Guy
Aww come on, you're a pretty girl. It's his loss. We all suffer set backs and we all have to deal with assholes and bitches, it's a part of life. When you get rejected, it reflects nothing on you but more on the other person. Of course it stings, it does for all of us, it's normal. The thing is, time heals it and it always does. You just have to decide you're not going to let it affect you much. I've been recently rejected and I felt lousy for a few hours but then I realized, why am I feeling like this? It's not and she is not worth worrying about for one more minute. When I realized that, I was totally fine and I actually felt good cuz she saved me all the headache of being with a mean bitch for lack of a better word lol and she showed me her true nature, not what she claimed it was. Words are cheap, actions are what counts. So buck up, smile and realize your ok and you're going to be ok.00|00|0
Most Helpful Girl
You're too old to be thinking like this.
I honestly thought this post was from a 15 year old girl.
C'mon stop it!
This is a joke !22|00|0
I knooooow XD


text:
What is JotForm?
JotForm is a free online form builder which helps you create online forms without writing a single line of code. No sign-up required.
At JotForm, we want to make sure that you're getting the online form builder help that you need. Our friendly customer support team is available 24/7.
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Email notifications of submissions have stopped being deliveredAsked by HappyfeetCT on March 04, 2014 at 04:01 PM
The email notification of form submissions has suddenly stopped working. How do I get this working again?
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text:
Hip Hop, and R&B in the 1990's was the "boom" of rap music, which eventually lead to is peak in the 2000's. While I'm not as much of a fan of 90's rap as I am 00's rap, I still enjoyed 90's hip hop much more than I do in this current decade. So, as I did before, I compiled 15 hip hop songs which were known, but not completely overplayed. Let's see if I can trigger your memory!
1. "Turtle Power" by Partners in Kryme (Released in 1990)
This rap duo were "one-hit wonders", but their one hit was a beat we could all relate to: TURTLE POWER! Who didn't like the "Teenage Mutant Ninja Turtles" as a kid?
2. "Hail Mary" by Tupac Shakur, featuring Eminem, and 50 Cent (Released in 1996)
This song was one of the many Tupac Shakur songs released after his death. It consisted of three of the most influential rappers as well.
3. "Ten Crack Commandments" by The Notorious B.I.G.(Released in 1997)
While I don't condone the lyrics of this song-At all-This is still one of the most powerful rap songs from the 90's I can think of, and one of Biggie's most underrated songs.
4. "Hard Knock Life" by Jay-Z (Released in 1998)
Sampling songs from others isn't new these days, but back in the 1990's, Jay-Z was a true "daredevil" to sample a song from the classical musical Annie.
5. "Gangsta's Paradise" by Coolio featuring L.V. (Released in 1994)
This is another "One-hit wonder" song, and Weird Al even made a parody of it. What isn't there to like?
6. "Guilty Conscience" by Eminem featuring Dr. Dre (Released in 1999)
This song explores the battle between "Good", and "Evil." The lyrics are disturbing to some extent-But that's Eminem for ya!
7. "Momma Said Knock You Out" by LL Cool J (Released in 1991)
From 1990-2009, 1991 has to be THE worst year for hip-hop music. Absolutely terrible. But, momma told me I gotsta knock you out.......
8. "Ghetto Red Hot" by Super Cat (Released in 1992)
This catchy beat was later sampled as the "Red Mountain" theme in the video game Sonic Adventure.
9. "Shame on a Nigga" by Wu-Tang Clan (Released in 1993)
The Wu-Tang Clan collaborated with System of a Down in the 00's to make "Shame on a Nigga", which was a bizarre remix of this song.
10. "Shimmy Shimmy Ya" by Ol' Dirty Bastard (Released in 1995)
1995 was another dead year for hip hop music. Ol' Dirty Bastard was a 90's saga which died off as soon as the 00's hit too.
11. "Jump On it" by Sir Mix-A-Lot (Released in 1996)
THIS is the Sir Mix-A-Lot song everyone should be talking about. And now, we dance to it every wedding reception we go to.
12. Who I am (What's My Name) by Snoop Doggy Dogg (Released in 1994)
Whether he goes by Snoop Doggy Dogg, Snoop Dogg, or Snoop Lion, he will always have a place in our musical hearts.
13. "Waterfalls" by TLC
The movie We're the Millers inspired me to post this song. If you haven't seen the movie, you won't get it.
14. "I'll Be Missing You" by Puff Daddy featuring Faith Evans, and 112 (Released in 1997)
This isn't just another version of "Watching You" by The Police. This song goes much deeper than that(And much more ethical as well).
