A window frame assembly for installation within a garage door having front and rear exposed surfaces and one or more window openings. The assembly includes front and rear window frame members of injection molded plastic which are installed within the door opening on the front and rear exposed surfaces. The window frame members have engagement elements located about their peripheries which snap together in mating fashion to mount the frame members within the window opening. The engagement elements are also disenageable with a hand tool to separate the frame members and remove the members from the window opening.

A. Field of the Invention
This present invention relates to decorative molding assemblies for framing openings of residential or commercial structures, and more specifically to a decorative window frame assembly for decoratively framing a garage door window opening of a residential or commercial garage door.
B. Description of the Prior Art
Modern garage door systems are typically comprised of doors having horizontally arrayed sections joined by hinges into a door unit. The door is mounted in a vertical track which curves upwardly into a horizontal position so that the door may be opened upwardly and supported horizontally in an open position. The sections are joined by the hinges along the longitudinal edges of the sections so that the overall door structure will generally conform to the radius of curvature of the track as it changes from vertical to horizontal. Customarily, each of the sections are fabricated separately and thereafter hinged together along a longitudinal edge to provide the complete overhead door structure.
Historically, the sections are fabricated from a galvanized and/or prepainted sheet metal stock which has been rolled or otherwise formed into the particular section facing, web and parallel interior flange configurations. Vertical stiles are usually secured to the section facing and interior flanges at spaced locations by spotweld or rivet techniques. Most prior art overhead door systems use hinges that are secured directly to the section stiles. While a majority of garage doors continue to be manufactured from mild steel stock, some manufacturers offer overhead doors made from synthetic materials such as various types of vinyl.
Molding assemblies are used in a variety of applications to frame or "surround" doorways, windows, patio doors, garage doors etc., to provide a decorative, aesthetically appealing framing for the opening. In recent years, these surround molding assemblies have been manufactured from plastics and are often injection molded. In general, plastics provide significant advantages in most installations. For example, molding or framing assemblies or components thereof manufactured from plastic are low in maintenance. Plastic molding assemblies are not susceptible to moisture and therefore will not typically decay, warp or splinter. Advantageously, plastic surround molding assemblies or components thereof can be sawed, drilled, glued or nailed. Still further, during the manufacture of plastic molding assemblies, plastic can be tinted with dyes or other materials to provide molding assembly components which are of desired colors, thus obviating the need for painting prior or subsequent to installation on a structure. Molding plastics are also available as UV stable materials which are resistant to degradation upon exposure to the surrounding environment.
Particularly in the area of residential garage doors, a number of manufacturers offer plastic window frame assemblies which are fitted within openings provided in the garage door and which typically feature a central opening which contains a transparent pane which may be of glass, plastic or such newer materials as acrylics. The central opening in the window frame assembly may also contain a decorative trim member which is sandwiched between the transparent pane and other framing components.
The prior art window frame assemblies for overhead garage doors have typically been assembled in a "stick built" fashion using mounting clips. A front frame member of injection molded plastic is received into the door opening from the front side. The front frame member has a central opening for receiving the window pane, decorative trim, etc. The front frame member and pane and then retained in position by hammering four mounting clips, sometimes referred to as "stick" strips, on the back side of the door. The front frame member has an inner periphery equipped with a locking rail which matingly engages a groove in the locking strips. The locking strips have corners which are diagonally cut and fit. Once hammered into position, it was generally necessary to cut off the locking strips in order to disassemble the window frame components in order to, for example, replace the pane. Thus, while the prior art technique was generally effective in securing the window frame assembly to the door structure, the use of stick built framing techniques added to the time and expense associated with installing the complete assembly. Once installed, should one component of the surround molding assembly need to be removed or replaced, the use of such an assembly technique complicated the task of removing and replacing the sub-components of the window frame assembly.
Accordingly, it is an object of the present invention to provide a window frame assembly for an overhead garage door which provides a decorative and aesthetically pleasing appearance, while securely supporting the various window frame components.
It is a further object to provide a versatile window frame assembly that can accommodate various other trim components that may abut the frame components.
It is yet another object of the present invention to provide a window frame assembly for a garage door which provides a decorative, aesthetically pleasing appearance, and in which the components of the window frame assembly include reversibly interlocking portions adapted to interconnect components of the assembly together. In this manner, the decorative window frame assembly can be securely, yet releasably held to the structure, while reducing the time required for assembly and without requiring the use of nails, threaded fasteners or other like fastening elements.
Accordingly, it is another object of the present invention to provide such a window frame assembly which can be secured to the structure in a secure fashion and yet which can be released and removed with the use of a simple hand tool such as a screw driver.

Garage door window frame and method of installation


An electron source having a cathode and a permanent magnet perforated by a plurality of channels extending between opposite poles thereof. The magnet generates, in each channel, a magnetic field which forms electrons received from the cathode into an electron beam for guidance towards a target. An electrode grid is disposed between the cathode and the magnet for controlling flow of electrons from the cathode into each channel. A magnetic field null region of each magnetic field is positioned at a location remote from the electrode grid. Because the null region is positioned remotely from the grid electrodes, flow of electrons can be improved without increasing electrode drive voltage.

1. Technical Field
The present invention relates to a magnetic matrix electron source and methods of manufacture thereof.
A magnetic matrix electron source of the present invention is particularly although not exclusively useful in display applications, especially flat panel display applications. Such applications include television receivers and visual display units for computers, especially although not exclusively portable computers, personal organizers, communications equipment, and the like. Flat panel display devices based on a magnetic matrix electron source of the present invention will hereinafter by referred to as Magnetic Matrix Displays.
2. Prior Art
Conventional flat panel displays, such as liquid crystal display panels, and field emission displays, are complicated to manufacture because they each involve a relatively high level of semiconductor fabrication, delicate materials, and high tolerances.

International Business Machines Corporation


Methods and apparatus related to using document feature(s) of a document that is responsive to a query, and optionally query feature(s) of the query, to determine a presentation characteristic for presenting a search result that corresponds to the document. In some implementations, measures associated with the document feature(s) and/or query feature(s) may be used to determine the presentation characteristic. The measures may be based on past interactions, by corresponding users, with other documents that share one or more of the document features with the document, where a plurality of the other documents are different from the document (and optionally each different from one another). In some implementations, the document and/or the other documents include, or are restricted to, documents that are access restricted.

Search engines provide information about various documents such as web pages, images, text documents, multimedia content, and/or electronic communications. For example, in response to receiving a search query, a search engine identifies one or more documents that are responsive to the query. The search engine ranks the documents based on the relevance of the documents to the query and/or based on other ranking signal(s), and provides corresponding search results in response to the search query. The search results may include aspects of and/or links to the documents and may be provided based on the rankings.


The present invention provides a recording medium. First data is recorded in the medium, in the form of a track consisting of a plurality of bits. Second data is recorded in the form of a plurality of bits that are displaced in the direction at right angles to the track. The content data representing the contents of the first data is recorded in the recording medium, too. The content data includes identification data that indicates whether the second data is recorded in the recording medium.

As optical discs, compact discs (hereinafter referred to as "CDs") are used in increasing numbers. Audio data is recorded in a CD, by generating blocks of audio data, generating error correction codes, performing EFM (Eight to Fourteen Modulation) on the data blocks, and effecting NRZI (Non Return to Zero Inverted) modulation on the EFM-modulated data blocks.
As the result of the EFM modulation, the audio data is recorded in the CD, in the form of pits and lands that are alternately repeated. The pits and the lands can have nine different lengths 3T to 11T, where T is the fundamental period of the channel clock signal. The pits formed in the CD have a length of 0.87 to 3.18 [μm], a width of about 0.5 [μm] and a depth of about 0.1 [μm]. The range of length, 0.87 to 3.18 [μm], corresponds to 3T to 11T.
The audio data recorded in the CD has been sampled at the frequency of 44.1 [kHz]. It is two-channel data that has been quantized in units of 16 bits. It is demanded that the audio data should represent high-quality sounds and should be multi-channel data. Additionally, the CD should be so designed that the existing CD players may reproduce data from them. Further, it is not desirable that only a short audio program can be recorded in one CD when the data presents high-quality sounds and is multi-channel data.
Moreover, it is now desired that different items of information or related items of information be reproduced from the same CD in various modes.

Optical recording medium having multiple reproduction modes


A process for the generation of energy and of a hydrogen-rich mixture (30), includes the following steps:. a) a partial oxidation of an incoming hydrocarbon gas mixture (15) is carried out using an oxidant mixture (16) which contains oxygen, so as to obtain as output from the unit a reaction gas (17) which contains hydrogen and CO; PA1 b) the reaction gas produced at the end of step a) is passed into a membrane separator (24) which generates, as its permeate output, a permeate gas mixture (25) enriched in the more permeable components of the reaction gas and, as its retentate output, a retentate gas mixture (26) enriched in the less permeable components of the reaction gas; PA1 c) the retentate gas mixture (26) is treated in an electricity generation unit (27); PA1 d) the permeate gas mixture (25) is separated in a preferential adsorption separator (29) so as to obtain, as unadsorbed product gas, the desired hydrogen-rich gas mixture (30).

