text:
|Publication number
|Publication type
|Application number
|Publication date
|Oct 15, 2002
|Filing date
|Jul 7, 2000
|Priority date
|Jul 8, 1999
|Fee status
|Also published as
|Publication number
|Ying Sun, Ralph W. Oakeson, Stephen J. Wisniewski, Jonas C. T. Wang
|Original Assignee
|Johnson & Johnson Consumer Companies, Inc.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (66), Non-Patent Citations (10), Referenced by (71), Classifications (22), Legal Events (14)
|External Links: USPTO, USPTO Assignment, Espacenet
This application claims benefit to Provisional Application Ser. No. 60/142,878, Filed Jul. 8, 1999.
The present invention relates to a delivery device comprising a heating element and the use thereof for enhanced topical and transdermal delivery of active agents.
Topical dosage forms have been widely prescribed for decades in the treatment of systemic diseases and local conditions such as those involved with the skin and underlying tissues. Certain drugs are relatively easy to be delivered via the transdermal or transmucosal route because they can easily permeate through the skin or mucosal membrane at a high potency. Permeation of the drug across the skin or mucosal membrane from a transdermal patch or a mucosal patch is a result of the chemical potential gradient across the skin or mucosal membrane. Examples of these drugs include nitroglycerin, scopolamine, nicotine, hydrocortisone, betamethasone, benzocaine, and lidocaine.
Most drugs and biological active ingredients, however, cannot readily penetrate through the skin or mucosal membrane. Therefore, to increase skin permeation of these drugs, various chemical and physical permeation enhancing methods have been employed. Chemical permeation enhancing agents may be applied typically to increase transdermal delivery of drugs. Generally, chemical permeation enhancing agents are cost effective and safe. An extensive review of chemical penetration enhancing agents is reported in Buyuktimkin et al., "Chemical Means of Transdermal Drug Permeation Enhancement", Transdermal and Topical Drug Delivery Systems, Interpharm Press, Inc., 1997, pages 357-475. One major disadvange associated with chemical penetatration enhancers is potential skin irriation.
Physical penetration enhancing methods can also be used to improve transdermal drug delivery. The energy forms employed for this purpose include electricity (e.g., iontophoresis), ultrasound (e.g., phonophoresis) and thermal energy (e.g., heat-assisted delivery), which are reviewed by Sun, "Skin Absorption Enhancement by Physical Means: Heat, Ultrasound, and Electricity", Transdermal and Topical Drug Delivery Systems, Interpharm Press, Inc., 1997, pages 327-355.
U.S. Pat. No. 4,898,592 relates to a device for the application of heated transdermally absorbable active substances that includes a carrier impregnated with the transdermally absorbable active substance and a support. The support is a laminate made up of one or more polymeric layers and optionally includes a heat conductive element. This heat conductive element is used for distribution of the patient's body heat such that absorption of the active substance is enhanced. This device, however, has no heat-generating element or function. The use of only a heat conductive element to distribute body heat, however, is not an efficient or reliable method of enhancing transdermal absorption by heating since the amount of body heat given off by a patient can vary depending on the ambient air temperature and the physical conditions of the patient.
U.S. Pat. No. 4,747,841 discloses a method and apparatus for "moxibustion" using a heat-generating element to heat and vaporize "moxall " for treatment of a patient's skin without leaving burn scars. The objective of this method and apparatus, however, is to achieve heat stimulation of the body and not to increase skin permeability.
U.S. Pat. No. 4,230,105 discloses a bandage with a drug and a heat-generating substance, preferably intermixed, to enhance the rate of absorption of the drug by the user's skin. Separate drug and heatgenerating substance layers are also disclosed. Water must be applied to the bandage to activate the heating substance to release solvation heat. Because the exothermal reaction during the hydration of the electrolytes disclosed in this patent only produces a transient low level of heat, it cannot be effectively used as a penetration enhancing method over a long period of time (e.g., for up to one day). Further, the speed of the hydration process is rather difficult to control.
U.S. Pat. No. 4,685,911 discloses a skin patch including a drug component and an optional heating element for melting the drug-containing formulation if the user's body temperature is inadequate to do so. The heating element is not substantially co-extensive with the drug reservoir, the latter being quite thick and, thus, not susceptible to even and rapid onset of heating. There is also no description on how to control the exothermic reaction to have prolonged and even heating.
U.S. Pat. No. 4,963,360 describes an exothermic device having a carrier layer, which comprises a medicinal component, and an exothermic layer, which develops heat when exposed to the air to enhance absorption of the medicinal component through the skin. The exothermic layer comprises a mixture of iron powder, carbon powder, salts (i.e., sodium chloride and aluminum chloride), and water. There is a base sheet to separate the exothermic layer from the medicinal layer in two separate chambers, and an air-permeable film that covers the exothermic layer.
U.S. Pat. No. 5,658,583 describes a heat-generating apparatus for improved dermal permeation of pharmaceuticals. The apparatus includes a thin drug formulation reservoir and a heat-generating chamber separated by a non-permeable wall. The drug formulation reservoir houses a predetermined amount of a formulation containing pharmaceutical agents. The heat-generating/temperature-regulating chamber includes a heat-generating medium consisting of carbon, iron, water and/or salt which is activated upon contact with oxygen in the air. The structure of the apparatus also includes a cover that is not permeable to air, but is perforated with holes to regulate the contact between the heatgenerating medium and air, thereby, controlling the heating temperature.
U.S. Pat. No. 5,662,624 describes a heat dressing for treatment of skin areas comprising a heat generating unit and a liquid-absorbing adhesive layer that, prior to use, is coated with a release layer. The adhesive layer is preferably made of a hydro-colloidal material and may optionally contain one or more medicaments or may be coated with alginate fiber mats. The heatgenerating unit generates heat preferably by means of galvanic or chemical energy, and the heat dressing may further comprise elements for controlling the heat development and/or the surface temperature. Such elements include a cover sheet for the heat-generating unit that is perforated for air passage, is covered by a heat-reflecting foil, or is a polymeric foam to better retain the heat.
The present invention relates to an exothermic delivery bandage device for administration of active agents through a barrier membrane (e.g., the skin, nail or mucosal membrane of a human). The advantages of the present device include: significantly simplifying the fabrication process of the device manufacturing; providing a means for the skin under the device to breath; and improving the delivery profile of active agents by minimizing the lag-time in drug delivery to further shorten the onset time for the active agent's intended therapeutic effect.
In one aspect, the invention features a multi-layer exothermic bandage, said bandage comprising: (a) an oxygen-impermeable layer; (b) a water-impermeable layer; (c) a heating element layer, said heating element layer comprising an oxidizable material, and where said heating element layer is between said oxygen-impermeable layer and said water-impermeable layer; and (d) an active agent layer, said active agent layer comprising an active agent; wherein said water-impermeable layer is between said heating element and said active agent layer.
In another aspect, the invention features a method of topically delivering an active agent to a mammal, said method comprising attaching the bandage of the present invention to a barrier membrane of said mammal.
Other features and advantages of the present invention will be apparent from the detailed description of the invention and from the claims
FIG. 1 is a cross-sectional view of an exothermic delivery device for active agents showing one embodiment of the present invention. During operation, oxygen from air reaches the heat-generating layer 140 only from the sides of the device as indicated by the block arrow.
FIG. 2 is a cross-sectional view of an exothermic delivery device for active agents showing one embodiment of the present invention. During operation, oxygen from air reaches the heat-generating layer 140 from the sides of the device and the gas-permeable outer cover 165 as indicated by the block arrows.
FIG. 3a is a prospective view of an exothermic delivery device with skin-breathing holes showing one embodiment of the present invention.
FIG. 3b is a cross-sectional view of the same device showing one embodiment of the present invention. During operation, oxygen from air reaches the heat-generating layer 140 both from the sides of the device and from the "breathable" holes as indicated by the block arrows.
FIG. 4 is a cross-sectional view of an exothermic delivery device for active agents showing one embodiment of the present invention.
It is believed that one skilled in the art can, based upon the description herein, utilize the present invention to its fullest extent. The following specific embodiments are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Also, all publications, apatent applications, patents, and other references mentioned herein are incorporated by reference.
The present invention relates to a novel exothermic delivery device of active agent(s) to the barrier membrane, such as human skin, mucosal membrane (e.g., buccal membrane), and nail. The exothermic delivery device of the present invention does not suffer from many of the disadvantages of the existing apparatuses previously described. For example, all of the prior heat-assisted delivery devices based on oxidation heat generation rely on the use of a cavity-like structure or a "chamber" to hold the heat-generating medium. Unfortunately, the chamber design represents a problem for high speed, automated manufacturing process, that is common in bandage manufacturing processes. The exothermic bandage device in the present invention has a multi-laminate structure that can be cut to any size and shape and used as a bandage, thus significantly simplifying the manufacturing process. In addition, prior devices discussed above deprived the skin from gas and moisture exchanging with the environment ("breathing") which is known to cause occlusion-related irritation and therefore, is generally poorly accepted by users.
There, thus, is a need in topical and transdermal delivery of active agents to reduce or to eliminate the therapeutic lag-time for active agents, which is the time required to build up the active agent concentration to the minimum effective level. This problem has not been addressed adequately in the prior devices. Since the skin opermeation of a drug is proportional to the temperature of a drug formulation on the skin (see, e.g., Sun, "Skin Absorption Enhancement by Physical Means: Heat, Ultrasound, and Electricity", Transdermal and Topical Drug Delivery Systems (Interpharm Press, Inc., 1997) pages 327-355), it is intuitive that simply increasing the operating temperature of a heat-generating drug delivery device would increase drug delivery and shorten the onset time of the therapeutic effect. However, it is also known that although people can generally tolerate relatively high temperature for a short time (e.g., up to 90� C. in low humility sauna or between 45� C.-50� C. in a hot shower), a prolonged skin contact to a heated body at temperatures above 43� C. could cause serious burn injury.