15. "U Can't Touch This" by MC Hammer (Released in 1990)
I fibbed a little bit: I posted a song which is very well known. But this was the start of 90's rap, and the true BOOM. Who doesn't love this song?


text:
Learn more about MILTOS PROPERTIES LIMITED. Check the company's details for free and view the Companies House information, company documents and list of directors.
Know about every new company document that is added!
Take advantage of our watch this company feature free of charge and have notifications sent directly to your inbox. Whenever a new document appears on this website, or if their particulars change, you will be immediately informed about such changes. To monitor these changes, all you need to do is click on watch this company.
|Tangible Fixed Assets
|£ 3,597,940
|Current Assets
|£ 17,575
|Tangible Fixed Assets Depreciation
|£ 32,224
|£ 481
|Profit Loss Account Reserve
|£ 868,315
|Revaluation Reserve
|£ 2,236,988
|Called Up Share Capital
|£ 1,000
|Net Assets Liabilities Including Pension Asset Liability
|£ 3,106,303
|Total Assets Less Current Liabilities
|£ 3,541,475
|Net Current Assets Liabilities
|£ 56,465
|Creditors Due Within One Year
|£ 74,040
|Cash Bank In Hand
|£ 17,575
|Share Capital Allotted Called Up Paid
|£ 1,000
|Par Value Share
|1631 each
|Number Shares Allotted
|£ 1,000
|Tangible Fixed Assets Additions
|£ 91
|Tangible Fixed Assets Cost Or Valuation
|£ 3,629,611
|Tangible Fixed Assets Depreciation Charged In Period
|£ 644
|Creditors Due After One Year
|£ 435,172
Information about the Private Limited Company MILTOS PROPERTIES LIMITED has been prepared for information purposes only. It is not intended to be nor does it constitute legal advice. This is public information provided by the official company register.


text:
During the opposition to the Iraq War, Bush decides that he won't tolerate anti-American protests in the United States and orders the military police to fire upon the protesters. This is where the United States becomes a police state. (still in progress, advice would be helpful)
- January 16th
- 12:23 pm - Anti-war protesters attended the rally in the National Mall in Washington D.C.
- 12:24 pm - George W. Bush was informed about the protest and orders the military police to fire upon the protesters.
- 12:30 pm - United States military police troopers arrived at the National Mall and fired upon the protesters, the death toll is 89. It is called the Anti-War Protest Massacre.
- January 17th - Bush passes the law that bans anti-war protests.
- January 20th - Bush also passes the 28th Amendment that repeals the 22nd Amendment and gives him a life-long term in office.
- February 12th - Protesters rebel against Bush's new laws by causing riots in various towns and cities across the nation.
- February 13th - George W. Bush issues the military police force to put an end to the riots.
- February 14th - Military police forces in various cities open fire upon the protesters, the death toll is 373, it was known as the Second St. Valentine's Day Massacre.
- February 15th - The United States of America becomes a police state.
- February 16th - The United States Police Force is created in order to preserve law and order in the US.
- May 17th - Filmmaker Michael Moore releases a movie called "America in the Toilet", which shows the ways of the United States government.
- May 18th - Bush becomes enraged by the anti-American film and he sends out the police to arrest Michael Moore.
- May 19th - Michael Moore is found guilty of mocking the United States and executed by hanging.
- May 20th - The Westboro Baptist Church, a hate group were arrested by the United States Police Force, put on trial and found guilty for badmouthing the United States of America and executed.
- May 21st - Michael Moore's execution and the WBC executions are put on live TV, which warns the rest of the nation that anyone badmouthing the USA will be put to death.
- May 22nd - Bush passes the 'Punishment' law that enforces death penalties across the nation, therefore repealing the 'Protected Speech' law.
- May 23rd - Bush orders the MP to round up all of the Muslims in the US.
- May 26th - Hundreds of Muslims are rounded up and executed by fire bombs.
- May 27th - Bush passes a fierce immigration law which ensures that any illegal immigrants caught will either be transfered back to Mexico or executed.
- May 30th - Bush orders nuclear missiles to be re-built from old ones.
- June 1st - All of the illegal immigrants are captured and ordered to be transported back to Mexico, but it then changes to execution, in order not to let Mexico attack any of the major areas near the US-Mexico border.
- June 10th - Bush threatens the governments of Iraq, Iran, Afghanistan and Pakistan with the destruction of the Middle East, if they don't give him the whereabouts of Bin Laden.
- June 11th - Bush orders a missile to be launched at Tehran, Iran. At 12:00 Noon, Tehran is destroyed.