Many processes have been reported in the literature, relating to the production of hydrogen and/or energy, on the basis of partial oxidation of hydrocarbon mixtures (such as coal, natural gas, naphtha and heavy fuel oil), and giving rise, depending on the reaction conditions (temperature, pressure and composition of the reactive gases), to a highly variable composition of the reaction gas produced. Reference will be made to the many articles published in the name of TEXACO, SHELL or WESTINGHOUSE.
The reaction gas produced as output from a partial oxidation unit usually contains several tens per cent of the H.sub.2 /CO mixture, but also nitrogen, CO.sub.2, argon, etc.
The available processes usually include, downstream of the partial oxidation unit, one or more reaction gas purification steps: removal of CO generally by catalytic reaction with steam, of all or part of its H.sub.2 S, of COS (carbonyl sulphide) and of NOx (purification steps well known to those skilled in the partial oxidation art).
Downstream of these purification steps, the reaction gas thus purified is usually sent to a preferential adsorption separator (for example of the PSA type) or else to a membrane-type separator, so as to produce, according to the required specification in each case, energy or a hydrogen stream or a stream of CO.
Among the oxidants most often cited in the literature regarding POX are air or air enriched in oxygen up to 35% or even more.
From this copious literature, mention may be made of the document EP-A-217,505 which describes the simultaneous generation of energy and of a mixture having at least 50% hydrogen, the mixture containing the hydrogen being produced as the "unadsorbed product" stream from a preferential adsorption separator, in which the reaction gas produced as output from a POX unit has been treated, the energy being moreover produced by sending the gas mixture adsorbed in the separator (rich in CO, CO.sub.2, N.sub.2, CH.sub.4, etc) into a unit for the generation of electricity by catalytic combustion followed by expansion in a gas turbine.
Since the objective of this document is to provide a mixture containing hydrogen used for the synthesis of ammonia, relatively low concentrations of argon are tolerated. The author however mentions that the gas generated by the adsorption separator contains non-negligible quantities of argon (which derives from the oxidant gas supply used), argon that the document declares is tolerated without any inconvenience.
Work successfully carried out by the Applicant in this field has confirmed that, in the case of such argon-containing oxygen supplies, this argon is largely found in the hydrogen-rich mixture produced by the process. However, although in many subsequent applications using such a hydrogen-rich mixture the argon presents no inconvenience, in other cases (such as hydrodesulphurization or hydrocracking processes), the argon lowers the partial pressure of the hydrogen in the gas mixtures used, giving rise to markedly inferior reactions.
Faced with this problem, it may be firstly envisaged to use very pure (typically 99.5%) oxygen, thus further increasing the operating costs of the unit.
Another technically achievable solution might consist in sizing a PSA preferential adsorption unit so as to stop the argon much better, but such sizing would then be not without consequences with regard to the cost of the plant and to its performance (reduction in the hydrogen extraction yield and increase in the quantity of low-value low-pressure adsorbed retentate gas).

Process for the production of hydrogen and of energy

L'Air Liquide, Societe Anonyme Pour L'Etude et L'Exploitation des Procedes Georges Claude


Surgical clips, and methods of use thereof, are provided for tissue approximation and attachment, and more particularly, for sealingly joining a graft vessel to a target vessel. The graft vessel has a free end and a graft vessel wall defining a graft lumen. The target vessel has a target vessel wall defining a target lumen and has an opening in the target vessel wall. The anastomosis clip includes a clip body having a distal extremity with a distal end and a proximal extremity with a proximal end. The distal end is configured to penetrate through the graft vessel wall near the free end and through the target vessel wall near the opening such that both the distal and proximal ends of the clip body are outside the graft and target vessels. At least a portion of the clip body is shapable so as to compress the graft vessel wall against the target vessel wall with the target vessel lumen in communication with the graft vessel lumen.

In coronary artery disease, one or more of the coronary arteries which supply oxygenated blood to the heart are partially or entirely blocked by a build-up of atherosclerotic plaque within the artery. This deprives the heart muscle of oxygen and nutrients, leading to myocardial infarction and even death.
Coronary artery bypass grafting remains the gold standard for the surgical treatment of severe coronary artery disease. In coronary artery bypass grafting, or CABG, a graft vessel is used to bypass a blockage in a coronary artery by connecting the distal end of the graft vessel to the coronary artery downstream of the blockage and connecting the proximal end of the graft vessel to a source of arterial blood upstream of the blockage. Various types of graft vessels may be used, including a saphenous vein taken from the patient's leg, a radial artery removed from the patient's forearm, or a prosthetic graft made of expanded polytetrafluoroethylene, Dacron, or other suitable material. Additionally, the left or right internal mammary arteries, which originate from the subclavian artery and reside on the top of the chest wall, may be resected at a distal location and left intact proximally, the free distal end then being connected to the diseased coronary artery downstream of the blockage. Similarly, the gastroepiploic artery, which originates from the gastroduodenal artery in the abdomen, may be resected at a distal location in the abdomen and passed into the thorax through a puncture in the diaphragm for attachment to the diseased coronary artery. Other types of graft vessels may also be used, as well as combinations of several different types of graft vessels in order to bypass multiple coronary blockages.
The surgical interconnection of two vascular structures, such as a graft vessel and a coronary artery, is a process known as anastomosis. In CABG, the anastomosis of a graft vessel to a coronary artery is particularly challenging. Several factors contribute to this challenge. First, the scale of the vessels is extremely small, the coronary arteries having a diameter on the order of about 1-5 mm, and the graft vessels having a diameter on the order of about 1-4 mm for an arterial graft such as a mammary artery, or about 4-8 mm for a vein graft. In addition, the completed anastomosis must not only provide a sealed connection and a patent blood flow path between the graft vessel and the coronary artery, but must further provide a connection which minimizes the exposure of the blood to foreign material or external vessel surfaces which can cause thrombosis at the anastomosis site. Moreover, recent studies suggests that the anastomosis site should not be dramatically different in compliance relative to either the coronary artery or the vascular graft, since such a "compliance mismatch" may also cause thrombus to form at the anastomosis.
Suturing is the technique of choice for coronary anastomosis in the vast majority of CABG cases today. The anastomosis is performed by creating a small opening, or arteriotomy, in the coronary artery, and passing a series of running stitches through the walls of the graft vessel and the coronary artery, respectively, around the perimeter of the arteriotomy so as to compress the end of the graft vessel against the side wall of the coronary artery. The surgeon has a great deal of flexibility in selecting the optimum location for each stitch, based on the shape, structure and condition of the two vessels. The suture needle may be placed initially through the graft vessel wall, and, before the two vessels are closely approximated, the needle then independently placed through the desired location in the target vessel wall. The suture is then tensioned to approximate the two vessels and create a tight, hemostatic seal. The sutured anastomosis thus offers a secure, sealed and patent connection between the two vessels, while having a substantial degree of compliance due to the flexible nature of the suture material.
A drawback of the sutured anastomosis is, however, the high degree of skill, dexterity, and acute visualization required. In addition, the completion of the anastomosis takes a significant amount of time, during which the patient is maintained under cardioplegic arrest and cardiopulmonary bypass. The period of cardioplegic arrest should generally be minimized in order to minimize damage to the heart muscle. Further, in recent years, some attempts have been made at reducing the invasiveness and trauma of CABG surgery by working through smaller incisions or "ports" between the ribs and using endoscopic surgical techniques. Performing microvascular anastomoses with conventional sutures is extremely difficulty when working through small ports, particularly if direct vision of the anastomosis site is not possible and reliance upon endoscopic visualization techniques is necessitated.
Various ideas have been proposed for simplifying and accelerating the process of coronary anastomosis using sutureless anastomosis devices. For example, in U.S. Pat. No. 4,350,160 to Kolesov et al., a device is disclosed for creating an end-to-end anastomosis by everting each vessel end over a split bushing and driving a plurality of staples through the everted vessel ends. For coronary anastomosis, this device requires that the coronary artery be severed downstream of the blockage and the downstream end dissected away from the surface of the heart in order to allow it to be connected end-to-end to the graft vessel. This adds an undesirable increase in time, difficulty and risk to the procedure. In addition, the staples in the Kolesov device are always positioned in a fixed pattern, allowing no flexibility in selecting the location in which each staple is to be driven through the vessels.
In U.S. Pat. No. 4,624,257 to Berggren et al., a device is disclosed for creating either end-to-end or end-to-side anastomoses. The device consists of a pair of rigid rings each having a central opening through which the end of the coronary or graft vessel may be drawn through and everted over the ring. A set of sharp pins extend outwardly from the face of each ring and pierce through the vessel wall to maintain the vessel in the everted configuration. The rings are then joined together to align the end of the graft vessel with the opening in the target vessel. While this device may be suitable for end-to-side anastomosis, eliminating the need to sever and isolate a free end of the coronary artery, the device requires that the side wall of the coronary artery be everted through the central opening of the ring, a maneuver which is likely to be extremely difficult in coronary anastomosis due to the structure and size of the coronary arteries. Moreover, the use of rigid rings that completely encircle the graft vessel and the arteriotomy creates a severe compliance mismatch at the anastomosis site which could lead to thrombosis.
An additional device which has been proposed for end-to-side anastomosis is seen in U.S. Pat. No. 5,234,447 to Kaster et al. This device consists of a rigid ring having a plurality of pointed legs extending from the ring axially in the distal direction and a plurality of angled legs extending axially from the ring in the proximal direction. The graft vessel is placed through the middle of the ring and the end is everted over the pointed legs, which puncture the vessel wall and retain it on the ring. The pointed legs are then bent outwardly, and the everted end of the graft vessel and the outwardly-oriented pointed legs are inserted through an arteriotomy in the target vessel so that the pointed legs engage the interior wall of the target vessel. The angled legs on the proximal end of the ring are then bent toward the target vessel to penetrate the outer wall thereof. While the Kaster device has a simple one-piece design and avoids the need to evert the wall of the target vessel over the device as proposed in Berggren, the device maintains a rigid ring structure which results in inadequate compliance at the anastomosis. In addition, the rigidity of Kaster's device leaves the surgeon little flexibility in selecting the optimum location where each leg of the device should be driven into the graft and target vessels, in contrast to the flexibility available when placing suture stitches.
U.S. Pat. No. 4,586,503 to Kirsch et al. discloses an alternative scheme for creating microvascular anastomoses. The Kirsch device consists of a plurality of individual clips each consisting of a pair of arcuate legs interconnected by a bridging section. The edges of the vascular tissue to be anastomosed are approximated and everted outwardly so that a clip can be placed over the tissue edges, and the clip is then crimped to permanently deform the legs in an inward position. The clip thereby retains the edges of the tissue together without puncturing the tissue. A plurality of clips are placed around the graft vessel in this manner to accomplish the anastomosis. The Kirsch device eliminates the compliance problems of rigid ring-type devices, and allows the surgeon the flexibility to select the optimum location for the placement of each clip. However, the Kirsch clips suffer from several disadvantages. For example, placement of the clips while maintaining eversion and approximation of the tissue edges is difficult and time-consuming. Typically, two pairs of forceps are needed to hold the tissue edges in approximation while a third hand applies the clip, in contrast to suturing, where only one tissue edge needs to be held at one time while the suture needle is driven through it. The Kirsch clips are especially awkward in endoscopic applications, where access, visualization, and maneuverability of instruments are limited. Moreover, in end-to-side anastomosis, the tissue edges along the arteriotomy must be everted outwardly and approximated with the everted end of the graft vessel, a maneuver which becomes increasingly difficult as the ends of the arteriotomy are approached. In addition, due to variation in vessel size and structure, variation in the crimping force applied, and other factors, the clips may not reliably maintain the anastomotic connection.
In view of the foregoing, devices and methods are needed which facilitate the performance of vascular anastomosis, especially coronary anastomosis, but which eliminate the various drawbacks of prior devices. The devices and methods should allow the surgeon to select the specific locations on the graft and target vessels where the device is to be applied, similar to selecting the location of each stitch in a sutured anastomosis. The devices and methods should be relatively simple to utilize without requiring an undue degree of skill and dexterity, even at the small scale of the coronary arteries, and even in endoscopic applications. The devices and methods should be useful for performing end-to-side, end-to-end and side-to-side anastomoses. Further, the devices and methods should produce an anastomosis which is reliably sealed and patent, with a degree of compliance comparable to sutured anastomosis.