At the beginning of the application, the exothermic bandage device of the present invention produces more heat to raise the device temperature between about 43� C.-50� C. for a short period of time, since the oxygen from air readily react with the exposed heat-generating layer around the sides of the device. After the initial stage of the oxidation reaction, heat generation is reduced since the exposed reactive material has been consumed and oxygen needs to travel a greater distance to reach deeper temperature of the device is subsequently lowered to between about 40� C.-42� C.
One embodiment of the present invention is represented schematically in FIG. 1. The device 500 of a multi-laminate construction consists of a removable release liner 110, an active-agent containing layer 120, an water-impermeable layer 130 separating the active agent-containing layer 120 of the device from a heat-generating layer 140, an oxygen-impermeable membrane 150, and a heat-insulating layer 160.
The water-impermeable layer 130 is impermeable to the active agent in the active agent-containing layer 120 and any solid or liquid material in the heat-generating layer 140. The water-impermeable layer may be made of flexible material well-known in the art to be impermeable to water, e.g., polymers such as polyethylene, polypropylene, polyvinyl acetate, polyurethane, silicone rubber, and polyvinyl chloride.
The active agent-containing layer 120 comprises the active agent. The active agent-containing layer may further comprise a carrier such as a hydrogel, a polymeric adhesive, a semi-solid carrier such as a cream, lotion, ointment, or liquid crystal. It may also comprise a solid supporting matrix (e.g., a gauze or non-woven or sponge-like materials). Active agents such as drugs and nutrients and other biologically active agents are incorporated into carrier within the active agent-containing layer 120, e.g., as dissolved molecules and ions, dispersed solid particles, or liquid droplets.
As used herein, the term "active agents" refers drugs and nutrients for local treatment or systemic treatment (e.g., a therapeutic or cosmetic benefit). Typically these agent include, but are not limited to, antihypertensive drugs (e.g., clonidine), analgesic drugs (e.g. fentanyl, ibuprofen, benzocaine, and lidocaine), drugs to assist wound healing (e.g., PDGF), drugs to treat coronary artery diseases (e.g., nitroglycerin, low molecular weight heparin), antimicrobial agents, antipsoriatic agents, antiinflammatory agents, anticancer agents, endocrine and metabolic medication (e.g., testosterone, estradiol), neurologic medications, medication for cessation of chemical additions (e.g., nicotine), motion sickness (scopolamine), and protein and peptide drugs. Most of these agents are known and may be used at concentrations and for durations of time which have proved effective against their respective disease states. These therapeutic agents are described in "Goodman & Gilman's The Pharmcological Basis of Therapeutics", 9th Edition by J. G. Hardman,et al., (McGraw-Hill Companies, 1996).
Other active agents include those commonly used as for topical treatment and in cosmetic treatment of skin tissues, such as salicylic acid, benzoyl peroxide, resorcinol, resorcinol monoacetate, and sulfur for acne, topical antibiotics for wounds, topical antifungal drugs to treat fungal infections of the skin and nails, and antipsoriatic drugs to treat psoriatic lesions of the skin and psoriatic nails. Examples of antifungal drugs include but are not limited to miconazole, econazole, ketoconazole, itraconazole, fluconazole, voriconazole, clioquinol, bifoconazole, terconazole, butoconazole, tioconazole, oxiconazole, sulconazole, saperconazole, clotrimazole, undecylenic acid, haloprogin, butenafine, tolnaftate, nystatin, ciclopirox olamine, terbinafine, amorolfine, naftifine, elubiol, griseofulvin, and their pharmaceutically acceptable salts. In one embodiement, the antifungal drugs are an azole, an allylamine, or a mixture thereof.
Examples of antibiotics (or antiseptics) include but are not limited to mupirocin, neomycin sulfate bacitracin, polymyxin B, 1-ofloxacin, tetracyclines (chlortetracycline hydrochloride, oxytetracycline hydrochloride and tetrachcycline hydrochoride), clindamycin phsphate, gentamicin sulfate, benzalkonium chloride, benzethonium chloride, hexylresorcinol, methylbenzethonium chloride, phenol, quaternary ammonium compounds, triclocarbon, triclosan, tea tree oil, and their pharmaceutically acceptable salts.
Examples of antipsoriatic drugs include but are not limited to corticosteroids (e.g., betamethasone dipropionate, betamethasone valerate, clobetasol propionate, diflorasone diacetate, halobetasol propionate, triamcinonide, dexamethasone, fluocinonide, fluocinolone acetonide, halcinonide, triamcinolone acetate, hydrocortisone, hydrocortisone verlerate, hydrocortisone butyrate, aclometasone dipropionte, flurandrenolide, mometasone furoate, methylprednisolone acetate), methotrexate, cyclosporine, calcipotriene and anthraline.
Additional examples of active agents include but are not limited to minoxidil, minoxidil sulfate, retinoids, cysteine and acetyl cysteine, methionine, glutathione, biotin, finasteride and ethocyn, as well as pharmaceutically acceptable salts of these compounds.
The active agents in the present invention may provide certain benefits to the superficial tissues such as the skin, for example: anti-aging, wrinkle removal, depigmentation (e.g., removal of "age spot"), skin tone improvement. The exothermic device in the present invention may be made into facial and body masks of various shape and size to fit the contours of the anatomic locations. The materials for the each layer of the multi-laminate device is preferably pliant for this purpose. The examples of active agents for aforementioned purposes include, but are not limited to: amino acids, and their derivatives, biotin, vitamins, vitamin B complex: thiamine, nicotinic acid, biotin, pantothenic acid, choline riboflavin, vitamin B6, vitamin B12, pyridoxine, inositol, carnitine; ascorbic acid, ascorbyl palmitate, vitamin A, vitamin K, vitamin E, vitamin D, cysteine and N-acetyl cysteine, herbal extracts, and their derivatives; soy extracts, calcium pantothenate, calcium carbonate, and calcium gluconate.
Examples of retinoids include but not limited to retinol (Vitamin A alcohol), retinal (Vitamin A aldehyde), retinyl acetate, etinyl palmitate, retinoic cid, 9-cis-retinoic acid and 13-cis-retinoic acid. Examples of flavonoids include but not limited to naringenin, quercetin, catechins (e.g., epigallocatechin gallate), theaflavins, robustaflavone, hinokiflavone, amentoflavone, agathisflavone, volkensiflavone, morelloflavone, rhusflavanone, and succedangeaflavanone.
The exothermic device 500 is suitable to be used deliver agents to remove corn, callus, ingrown toe nails, and diseased nails from infections. The active agents for such a treatment include, but are not limited to, salicylic acid, urea, sodium sulfide, tannic acid, salts of thioglycolic acid, cysteine and acetyl cysteine.
The exothermic device is also suitable to be used deliver agents such as salicylic acid and benzoyl peroxide to treat acne.
The exothermic device is also suitable to be used deliver agents such as retinoids and herbal and soy extracts to provide anti-aging benefits including wrinkle and age-spot removal and improving skin tone.
In another embodiment, the device does not comprise an active agent-containing layer (e.g., it is used to help promote wound healing as a bandage).
The heating unit of the device 500 comprises a heat-generating layer 140 in which heat-generating materials are immobilized. The heat-generating layer 140 comprises a mixture of oxidizable materials (e.g., oxidizable metal powder(s)) and carbon or activated carbon powder. Examples of oxidizable metal powders include, are but not limited to, iron, aluminum, magnesium, zinc, and a mixture thereof. Other oxidizing material that can be used in the present invention to generate heat include those described in U.S. Pat. No. 4,114,591 (e.g., ferrosoferric oxide, plumboblumbic oxide, trimanganese tetroxide, black copper oxide and manganese dioxide in the form of fine particle).
The heat-generating layer also contain electrolytes/salts. The electrolytes/salts include, but are not limited to the salts of sodium, potassium, lithium, calcium, iron, magnesium, and aluminum.
Examples of electrolytes include, but are not limited to, NaCl, KCl, LiCl, CaCl2, FeCl3, FeCl2, MgCl2, AlCl3, Na2SO4, K2SO4, Fe (SO4) 3, FeSO4, or MgSO4.
The oxidation material may be immobilized by various means including but not limited to a water-permeable bag, mesh, non-woven pad or other fabric materials, and binding agents (e.g., polymers) such as cellulose polymers, polyacrylic polymers, polyurethanes, gelatins and gums. Exampels of such polymers include hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, cellulose actates, polyvinylvinylidone (PVP), and copolymers of polyacrylic acid and polyacrylates (Carboset�, Carbopol� and Carbomer�).
Water may also be contained in the heat-generating layer 140. In one embodiment, water is added to the heat-generating layer 140 in an oxygen-free environment immediately before being sealed into an oxygen-proof package. In another embodiment, water is absent in the heat-generating layer 140, and the user can add the water to the device 500 at the time of application by wetting it.
There may be optional organic solvents such as glycerin, propylene glycol, and polyethylene glycols of various molecular weights in the heat-generating layer 140. The presence of the binding agent(s), immobilizing structures (e.g., mesh and nonwoven pads), and solvents (water and the organic solvents) further enables the heat-generating layer 140 to maintain its physical integrity both during manufacturing process and during application on the user's skin.
Because the oxygen-impermeable membrane 150 is impermeable to oxygen, oxygen can only reach the heat-generating materials of the heat-generating layer 140 from the side as shown in FIG. 1. The dense, preferably gelled, structure of the heat-generating layer 140 serves as means of controlling the oxygen availability to the oxidizable materials in the heat-generating layer 140, thus leading to prolonged heating. The oxygen-impermeable layer may be made of flexible material well-known in the art to be impermeable to oxygen, e.g., polymers such as polyethylene, polypropylene, polyvinyl acetate, polyurethane, silicone rubber, and polyvinyl chloride.
The heat-insulating layer 160 is a layer with good heat insulation property, preferably being a polymeric foam (e.g., polethylene and polyurethane foam) of sufficient thickness to maintain the generated heat within the device.
All the layers in the multi-laminated device 500 may be held together by adhesives (not shown in the figures) or by heat fusion processes.
Another embodiment of the present invention is schematically represented in FIG. 2. The absence of the oxygen-impermeable membrane 150 enables oxygen to enter the device 500 from the outer cover 165 as shown by the block arrows in FIG. 2. As oxygen can more easily access all of the surface of heat-generating layer 140, this design is more suitable for an exothermic bandage device of a shorter duration.
The outer layer 165 may be made of highly oxygen-permeable polymer membranes such as silicone, polyurethane, polyethylene, and polypropylene. It preferably of a microporous nature such as an open-cell foam, close-cell foam, or open-cell foam with a thin liquid-impermeable polymer layer on one or both side of the outer layer 165. The extent of oxygen permeability of the outer layer 165 is determined by the material it is made of, its thickness, and its porosity. Optional, there may be a removable cover sheet that is essential impermeable to oxygen (not shown in the figures) that is made of similar material as oxygen-impermeable layer 150. The removable cover sheet may be partially or fully removed to adjust the area available to oxygen permeation, thus adjusting the heating produced by the device. The removable cover sheet may have an adhesive coated on one side in order to affix it to the outer layer 165.