- June 19th - US forces bombed several cities in the Middle East while assisting Israel, the Middle East refused to let the 'Americans' take what they want.
- January 24th - In outrage, the Northeastern States secede from the United States, declaring themselves an independent state known as the New England Federation.
- February 14th - Texas and California soon follow suit, declaring sovereignty and reforming their old countries.
- March 15th - Outraged, Bush orders a complete Invasion of New England to place it back under American rule.
- March 16th - The Second American Civil War begins.


text:
The Gardener by S. A. Bodeen
Esmeralda Serrano
Before reading The Gardener, I thought that the book was going to be about a garden or about a green house.
Evolution is a gradual development of something especially from a simple to a more complex form. In The Gardener, evolution is important because the are watching them grow and develop on there own.
A heterotroph is an organism deriving its nutritional requirements from complex organic substances. In The Gardener, heterotroph is important because the kids are trying to survive by making there own food.
Photosynthesis is a plant that uses sunlight to make its own food. In The Gardener, photosynthesis is important because they feed on the sun light.
Autotroph are organism that are able to form nutritional organic substances such as carbon dioxide. In The Gardener, Autotroph is important because in order for them to stay alive they need energy from the sun witch makes there nutrition.
My favorite questions asked while we were reading were
Is mason's dad a plant?
Why does the dad and the girl have the same tatoo?
We found out the answers as we read. Here they are.
1. Mason's dad is the gardener.
2. The dad and the girl bot have the same tattoo because the both come from the greenhouse.
The setting
The Gardener takes place in three different places Washington, TroDyn and Portland Oregon.
In Washington was when mason first found the girl then he took her to portland to keep her away from people wanting to her. At the end he ended up having to take her to TroDyn so she would survive.
Medical Ethics
One of the ethical issues in The Gardener is whether or not it's right to do experiments on humans. I think human experimentation is a bad thing because you are testing real life humans that still have for to life. In The Gardener, the experiments they do on humans are unbelievable because they are making these kids feed on there own food.
Climate Change & Food Crisis
Climate change is a problem in where we live. Its a problem because if the weather is changing where we grow tropical fruit the all of a sudden it gets to hot to grow food.
Food Crisis is also another problem to our society. Its a problem because if we have no food our population will start to decrease.
Dear Future Generations, Sorry
The song "Dear Future Generations, Sorry," is about how tryst to tell us and the people in the future that if we don't make a change in our environment we won't have an environment to live in.
Both The Gardener by S. A. Bodeen and "Dear Future Generations: Sorry" deal with the common theme of Food Crisis. They are common because the kids our feeding on sunlight and providing there own food. In "Dear Future Generations: Sorry" is if we keep cutting down trees we won't have any oxygen to live and cutting trees won't let are food grow as well.
The Karner Blue
The Karner Blue is a blue butterfly that lays its eggs on blue lupine. The problem with laying its eggs is here is that the there getting cut down. In The Gardener, we see the Karner Blue as a representation for the kids. If we can compare the Karner Blue to humans, Then eventually humans will become endangered because our nature is changing.
My Final Thoughts
My prediction from the beginning, where I thought the story was going to be about a garden or a green house was not exactly what it turned out to be. Actually, my prediction was as far of as I thought The Gardener was involved around the green house towards the end of the story.


text:
|Publication number
|Publication type
|Application number
|PCT number
|Publication date
|Sep 8, 2009
|Filing date
|Feb 7, 2003
|Priority date
|Feb 7, 2002
|Fee status
|Also published as
|Publication number
|François Teytaud
|Original Assignee
|Teytaud Francois
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (23), Referenced by (7), Classifications (18), Legal Events (2)
|External Links: USPTO, USPTO Assignment, Espacenet
The present invention relates to methods and devices for comprehension of a language, particularly a modern language other than the mother tongue and, in particular, in order to learn it.
It is already known how to understand a foreign language by listening to statements recorded on disks or on cassettes and by following their notation printed in this language and also their translation into the mother tongue in a booklet. When the listener pauses, he finds it very difficult to relocate the statement in the foreign language where he paused, as he has poor mastery of the foreign language he wishes to learn. As the listener necessarily has to pause, the statements he hears, and the notations he reads in the booklet, are subdivided into lessons. Between the lessons, the listener hears statements in the mother tongue enabling him easily to recognize the point in the booklet where he has to restart listening. These statements in the mother tongue are in themselves useless for the purposes of understanding the foreign language and take up space in the statement-emitting device and also in the booklet. Actual understanding of the language is made difficult because the listener has to pay attention not only to the sounds he is hearing and to the notations he is seeing, but also to making a connection between them, since the phonemes and the notations are made to correspond by means of their order of succession. The mental effort required for this connection is to the detriment of the level of attention required to understand the language.