Surgical clips and methods for tissue approximation


In a double-chuck mechanical pencil provided with an eraser, the torsional breakage of a lead gripped by a front lead chuck and a back lead chuck due to the turning of a lead tank caused when an eraser is used is prevented, and inconvenience to a lead supplying operation caused by the abrasion of the eraser is eliminated.

1. Field of the Invention
The present invention relates to a double-chuck mechanical pencil provided with a front chuck for gripping a lead, and a back chuck provided with a chuck ring loosely put thereon to project a lead by a fixed length and, more particularly, to a double-chuck mechanical pencil provided with an eraser support structure in its back portion.
2. Prior Art
There have been proposed various double-chuck mechanical pencils incorporating improvements to reduce waste leads. In the double-chuck mechanical pencil of this kind, if either the front or the back chuck is turned by some cause while a lead is gripped by both the front and the back chuck, the lead is twisted and broken. Fragments of the broken lead remaining in a space between the front and the back chuck obstruct a lead projecting operation, and a front portion and a back portion of the broken lead are dislocated relative to each other in projecting the broken lead to make the projection of the broken lead impossible.
If the user turns a push cap or an eraser holder connected through a lead tank to the back chuck inadvertently or the back chuck is turned together with the lead tank when an eraser is used, a lead gripped by both the front and the back chuck is twisted and broken.


An elliptical exercise machine includes a frame, an impedance unit, two linkage units and a stride-adjusting unit. The impedance unit includes a flywheel supported on the frame and two cranks connected to the flywheel. Each linkage unit includes a rocking element and a moving element. The rocking element includes an upper end and a lower end. The moving element includes a rear end and a front end connected to the lower end of the rocking element. The stride-adjusting unit includes a threaded rod and a carrier. The threaded rod is supported on the frame. The carrier is connected to the upper end of the rocking element and formed with a screw hole for receiving the threaded rod so that the threaded rod can rotate to move the carrier and the upper end of the rocking element to adjust a stride of the elliptical exercise machine.

1. Field of Invention
The present invention relates to an elliptical exercise machine and, more particularly, to an elliptical exercise machine capable of providing an adjustable stride.
2. Related Prior Art
There are various types of exercise machines to help users exercise various parts of their bodies. For example, there are treadmills and elliptical exercise machines. An elliptical exercise machines provides an elliptical trace of movement for a user.
An elliptical exercise machine includes a frame, two linkage units and an impedance unit. The frame includes a post supported on a base. The impedance unit is supported on the base and connected to the linkage units. For example, the impedance unit includes a belt wound on a flywheel. The linkage units are placed on two opposite sides of the frame. Each of the linkage units includes a rocking element, a moving element and a pedal. The rocking element includes an upper end connected to the post and a lower end connected to a front end of the moving element. The moving element includes a portion connected to a crank connected to the flywheel. A user sets his or her feet on the pedals of the linkage units and moves the feet along substantially elliptical paths. All users are limited to a common stride since the distance between two ends of each of the substantially elliptical paths is constant although tall users generally want long strides while short users like short strides.
Therefore, the present invention is intended to obviate or at least alleviate the problems encountered in prior art.


Enhanced resolution for a real-time clock is implemented, which includes a real-time clock configured to operate at a first time resolution, at least one processing unit configured to operate at a second time resolution, wherein the second time resolution has a higher frequency than the first time resolution, a memory for storing data at a location including data from the real-time clock and the at least one processing unit, an interrupt configured to load information into the memory at the location using the at least one processing unit, the interrupt further configured to operate at a frequency associated with the second time resolution, a timing service configured to read information from the memory at the location, the timing service configured to operate at the second time resolution, and a calibration module configured to re-calibrate the real-time clock.

It is common for an electronic device to be installed at a remote location with a network connection to a second device. The second device can gain access to, interact with, and/or control the electronic device. Typically, these electronic devices have a central processing unit (CPU or processor) for performing the processing needed to provide the desired functionality. Fundamental to CPUs is the utilization of a real-time clock for coordinating and scheduling the activities the CPU needs to perform to provide the required results. An electronic power meter is one example of an electronic device that is equipped with a CPU that keeps time based on a real-time clock circuit or chip.
It is also very common that an electronic device is installed at a remote location and expected to perform its functions for many years, if not decades. Technology rapidly improves, especially in the cloud and via connected and mobile devices. Yet many of the electronic devices in remote locations have limited functionality and/or perform very basic functions. This type of electronic device can perform its needed function for a long time despite having outdated hardware. The cost to replace these devices in favor of new hardware often outweighs the savings achieved by maximizing and enhancing the functionality of the existing electronic devices via downloading new firmware or software, for example. This is especially true when the hardware is rugged and still has a long existing useful life.
In electronic power meters, for example, it is common for an operator, utility, or other system to need a higher time resolution than the real-time clock chip can provide in an existing meter. It would be beneficial if the system were able to interact with the real-time clock as if the real-time clock had a higher resolution than it natively provides, rather than completely removing and replacing the meter.

Enhanced time resolution for real-time clocks


The processes for producing highly water absorptive resins of the present invention comprise the following steps: (A) suspending an aqueous solution of partially neutralized alkali metal acrylate and optionally partially neutralized acrylamido alkane sulfonate in a hydrocarbon solvent containing a surfactant having a HLB value of 3.apprxeq.6 or 8.apprxeq.12; (B) subjecting the mixture to inverse suspension polymerization in the presence of at least one water soluble radical polymerization initiator; (C) if necessary, separating the moisture from the produced polymer by azeotropic distillation to reduce the water content to about 15 to 55% by weight; (D) adding a crosslinking agent having two or more reactive groups such as epoxy groups, if desired, as a solution form to subject the surface of the polymer to crosslinking reaction; and optionally (E) subjecting to coagulation with the use of a coagulant in the presence of an inert solvent, whereafter drying the resultant coagulate to obtain the water absorptive resin.

