Abstract: The present invention relates to efficient synthetic processes useful in the preparation of uridine, which is useful in the production of nucleosides and nucleotides that may be active as antiviral agents, as well as compositions and methods thereof.

Abstract: The present invention relates to efficient synthetic processes useful in the preparation of antiviral nucleosides, particularly uridine 4-oxime 5?-(2-methylpropanoate) {(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl]oxolan-2-yl}methyl 2-methylpropanoate and pharmaceutically acceptable salts, derivatives, tautomers, isomers, and prodrugs of, which may be active as antiviral agents, as well as compositions and methods thereof. The present invention also encompasses intermediates useful in the disclosed synthetic processes and the methods of their preparation.

Abstract: Method and devices are provided for extended and controlled delivery of parathyroid hormone to a patient. The method includes implanting a medical device into the patient, the medical device comprising a substrate, a plurality of reservoirs in the substrate, a release system contained in each of the reservoirs, wherein the release system comprises parathyroid hormone; and controllably releasing a pharmaceutically effective amount of the parathyroid hormone from the reservoirs. The parathyroid hormone can be released intermittently, such as once daily over an extended period (e.g., two months, ten months, or more.). The device can further include reservoirs containing a bone resorption inhibitor or other drug for release. The devices are useful in delivering PTH for the treatment and prevention of bone loss, such as associated with osteoporosis.

Abstract: Devices and methods are provided for the controlled release or exposure of reservoir contents. The device includes a substrate, a plurality of reservoirs in the substrate, reservoir contents disposed in the reservoirs, discrete reservoir caps covering each reservoir to seal the reservoir contents in the reservoirs, and control circuitry for selectively disintegrating the reservoir caps to release or expose the reservoir contents in vivo. At least one of the reservoir caps comprises a first electrically conductive layer coated with one or more protective layers. In one embodiment, the control circuitry comprises an electrical input lead and an electrical output lead connected to and directly contacting each of said reservoir caps and a source of electric power for applying an electrical current through each reservoir cap in an amount effective to rupture each of the reservoir caps.

Abstract: Devices and methods for the controlled release or exposure of reservoir contents, and methods of manufacture thereof, are provided. The device includes a reservoir cap formed of an electrically conductive material, which prevents the reservoir contents from passing out from the device and prevents exposure of the reservoir contents to molecules outside of the device; an electrical input lead connected to said reservoir cap; and an electrical output lead connected to said reservoir cap, such that upon application of an electrical current through the reservoir cap, via the input lead and output lead, the reservoir cap ruptures to release or expose the reservoir contents. The reservoir contents can comprise a release system containing drug molecules for release or can comprise a secondary device, such as a sensor. The controlled release system may be incorporated into an implantable drug delivery or biosensing device.

Abstract: Method and devices are provided for extended and controlled delivery of parathyroid hormone to a patient. The method includes implanting a medical device into the patient, the medical device comprising a substrate, a plurality of reservoirs in the substrate, a release system contained in each of the reservoirs, wherein the release system comprises parathyroid hormone; and controllably releasing a pharmaceutically effective amount of the parathyroid hormone from the reservoirs. The parathyroid hormone can be released intermittently, such as once daily over an extended period (e.g., two months, ten months, or more.). The device can further include reservoirs containing a bone resorption inhibitor or other drug for release. The devices are useful in delivering PTH for the treatment and prevention of bone loss, such as associated with osteoporosis.

Abstract: Devices and methods are provided for the controlled release or exposure of reservoir contents. The device includes a reservoir cap formed of an electrically conductive material, which prevents the reservoir contents from passing out from the device and prevents exposure of the reservoir contents to molecules outside of the device; an electrical input lead connected to said reservoir cap; and an electrical output lead connected to said reservoir cap, such that upon application of an electrical current through the reservoir cap, via the input lead and output lead, the reservoir cap ruptures to release or expose the reservoir contents. The reservoir contents can comprise a release system containing drug molecules for release or can comprise a secondary device, such as a sensor. In one embodiment, the controlled release system is incorporated into an implantable drug delivery device.