An attempt was made to solve this problem in German patent application 4 013 070 by causing words to be heard, for example in English, and by simultaneously displaying both these English words and their translation into German, simultaneity being marked, for example, by the fact that the word just displayed and its translation appear in bold.
The invention relates to a method and a device that facilitate comprehension of the language, relieving the listener not only of any effort of sequencing that is not strictly necessary for the purpose pursued, but also of a simultaneous-comprehension effort.
The subject of the invention is therefore a method for enabling a source language to be understood by a listener mastering a target language, in which the listener is played a statement consisting of a succession of several contents, in the source language, and is shown, simultaneously with listening to the statement, a succession of notations marking the succession of contents in the source language, showing a notation marking a content only from the moment when it is made possible for it to be heard, and a sequence of inscriptions is shown in the target language corresponding to the meaning of the entire statement, characterized in that the entire series of inscriptions is shown before the beginning of the statement.
By showing the inscription, prior to the start of the statement, the listener is relieved of the comprehension effort to be made at the same time as the listening and notation-following effort. Experience shows that the mind takes precedence over the ear, and that the listener will not truly pay attention to the sound unless his mind is not taken up with seeking the meaning at the time of hearing.
According to a highly preferred embodiment, for good comprehension of the language, the contents are all phonemes. Unlike the German document mentioned above, words without phonic relevance are no longer displayed, but notations corresponding to the phonemes themselves are. One word in the source language, such as "understand", will correspond to three distinct, successive phonemes, such as "un" "der" "stand".
Simultaneity of listening to the phoneme and the notation appearing now enables them to be associated without effort and automatically.
In particular, it is possible to show the notation at the same time as the corresponding phoneme is uttered or to show it before the following phoneme is uttered.
Preferably, the notation marking the phoneme is shown up until the moment when the statement is finished. The listener does not have to follow any reference system, which might, in the meantime, conceal notations. On the screen where the succession of notations is displayed, there is discrimination between the succession of notations that are already apparent and the remainder of the blank line where the following notations will appear. It is also possible to use for this purpose bold-accentuated or color-accentuated writing, an accompanying light beam, a mask that is removed step by step, or another graphic distinction as they appear.
According to one embodiment, simultaneously with the hearing of the succession of phonemes, a series of words in the target language is shown, each word in the series of words in the target language corresponding to a group of phonemes in the source language, a word being shown only from the moment when the first phoneme in the group of phonemes in the source language corresponding to this word is played, one group including one or more phonemes.
Preferably, the succession of notations of the phonemes in a first line is shown superposed over a second line in which the series of words is shown by aligning vertically the first character of each notation of a group of phonemes with the first character of the word corresponding to this group of phonemes, the vertical superposition of the first characters of each phoneme and word greatly lessening the attention effort the listener has to make.
The invention also relates to a device emitting a statement composed of a succession of phonemes, a screen, and means for displaying a succession of notations on the screen, respectively marking the phonemes in the succession of phonemes, means for synchronizing the emitting device and the display means so as to display the notations on the screen only as the phonemes that they mark are emitted.
According to the invention, the display means comprise means for placing a series of inscriptions in the form of a series of electrical translation signals, and the means for placing a series of inscriptions in the form of a series of electrical translation signals are such that the electrical translation signals appear before the first phoneme is emitted.
According to one embodiment that is particularly simple to implement, the emitting device comprises means for placing the succession of phonemes in the form of a phonetic electrical signal train, the display means comprising means for placing the succession of notations in the form of a script electrical signal train, and the synchronizing means synchronizing the phonetic electrical signals and the script electrical signals, this synchronization being effected also in respect of the electrical signals that a person skilled in the art is well able to synchronize.
According to one embodiment, provision is made for means synchronized by emitting device and display means synchronized return synchronization means. The listener may thus immediately listen again to a phoneme and see its notation reappear at the same time (a word, a sentence, a verse, a strophe and/or a paragraph).
Lastly, the invention relates to a display panel including a first line of notations subdivided into groups separated by first intervals, the first line being superposed on a second line of a series of words separated by second intervals, characterized in that the first character in each group is in line with the first character of a word, a first interval has a length different than that of another first interval, and a second interval has a length different than that of another second interval. This panel may be produced in advance and, associated with accentuation means, revealed to the listener at the time of listening or be produced, at the same time as listening takes place, on a screen.