1. Field of the Invention
The present invention relates to processes for producing highly water absorptive resins having excellent water absorbency and saline solution absorbency. More particularly, it relates to processes for producing highly water absorptive resins having a high water absorption rate and water absorptive capacity, and an excellent gel-strength.
2. Description of the Prior Art
Various water absorbing materials such as sponge, pulp, paper and the like, are well known in the art. Also various synthetic products made by graft polymerization of materials containing a hydrophilic group, such as --OH, --NH.sub.2, --COOH, and the like, have been used conventionally. However, such water absorbing materials, e.g. a sponge, a pulp, and a paper, are characterized with physical mechanisms for absorbing water so that such materials have defects in that the majority of the absorbed water can be easily squeezed out by the application of external pressure. In recent years, in order to solve these defects, synthetic water-absorptive products having particular physical and chemical characteristics have been developed. The majority of such synthetic products are crosslinked polyacrylic acid salts, polymethacrylic acid salts, crosslinked polyacrylic acid-methacrylic acid copolymer salts, crosslinked saponification products of starch-acrylonitrile graft copolymer, and cellulose and acrylate-grafted copolymer. Such grafted products are on the market as sanitary napkins, sanitary pads, and diapers in the sanitary field, water absorbing containers in the civil and gardening field, and anti-dewdrop agents in the construction field.
However, although saponificated products of starch-acrylonitrile graft copolymer have a relatively high deionized water-absorbency, the saline-solution thereof is poor. Also, long-term storage is impossible due to the main component being starch.
On the other hand, partially crosslinked polyacrylic acid salts have high water absorption rates and capacity in saline solution as well as in deionized water, and they can be stored for a long period of time. Particularly, commercially available alkali metal acrylates are used as a starting material to prepare a water absorptive resin in the present invention.
Various processes are known for polymerizing acrylic acid and alkali acrylate, including bulk polymerization, aqueous solution polymerization, spray polymerization, inverse emulsion polymerization, inverse suspension polymerization, and the like. With the exception of inverse emulsion polymerization and inverse suspension polymerization, it is difficult to remove the heat of polymerization, and the viscosity of the polymerization mixture becomes too high to carry out general polymer production. Moreover, according to these processes it is difficult to obtain particulate polymers.
An example of the inverse emulsion polymerization process is disclosed in U.S. Pat. No. 3,284,393. When, for example, acrylic acid is used as the starting material, the obtained polymer is insoluble in water and does not have such an absorbency that the polymer can be called a water absorptive resin even if it is neutralized with an alkali such as sodium hydroxide or the like.
As a process for producing an acrylic acid-alkali metal acrylate polymer having a water absorbency, the inverse suspension polymerization process is mentioned in Japanese Patent Publication No. 79-30710. According to this process, a water absorptive polymer is prepared through a stable reaction by the use of a sorbitan fatty acid ester having a HLB (Hydrophilic-Lipophilic Balance) value of 3.about.6. The resin thus obtained has a high deionized water absorbency corresponding to 400.about.500 times its own weight; however, the saline solution-absorbency of said water absorptive resin is as low as 35.about.50 times its own weight.
In U.S. Pat. No. 4,497,930, there is disclosed a method for producing a water absorbent polymer comprising the steps of subjecting acrylic acid and sodium acrylate to polymerization in the presence of a sorbitan fatty acid ester having a HLB value of 3.about.6 as a dispersing agent, and adding a crosslinking agent with stirring in methanol to crosslink the surface of the resulting polymer. However, a disadvantage is that the water absorptive resin prepared by this method is unsatisfactory in water absorptive capacity because the polymerization reaction is carried out at temperatures too low (70.degree.-75.degree. C.) to stabilize the reaction.
In general, a highly water absorptive resin requires good water absorption rate, water absorptive capacity and gel-strength. These characteristics exhibit mutually opposing correlations with each other; therefore, some characteristics are partially sacrificed in order to improve other characteristics.
The foregoing three properties, namely the water absorptive capacity, the water absorption rate and the gel-strength in the water absorbent resin, are influenced by many factors such as a polymer particle's size and shape, the kinds of crosslinking agent and dispersing agent used, CMC (Critical Micelle Concentration), polymerization temperature, and so on.
In the inverse emulsion polymerization and the inverse suspension polymerization W/O systems, it is known that the use of a surfactant having a HLB value of 3.about.6 produces a stable system. But according to these polymerization reactions, the resultant particles are too minute and have many hydrophobic groups in their surface, such that the particulate polymer is swollen too slowly when contacted with water. Consequently, the water absorption rate and the water absorptive capacity become deteriorated. To solve the foregoing problem, a surfactant having a HLB value of 8.about.12, which is known to be unstable in the inverse emulsion and suspension polymerization systems, may be used. However, another problem, reaction control, arises due to agglomeration.
On the other hand, U.S. Pat. No. 4,340,706 discloses a water absorbent resin suitable for usages which require stability in the fluid-absorbed state for long periods of time. However, even the resin obtained by this method is insufficient in its rate of water absorption due to a lack of surface-crosslinking. Furthermore, in cases where the resin is prepared at low temperatures (55.degree..about.60.degree. C.) using this method, undesired residual monomers are obtained in large quantities.
Representative methods for improving the water absorption rate include increasing the surface area of the resin (i.e. decreasing the apparent specific gravity), crosslinking the surface of the particulate polymer after polymerization, or adding inorganic materials. Among the foregoing methods, the method of adding inorganic materials such as silica is advantageous. The dispersing rate of particulate polymer is remarkably improved and agglomeration of polymer particles is prevented. However, there is a disadvantage in that it is difficult to obtain the desired water absorption rate due to a poor sedimentation rate of the particulate polymer. When using the method of crosslinking the surface of the particulate polymer to improve the water absorption rate, there are also disadvantages. Minute particles which are formed tend to blow off and to agglomerate together, making it difficult to obtain a satisfactory water absorption rate.

Processes for producing highly water absorptive resins


An air-bag is provided with a controllable vent, for example a tube, which is normally maintained in a closed condition by being retained by a clamp. The clamp is opened in response to a signal from a sensor. The clamp may be opened when it is desired for the air-bag to have a “soft” inflation, thus permitting a relatively high rate of flow of gas exiting from the air-bag.

1. Field of the Invention
The present invention relates to an air-bag arrangement, and more particularly relates to an air-bag arrangement intended to provide protection for an occupant of a vehicle in the event that an accident should occur.
2. Description of Related Art
It has been proposed to provide an air-bag which, in the event of an accident situation arising, becomes inflated to provide a protective "cushion" in front of or adjacent an occupant of a motor vehicle. Whilst initially it might be thought that a substantially air-tight air-bag would be preferred, to ensure that the air-bag remains inflated for a maximum period of time, it has been found that it is preferable to include at least one air-vent in an air-bag, since otherwise an occupant would simply rebound from the air-bag when hitting it. An air-bag provided with a vent hole provides an ideal "cushioning" effect, even though the air-bag will, of course, become deflated quite rapidly following deployment of the air-bag. However, air-bags are typically deployed, by appropriate sensors, at such a time that the air-bag is inflated when an occupant of a seat, to be protected by the air-bag, actually moves into contact with the air-bag.
It has now been found that ideally the internal pressure of the air-bag, or the "cushioning" effect provided by the air-bag, should be adjusted in dependence upon various parameters, such as, for example, the size of the seat occupant, the position of the seat occupant and whether the seat occupant is wearing a seat-belt or not. An unbelted seat occupant may require a rather "stiffer" air-bag than a belt seat occupant. Also, a larger occupant requires a "stiffer" air-bag than a smaller occupant. However, an occupant sitting close to the air-bag should be provided with a relatively "soft" air-bag if at all possible.
Attempts have been made to provide air-bags with these characteristics by sensing the relative parameter and by adjusting the amount of gas injected into the air-bag by means of the gas generator. Such arrangements are relatively complex and thus expensive.


A method and apparatus for communicating between two, or more, devices receiving a variable-length bit stream. The method and apparatus allocate an input buffer larger than any read size selected for the receiving unit and the reception stops when the input buffer is full.

1. Field of the Invention
This invention relates generally to communication protocols and more specifically to a communication protocol for communication between devices that do not recognize bit or character oriented protocols.
2. Background of the Invention
Some communication systems use bit and character oriented protocols which use a standard method for transmitting and receiving data. These protocols also use a standard method for recognizing the end of a receive frame. In other communication systems there are many devices that transmit or receive variable length bit streams. Some of these devices are unable to recognize bit or character oriented protocols. In such communication systems data is sent from a transmitting device in variable-length bit streams. These bit streams do not include parity, frame check sequence, or bit boundaries. At the receiving end, the amount of data to be received is unknown. There is no trailing character in the bit stream to denote the end of the stream. There is a maximum boundary of the data format being sent.
In a prior system, a sending device drops a control signal and the receiving device terminates a read on a change in the control signal. This method has the disadvantage that control signals are required to denote the termination of the received bit streams and some communication systems lack such control signals.

System for operating system software providing input buffer for receiving variable-length bit stream with a header containing synchronization data recognized by universal serial controller


Discloses is a process for preparation of a compound of formula 7, or a derivative thereof, wherein PG1 is an alcohol protecting group. Also, disclosed are intermediates and processes for their preparation. The compound of formula 7 can be useful in the preparation of halinchondrin analogs such as Eribulin.

Halinchondrin analogs have been disclosed as having anti-cancer and antimitotic activity (U.S. Pat. No. 6,214,865, incorporated herein by reference). In particular, Halichondrin B has been reported as a potent anticancer agent that was first isolated from the marine sponge Halichondria okadai (U.S. Pat. No. 6,214,865; WO 2005/118565 A1 and WO 2009/124237 A1, all incorporated herein by reference).

2,5-disubstituted (2S,5S)-3-methylene-tetrahydrofurans, such as the compound of formula 7a, can be an important building block for the synthesis of the halichondrin natural products and derivatives, as described in U.S. Pat. Nos. 6,214,865 and 5,436,238, and incorporated herein by reference.
wherein Piv is (CH3)3C—C(═O)—.
The synthesis of compounds, similar to the compound of formula 7a, has been described by Kishi (Pure Appl. Chem. 2003, 75, 1-17; J. Am. Chem. Soc. 2009, 131, 15642-15646; J. Am. Chem. Soc. 2009, 131, 15636-15641), Phillips (Angew. Chem., Int. Ed. 2009, 48, 2346) and Burke (Org. Lett. 2002, 4, 3411-3414, J. Org. Chem. 2003, 68, 1150-1153), all incorporated herein by reference. However, these methods can be undesirable for commercial manufacturing. For example, all these routes rely on asymmetric reactions that, despite their high degree of selectivity, can give rise to epimers, which are of particular concern in cases where the intended use of the molecule is in the manufacture of an active pharmaceutical ingredient. Furthermore, many of these asymmetric reactions employ chiral ligands that are not necessarily easily commercially available, and which can be a hindrance for large scale production.
There is a need in the art for a process for preparation of 3-((2S,5S)-4-methylene-5-(3-oxopropyl)tetrahydrofuran-2-yl)propanol (7a), and its analogs (7), that can be used in the preparation of halichondrin natural products, its derivatives and analogs, such as, for example and without limitation, eribulin, the compounds described in recent publication of S. Narayan and others (Bioorganic and Medicinal Chemistry letters, 2011, 1630-1633; Bioorganic and Medicinal Chemistry letters, 2011, 1634-1638, Bioorganic and Medicinal Chemistry letters, 2011, 1639-1643), and other eribulin analogs with modified side chains on position C32 of eribulin. In addition, there is a need in the art for a process for preparation of 3-((2S,5S)-4-methylene-5-(3-oxopropyl)tetrahydrofuran-2-yl)prop-1-yl pivaloate (7a), and its analogs (7), that can be prepared from commercially available starting material. Moreover, there is a need in the art for a process for the preparation of 3-((2S,5S)-4-methylene-5-(3-oxopropyl)tetrahydrofuran-2-yl)prop-1-yl pivaloate (7a), and its analogs (7), that can avoid the use of asymmetric reactions, including chiral ligands. In addition, there is a need in the art for a process for preparation of 3-((2S,5S)-4-methylene-5-(3-oxopropyl)tetrahydrofuran-2-yl)prop-1-yl pivaloate (7a), and its analogs (7), where the process is scalable and can lead to a product having high stereochemical purity.