During use, the removable cover sheet may be used to completely cover the outer layer to close the oxygen pathway and, thus, stop the heating process. It may later be reopen to re-start the heating process. In this way, the device in the present invention can provide a pulsatile mode of enhance active agent delivery (e.g., alternating between baseline and heat-assisted delivery).
Another embodiment of the present invention is schematically represented in FIGS. 3a & 3 b. The exothermic device 500 is perforated with holes to allow the barrier membrane (e.g., the skin) to "breath" during application. There is no limitation on the size, shape and density (i.e., the number of the holes on a given area) of the skin-breathing holes. The skin-breathing holes may optionally go through the removable release liner 110 for the convenience of manufacturing. The skin-breathing holes also serve a way of facilitating oxygen availability to the heat-generating layer 140 and therefore, can be used to adjust the extent and duration of the heating process by their size, shape, density and spacing. Optionally, the skinbreathing holes may also be present on the device shown in FIG. 2.
Another embodiment of the present invention is schematically represented in FIG. 4. The active agent-containing layer 120 is placed in water-impermeable chamber 135. According to this embodiment, the part of device 500 containing both the active-agent containing layer 120 and the water-impermeable chamber 135 may be a transdermal patch such as one of those transdermal active agent delivery devices and topical treatment devices currently in the market. The examples include transdermal patches of fentanyl (Duragesic� by Janssen Pharmaceutical), nitroglycerin (Nitrodisc� by Roberts Pharmaceutical/G.D., Searle, Nitro-Dur� by Schering/Key Pharmaceutical, and Transderm-Nitro� by Ciba-Geneva, Minitran� by 3M Riker), 17-β-estradiol (Estraderm� by Ciba-Geneva), clonidine (Catapres�-TTS by Boehringer Ingelheim), testosterone (Testoderm� by Alza, Androderm� by SmithKline Beecham), scopolamine (Transderm-Scop� by Ciba-Geigy), nicotine (Nicoderm� by Marion Merrell Dow, Habitrol� by Ciba-Geigy, Nicotrol� by McNeil Consumer Products, Prostep� by Lerderle Lab), and antibiotics, e.g., polymyxin B sulfate and bacitracin zinc (Antibiotic Band-aid� by Johnson & Johnson Consumer Products).
Alternatively, the part of device 500 containing both the active-agent containing layer 120 and the water-impermeable chamber 135 may be a iontophoretic, electroporetic, or phonophoretic device such as one of those devices well-known in the art, e.g., as disclosed in U.S. Pat. Nos. 4,927,408, 5,042,975, 5,224,927, 5,344,394, 5,667,491, 4,767,402, and 5,636,632.
The device 500 may comprise a pressure-sensitive adhesive either within the active agent-containing layer 120 or attached to chamber 135 (see adhesive layer 180 in FIG. 4) to assist affixing the device 500 to the user's barrier membrane (e.g., dermal or mucosal barrier membrane). The adhesive may be a polymeric, pressure sensitive and nonconductive and remains adherent even after prolonged exposure to water. Typically, the adhesive has a broad working temperature range. Suitable adhesive materials include, but are not limited to, silicones, polyisobutylenes and derivatives thereof, acrylics, natural rubbers, and combinations thereof. Suitable silicone adhesives include, but are not limited to, Dow Corningo� 355 available from Dow Corning of Midland, Mich.; Dow Corningo� X7-2920; Dow Corning� X7-2960; GE 6574 available from General Electric Company of Waterford, N.Y.; and silicone pressure sensitive adhesives, such as those disclosed in U.S. Pat. Nos. 2,857,356, 4,039,707, 4,655,767, 4,898,920, 4,925,671, 5,147,916, 5,162,410, and 5,232,702. Suitable acrylic adhesives include, but are not limited to, vinyl acetate-acrylate multipolymers, including, such as Gelvao� 7371, available from Monsanto Company of St. Louis, Mo.; Gelva� 7881; Gelvao� 2943; I-780 medical grade adhesive available from Avery Dennison of Painesville, Ohio; and acrylic pressure sensitive adhesives, such as those disclosed in U.S. Pat. Nos. 4,994,267, 5,186,938, 5,573,778, 5,252,334, and 5,780,050.
A removable liner sheet 110 covers the active agent-containing layer 120 and is attached to the adhesive layer 180 or the adhesive in active agent layer 120. The selection of the removable release-liner 110 is dependent on the type of the adhesive in use, and is well known to a person skilled in the art. The releaseliner 110 is typically a polymer sheet or a paper coated with a polymer, which have rather weak adhesion toward the adhesive layer 180, therefore allowing itself being easily removed prior to use without damaging the adhesive layer 180.
In addition to or in lieu of the adhesive, the apparatus 500 may be fastened to the body surface with an adhesive tape, an elastic band, a band with a buckle (similar to a leather watch band), or a Velcro� band or the like.
In order to use the device 500, the removable release liner 110 is peeled off, and the pressure-sensitive adhesive 180, if present, and the active agent-containing layer 120 of the device 500 is affixed to the a barrier membrane (e.g., the skin) of the user. For the devices shown in FIGS. 1-3, it is affixed to the go skin directly if the active agent-containing layer 120 contains an adhesive, or it is affixed to the skin with additional adhesive bandage on their peripheral edges as an integral part of the device (not shown in the figures).
The target temperature range according to the present invention is between about 38� to about 50� C. (e.g., between about 40� C. to 42� C). The heating period in the present invention may vary dependent on the active agent being delivered and may range from a few minutes to longer than a day. In general, if the heating duration is short (e.g., less than 10 minutes), the operating temperature may be at the higher end of the above temperature range. However, if the heating period is longer, a lower operating temperature (e.g., less than about 43� C. )is used to avoid heat-related tissue injury.
It is understood that while the invention has been described in conjunction with the detailed description thereof, that the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the claims.
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|Imtiaz Chaudry
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|Imtiaz Chaudry
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|Huan-Chen Li
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|Rosati Coni F
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|Michel Guillon
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|Rosati Coni F
|Method and apparatus for supplying gas to an area
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|Jie Zhang
|Heat assisted lidocaine and tetracaine for transdermal analgesia
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|Oct 8, 2003
|Apr 14, 2006
|Fee payment
Year of fee payment: 4
|May 24, 2010
|Maintenance fee reminder mailed
|Oct 15, 2010
|Reinstatement after maintenance fee payment confirmed
|Oct 15, 2010
|Lapse for failure to pay maintenance fees
|Dec 7, 2010
|Expired due to failure to pay maintenance fee
Effective date: 20101015
|Feb 23, 2012
Owner name: ZARS PHARMA, INC., UTAH
Free format text: CHANGE OF NAME;ASSIGNOR:JOHNSON & JOHNSON CONSUMER COMPANIES, INC.;REEL/FRAME:027754/0112
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Owner name: ZARS PHARMA, INC., UTAH
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Effective date: 20070730
|May 3, 2012
|Surcharge for late payment
|May 3, 2012
|Fee payment
Year of fee payment: 8
|Jun 4, 2012
|Patent reinstated due to the acceptance of a late maintenance fee
Effective date: 20120604
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Owner name: NUVO RESEARCH AMERICA, INC., DELAWARE
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ZARS PHARMA, INC.;REEL/FRAME:028330/0540
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text:
Aia Software declared 'strong performer' in a report by Independent Research Firm Forrester
Amsterdam, October 19, 2011 – Aia Software, producer of the ITP Document Platform, has been identified as one of the strongest performers in The Forrester Wave™: Document Output For Customer Communications Management, Q3 2011 (DOCCM) report. The company is one of only twelve vendors globally to meet Forrester's Wave participation requirements.
The Forrester Research report states that Aia Software 'has the strongest overall leverage of SharePoint, particularly with Microsoft Dynamics integration'.
Leon Pillich, co-CEO: "Our business oriented strategy includes the leverage of Sharepoint and the Microsoft Dynamics packaged app environment, which Forrester recognizes. This helps companies to streamline their multichannel, personalised customer communications workflows. With this strategy we believe we live up to the Forrester report's statement that this market space has hit its stride!"
(Aia Software demonstrated 30% overall growth in 2011.)
The Forrester report highlights the importance of business-side control of document content and templates. Aia Software's ITP/CCM products offer a 'self-service' approach for businesses. The software gathers output generated from both traditional and modern output production components to create batch, on-demand and interactive document output. It extracts and synchronizes metadata with the corporate CRM system to establish a customer communication profile. The resulting profiles and rules can be managed by business users who can use the tools to analyze, manage, combine and enhance all output, throughout the enterprise.
Paul Dirven, co-CEO at Aia Software: "We are delighted to be rated as 'strong performer' in this new Forrester Consulting research. We feel this demonstrates that Aia is now recognized as a mature, major player in the DOCCM field."
Notes to editors
About Aia Software
Aia Software is a leading global supplier of documentation solutions. Their ITP Documentation Platform helps staff create relevant and personalised business-critical documentation. Over 1,000 organisations use ITP as their integrated total solution for large-scale automated generation of standard documents, individualised snippet-based correspondence, and dynamic form-based data entry. ITP integrates seamlessly with existing business applications. Aia Software is a fully independent company with its head office in the Netherlands and branch offices in the United States, the United Kingdom, Germany and Australia. www.aia-itp.com.
The ITP Document Platform
The ITP Document Platform provides sophisticated document production services. It helps create structured, on-demand and interactive documents and electronic forms. ITP enables fully automated high volume document production whilst the interactive interview process facility enables electronic forms as well as document creation through a combination of user input and automatically populated fields. All ITP document production is template based and the templates can contain sophisticated logic enabling conditional data retrieval, conditional user input, conditional formatting and derived data fields. The templates are supported by ITP´s powerful data handling facilities that can retrieve data from multiple and various sources, including but not limited to XML data, Web Services and ODBC enabled data sources.
Details of the Forrester Report: http://preview.tinyurl.com/699sad4
Join our media list to receive relevant updates for Aia Software: http://eepurl.com/eM33c
UK Contact
Claire Thompson, Waves PR
Claire [@] wavespr.com (removing the [anti-spamming] brackets)
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Corporate Contact (NL)
Ingrid Wong, WongWorks, Marketing|Communicatie|PR
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text:
Friday, April 8, 2016 (9 a.m. – 9 p.m.)
Saturday, April 9, 2016 (9 a.m. – 4 p.m)
Falls Church Community Center, Falls Church, VA,
223 Little Falls Street, Falls Church, just off Route 7.
Antiquarians….Mystery Lovers…Cooks…Historians…Children…Bargain Hunters…
More than 40,000 books for browsing and buying. Huge selection.
Most books priced at $3 or less.
** Book Donations may be left in Recycle Bins at the Community Center Front desk from mid September through mid October and 6 weeks prior to sale **
For more information about the book sale, contact email@example.com.