In the appended drawing, given solely by way of example:
The device according to the invention comprises a database 1 in which a statement composed of a succession of phonemes in electrical form is memorized. This database 1 is connected by a line 2 to a loudspeaker 3 in which the phonetic electrical signals from the database 1 are converted into sounds. The device also comprises a database 4 memorizing a succession of notations corresponding to the succession of phonemes and presented in the form of a script electrical signal train conveyed by a line 5 to a synchronizing device 6 that conveys them via a line 7, with interposition of a transducer 8, reconverting the electrical signals into script signals at a screen 9 on which the notations corresponding to the phonemes are displayed. A line 10 connects the database 1 to the synchronizing device 6 such that a notation corresponding to a phoneme appears on the screen 9 only when the phoneme is emitted by the loudspeaker 3.
The device also comprises a database 11 in which translation electrical signals conveyed by a line 12 and, via a transducer 13, to the screen 9 are memorized. However, unlike the signals emitted from the database 4, which appear on the screen only as the corresponding phonemes are heard, the inscriptions corresponding to the translation electrical signals appear at the same time on the screen just before the appearance of the first phoneme of the statement.
Provision is also made for a return device 14 synchronized for the emitting device and for the display means of the script electrical signals controlled by a control unit 15 and arranged such that it causes all or some of the most recent phonemes to be reheard and deletes the corresponding notations that appeared on the screen.
In a database 16, a series of words corresponding to a word-by-word translation of the succession of phonemes is memorized. The electrical signals corresponding to this series are conveyed by a line 17 to the synchronizing device 6, which synchronizes them, first character of one group of phonemes with first character of a word, before conveying them to the screen 9 via a line 18 after passage via a transducer 19.
The time chart in
The first line, that which is the highest on the screen, notes a succession of phonemes in the source language, in this case English. In the case in point, there are eight phonemes P1 to P8. It will be noted most particularly that the word "understand" in English corresponds to the three successive, distinct phonemes P6, P7 and P8. Each phoneme is separated from the phoneme that follows it by an interval denoted, for the interval separating the phoneme P1 and the phoneme P2, "interval P1P2", for the interval separating the phoneme P2 and the phoneme P3, "interval P2P3", etc.
In the second line, just below the first line, there is a series of words in the target language, in this case French, each word in the series of words corresponding to a group of phonemes. The word M1 "c'est" corresponds to the phoneme P1, the word M2 "dur" corresponds to the phoneme P2, and so on for the phonemes P3, P4, P5 and the words M3, M4, M5, but the word M6 corresponds to the group of three phonemes P6, P7 and P8.
The intervals between the words are denoted in the same manner as in the first line by M1M2 for the interval between the word M1 and the word M2, M2M3 for the interval between the word M2 and the word M3, etc.
The first character of P1, namely I is aligned vertically with the first character of the word M1, namely C. The interval P1P2 is equal to the interval M1M2. The first character H of P2 is aligned vertically with the first character D of M2. However, as M2 has one character less than the notation corresponding to the phoneme P2, and as the first character of P3, namely F, is aligned vertically with the first character P of M3, the interval M2M3 is longer than the interval M1M2. As the number of characters of the notation of P3 is smaller than the number of characters of the word M3, the notation P4 is offset to a greater extent, and P3P4 is longer than P2P3. Certain intervals between the notations are longer than the minimum interval. Certain intervals between the words, for example P2P3, are longer than the minimum interval.
Alignment takes place in the following manner:
Step 1 Enumeration of the letters and/or signs corresponding to one phoneme or to several phonemes constituting a word in the source language.
The number of these words and/or of these signs constitutes an "Original Value Unit, Line 1" (UVO1).
Step 2 Enumeration of the letters and/or signs corresponding to the words of the target language chosen to represent the "word-by-word" translation of the corresponding words in the source language.
The number of these words and/or of these signs constitutes an "Original Value Unit, Line 2" (UVO2).
Step 3 Joining-up, in the form of binomials, of the UVO1s and UVO2s that correspond.
Step 4 Creation, if appropriate, of "Equivalent Value" (VE) if UVO1# UVO2.
In this case: addition to the smallest value (either UVO1 if <UVO2, or UVO2 if <UVO1) of as much blank space as corresponds to a letter or to a sign as is necessary to create an Equivalent Value, VE, equal to the highest value: (either UVO1 if >UVO2, or UVO2 if >UVO1) such that either UVO1=VE or UVO2=VE.
Binomial number 1: "It's" and "C'est": UVO1 of "It's"=4, UVO1 of "C'est"=5, hence VE1 of value 5 replaces UVO1.