Process for preparation of 3-((2S,5S)-4-methylene-5-(3-oxopropyl)tetrahydrofuran-2-yl)propanol derivatives and intermediates useful thereof


A method for coordinating control of radio resources for multicast/broadcast services in distributed radio resource management. The method includes communicating information between a plurality of units having radio resource management responsibilities. The communicated information is related to coordinating at least one multicast/broadcast service provided by the plurality of units.

1. Field of the Invention
This invention relates generally to communication systems, and, more particularly, to wireless communication systems.
2. Description of the Related Art
In the field of wireless telecommunications, such as cellular telephony, a typical system 100, as shown in FIG. 1, is a hierarchical architecture and includes a plurality of base stations 130 (e.g., Node Bs) distributed within an area to be serviced by the system. Various access terminals 120 (ATs, also known as User Equipment (UE), mobile devices, and the like) within the area may then access the system and, thus, other interconnected telecommunications systems, such as a publicly switched telephone system (PSTN) 160 and a Data network 125, via one or more of the base stations 130. Typically, an AT 120 maintains communications with the system 100 as it passes through an area by communicating with one and then another base station 130, as the AT 120 moves. The AT 120 may communicate with the closest base station 130, the base station 130 with the strongest signal, the base station 130 with a capacity sufficient to accept communications, etc. The base stations 130, in turn, communicate with a Radio Network Controller (RNC) 138, which communicates with a Packet Data Serving Node (PDSN) 164 in a core network 165. Each RNC 138 and PDSN 164 is capable of supporting a plurality of base stations 130. Thus, as an AT 120 moves and communicates with different base stations 130, it may also communicate with different RNCs 138 and PDSNs 164.
The wireless link between the ATs 120 and the Base Stations 120 is typically referred to as the radio link, and in systems such as the Universal Mobile Telephone System (UMTS), much of the coordination of the radio link is handled by the RNCs 138 in a relatively centralized manner. For example, hand-offs of the ATs 120 from one base station 130 to another is determined by the RNCs 138. Similarly, owing to their proximity to one another, the base stations 120 can generate signals that interfere with one another. In some applications, the RNCs 138 control the transmissions of the various base stations 130 to reduce or minimize this type of interference.
However, the industry intends for UMTS to evolve away from the use of RNCs 138 with a distributed Radio Resource Management (RRM) architecture. The complexity of hand-offs and interference mitigation increases in the distributed RRM architecture, as the RRM functions are located at different physical locations. Moreover, the conventional distributed RRM architecture may not permit coordination of multiple node-Bs during multicast/broadcast transmissions, e.g. transmissions according to Multimedia Broadcast Multicast Service (MBMS) Thus, conventional distributed RRM architectures may not achieve the well known advantages of macro diversity combining of signals from different node-Bs at each mobile unit that receives the multicast/broadcast transmission.

Method for coordinated control of radio resources for multicasting in a distributed wireless system


A synaptic coprocessor may include a memory configured to store a plurality of Very Long Data Words, each as a test Very Long Data Word (VLDW) having a length in the range of about one thousand bits to one million or more bits and containing encoded information that is distributed across the length of the VLDW. A processor generates search terms and a processing logic unit receives a test VLDW from the memory, receives a search term from the processor, and computes a Boolean inner product between the search term and the test VLDW read from memory indicative of the measure of similarity between the test VLDW and the search term. Optionally, buffers within logic circuits of processing pipelines may receive the test VLDWs.

Artificial intelligence applied to many computer applications has grown in recent years and placed demands on the computational power of normal processors. For example, processor speeds have almost reached a maximum at about 4 GHz, ending the gains that have been reached through increased clock speeds as transistor dimensions shrink based upon Moore's law. As semiconductor technology advances and gate lengths decrease, greater numbers of gates are placed on one chip, often more than 10 billion gates per chip. It is becoming increasingly difficult to place even greater numbers of gates on chips. One approach is to place more processors on each chip, but this requires partitioning the processing workload, synchronizing the tasks, and feeding the input and output to all processors.
Despite the growing limitations associated with Moore's law, computationally intensive artificial intelligence (AI) applications have exploded in capabilities in the last few years, and it is necessary to exceed the computing limitations of traditional Von Neumann style central processing units (CPU's). New hardware developments have been specifically designed for artificial intelligence applications to accelerate training and performance of neural networks and reduce power consumption. The traditional solution was to reduce the size of logic gates to fit more transistors. Shrinking logic gates below about 5 nanometers (nm), however, may cause the chip to malfunction because of quantum tunneling.
New artificial intelligence hardware includes processors that enable faster processing of these AI applications with enhanced machine learning, neural networks and computer vision. Some graphic processing units (GPU's) use massively parallel architecture with thousands of smaller, more efficient processing cores to handle multiple tasks simultaneously, instead of using a few cores optimized for sequential serial processing as in the more conventional central processing units available on the market. Other techniques for increasing process capabilities for AI include application-specific integrated circuits (ASIC), but these specialized hardware circuits suffer the drawback of implementing traditional Von Neumann architecture and floating point operations, even though there have been some improvements with a neural net architecture.
A field programmable gate array (FPGA), on the other hand, may enable greater customization after manufacturing using a hardware description language, and may include the application of neural networks to analyze large amounts of data. The use of programmable circuitry in a FPGA rather than customary software instructions enables complex neural nets to be configured and reconfigured seamlessly for deep data uses. These FPGA systems, however, have limited memory and slower clock rates.
Other possibilities to meet the increasing demands of artificial intelligence applications include quantum computers, which work significantly different than conventional computers. Instead of employing conventional "on" and "off" switches and bits depending on the electrical state, quantum computers use qubits, in which an individual bit can be in one of three states, i.e., on, off, or uniquely both on and off simultaneously. Instructions do not load sequentially, but may execute simultaneously, thus increasing speed dramatically. Advances in quantum computing are limited and it is difficult to access many items in a database at the same time and analyze different images or data points until further advancements are made in this technology area.
Although some advanced computer systems increase processing speed dramatically, these computer systems do not mimic the human mind, and instead use traditional floating point operations. Central processing units operate in a sequential manner, and even the more advanced graphic processing units operate via massive parallel processing. It is still linear processing, but the human mind is highly non-linear. The human brain has many billions of neurons and may each have up to 10,000 connections to other nerve cells, and externally and internally host hundreds of thousands of coordinated parallel processes that are mediated by millions of protein and nucleic acid molecular interactions. The complexity of the human brain is staggering. Many millions of neurons are employed at the same time with little power demand as compared to electronic circuits. Some of the more advanced chips may mimic the brain's architecture, but these use vastly greater amounts of power with a magnitude fewer computational connections. Even advanced neuromorphic chips that have recently been designed are limited in the number of artificial neurons that are used because of their design limitations and manufacturing tolerances.
Some very long instruction word computer architectures take advantage of instruction level parallelism, where a fixed number of operations are formatted as one large instruction in a massively parallel architecture. The processors may reduce hardware complexity, and a compiler may create each very long instruction word, but the design limitations associated with normal processors still applies.


A transparent conductive layered structure which has the functions of preventing electrostatic charging or shielding an electric field, and preventing reflection, the two-layered film of which has an excellent scratch strength, and with which a reduction in production cost is expected and a method of producing the same, and a transparent coat layer forming coating liquid used in the method of producing the same, and a display device to which the transparent conductive layered structure is applied, are provided. A transparent conductive layered structure of the present invention, comprises a transparent substrate and a transparent two-layered film being composed of a and a transparent coat layer being formed in succession on the transparent substrate, wherein the transparent conductive layer comprises, as its main components, conductive microparticles having a mean particle diameter of 1 to 100 nm and a binder matrix of silicon oxide, and wherein the transparent coat layer comprises, as its main component, a binder matrix of silicon oxide including one or more types of alkyl groups selected from long chain alkyl groups containing 7 to 30 carbon atoms.