Abstract: Devices are provided for the controlled exposure or release of contents stored in hermetically sealed reservoirs. The devices comprise a primary substrate having a front side and a back side, and including one or more hermetic sealing materials; a plurality of reservoirs in the primary substrate positioned between the front side and the back side; reservoir contents, which comprise chemical molecules (such as drugs) or a secondary device (such as a glucose sensor), located inside the reservoirs; a hermetic sealing substrate having a surface composed of one or more hermetic sealing materials; and a hermetic seal formed between and joining the primary substrate and the hermetic sealing substrate, wherein the hermetic seal independently seals the reservoirs.

Abstract: Method and devices are provided for extended and controlled delivery of parathyroid hormone to a patient. The method includes implanting a medical device into the patient, the medical device comprising a substrate, a plurality of reservoirs in the substrate, a release system contained in each of the reservoirs, wherein the release system comprises parathyroid hormone; and controllably releasing a pharmaceutically effective amount of the parathyroid hormone from the reservoirs. The parathyroid hormone can be released intermittently, such as once daily over an extended period (e.g., two months, ten months, or more.). The device can further include reservoirs containing a bone resorption inhibitor or other drug for release. The devices are useful in delivering PTH for the treatment and prevention of bone loss, such as associated with osteoporosis.

Abstract: Devices and methods are provided for the controlled release or exposure of reservoir contents. The device includes a substrate, a plurality of reservoirs in the substrate, reservoir contents disposed in the reservoirs, discrete reservoir caps covering each reservoir to seal the reservoir contents in the reservoirs, and control circuitry for selectively disintegrating the reservoir caps to release or expose the reservoir contents in vivo. At least one of the reservoir caps comprises a first electrically conductive layer coated with one or more protective layers. In one embodiment, the control circuitry comprises an electrical input lead and an electrical output lead connected to and directly contacting each of said reservoir caps and a source of electric power for applying an electrical current through each reservoir cap in an amount effective to rupture each of the reservoir caps.

Abstract: An implantable medical device is provided for controlled delivery or exposure of reservoir contents. The device may include a substrate; a plurality of discrete reservoirs in the substrate, wherein the reservoirs have interior walls and at least one opening in the substrate; reservoir contents disposed in the reservoirs; a reservoir cap closing the at least one opening of each of the reservoirs to seal the reservoir contents in each of the reservoirs; and control circuitry for selectively disintegrating the reservoir caps to release or expose the reservoir contents in vivo, wherein the interior walls of the reservoirs comprise a material to protect the substrate in vivo. For example, to enhance the resistance of the substrate to etching in vivo, the interior sidewalls of the reservoirs may include a protective coating (such as gold, platinum, carbon, silicon carbide, silicon dioxide, or platinum silicide), or the sidewalls may include a doped silicon.

Abstract: Devices and methods are provided for the controlled release or exposure of reservoir contents. The device includes a reservoir cap formed of an electrically conductive material, which prevents the reservoir contents from passing out from the device and prevents exposure of the reservoir contents to molecules outside of the device; an electrical input lead connected to said reservoir cap; and an electrical output lead connected to said reservoir cap, such that upon application of an electrical current through the reservoir cap, via the input lead and output lead, the reservoir cap ruptures to release or expose the reservoir contents. The reservoir contents can comprise a release system containing drug molecules for release or can comprise a secondary device, such as a sensor. In one embodiment, the controlled release system is incorporated into an implantable drug delivery device.

Abstract: Methods are provided for making a multi-reservoir device comprising (i) patterning one or more photoresist layers on a substrate; (ii) depositing onto the substrate at least one metal layer by a sputtering process to form a plurality of reservoir caps and conductive traces; (iii) removing the photoresist layers using a liftoff process; (iv) forming a plurality of reservoirs in the substrate; (v) loading each reservoir with reservoir contents (such as a drug or sensor); and (vi) sealing each reservoir. Optionally, the reservoir cap comprises a first conductive metal layer coated with one or more protective noble metal films. To enhance the resistance of the substrate (e.g., a silicon substrate) to etching in vivo, the interior sidewalls of the reservoirs optionally can include a protective coating (e.g., gold, platinum, carbon, silicon carbide, silicon dioxide, and platinum silicide), or sidewalls comprising silicon can be doped with boron or another impurity.