Binomial number 2: "hard" and "dur": UVO1 of "hard"=4, UVO2 of "dur"=3, hence VE2 of value 4 replaces UVO2.
Binomial number 3: "for" and "pour": UVO1 of "for"=2, UVO2 of "pour"=4, hence VE1 of value 4 replaces UVO1.
Binomial number 4: "us" and "nous": UVO1 of "us"=2, UVO2 of "nous"=4, hence VE1 (of value 4) replaces UVO1.
Binomial number 5: "to" and "de": UVO1 of "to"=2, UVO2 of "de"=2, hence no readjustment.
Binomial number 6: "understand" and "comprendre": UVO1 of "understand"=10, UVO2 of "comprendre"=10, hence no readjustment.
|Cited Patent
|Filing date
|Publication date
|Jan 18, 1980
|May 4, 1982
|Sharp Kabushiki Kaisha
|Means for displaying at least two different words and for providing independent pronunciations of these words
|Dec 12, 1985
|Jan 13, 1987
|Robert Mossman
|Method for teaching reading
|Feb 2, 1989
|Apr 23, 1991
|American Language Academy
|Interactive language learning system
|Feb 10, 1992
|Dec 28, 1993
|Marek Kaminski
|Audio-visual language teaching apparatus and method
|Feb 7, 1994
|Feb 7, 1995
|Corder; Paul R.
|Instructional system for improving communication skills
|Sep 25, 1992
|Feb 28, 1995
|Northeastern University
|Interactive speech pronunciation apparatus and method
|Jun 7, 1993
|Sep 19, 1995
|Joseph R. Black
|Method of teaching reading including displaying one or more visible symbols in a transparent medium between student and teacher
|Jan 5, 1993
|Nov 7, 1995
|Mankovitz; Roy J.
|Apparatus and methods for displaying text in conjunction with recorded audio programs
|Nov 28, 1994
|Dec 16, 1997
|Softrade International, Inc.
|Method and system for aiding foreign language instruction
|Nov 27, 1996
|Mar 16, 1999
|Softrade International
|Method and system for aiding foreign language instruction
|Feb 7, 2001
|Jan 29, 2002
|Arkady G. Zilberman
|Method and system for acquiring a foreign language
|Jun 15, 1998
|Apr 9, 2002
|Maria Ruth Angelica Flores
|Apparatus and methods for multi-lingual user access
|Jun 28, 1999
|Aug 20, 2002
|Richard Henry Dana Crawford
|Bitextual, bifocal language learning system
|Oct 10, 2001
|Feb 14, 2006
|Pierre Mestre
|Process and device for translation expressed in two different phonetic forms
|Apr 25, 2002
|Aug 1, 2006
|International Business Machines Corporation
|Foreign language teaching tool
|Jun 3, 2002
|Dec 26, 2006
|Boys Donald R
|Audio-visual language instruction system without a computer
|Dec 5, 2000
|Jun 6, 2002
|Pinky Ma
|Computer-aided language learning method and system
|Sep 28, 2001
|Apr 3, 2003
|Philips Electronics North America Corp.
|Multi-lingual transcription system
|Sep 17, 2001
|Feb 12, 2004
|Johnson Carol M.
|Automated language acquisition system and method
|Jul 4, 2001
|Feb 19, 2004
|Sang-Jong Han
|Divided multimedia page and method and system for learning language using the page
|Apr 25, 1990
|Oct 31, 1991
|Pierre Damien Muralt De
|Audio-visual teaching equipment - performs simultaneous signal reprodn. from Manchester II coded digital recordings of speech and video information on tape of audio cassette
|Sep 5, 1995
|Mar 14, 1996
|Lebowitz Ellen Rubin
|Reading tutorial system
|Jul 7, 1998
|Apr 1, 1999
|Hyung Taek Lim
|Method and apparatus for searching and displaying data
|Citing Patent
|Filing date
|Publication date
|Jun 16, 2006
|Jul 12, 2011
|Samsung Electronics Co., Ltd.
|String matching method and system and computer-readable recording medium storing the string matching method
|Aug 17, 2009
|Sep 27, 2011
|Francois Teytaud
|Method and device for a source language to be understood by a listener mastering a target language
|Dec 11, 2006
|Feb 14, 2012
|Samsung Electronics Co., Ltd.
|String matching method and system using phonetic symbols and computer-readable recording medium storing computer program for executing the string matching method
|Nov 30, 2012
|Jun 13, 2017
|Arkady Zilberman
|Reverse language resonance systems and methods for foreign language acquisition
|Jun 16, 2006
|Mar 8, 2007
|Samsung Electronics Co., Ltd.