1. Field of the Invention
The present invention relates to a transparent conductive layered structure comprising a transparent substrate and a transparent two-layered film being composed of a transparent conductive layer and a transparent coat layer being formed in succession on the transparent substrate, which is used in front panels, etc., of display devices such as Braun tubes (CRTs), plasma display panels (PDPs), vacuum fluorescent display (VFDs), liquid crystal displays (LCDs). The present invention particularly relates to a transparent conductive layered structure having the functions of preventing electrostatic charging or shielding an electric field, and preventing reflection, the two-layered film of which has an excellent scratch strength, and with which a reduction in production cost is expected and a method of producing the same, and a transparent coat layer forming coating liquid used in the method of producing the same, and a display device to which the transparent conductive layered structure is applied.
2. Description of the Related Art
Many OA devices have been introduced to the office as a result of office automation (OA) in recent years and an environment in which the entire day work must be done facing the display of OA device is no longer uncommon.
However, when a job is done next to a cathode ray tube (referred to as the above-described Braun tube: CRT) of a computer, etc., as an example of OA equipment, it must be easy to see the display screen in order to prevent visual fatigue, as well as prevent deposition of dust and electric shock induced by the electrostatic charge on the CRT screen, etc. Furthermore, in addition to these requirements, etc., there has recently been concern over the detrimental effects of low-frequency electromagnetic waves generated by CRTs on the human body and there is a demand for CRTs with which there is no leakage to the outside of such electromagnetic waves.
As measures for such prevention of electrostatic charging or prevention of leakage of electromagnetic waves (electric field shielding), there have been adopted conventionally a method of coating the front panel surface of a CRT, etc., with a transparent conductive layer, and other methods.
Additionally, it is desired that surface resistance of these transparent conductive layers be in the order of 107 to 1011 Ω/□ (ohm per square) for prevention of electrostatic charging, and be at least no more than 106 Ω/□ for prevention of leakage of electromagnetic waves, preferably no more than 5×103 Ω/□, and more preferably no more than 103 Ω/□.
Therefore, several suggestions have been made thus far for meeting these requirements, but of these, the method wherein a coating liquid for forming a transparent conductive layer prepared by dispersing conductive microparticles in a solvent is applied to the front glass of a CRT and dried, and a coating liquid for forming a transparent coat layer comprising as its main component an inorganic binder such as silica sol, and then baked at a temperature of the order of 200° C. is known as a method with which low cost and low surf ac resistance can be realized.
This method that uses a coating liquid for forming a transparent conductive layer is very simple when compared to other methods of forming transparent conductive layers, such as vacuum evaporation and sputtering, has a low production cost, and is a very useful method.
Moreover, for the above-mentioned transparent microparticles, there are used transparent conductive oxide microparticles such as tin antimony oxide (ATO) or indium tin oxide or metal microparticles, etc. For example, in the case of application of ATO, because surface resistance of the film that is obtained is in the order of 107 to 1010 Ω/□, the film is used for preventing electrostatic charging.
In addition, although a coating liquid for forming a transparent conductive layer employing indium tin oxide is used for shielding an electric field, surface resistance of the film that is obtained is in the order of 104 to 106 Ω/□, which is insufficient to block leakage of an electric field, therefore a corrective circuit for canceling the electric field is needed.
On the other hand, when compared to coating liquids that use ITO, a film with somewhat lower transmittance, but also low resistance of 102 to 103 Ω/□, is obtained with coating liquids for forming transparent conductive layers that use metal microparticles for the above-mentioned conductive microparticles so that shielding an electric field can be performed without use of the above-mentioned corrective circuit.
Moreover, the metal microparticles that are used in the above-mentioned coating liquid for forming the above-mentioned transparent conductive layer are limited to noble metals, such as sliver, gold, platinum, rhodium, palladium, etc. that rarely oxidize in air, as shown in Japanese Patent Applications Laid-Open No. H 8-77832 and Laid-Open No. H 9-55175. This is because if microparticles of a metal other than a noble metal, such as iron, nickel, cobalt, etc., are used, an oxide film is invariably formed on the surface of such metal microparticles in an air atmosphere and good conductivity cannot be obtained as a transparent conductive layer.
Moreover, on the other hand, in order to make the display screen easy to see, anti-glare treatment is performed on the face panel surface to prevent reflection on the screen. This antiglare treatment is performed by the method whereby fine irregularities are made in the surface in order to increase diffused reflection at the surface, but it cannot be said that this method is a very desirable method because when used, resolution decreases and picture quality drops.
Consequently, it is preferred that antiglare treatment be performed by the interference method whereby the refractive index and film thickness of the transparent film be controlled so that there is destructive interference of the incident light by the reflected light.
A two-layered film structure wherein optical film thickness of film with a high refractive index and film with a low refractive index has been set at ¼λ and ¼λ, or ½λ and ¼λ, respectively, is usually used in order to obtain this type of low-reflection effect of the Interference method, and film consisting of the above-mentioned indium tin oxide (ITO) microparticles is also used as this type of film with a high refractive index.
Furthermore, of the optical constant (n−ik, n: refractive index, i2=−1, k: extinction coefficient) of metals, the value of n is small, but the value of k is very large when compared to ITO and therefore, even if a transparent conductive layer consisting of metal microparticles is used, the same anti-reflection activity induced by interference of light as seen with ITO is obtained with the two-layered film structure.
Moreover, in recent years, in addition to the properties such as the above-mentioned good conductivity, low reflectance, etc., this type of transparent conductive layered structure is requested to have the property of improving the contrast of images by adjusting the transmittance to the predetermined range (40 to 75%) lower than 100% in order to make the display screen easier to see. In this case, the mixing of color pigment microparticles, etc., into the above-mentioned coating liquid for forming a transparent conductive layer also has been performed.
In addition to this, as treatment for water resistance, brine resistance or anti-smudge of these transparent conductive layers, several attempts to make the layers water-repellent have been carried out recently.
Such a transparent conductive layered structure having a transparent two-layered film being composed of a transparent conductive layer and a transparent coat layer is produced, as mentioned above, by applying a coating liquid for forming a transparent conductive layer on a transparent substrate, and drying, and applying a coating liquid for a transparent coat layer as its main components silica sol, etc., and then conducting a heat treatment at a temperature of the order of 200° C.
Moreover, because the above-mentioned transparent coat layer comprises as its main component silicon oxide, the layer is formed as a film of relatively high strength by heat treatment at a temperature of the order of 200° C.
However, depending on the producers or makers of CRTs, there are cases where the above-mentioned heat treatment temperature is performed only under the condition of the order of 160° C. because of the limitation of facility aspect, etc., so that the strength of some transparent coating films may be insufficient due to the low temperature heating.
Similarly, for a coating liquid for forming a transparent conductive layer using the above-mentioned noble metal microparticles, the coating strength of some transparent two-layered films that are obtained is insufficient. It is considered that this is because when compared to conductive oxide microparticles such as ITO, etc. noble metal microparticles are chemically inert, and thus the binding between noble metal microparticles and an inorganic binder matrix is not so strong, and therefore the coating strength of the transparent two-layered films decreases.

This patent is subject to a terminal disclaimer.

Transparent conductive layered structure and method of producing the same, and transparent coat layer forming coating liquid used in the method of producing the same, and display device to which transparent conductive layered structure is applied


The present invention describes an actuator in a microfluidic system for inducing an electroosmotic liquid movement in a microchannel.