text:
Mahatma Otoo boost for Hearts as he returns from Turkey
Posted: Friday, 21st December 2012 1 comment so far - add yours!
Hearts striker Mahatma Otoo will be available for Sunday's Premier League home game against Aduana Stars on Sunday.
The 20-year-old travelled to Turkey last week to undergo trials with top-flight side Denizlispor.
But he has returned in time for the must-win game against Aduana after he joined his colleagues at the team's training grounds on Thursady.
In the absence of the captain, Hearts suffered a 2-0 defeat at Heart of Lions.
He will be required to inspire team confidence ahead of the crunch game against the table-toppers at the Accra sports stadium.


text:
We want to shed a little light on the role of lighting.
Like most aspects of a beautiful interior, good lighting has both functional and aesthetic more >
When it comes to properly setting a table, theres a lot more rules to remember than youd think. According to the etiquette handbooks of yore, sala more >
Buongiorno! Curious as to why were starting this weeks Bova blog with an Italian greeting? Its because today we are featuring an Italian furnit more >


text:
Illinois Show or hide ACES linksHide ACES links
College of ACES Extension and Outreach
The College of ACES extends its knowledge to make life better, healthier, and safer for individuals and communities locally and throughout the world. These programs are a sample of our many agricultural, consumer, and environmental outreach efforts.
The flagship outreach effort of the University of Illinois, U of I Extension offers educational programs to residents of the state's 102 counties and beyond.
Agricultural Education
High school vocational agriculture programs and FFA organizations in Illinois and other states use instructional materials and curricula developed by the College of ACES.
Agricultural Safety and Health
Research-based resources help individuals and organizations understand and prevent injury and illness while working in and around Illinois agriculture.
Agronomy Day
Discover the latest research findings related to plant breeding, pest control, biomass production, horticulture, and more.
Certified Livestock Manager Training
Training required by the Illinois Livestock Management Facilities Act is provided by U of I Extension.
Crop Sciences Variety Testing
Annual crop performance tests inform farmers, extension personnel, and seed companies about hybrids and varieties of the major Illinois field crops.
Dudley Smith Initiative
Innovative research and outreach supports the agricultural system in Illinois.
Farmdoc Daily
Crop and livestock producers in the U.S. Corn Belt have round-the-clock access to integrated information and expertise to better manage their farm businesses.
Illinois Center for Urban Agricultural Education
This educational initiative in the Chicago High School for Agricultural Sciences enhances urban students' interest and preparation for higher education and careers in the agricultural, consumer, and environmental sciences.
Illinois Corn and Soybean Classics
Conducted in multiple Illinois locations, this annual program addresses issues of the day in crop production and pest management.
Illinois Livestock Trail
These resources are devoted to beef, dairy, horse, pork, poultry, sheep/goat, pasture, and manure.
National Soybean Research Laboratory
NSRL promotes soybean research, education, and outreach in production, nutrition, and international development.
Pesticide Safety Education Program
PSEP provides education on the effective, economic, and environmentally sound use of pesticides.
Research and Education Centers
Six U of I research and education centers throughout Illinois serve crop producers, landowners, crop consultants, advisors, and the agricultural industry.
The Autism Program
This statewide network offers resources on autism spectrum disorders for families, professionals, and students.
Bevier Café & Spice Box
Staffed and managed by U of I students, the Bevier Café and Spice Box restaurant offer exceptional food choices while providing hands-on education.
Center for Economic and Financial Education
Resources to improve the economic and financial well-being of consumers and their families.
Child Care Resource Service
Serving Champaign, Vermilion, Macon, Douglas, Iroquois and Piatt counties, the program supports the well-being of children and families by promoting the availability of quality child care services in the area.
Child Development Laboratory
This university-based preschool and child care program provides a site for training, research, and model programs in child development and early childhood education.
Illinois 4-H
4-H helps youth reach their fullest potential through developing skills in science/engineering/technology, healthy living, and citizenship.
Illinois Master Gardeners
The Master Gardener program trains interested adults to provide education and develop community programs related to horticulture.
Illinois Tax School
High-quality, low-cost tax education is provided annually to tax professionals.
Plant Clinic
The clinic helps with plant problems through identification, diagnosis,, and recommendations on issues caused by diseases, insects, weeds, chemicals, and nutrient deficiencies.
Research Apprentice Program
Through this on-campus program, high school freshmen and sophomores of underserved and economically disadvantaged groups develop valuable skills and learn about careers in the agricultural, consumer and environmental sciences.
Illinois Forest Resource Center
The center provides leadership, land management, and workshops on various aspects of land ownership and forestry.
Illinois-Indiana Sea Grant
Sea Grant empowers southern Lake Michigan communities to secure a healthy environment and economy.
National Great Rivers Research and Education Center
This partnership of the College of ACES, Illinois Natural History Survey, and Lewis and Clark Community College studies great river systems and the communities that use them.
University of Illinois Arboretum
A living laboratory of plant collections and facilities supports teaching, research, and public service programs.