|String matching method and system and computer-readable recording medium storing the string matching method
|Dec 11, 2006
|Jul 5, 2007
|Samsung Electronics Co., Ltd.
|String matching method and system using phonetic symbols and computer-readable recording medium storing computer program for executing the string matching method
|Aug 17, 2009
|Dec 10, 2009
|Francois Teytaud
|Method and device for a source language to be understood by a listener mastering a target language
|U.S. Classification
|704/2, 434/319, 704/4, 704/3, 704/6, 704/8, 704/7, 704/5, 434/318, 434/317, 715/264
|International Classification
|Cooperative Classification
|European Classification
|Feb 15, 2013
|Fee payment
Year of fee payment: 4
|Apr 21, 2017
|Maintenance fee reminder mailed


text:
- List your item for as low as $30 - Advertise your item in both print and online
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Ron Horner has found another old-school excavator classic, this time a 1968 Kato 750G.+MORE
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The SMO mulcher has all the qualities of a perfect mower for vineyards and orchards. For almost 30 years it has worked to the satisfaction of professionals around the world.
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Hyundai India has recalled over 7,000 units of its entry-level hatchback, the Eon in India, over an issue with the car's clutch.
Hyundai India has recalled 7, 657 units of the Eon, owing to an issue with its clutch cable, that is fouling with the hatchback's battery cable.
The recalled cars include the ones manufactured between January 1, 2015 - January 31, 2015. The issue will be fixed at no extra costs for customers.
Hyundai will get in touch with customers who own affected Eons in India in a phased manner. The cars will be inspected and if the clutch cable and battery cable are found faulty, they will be replaced.
In a stement from Hyndai, the carmaker said, Hyundai motor India continues to ensure the quality of products offering to its customers and encourage owners of all affected Eon cars to take them to authorized Hyundai Dealers."
"Hyundai Motor India will deliver best service and attention to its customers with its strong service and support network across the country."


text:
Check prices on hotels in Eleuthera and Harbour Island
Top 10 Hotels in Eleuthera and Harbour Island
Coral Sands Hotel
Chapel St, Dunmore Town3.5 out of 5.0
Arrayed on an eight-acre gardened hillside facing Harbour Island's three-mile beach of pale-pink sand, this petite resort …
The Cove Eleuthera
Queen's Highway, BS, Gregory Town 15484.0 out of 5.0
Nestled on the beach, this Gregory Town resort is 2.4 mi (3.8 km) from Gaulding Cay Beach and 2.6 mi (4.2 km) from Queens Bat …
Pink Sands Resort
Chapel Street, Dunmore Town4.0 out of 5.0
Located in Harbour Island, this beachfront resort is in the historical district and within a 10-minute walk of Pink Sand Beac …
Romora Bay Resort & Marina
Colebrooke Street, Dunmore Town3.5 out of 5.0
Harbour Island is home to some of the most pristine pink-sand beaches. These secluded beaches spread more than 3.5 miles an …
Royal Palm Hotel
Harbour Island, Dunmore Town2.5 out of 5.0
Located in Harbour Island, this hotel is steps from Dr. Albert Johnson Memorial and Government Dock. Fisherman's Dock and Sir …
Tingum Village Hotel
Colebrook St, Dunmore Town3.0 out of 5.0
This family-friendly Dunmore Town hotel is located near the beach, within a 10-minute walk of Sir George Roberts Memorial …
Daddy Joes
Queen's Highway North, Gregory Town2.0 out of 5.0
Situated near the beach, this motel is within a 15-minute walk of Gaulding Cay Beach and Queens Bath. Glass Window Bridge i …
Surfers Manor
Eleuthera Island Shores, Gregory Town 255113.0 out of 5.0
Situated in Gregory Town, this hotel is within 1 mi (2 km) of Surfers Beach and Hatchet Bay Cave. Gaulding Cay Beach and …
Villa Allamanda
Jacaranda Drive, Cigatoo Estates, Governor's Harbour3.0 out of 5.0
Situated by the ocean, this resort is 1.8 mi (2.9 km) from Hut Point Beach and 2.2 mi (3.5 km) from Haynes Public Library. …
French Leave Resort, Autograph Collection
Queen's Highway, Governor's Harbour4.0 out of 5.0
Situated near the beach, this aparthotel is 0.7 mi (1.1 km) from Haynes Public Library and within 3 mi (5 km) of Leon Levy …
Recent Reviews in Eleuthera and Harbour Island
Very pleasent
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A+ on location, staff & accomodations!