Much research is currently put into developing electroosmotic and other micropumps for microfluidic systems (which is a sort of micro electromechanical systems (MEMS) or microsystem technology (MST)).
Microfluidics is an emerging technology which is expected to get vast implications in a number of technical fields. A microfluidic device typically consists of a number of microsensors or microanalyzers, connected to each other and the environment by microchannels. The liquid to be analyzed or delivered as well as reagents should preferably be pumped by means of microfabricated pumps. While the other components have already been commercially available for some time, the development of microactuators/-pumps is still at an early stage and several problems remains to be solved. Thus, the real breakthrough and commercialization of this technology is expected to come when improved actuators have been developed. It is an object of the present invention to provide actuators for microfluidic systems which are suited as micropumps or mixers with an improved flow through of fluid.
One class of known micropumps is the reciprocating pumps, which involves mechanical actuations. Usually, a membrane is actuated by piezoelectric, electrostatic or other forces. Common to them is the involvement of moving parts, which complicates fabrication and may reduce their useful life.
Field-induced flow pumps include electrohydrodynamic (EHD), magnetohydrodynamic (MHD) and electroosmotic (EO) pumps. One obvious advantage is the lack of movable parts. However, these pumps have a requirement for high voltages, with EO pumps being the most versatile.
Further, the EHD pumps are restricted to non-conducting liquids, ruling out all applications where a solution of significant ion concentration should be transported (e.g. body fluids). Also, high voltages are needed. PCT WO 02/07292 A2 describes an EHD micropump operating at 25 kV.
MHD pumps on the other hand are restricted to conducting solutions, omitting applications with very dilute solutions.
Electroosmotic (EO) micropumps is considered an especially promising technology for many applications, as it is relatively simple to fabricate, and good performance can be obtained for a wide range of concentrations. However, several technological challenges still remain to be solved. The main problems are i) electrode gas evolution, ii) electrochemical reactions, iii) stability and iv) need for large electric potentials. These challenges will be detailed below:
Electrode gas evolution: Relatively strong electric fields must be applied, and a direct current component is necessary. This results in gas evolution on the electrodes.
Electrochemical reactions: These reactions are responsible for the gas evolution and may also occur in other part of the system. In cooling applications, de-ionized water cold be used as liquid medium, resulting in the formation of H2 and O2 gas only. However, for "lab-on-a-chip"—applications, fluids could be altered due to reactions, which could influence or ruin the analysis or system operation. Also, substances harmful to the system could be produced, e.g. corrosive gases like Cl2 resulting from electrolysis of NaCl solutions. In addition, reaction products and concominant pH changes can also influence the pump surface potential, resulting in altered electro osmotic characteristics, e.g. reverse flow.
Stability: In addition to the influence of electrochemical reactions, establishment of pore concentration profiles along pore axis in a direct electric field may hamper the EO transport over time. Also, various phenomena like diffusiophoresis and osmosis might reduce the flow. Thus, DC electroosmosis usually degrades over time, ultimately zero flow is obtained, due to the side-effects described. These effects can be reduced by using a pulsating field, but as classical EO is linear in the field, the DC component must always be present, and thus the side effects also to some degree.
Large electric potentials (kV range) are usually required, demanding expensive and bulky (reducing portability) power-supplies. Also, this leads to danger in the case of leakage currents, especially for devices to be used close to the body.
PCT WO 02/070118 A2 discloses a microfabricated pump, where the problem of electrode gas evolution is met by separating the channel from the electrodes by a non-porous ion-conducting membrane. The gas bubbles are allowed to escape from the electrode chamber to the environment. Drawbacks include the need for an open structure, possible production of harmful reaction products and relatively complicated structure.
US 2003/0085024 A1 describes a cooling device with an EO micropump with separate chambers for catalytic gas recombination (platinum catalyst). This device is limited to pure or buffered water as the working fluid. As it is not guaranteed that the gas recombination is complete, gas is also allowed to escape the system through a membrane. Good pump performance was obtained, but without obtaining complete gas recombination. Obvious disadvantages of this system are the cost of catalyst, and size of recombiner. Also, the combiner was only designed to deal with the dissociation products of pure water, not e.g. Cl2 formed from NaCl solutions. A 2 kV electric potential difference was applied.
In U.S. Pat. No. 6,568,910 B1 an EO pump is described, for which the liquid is pumped from a first channel containing electrodes into and through a second channel where no electric field is present. Again, this solution is aimed at avoiding the electrode gas evolution to take place in the microchannel of primary interest.
In [J. G. Santiago, "electroosmotic flows in microchannels with finite inertial and pressure forces", Anal. Chem., 73: 2356-2365, 2001] is described a pump using a capillary containing a porous frit of 3.5 μm silica particle for reducing pore-size (and thus increasing pressure). A flow of 3.6 μl/min was achieved using 2 kV potential difference. Deionized water was used as the working fluid, but still gas evolution was observed at the electrodes. Pumps with channel diameter 0.5 and 0.7 mm were used, while the length of the porous frit was 5.4 cm.
Using an open glass channel of dimensions 1 mm (length), 0.9 mm (height) and 38 mm (width), an electroosmotic velocity degrading from 15 to 0.2 μl/min in two months was obtained [Chen, C. H., Zeng, S., Mikkelsen J. C. and Santiago, J. G. "Development of a Planar Electrokinetic Micropump", Department of Mechanical Engineering, Stanford University]. The potential difference was 1 kV. Again, deionized water was used as working fluid, but electrode reactions (gas evolution) were present.
Because of small channel size, the Reynolds number is low and the flow normally laminar. As a consequence, mixing mainly takes place by diffusion, which is in many cases efficient in micrometer dimensions. However, for large molecules (e.g. DNA), bacteria and cells, convection is the only way to achieve rapid mixing. Different methods have been tested for introducing chaotic flows in microchannels, but this is still considered a challenge.
The paper [Shishi, Q. and Haim H. Bau. "A Chaotic Electroosmotic Stirrer", Anal. Chem., 74(15):3616-3625, 2002] describes a solution where mixing was possible by varying the wall surface potential in time and along the channel length coordinate, which could be done by introducing field effect control in short adjacent channel sections, by means of several electrodes and a control unit. This system has the drawback of having a relatively complicated structure.
An electrokinetic instability micromixer was also produced by using a sinusoidally electric field above 100 V/mm [Oddy, M. H., Santiago, J. G. and Mikkelsen, J. C. Anal. Chem. 73, 5822-5832 (2001)].
An EO driven micropump for insulin delivery is described in [E. L. P. Uhlig, W. F. Graydon, and W. Zingg. "The Electro-Osmotic Actuation of implantable Insulin Micropumps", Journal of Biomedical Materials Research, 17:931-943, 1983]. The electrochemical cell (Ag|AgCl|NaCl| cation exchange membrane |NaCl|AgCl|Ag) was used for actuation, where the current was reversed every 10 minutes. The reversing was necessary in order not to run the reactions in one direction until termination, after which little or no current would flow. An electro-magnetically controlled valve was used to obtain uni-directional flow in a secondary channel despite the current reversals. This channel was in contact with a metal bellows containing the insulin, which could then be pumped into the body. This system has the drawback of being complicated, and involving moving parts.
Further prior art is described in US2003164296A1, U.S. Pat. No. 5,985,119, and in the following publications:
Dukhin S. S.: "Electrokinetic phenomena of the second kind and their applications" ADVANCES IN COLLOID AND INTERFACE SCIENCES vol. 35, 1991, Elsevier Science Publishers B. V. Amsterdam, pages 173-196, XP002976010.
Dukhin S. S.: et al: "Intensification of electrodialysis based on electroosmosis of the second kind" JOURNAL OF MEMBRANE SCIENCE vol. 79, 1993, Elsevier Science Publishers B. V. Amsterdam, pages 199-210, XP002974593.
Mishchuk N. A.: "Electro-osmosis of the second kind near the heterogeneous ion-exchange membrane" COLLOIDS AND SURFACES A: PHYSICOCHEMICAL AND ENGINEERING ASPECTS vol. 140, 1998, pages 75-89, XP002974594.
Mishchuk N. A. et al: "Electroosmosis of the second kind" COLLOIDS AND SURFACE A: PHYSICOCHEMICAL AND ENGINEERING ASPECTS vol. 95, 1995, Ukraine, pages 119-131, XP002976009.
It is clear that even if EO micropumps have several advantages, important problems are not satisfactory solved by the current state of the art. Generally, the electrode gas evolution problem is met by i) using special liquids (deionized water and possibly a buffer) which limits the field of applications greatly, or ii) by moving the electrodes away from the area of EO pumping, to some device where gas bubbles can escape. The latter requires even larger potentials as the potential difference is proportional to the electrode distance. It also makes the design more complicated, especially if the structure involves several pumps with respective electrode pairs.
It is an object of the present invention to develop new actuators for which the technological challenges are solved. Specifically, it is an object of the present invention to provide an actuator which can be driven with no DC signal using much lower potentials, and being less influenced by the system chemistry. In many cases, it will be possible to arrange the electrodes close to the pump, which brings the minimum voltage further significantly down, and is excellent for producing multi-pump systems. Further, it is an object to provide a solution with much higher flow velocities than can be obtained by prior art solutions. Further, it is an object to provide actuators which can be used for mixing liquids in microchannels, which is also a challenge in microfluidics. For most designs, the actuator in accordance with the present invention can operate reversibly, showing identical pumping characteristics in either direction.
It is an object of the invention to provide microchannels which are capable of transporting a fluid from the inlet of the channel to the outlet Compared to known prior art solutions based on traditional electroosmosis the microchannels according to the present invention provides an increased fluid flow, i.e. that the liquid is forced to flow through the microchannel with an increased flow rate. The net flow, i.e. the amount of liquid forced through the microchannel is increased. This improved flow is obtained by arranging conducting means with specific geometrical shapes in the microchannel. More precisely, a surface portion of said conducting means is curved, or inclined with respect to the electrical field applied to the microchannels.
The underlying theoretical concept for the invention is so called "electroosmosis of the second kind" (EO2) or "superfast electroosmosis". A number of conditions have to be fulfilled in order to obtain EO2, especially if directed transport shall be achieved.
Liquid transport by EO2 is 10-100 times faster than for classical electroosmosis (EO1) applying the same electric field strength E. Lowering the electrical field strength E reduces the problem with electrochemical reactions, and also reduces the dangers of possible leakage current, which is especially important for implantable devices, and devices to be used close to the body. In addition, the needs for high voltage generators are eliminated, reducing the system cost and size, while enhancing portablility.
Being non-linear in the electric field strength, EO2 also makes it possible to achieve directed liquid transport using an alternating electric field, with little or no direct field component. Thus, the stability problems mentioned above can be reduced or eliminated. In addition, electrode reactions (including electrode gas evolution) will also be reduced or eliminated in an alternating field, as the polarization current will be larger, and the faradayic current smaller for alternating fields.

Actuator in a microfluidic system for inducing electroosmotic liquid movement in a micro channel


An apparatus for sealing approximated edges of tissue with thermal energy includes a clamp having members which grasp and hold tissue. A transmissive material is supported by at least one of the members. The members pivot to pull the tissue edges in tight approximation against the transmissive material to form a seam. Thermal energy is then directed at the tissue through the transmissive material and at the seam with sufficient intensity and duration to heat the tissue to an adhesive proteinaceous substance to seal the seam. The approximated seam is held against the transmissive material with an appropriate pressure to avoid over inverted or over everted tissue approximation.