text:
Facing South Florida: The Search for Tiffany Sessions
February 10, 2014 2:15 PM
Jim DeFede
Jim DeFede joined CBS4 News in January 2006, providing reg...Read More
25 years ago, Tiffany Sessions, a young South Florida woman and a student at the University of Florida in Gainesville, disappeared. Her body has never been found. Detectives have just identified the prime suspect in this cold case. Jim talks to the Alachua County Sheriff about the big break.
Click on the above picture to watch the interview.


text:
BFX018- Backgrounds
All EBA FX stencils come in a reusable plastic Mylar stencil material. EBA Stencils are offered in standard and custom sizes to fit your project. Background and scale stencils assist artist to create realistic backgrounds. Stencils can be interconnected and overlapped providing an unlimited area of coverage.
Contact | Home | Shop Online | Services | EBA Club | About | FAQ | Sitemap | Press Releases | Related
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text:
Peek #9: FAST to GL Translate Tool
When PeopleSoft's Financial Management module is implemented in July, we'll all be using ChartField Combinations instead of our old ten-digit FAST accounts (see Peek #8 for more about ChartFields).
Don't worry: you won't need to memorize your new ChartField Combinations. To help ease the transition from using your legacy FAST account to using PeopleSoft's ChartField Combinations, the Project Enterprise team has developed the FAST to GL (General Ledger) Translate Tool. This tool is web-based and can be accessed from the PeopleSoft portal page (the page you get to after you log in with your id and password). Click on University of Maine System, then click on Financials, and then on FAST to GL Translate.
The Translate screen provides you with the following two Look Up options:
FAST Look Up: Allows you to enter a FAST account to obtain the associated ChartField Combinations.
FAST Reverse Look Up: Allows you to enter ChartField Combinations to obtain the associated FAST account.
The FAST Reverse Look Up option will be an especially helpful tool for ISIS users who need to locate the FAST account/object code combination that represents the Department/Account/Class combination in PeopleSoft.
The FAST to GL Translate tool will remain in use as long as it is needed to transition from the FAST legacy systems to the new PeopleSoft system.
If you have attended a session of "How Business Will Change," you should be able to access the FAST to GL Translate tool. If you don't find it on your portal, contact your campus Training and Communication Coordinator. For a list of these folks, see Peek #5: Training.
March 2005


text:
DEL CITY — When her knee buckled during a practice early in the season last year, Del City guard Dionna Collins thought the worst.
Class 5A girls basketball: Del City's Dionna Collins back from torn ACL, leading Eagles into state tournament
"It was just devastating," Collins said. "I was like, 'Dang. Career over.'"
She knew right away what the buckling meant — a torn anterior cruciate ligament.
Now, just more than a year later, Collins is set to lead Del City into the Class 5A state tournament she watched from the bench last year.
The Eagles open the tournament against Tulsa East Central at 2 p.m. Thursday.
After her injury, Collins spent most of the next two months thinking she'd never play the sport again, at least competitively.
But Del City coach Karri Sears wasn't about to let Collins dwell in negativity.
Sears had torn her own ACL in her mid-20s, when she was already helping coach at Del City.
"D, my leg that I tore is stronger, even at my age," Sears told Collins. "The one I hurt is better than my good leg."
Collins wasn't having it.
"Coach, I'm going to be weak," Collins responded. "I'm going to lose my speed."
But Sears kept pushing, both letting Collins know that she'd return as good as ever and that she still had a role on last year's team.
Finally, about two months after her surgery, Sears' words started to sink in.
She began to see a light at the end of what had been a dark journey.
"It was those texts she sent that helped me turn my attitude around," Collins said.
Once Collins made that decision, it was over.
Her doctor wanted her to wait until late in the summer to run. Collins was sprinting in the gym three months after her surgery.
Continue reading this story on the...