Abstract: Devices and methods for the controlled release or exposure of reservoir contents, and methods of manufacture thereof, are provided. The device includes a reservoir cap formed of an electrically conductive material, which prevents the reservoir contents from passing out from the device and prevents exposure of the reservoir contents to molecules outside of the device; an electrical input lead connected to said reservoir cap; and an electrical output lead connected to said reservoir cap, such that upon application of an electrical current through the reservoir cap, via the input lead and output lead, the reservoir cap ruptures to release or expose the reservoir contents. The reservoir contents can comprise a release system containing drug molecules for release or can comprise a secondary device, such as a sensor. The controlled release system may be incorporated into an implantable drug delivery or biosensing device.

Abstract: Microchip devices and methods of manufacture thereof are provided to increase the uniformity and reliability of active exposure and release of microchip reservoir contents. In one embodiment, the microchip device for the controlled release or exposure of molecules or secondary devices comprises: (1) a substrate having a plurality of reservoirs; (2) reservoir contents comprising molecules, a secondary device, or both, located in the reservoirs; (3) reservoir caps positioned on the reservoirs over the reservoir contents; (4) electrical activation means for disintegrating the reservoir cap to initiate exposure or release of the reservoir contents in selected reservoirs; and (5) a current distribution means, a stress induction means, or both, operably engaged with or integrated into the reservoir cap, to enhance reservoir cap disintegration.

Abstract: Methods are provided for hermetically sealing the reservoirs of microchip devices and for hermetically sealing the substrate assemblies in a hermetic packaging structure.

Abstract: Devices and methods are provided for the controlled release or exposure of reservoir contents. The device includes a reservoir cap formed of an electrically conductive material, which prevents the reservoir contents from passing out from the device and prevents exposure of the reservoir contents to molecules outside of the device; an electrical input lead connected to said reservoir cap; and an electrical output lead connected to said reservoir cap, such that upon application of an electrical current through the reservoir cap, via the input lead and output lead, the reservoir cap ruptures to release or expose the reservoir contents. The reservoir contents can comprise a release system containing drug molecules for release or can comprise a secondary device, such as a sensor. In one embodiment, the controlled release system is incorporated into an implantable drug delivery device.

Abstract: A method for analyzing the vibration of a tire uniformity machine having a number of rotating components uses the signals from load cells when the machine idle to output voltage signals that are then amplified and input into a computer as unfiltered, amplified voltage signals. The signals are converted into a power spectrum and selected groups of frequencies and their amplitude are compared with acceptable amplitudes for the frequencies generated by various rotating parts of the machine. When at least one of the amplitudes for different frequencies is greater than at least one of the acceptable amplitudes for the frequencies generating different rotating parts of the machine, the computer outputs an alarm signal.

Abstract: A method and apparatus for grooving a tire tread in which a computerized numerical controller regulates the positional relationships between the tire and a hot cutting knife. The controller, through a plurality of servo motors, causes the tire to rotate in a vertical plane while effecting lateral and rotational movement of the cutter knife in each of two planes. During the cutting operation, the controller regulates the temperature of the cutting knife in accordance with the contour of the cut and the rate at which it is being made. Additionally, the computerized numerical controller is operator-programmable, providing for the generation of a program while the knife is caused to trace a tread design. The method and apparatus achieves simultaneous five-axis control of the tire grooving operation with concurrent regulation of the knife temperature.

Abstract: A plastic resin hole plug to fill a hole in a flat thin panel comprises a one-piece unitary injection-molded plastic member having a top dome closure wall whose bottom surface has a flat ledge which rests on the panel and an undercut ring. The plug has a tubular shank portion which extends from the top closure wall portion and whose outer face retains the plug in the hole. The shank's outer face has a first circumferential band canted inwardly and a second circumferential band joined thereto which is canted outwardly. At least one, and preferably two, side flats are formed on the shank portion, which flats flex inward when the plug is inserted into the hole.