This invention relates to a method and apparatus for sealing incisions on skin or other organ surfaces by drawing and holding the edges of the incision in tight proximity to form a seam while directing thermal energy onto the seam to denature the protein substance therein.
Optical energy transformed to thermal energy has been used to convert biological tissue into a denatured proteinaceous substance for facilitating healing and wound closure. This healing technique is referred to generally as laser tissue welding. Examples of such laser tissue welding methods are described in U.S. Pat. No.'s 4,672,969, 4,854,320, 5,002,051, and 5,140,984. These methods deliver optical energy to tightly approximated tissue in the vicinity of a wound. This application of thermal energy results in the denaturation of tissue protein including collagen, with disruption of the cell walls which allows the intra- and intercellular fluids to mix. Additional heat further denatures this protein soup which binds together creating something akin to a "biological glue".
In many prior methods of optical energy wound closure, thermal energy is delivered through an optical fiber to the tissue being reconstructed. Typically, one end of the fiber is connected to a laser that supplies optical energy to the wound site. Another end of the fiber is typically spaced a predetermined distance from the tissue, the distance depending on the tissue type. A foot pedal or hand held device activates and deactivates the laser. The parameters such as intensity and duration of the optical energy are controlled so that substantially all of the tissue being heated is raised to a predetermined non-destructive temperature. The minimum predetermined temperature is one at which tissue is converted to a denatured proteinaceous substance. The maximum predetermined temperature is one at which water in the tissue boils.
Critical to tissue welding methods is the necessity to place edges of tissue being repaired in tight approximation. Placing the tissue edges in close or tight proximity allows the denatured tissue constituents to form an intercellular matrix resulting in tissue fusion. Certain skin tissue types require precision when applying the optical energy to seal the edges. A drawback to a current skin tissue welding procedures is that to ensure precision, the optical energy must be applied slowly and carefully thereby increasing the application time.
Another drawback to a laser tissue welding procedure is that when closing an incision, the laser tissue welding surgery can be unnecessarily tedious as the surgeon welds at successive points along the incision. This welding process is complicated because the distal end of the optical fiber that directs the energy for the welding must be placed a predetermined distance to the tissue being reconstructed or the area being reconstructed. If the distal end of the fiber is not at the predetermined distance from the area being sealed or reconstructed, the tissue temperature would be heated outside the aforementioned predetermined temperature range for proper tissue fusion.

Method and apparatus for simultaneously holding and sealing tissue


The invention concerns a process for the hydrogenation of aromatic compounds contained in feeds with an initial boiling point of more than 100.degree. C. and which contain at least 10% by weight of aromatic compounds. It consists of introducing chlorine in a concentration of 0.5-500 ppm by weight with respect to the feed at a temperature of between 200.degree. C. and 450.degree. C., a pressure in the range 1 MPa to 25 MPa, an HSV of between 0.1 h.sup.-1 and 10 h.sup.-1 and a volume ratio of hydrogen to feed of 100-2000. The catalyst used is a noble metal type and contains less than 1% of at least one halogen. Preferably, the catalyst is fluorinated or chlorinated.

Specifications concerning the concentration of aromatic compounds in gas oils will be coming into force in the future.
At the moment, desulphurizing units for this type of feed are not capable of satisfactorily hydrogenating aromatic compounds at the same time.
It is thus highly probable that in the future, new types of units will be developed which will not only carry out intensive desulphurization but will also carry out high efficiency hydrogenation of the aromatic compounds.
These new units may be constituted by two reaction zones. The first reaction zone (which may be a reactor) will reduce the concentration of sulphur to a low value. Then the second reaction zone will hydrogenate the aromatic compounds present in the effluents from the first zone. Catalysts based on noble metals are the best hydrogenation catalysts. Unfortunately, catalysts based on noble metals are usually extremely sensitive to the presence of sulphur.
Our research has led us to explore the possibility of adding chlorine to a feed which may optionally have been desulphurized to increase the hydrogenating activity of the catalyst. Chlorine injection may be continuous or otherwise depending on the desired level of activity.
U.S. Pat. No. 3,639,227 and U.S. Pat. No. 3,816,299 describe processes for the hydrogenation of aromatic compounds in the presence of chlorine.
U.S. Pat. No. 3,816,299 describes the addition of carbon tetrachloride to the hydrogenation zone in a concentration of 0.01-1% by volume (HCl equivalent) with respect to the total gaseous phase. The zone contains a catalyst based on a noble metal and operates between 93C and 538C at 1-300 atm. In the treated feeds, the aromatic compounds are essentially monocyclic and are thus mainly kerosines. Comparative examples III-VI demonstrate that process does not work at all well when chlorinated compounds such as HCl, C.sub.3 H.sub.7 Cl and CH.sub.2 Cl.sub.2 are used instead of CCl.sub.4.
U.S. Pat. No. 3,639,227 also shows that the addition of chlorine to a hydrogenation zone improves the reaction yield in the presence of a catalyst containing a noble metal and about 0.3% of chlorine but containing no fluorine. The quantities of chlorine added, in particular when using C.sub.3 H.sub.6 Cl.sub.2, are in the region of 0.6%. The feeds which can be treated are kerosines or spirits containing at most 0.5% of sulphur.

Process for the hydrogenation of aromatic compounds comprising chlorine injection, using catalysts based on a noble metal


The present invention relates to compounds having the structure (and pharmaceutically acceptable derivatives thereof)

Many natural products, usually bacterial metabolites, feature a macrolide fused to a monocyclic benzenoid matrix, bearing a resorcinol-like substitution pattern. Not infrequently, the resorcinol moiety carries additional functionality, resulting in higher levels of oxidation. Natural products in this family (cf. inter alia radicicol (Delmotte, P.; Delmotte-Plaquee, J. Nature 1953, 171, 344; incorporated herein by reference), LL-Z-1640s (McGahren, W. J. J. Org. Chem. 1978, 43, 2339–2343; which is incorporated herein by reference), monocillins (Ayer, W. A.; Lee, S. P.; Tsuneda, A.; Hiratsuka, Y. Can. J. Microb. 1980, 26, 766–773; incorporated herein by reference), nordinone (Ayer, W. A.; Pena-Rodriguez, L. Phytochemistry 1987, 26, 1353–1355; incorporated herein by reference) and zearelenone (Sugawara, F.; Kim, K. W.; Kobayashi, K.; Uzawa, J.; Yoshida, S.; Murofushi, N.; Takahashi, N.; Strobel, G. A. Phytochemistry 1992, 31, 1987–1990; incorporated herein by reference) possess potentially exploitable patterns of antitumor, antibiotic, and antimalarial activity.
Radicicol (Delmotte et al. Nature 1953, 171, 344; Ayer et al. Canad. J. Microbiol. 1980, 26, 766) (1) and monocillin I (Ayer et al. Canad. J. Microbiol. 1980, 26, 766) (2) are resorcylic macrolides which can both be isolated from Monocillium nordinii (Ayer et al. Canad. J. Microbiol. 1980, 26, 766) (FIG. 1). While the skeletal structure of radicicol was determined in 1964, (McCapra et al. Tetrahedron Lett. 1964, 869; Mirrington et al. Tetrahedron Lett. 1964, 365) its relative and absolute stereochemical configuration was not unambiguously established until 1987 (Cutler et al. Agric. Biol. Chem. 1987, 51, 3331). The structure of monocillin I was confirmed by its direct conversion into radicicol. Affirmation of these structures was achieved by their only total synthesis through the efforts of Lett and Lampilas (Lampilas et al. Tetrahedron Lett. 1992, 33, 773 and 777).
Both radicicol (1) and monocillin I (2) (see FIG. 1) exhibit a variety of antifungal and antibiotic properties not shared by other members of this class of natural products. Recently, the antitumor properties of radicicol have come into focus as its ability to suppress the transformed phenotype caused by various oncogenes such as src, ras, and raf has been linked to its tight binding (20 nM) and inhibition of the Hsp90 molecular chaperone (Roe et al. J. Med. Chem. 1999, 42, 260–266). This 'anti-chaperone' activity may stimulate depletion of oncogenic proteins, and could therefore be of clinical interest. Specifically, occupancy of the ATP binding pocket of Hsp90 is believed to lead to the degradation in the proteasome of a subset of proteins involved in signal transduction that require Hsp90 for conformational maturation (see, Schneider et al. Proc. Natl. Acad. Sci. USA 93: 14536–14541, 1996; Mimnaugh et al. J. Biol. Chem. 271: 22796–22801, 1996; Whitesell et al. Mol. Endocrinol. 10: 705–712, 1996). These proteins include the HER and insulin receptor families of tyrosine kinases, Raf-1 serine kinase and steroid receptors to name a few. Downregulation of any of these would be expected to have positive antiproliferative effects, so that Hsp90 is an attractive target for the development of antitumor drugs.
More recently, five new 14-membered resorcyclic macrolides, termed aigailomycins A–E, were isolated from the marine mangrove fungus Aigialus parvus BCC5311 (Isaka, M.; Suyarnsestakorn, C.; Tanticharoen, M.; Kongsaeree, P.; Thebtaranonth, Y. J. Org. Chem. 2002, 67, 1561–1566; incorporated herein by reference). Among the aigailomycins, aigailomycin D exhibits potent antimalarial activity (IC50: 6.6 μg/mL against P. falciparum) and antitumor activity (IC50: 3.0 μg/mL against KB cells) (Isaka, M.; Suyarnsestakorn, C.; Tanticharoen, M.; Kongsaeree, P.; Thebtaranonth, Y. J. Org. Chem. 2002, 67, 1561–1566; incorporated herein by reference).
The demonstrated ability of radicicol to bind to and inhibit the activity of Hsp90 has generated an interest in further exploring the biological and pharmacological activity of radicicol and analogues thereof. Significantly, to date, only one synthesis of radicicol itself has been recorded (Lampilas et al. Tetrahedron Lett. 1992, 33, 773 and 777). Other groups have accessed a variety of analogues from the natural product itself (see, U.S. Pat. No. 5,650,430; U.S. Pat. No. 5,731,343; U.S. Pat. No. 6,239,168; U.S. Pat. No. 5,977,165; and U.S. Pat. No. 5,597,846; each of which is incorporated herein by reference), but have been limited in the range of analogues that can be generated. Thus, there remains a need to develop a practical synthesis of radicicol and other resorcyclic macrolides to generate novel analogs and conjugates to explore novel biological and pharmacological activities, and to improve the stability and therapeutic efficacy of radicicol, monocillin, and aigialomycins in the treatment of cancer.

Abstract: wherein R0–R4, Z, X, A—B, D—E, G—J, and K—L are as defined herein, the synthesis thereof and the use of these compounds as therapeutic agents.

Sloan-Kettering Institute for Cancer Research