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Offshore drilling will not make us conserve oil
February 17 2010 | Oil Pollution, Jim's Blog,
by Jim
This is a 1965 Volvo 122S. My dad drove a red one.
Aside from being fun to drive, my dad drove a Volvo because of its fuel economy. But my dad wasn't a dyed-in-wool tree hugger; my dad worked in the oil industry. He drove small fuel-efficient cars because he knew oil was a valuable, finite natural resource. He knew oil, like all natural resources, should not to be wasted.
Fast forward to today and there is less oil available on the planet, not more. It was clear in the 1970s that we needed to conserve the remaining oil we have and that we needed alternative sources of energy. It's even more clear today. Tomorrow, it'll be clearer.
Yet look at the past two decades of fuel economy (more here, PDF). The chart to the right illustrates what we saw on the roads... Hummers instead of hybrids.
The truth is that we don't just consume oil, we waste it. President Bush used the word "addiction" to describe our relationship with oil. Think about food, drink and spending... we know what happens when we become addicted. It's not pretty.
The way to address an addiction is not to seek new ways to fuel it.
The way to address an addiction is to seek alternatives to the addiction.
We need to stop producing large, wasteful vehicles. We must embrace the fact that we are running out of a natural resource and act accordingly. We can not drill our way out of this problem. Offshore drilling wouldn't even allow us to top our cars off, we'd only get 10% from offshore drilling and the trade-off is massive as we would put coastal economies and ecosystems at risk.
We must conserve the oil we have and find new energy sources that have low impacts on our planet.
My dad drove a small Volvo when I was a kid and that has had an impact on me. I grew up understanding why that was a smart (and fun) decision and today I drive a Mini. I love my Mini yet I know that just because it gets 40 mpg on the highway, I'm not "green." The truth is that I drive too much, period. I know that even if I was getting 70 mpg on the highway, carpooling or telecommuting would still be better options. That tension--knowing we haven't arrived and that we'll never arrive--is a good thing. But there is one thing that we SHOULD have an insatiable appetite for... perhaps even an addiction for... and that is finding new ways to use less resources.


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Friday - 4 September 2009
No. 135/2009
Gross Domestic Product 2008 - RevisionStatistics Iceland has now released a revision of the annual national accounts for 2007. The figures show Gross Domestic Product (GDP) in 2008 amounting to 1,476 billion ISK. In real terms, GDP grew at a rate of 1.3% after 5.6% growth in the year before.
The growth in GDP during last year can mainly be explained by 7.0% growth in exports, particularly exports from power intensive industry. Increase in exports together with a decline in imports by 18% resulted in considerable improvement in the balance on goods and services.
Gross Domestic Product 2008 - Revision - Statistical Series


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Top 10 Kindle Romance Bestseller
Hit #1 Historical Romance Kindle Bestseller
Reader's Choice Finalist: Best Historical
Rising Stars Finalist: Best First Book
Heart of Romance Finalist: Best Historical
TO SEDUCE A ROGUE, Southern Heat, Book One: ADAM
Includes excerpts from TO DESIRE A SCOUNDREL (Southern Heat, Book Two: TANNER) and the National Reader's Choice Winner TIDES OF PASSION!
Praise for TO SEDUCE A ROGUE:
"The battle of the sexes heats up the pages of this fun
and fresh romance by talented new writer Tracy Sumner."
—New York Times bestselling author Susan Wiggs
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—USA Today bestselling author Pamela Morsi
"Tracy Sumner has created endearing people
and a story to match. Engaging, warm and wonderful."
—Romantic Times
"As I began reading this book, I fell in love."
—Affaire de Coeur
Product Description:
In this battle of wills, passion becomes front-page news.
He challenged her legacy.
She challenged him to love.
In 1850s South Carolina, ladies with ambition and a penchant for wearing trousers are rare indeed. But that's Charlotte Whitney all over. Not only does Charlie yearn to resurrect her late father's newspaper, she wants to be its editor. That position, however, has been handed to Richmond newspaperman Adam Chase. Undeterred, Charlie convinces Adam to teach her the journalism trade. In doing so, she teaches him how to open his heart.
Adam Chase had one goal in mind: to return Edgemont's newspaper to its former glory and then make tracks back to the big city. But he faces one very tempting obstacle in outspoken Charlie Whitney. The newsroom becomes the battleground for a war between the sexes—until Adam surrenders to Charlie's sultry charms. Together, they discover that the power of the press doesn't hold a candle to the power of love.
Other Novels by Tracy Sumner:
TO DESIRE A SCOUNDREL, Southern Heat, Book Two: TANNER (novella)
TIDES OF LOVE, Seaswept Seduction Series, Book One: NOAH
TIDES OF PASSION, Seaswept Seduction Series, Book Two: ZACH
Coming April 2012, TRUE FATE, True Men Series, Book One: JUSTIN
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What is brandnewepisodes.com
BEWARE: brandnewepisodes.com is a website that claims to offer the latest episodes of current television shows. However, the site has only been registered since June of 2011 and requires the user to click on a link to take a survey before gaining access to the site. We find this to be very suspicious. More reliable mainstream sites with TV episodes databases are: hulu.com and Netflix.com.
Updated on Monday, February 06 2012 at 07:43AM EST
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Cate Blanchett was recently spotted heading to the theater in Manhattan for her matinee performance of The Maids. She's carrying both a quilted, burgundy red Roger Vivier Prismick Shoulder Bag, which is a new-for-fall variation on one of the brand's classic bags, and a taupe Givenchy Lucrezia Satchel.
Archives for: #Cate Blanchett
Cate Blanchett has always had a very well defined, slightly eclectic sense of style, so it makes sense that she would choose something like this two-tone nappa leather Roger Vivier Prismick Shoulder Bag for daytime. Here she is with her Prismick in tow, heading into Good Morning America in NYC to rustle up a little PR for her upcoming flick, Blue Jasmine, which opens in NYC and LA this Friday!


text: I have been a practicing professional in aquatic and fisheries biology for several decades and enjoy working on research and with students. I have served on the graduate committees of more than 40 students enrolled at the University of Idaho. I enjoy the challenging research in fisheries science and the perspective of the ecosystem. I was born in Southern California and have always been interested and engaged in outdoor activities. My personal interest in aquatic biology was kindled when I was an undergraduate student in Northern California. I have been lucky to find good academic mentors throughout my career. Aside from my work, I enjoy fishing, gardening, live music and drama.