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text:
Sony Xperia S is following the Apple's new iPad. The Apple device was subjected to overheating related issues and some of the users claimed that the tablet got hot after some time of usage. Now, Sony Xperia S is undergoing such issues. Some of the smartphones seem to have a display flaw as the screen gets a yellow tinge after the handset turns warm.
The brand has addressed this issue stating that they have identified the yellow tinge on the display. This is limited to some Xperia S smartphones and happens when the device is exposed to temperature of 40 degrees Celsius and above. Sony Mobile Communications claims that those who have such defected handsets can replace it for free with the local Sony retailer.
The smartphone is powered by the Android Gingerbread operating system and it can be upgraded to Android 4.0 ICS. It has a 4.3 inch high definition display, 1.5 GHz processor and a 12 MP camera. It also has a 1.3 MP front camera for video calling. The handset will be available for a price in India of Rs 30,000.
Read our article on Sony Xperia S comes to India in April.


text:
The 5 Best Cyber Monday Sales For Men
As the Thanksgiving holiday fast approaches, you'll doubtless have one thing on your mind: Eating. (Also possibly drinking.) Indeed, this is a weekend of unrestrained indulgence: a gluttonous free-for-all of comfort food and beer, of work-breaks and relaxation, and of everything drowned in gravy. But it's also the season's social cornerstone. Friendly gatherings, family reunions, time with scarce in-laws: it's an occasion to see rare faces and, as such, a time to make an impression. This Thanksgiving, don't just indulge your appetite for turkey—indulge your appetite for a new fall wardrobe. Throw together an outfit using these seasonal essentials for a Thanksgiving look that's unrivaled.
Fall fabrics lean thick and cozy, and few capture that vibe better than denim. This striped and faded take from J. Crew is designed to evoke the classic look of old-fashioned train engineers, but for us it's just as much throwback to the denim-heavy styles of the early 1980s. But that doesn't mean it's old-fashioned: It's the ideal first layer in the perfect fall look.
Engineer-Stripe Denim Shirt ($98) by J Crew, jcrew.com
11 Things You Should Never Get Monogrammed


text:
When I was in high school I was paying 13.9 cents/gal. for premium.
It only rose to 26.9 until 1974.
I remember my mother storming out of an Chevron station exclaiming that she'd never pay 32 cents a gallon.
I started driving in 1976. Many a time had to raid the ashtray of quarters to buy gas. Made it from Duluth to Minneapolis a few times on that loose change. And even younger, riding my bike down to the gas station to fill up a 2.5 gallon can for the go-cart or fishing boat was well within the range of a 10-year old with a lemonade stand.
They had high school back then?
I remember $.13/9 gasoline.
My '66 Chevy 396/425 motor got eight miles to the gallon.
No worries...


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Chris Krug's vehicle parked in the middle of Broad Street on Saturday looked much like any other black minivan. Then the side and rear doors opened hydraulically to reveal a helicopter engine.
Moments later, smoke poured from the engine and was quickly accompanied by a burst of flames. The heat singed a few leaves from the trees overhead.
Krug's jet van was one of the creations on display at Saturday's Super Happy Block Party, presented by The Clubhou.se, a downtown meeting space for tech professionals. It was held in conjunction with the National Day of Civic Hacking.
As attendees watched demonstrations of the latest technology such as 3-D printing, teams of techies gathered in workspaces to solve challenges issued by federal and local government agencies.
"What a hackathon is is you have a set amount of hours or a set time to try to come up with whatever the project is, so you want to develop that project within that set amount of time," said Clubhou.se co-founder Chris Williamson.
He said Saturday's event was designed to bring technology- and science-minded people to The Clubhou.se to see what it's about and hopefully attract more members.
Krug's friends are members of The Clubhou.se, and he is interested in technology. He reconfigured the minivan five years ago, after he and his family used it for a vacation to New York. He said he has always enjoyed drag racing and wanted to have an exhibition vehicle.
"I can't do 200 mph (like jet cars) but I can do burnouts and I can back up and go again," he said.
He also rode around Saturday on a motorized bicycle he built for using in the pits at the drag strip.
Much of the event was rained out, but by mid-afternoon, several demonstrations were set up under tents outside. Guests made buttons, took photos that were texted to them and sipped beer.
Williamson operated a racetrack for dragsters powered by carbon dioxide. He has been working with the Young Makers, a group of 8- to 17-year-olds who meet at The Clubhou.se twice a month, on the dragsters for the past two months.
"We've taught them about mechanical design, aerodynamics, timing systems, a little bit about electronics," he said. "We've just come out here to have fun, launching the cars down the track and see whose is the fastest."