text:
The National Directorate of Employment says it has trained over 8,000 persons for its Graduate Coaching Scheme in the past three years.
The NDE Director-General, Mr. Abubakar Mohammed, made this known on Thursday during the inauguration of the 2014 GCS programme in Calabar, Cross River State.
According to Mohammed, the programme established in 2012 is to engage unemployed youths to teach secondary school leavers, who have deficiencies in English Language and other science-related subjects.
Represented by the Director of Small Scale Enterprise in the Directorate, Mr. Jibrin Aye, the NDE boss said the scheme was ongoing in 20 states in the country.
Mohammed noted that the initiative had assisted many school leavers to secure admission to the nation's higher institutions.
He added that over 300 unemployed youths have so far benefitted from the programme as they receive a monthly allowance of N10, 000 each to teach the students.
"We recruit and coach instructors to teach this school leavers, and we pay them a monthly allowance of N10,000 and the programme runs for three months.
"The GCS is capable not only of reducing unemployment among the graduates, but also has the potential for curtailing early entry into the labour market.
"The effect of unemployment manifests in various forms, such as youth restiveness, kidnapping, armed robbery, prostitution, among others, which tend to stall our development and progress as a nation.
"It is for these reasons that governments at all levels are working hard to mitigate these effects and channel the efforts of our youths to productive venture'', he said.
Copyright PUNCH.
All rights reserved. This material, and other digital content on this website, may not be reproduced, published, broadcast, rewritten or redistributed in whole or in part without prior express written permission from PUNCH.
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In addition to the prospects Senior Analyst Rob Rang wrote about in his "five players to watch" blog post, take a look at these memorable ten one-on-one match-ups (plus a slew of honorable mention selections) while perusing this weekend's slate of college football games.
Because players move around based on different formations and what coaches see as favorable match-ups, these prospects won't go against each other on every snap. Scouts will pay attention when they do, however, because they rely on a player's film against top competition to determine their readiness for the NFL.
All times Eastern.
"*" Denotes an underclassman.
1. LSU Back Seven at Alabama RB *Trent Richardson (#3/5-11/224/4.52)
8:00 pm, CBS
If the talented Alabama offensive line and LSU defensive line negate each other in the run game on Saturday night, this year's "Game of the Millenium" could be determined by whether Heisman hopeful Richardson can defeat Tigers' linebackers at the second level. Thick weak side 'backer Ryan Baker (#22/6-0/236/4.77), fast Sam LB Stefoin Francois (#23/6-1/223/4.58), and inside guys former strong safety Karnell Hatcher (#37/6-1/223/4.64) and solid sophomore Kevin Minter, must keep their feet and wrap securely if they want to bring down Richardson before he turns a three-yard plow into a 10 or 20-yard gain. But let's face it -- few college defenders can chop down Richardson on first contact because of his thick frame, natural aggression and constantly-churning legs. That means the Tigers must swarm to the ball, with strong safety Brandon Taylor (#18/5-11/195/4.57), sophomores nickel corner Tyrann "Honey Badger" Mathieu and leading tackler free safety Eric Reid helping out the linebackers to stop the Alabama run game.
2. North Carolina Defensive Ends Quinton Coples (#90/6-6/285/4.76)/*Donte Paige-Moss (#98/6-4/260/4.67) at North Carolina State OT *R.J. Mattes (#79/6-6/305/5.19)
12:30 pm, ACC Network/ESPN3.com
North Carolina's defensive line is among the deepest -- and hyped -- in the country. Coples has the size/length to start on three or four-man fronts in the NFL, while Paige-Moss has the size and athleticism that made former Tar Heels DE Robert Quinn a top 15 pick last April. They've combined for just 10.5 tackles for loss and 5.5 sacks in nine games (7.5, 4.5 for Coples), however, after putting up 29 and 17 (15.5, 10 for Coples) last season. Facing an All-ACC candidate in Mattes is not an easy way to increase that production; the redshirt junior left tackle is looking to prove his overall athleticism to scouts after showing strength and tenacity while starting at right guard and right tackle in his first two seasons on the field (though a torn ACL cost him the last four games of 2009).
3. Texas A&M CBs Coryell Judie (#5/5-11/190/4.48)/Terrence Frederick (#7/5-10/187/4.52) at Oklahoma WR Ryan Broyles (#85/5-10/188/4.52)Texas A&M WRs Jeff Fuller (#8/6-3/220/4.52)/*Uzoma Nwachukwu (#7/6-0/195/4.42) at Oklahoma CBs Jamell Fleming (#32/5-11/192/4.54)/*Demontre Hurst (#6/5-9/182/4.46)
3:30 pm, ABC/ESPN2
This week's version of "Luck vs. Barkley" is A&M's athletic and strong-armed QB Ryan Tannehill (#17/6-4/222/4.65) against Oklahoma's junior pocket passer QB Landry Jones (#12/6-4/230/4.74). Scouts for teams needing a quarterback could use this game as a tie-breaker of sorts for the second or third spot in their rankings.
But NFL teams with a young passer already on the roster will be checking out this game, as well,since both Big 12 squads have legitimate NFL prospects at cornerback and receiver. Judie's hamstring has been a problem this year, and he'll need to be healthy to handle Broyles' crisp routes and elusiveness after the catch. The NCAA's all-time leader in receptions will also face stiff competition from Frederick, an ascending talent who gives no quarter to receivers of any size. When Tannehill is leading A&M's offense, he'll look for Fuller to use his size advantage and Nwachukwu his speed against Sooners corners Fleming and Hurst -- both of whom can take advantage of sideline and comeback throws Tannehill leaves too far inside.
4. South Carolina CB *Stephon Gilmore (#5/6-1/193/4.52) at Arkansas Receivers
7:15 pm, ESPN
Gilmore will be able to show NFL teams all of his skills no matter which of the Razorbacks' gaggle of receivers he may be facing Saturday night. He has the size and attitude to handle big receivers junior Cobi Hamilton (#11/6-3/209/4.57) and Greg Childs (#85/6-3/217/4.56) -- who has struggled coming back from last season's knee injury -- at the line of scrimmage or down the sideline. But scouts will be more interested to see if Gilmore can also handle the straight-line speed and quickness Jarius Wright (#4/5-10/180/4.34) and Joe Adams (#3/5-11/190/4.38) if in trail coverage or trying to chase them down after the catch in zone.
5. Missouri Defensive Tackle at Baylor C Philip Blake (#74/6-2/320/5.26)
7:00 pm, FSN
Danny Watkins took a circuitous route to NFL first round draft status, growing up in Canada, playing his first football in junior college before starting at left tackle for Baylor. Blake won't be selected that high and has played football for some time, but was also born in Canada and is advanced in age for a future rookie (Watkins turns 27 years old Sunday, Blake turns 26 later this month). He'll need to use his wide body and long arms to handle Missouri's trio of pro DT prospects: long and strong Dominique Hamilton (#90/6-5/305/5.24), athletic junior Sheldon Richardson (#34/6-3/290/4.86) and active DT Terrell Resonno (#93/6-3/295/5.08). The Bears have another big body up front, RG Robert T. Griffin (#79/6-6/330/5.38), who protects the team's athletic playmaking quarterback Robert Griffin III (who was actually born in Japan, where his father served for the U.S. Military). And no, that's not a typo -- the mammoth guard and unrelated 6-2, 220 pound quarterback have the same name.
6. Oregon Cornerbacks at Washington WR Jermaine Kearse (#15/6-1/208/4.50)
10:30 pm, FSN
The Huskies are one of college football's best stories that doesn't get talked about nearly enough. Washington fans can tell you that Kearse isn't the most consistent receiver in terms of his hands or physicality, but is a threat down the sideline to elude defenders after the catch when his game is on. Oregon's secondary has scoured by scouts for prospects over the years, but the 2011 group is a bit different. Three of the top four cornerbacks on the depth chart for this game are freshmen, and senior CB Anthony Gildon (#18/6-0/182/4.57) is erratic in his discipline outside. The wild card is junior CB Cliff Harris (#13/5-11/168/4.49), who packs a punch in press coverage that belies his wiry build, and also has the ball skills to knock away or intercept passes and had four punt returns for TDs in 2010. He may not play in this game, however, if unable to get out of head coach Chip Kelly's dog house because of an excessive speeding citation this summer and another traffic stop two weeks ago.
7. Michigan DEs *Craig Roh (#88/6-4/269/4.76)/Ryan Van Bergen (#53/6-6/288/4.84) at Iowa OTs *Riley Reiff (#77/6-6/300/4.94)/Markus Zusevics (#56/6-5/300/5.08)
12:00 pm, ESPN
Even though the Hawkeyes are coming off a brutal loss to Minnesota and the Maize-and-Blue is on top of the Legends Division of the Big Ten, Iowa still has games against the three teams tied atop the division in the Wolverines, Michigan State and Nebraska. To win any of those games, including Saturday's match-up, the team's two tackles must protect junior QB James Vanderberg. Reiff will face Roh (pronounced Row) on the weak side of the line on most plays; the more athletic pair should have good battles as Reiff tries to cut off Roh trying to use his length to turn the corner and anchors against the junior's relentless aggression. Van Bergen won't test the lateral movement of Zusevics (ZOOZ-uh-vicks) as much as the two-year starter's ability to hold his ground as the high-motor end attempts to push him into the pocket a part of the somewhat lean right tackle's game in which he does not always excel. Both tackles will also have to seal their men inside or outside in order for bruising sophomore RB Marcus Coker (252 yards vs. Minnesota last week) to move the ball against an improved Michigan defense (ranks 35th in the FBS in total defense, ranked 110th after the 2010 season).
8. Purdue DT *Kawann Short (#93/6-3/310/5.22) at Wisconsin Interior Offensive Line
3:30 pm, ABC/ESPN2
Short was the Big 10 Co-Defensive Player of the Week against Illinois two weeks ago (3.5 TFL, 2 sacks), and played well in a loss to Michigan going up against senior center David Molk. This weekend, however, he really gets a chance to show NFL scouts he is a legitimate top 75 pick by taking on future pro starters junior C Peter Konz (#66/6-5/315/5.16), RG Kevin Zeitler (#70/6-4/318/5.26) and redshirt sophomore LG Travis Frederick (#72/6-4/330/5.27). Michigan State's Jerel Worthy found a bit of success against this group a couple of weeks ago, but was also redirected out of plays when unable to use his hands to disengage. Short will have to be more consistently quick off the snap to pressure QB Russell Wilson and agile/strong enough to maintain his gap discipline against the Wisconsin running game to be considered an elite prospect this year or next.
9. Notre Dame WR Michael Floyd (#3/6-3/224/4.54) at Wake Forest CB *Kenny Okoro (#6/6-0/190/4.49)
8:00 pm, ABC/ESPN2
Floyd's talents are well-known, as he's used his NFL size and strong hands to rank in the top 20 nationally in receptions and receiving yards per game. The Irish have not always fed him as often as they should, as Pittsburgh and USC kept him under 30 yards on four catches. Okoro's an under-the-radar talent at corner with good size, speed and aggressiveness for the position. A big game against Floyd could draw the notice of scouts looking forward to the 2013 draft.
10. Minnesota WR Da'Jon McKnight (#6/6-1/212/4.54) at Michigan State CB *Johnny Adams (#5/5-11/175/4.42)- Junior
12:00 pm, Big Ten Network
McKnight has been an underappreciated talent playing for a lowly Gophers squad, but last week's big win over Iowa gave him and junior QB MarQueis Gray (#5/6-4/240/4.56) a bit of a boost with scouts. Adams' competitive nature allows him to test McKnight's ability to get off press coverage and separate from/make plays against NFL-caliber corners downfield. In a deep senior receiver class, Minnesota's leading pass-catcher needs to have a big game against a good corner like Adams to get drafted come April.
Honorable Mention:
Vanderbilt CB Casey Hayward (#19/5-11/188/4.53) at Florida WR Deonte Thompson (#6/5-11/200/4.44)
12:21 pm, SEC Network/ESPN3.com
Virginia WR Kris Burd (#18/6-0/200/4.53) at Maryland CB Cameron Chism (#22/5-10/190/4.52)
12:30 pm, ACC Network/ESPN3.com
Wyoming CB Tashuan Gipson (#4/6-0/203/4.57) at TCU WRs Antoine Hicks (#13/6-2/212/4.57)/*Josh Boyce (5-11/203/4.54)
2:00 pm, MTN
Northwestern LT Al Netter (#75/6-4/310/5.26) at Nebraska DE *Cameron Meredith (#34/6-4/260/4.79)- Junior
3:30 pm, Big Ten Network
Cincinnati WR WR D.J. Woods (#3/6-0/182/4.49) at Pittsburgh CB Antwuan Reed (#22/5-10/190/4.54)
Cincinnati LT Alex Hoffman (#59/6-6/298/5.28) at Pittsburgh DE Brandon Lindsey (#7/6-2/250/4.68)
7:00 pm, ESPNU
Houston OLB Sammy Brown (#8/6-2/240/4.67) at UAB LT Matt McCants (#71/6-6/295/5.26)
7:00 pm, CBS Sports Network
Arizona State DE Jamaar Jarrett (#92/6-5/262/4.90) at UCLA RT Mike Harris (#65/6-5/326/5.32)
Arizona State WRs Gerell Robinson (#8/6-3/222/4.58)/Mike Willie (#1/6-2/212/4.59) at UCLA CB *Aaron Hester (#21/6-1/206/4.49)
7:30 pm, Versus
Kansas State CB David Garrett (#27/5-8/175/4.58) at Oklahoma State WR *Justin Blackmon (#81/6-1/215/4.54)
8:00 pm, ABC/ESPN2
LSU CB *Morris Claiborne (#17/6-0/185/4.45) at Alabama WR Marquis Maze (#4/5-8/184/4.49)
LSU WR *Rueben Randle (#2/6-3/208/4.57) at Alabama CB *Dre Kirkpatrick (#21/6-2/192/4.49)
LSU RT *Alex Hurst (#72/6-6/340/5.22) at Alabama DE/OLB *Dont'a Hightower (#30/6-4/260/4.74)
8:00 pm, CBS
Louisiana Tech CB Terry Carter (#28/5-10/190/4.43) at Fresno State WR Devon Wylie (#7/5-10/185/4.38)
10:30 pm, ESPNU
--Contributed by Senior Analyst Chad Reuter Follow him on Twitter @ChadReuter


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It was a gift.
Lol yeah, "it's a European Shoulder Bag."
Also, once my stepfather left his ceramic mug, full of coffee on the top of his car.
anyway, this is pretty funny but it's not a forgetful lady driver, just a forgetful lady! It's on the passenger side, yeh?
Also, lady has bad taste in handbags..>>
thats what i thought this pic would be of...
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Market House in Annapolis
Miniatures samples of banners with floral designs that will decorating the historic Market House, when it re-opens. The designs were chosen from artworks submitted by local seniors from the Annapolis Senior Center. Photo by Kenneth K. Lam, Baltimore Sun
This photo is featured in these articles:


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Spirit away for some spook-tacular fun at a series of family-friendly Halloween events—from September 11 through November 1, 2015.
Trick-or-treat and enjoy ear-y entertainment at one of the most anticipated special events of the season.
Space Mountain has been overtaken by a phantom force! Don't miss your opportunity to brave ghost-ridden cosmos this season.
Celebrate Día de los Muertos at Zocalo Park in Frontierland—with a tribute to the art, symbols and customs of the Day of the Dead.
Ward off evil spirits by escaping to this ticketed party to enjoy tropical savors, exclusive swag and live entertainment.
Capture the spirit of the season with a colorful variety of Disney-centric gear including décor, apparel, costume tees, accessories and treats.
Disneyland Resort Area
Disneyland Resort
Valid Park Admission Required
- , 2015


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Friday, October 9, 2015
More New York Times Critics' Picks »
The following shows have received ratings of at least four stars from Times readers.
Most Highly Rated Shows »
The Pan Asian Repertory Theater's production of "Three Trees" looks at the life of Alberto Giacometti.
Full New York Times Review »
See all event listings »


text:
Dr. Jekyll & Mr. Hyde
Sat, Jan 12, 2013 2:00 pm
Durham Performing Arts Center, Durham, NC
Sorry, this event has already taken place. Please see similar events below.
|Oct 29 Thu 8:00 PM
|Dr. Jekyll & Mr. Hyde - Silent Film
|Schermerhorn Symphony Center
Nashville, TN
|Oct 30 Fri 8:00 PM
|Dr. Jekyll & Mr. Hyde
|Grand 1894 Opera House
Galveston, TX
|Oct 31 Sat 8:00 PM
|Halloween Organ with Film: Dr. Jekyll and Mr. Hyde
|Walt Disney Concert Hall
Los Angeles, CA


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Scherer and Nabholz(Moscow, Russia, Active ca. 1868-1900)
Exterior View of a Factory
ca. 1870photograph | albumen print
Not on view at this time; find out where you can see works from our collection at locations around the Bay Area while our building is closed for expansion
10 3/4 in. x 14 7/8 in. (27.31 cm x 37.78 cm)
Acquired 1999
Collection SFMOMA
Accessions Committee Fund purchase


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Silicon Valley Lines Model Railroad Club
We've been working on the railroad!
During the holiday break a lot of changes have been made on the layout. Bayshore has received a lot of attention at both the engine facility and the south bridge. Jacksonville's crossovers are all being upgraded to #8 turnouts. Hallelujah is getting new tenants (Cannery and PaperMill).
Pacing the Excursion Train
Riding through Tracy on the SVL
Founded in 1979, Silicon Valley Lines (SVL) is an HO Scale Model Railroad Club located in San Jose, California. In 1999, we moved to our current location on 148 E. Virginia Street in San Jose, where our 23' x 72' layout is in operation.
SVL operates trains using digital command control (DCC), which allows engineers to control locomotives independently on the same track. Members are given switchlist and must coordinate via radio with the dispatcher to obtain authority to move on the mainline and complete their work in a timely fashion. Our layout is constructed using some unique benchwork building techniques, with much of the layout supported by structural steel components.
We meet Friday nights starting at 7:30pm. The first Friday of each month we hold a club business meeting. Usually, the last Friday is Operations Night. All other Fridays we work on scenery, maintenance of the track and electronics, or the trains. We remain open until the last member leaves! Visitors are always welcome; if you like what you see, please consider joining our club! Membership is open, and we're always looking for new folks to help build, operate, and enjoy HO Scale Model Railroading.
If you are curious or considering joining the Silicon Valley Lines please see our pamphlet click here.
Click here for directions to SVL
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Paying for Funerals
Cremation as an Option
Typically, cremation is less expensive than a burial. Talk to your family member to see what his or her preference would be. The earlier you do this, the easier the talk will be.
Insurance is available if you plan far enough ahead. Talk to your agent.
Social Security Lump-Sum Death Benefit
You may be eligible for a Social Security Lump-Sum Death Benefit as well. (This link will tell you what to do related to Social Security benefits, step-by-step, when your family member dies).
Veteran's Benefits
If your family member was a spouse and a veteran, you will be eligible for benefits to help you pay for a funeral.
|Contact your local Veteran's Affairs office
|The NC Division of Veteran's Affairs can tell you if there are any additional benefits provided by NC that may be available to you.