Diphenylpyrrolyfuran derivatives represented by the following formula (I): ##STR1## wherein R.sub.1 and R.sub.2 may be the same or different and independently represent a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, or a lower alkylsulfenyl group; m and n independently represent an integer of from 1 to 3; R.sub.3 represents a hydrogen atom or a lower alkyl group, R.sub.4 represents a hydrogen atom, a lower alkyl group, or a lower acyl group; and R.sub.5 represents a hydrogen atom, a lower alkyl group which may have one or more suitable substituents, a lower alkoxy- or an aryloxy-carbonyl group, an acyl group, or a sufonyl group, and pharmaceutically acceptable salts thereof are disclosed. The compounds disclosed are useful as anti-inflammatory agent, anti-allergic agents, anti-platelet agents and the like.

1. Field of the Invention
The present invention relates to novel diphenylpyrrolylfuran derivatives. More specifically, the present invention relates to novel diphenylpyrrolylfuran derivatives useful as anti-inflammatory agents, anti-allergic agents, anti-platelet agents and the like.
2. Related Art
Since early 1970's, various non-steroidal anti-inflammatory agents, representative examples of such agents include indomethacin and ibuprofen, have been developed. The mechanisms of action of these drugs are mainly based on their inhibitory activities on the generation of prostaglandins by cyclooxygenases. However, these drugs selected from the view point of the inhibitory potency on the generation of prostaglandins have problems that they cannot achieve complete cure of intractable allergic and chronic inflammatory diseases [Hoshi, Iyaku Journal (Medicine and Drug Journal), 26, p. 933-937, 1990].
In general, it has been known that certain chemical mediators other than prostaglandins participate in inflammatory reactions. As such chemical mediators, bradykinin, serotonin, and complement activated products (C.sub.5a) as well as leukotriene, interleukins and the like have been known [Nakamura, Gendai Kagaku (Chemistry Today), 217, p. 38-45, 1989, Tokyo Kagaku Dojin]. Furthermore, it has also been known that, as a result of the inflammatory reactions, active oxygens produced by wondered leukocytes may deteriorate tissue damage, and that lipid peroxides produced are strong pain-inducing substances [Yagi, Kasankashishitsu to Shikkan (Lipid peroxides and Diseases), p. 210-217 (1981), Igaku Shoin].
Accordingly, developments of drugs have been strongly desired which inhibit the generation and activities of various inflammatory mediators as well as prostaglandins together with active oxygens.
The object of the present invention is to provide novel compounds having the activities described above.


The current disclosure provides pharmaceutical compositions containing an oxidized phospholipid, such as 1-hexadecyl-2-(4′-carboxybutyl)-glycero-3-phosphocholine (VB-201) and a thermosoftening carrier, e.g., a poloxamer. The pharmaceutical compositions may further comprise an anti-adherent agent, such as talc and/or a thixotropic agent. The current disclosure further provides processes for preparing the pharmaceutical compositions. The disclosure further provides capsules containing the pharmaceutical compositions. Uses of such pharmaceutical compositions and capsules in treating inflammatory disorders are also disclosed.

The present invention, relates to the field of pharmacology and more particularly, but not exclusively, to novel oral dosage forms of oxidized phospholipids.
Oxidized phospholipids have been previously described as useful in the treatment of medical conditions such as, for example, cardiovascular diseases, cerebrovascular diseases and inflammatory diseases and disorders.
International Patent Application No. PCT/IL2004/000453 (Publication No. WO 04/106486), by the present assignee, describes oxidized lipids for prevention and treatment of inflammation associated with endogenous oxidized lipids. An exemplary such compound is described and known as CI-201 (1-hexadecyl-2-(4′-carboxybutyl)-glycero-3-phosphocholine), also referred to in the art as VB-201. VB-201 was found to be an orally active drug, useful in the treatment of inflammatory disorders such as atherosclerosis, psoriasis, multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease.
International Patent Application No. PCT/IL01/01080 (Publication No. WO 02/41827), by the present assignee, describes oxidized lipids for prevention and treatment of atherosclerosis and related diseases.
Additional background art includes International Patent Application Nos. PCT/IL05/000735 (Publication No. WO 06/006161), PCT/IL02/00005 (Publication No. WO 02/053092) and PCT/IL08/000,013 (Publication No. WO 08/084,472), all being also by the present assignee.
All of the above cited publications are incorporated by reference as if fully set forth herein.
Recently, and in view of the promising therapeutic effect of VB-201, clinical studies were conducted in order to evaluate the toxicity, efficacy and pharmacokinetic parameters of orally administered VB-201. The obtained results showed that daily dosages of 80 mg VB-201 per day or less are safe, well-tolerated, and effective at inhibiting inflammatory processes, that a substantial percentage of VB-201 is absorbed into the bloodstream, and that plasma concentrations of VB-201 are relatively stable when VB-201 is administered once per day, and are described in International Patent Application PCT/IL2011/000008, filed Jan. 5, 2011, which is incorporated by reference as if fully set forth herein.
In view of the potential therapeutic effects of oxidized phospholipids (e.g., VB-201), a need arises for industrially and pharmaceutically applicable formulations containing oxidized phospholipids, such as VB-201, as the active ingredient.

Formulations and dosage forms of oxidized phospholipids


A door assembly for a motor vehicle. The door assembly comprises a molded door panel having a first side and a second side. The first side of the door panel is adapted to face into a passenger compartment of the motor vehicle. The second side of the door panel supports a belt line reinforcement, a lock and catch assembly, and a window lift assembly. The door assembly is adapted for joining with a door exterior.

Automotive doors normally include sheet metal inner and outer door panels, an interior trim panel which faces into the passenger compartment, and various hardware situated between the panels. Conventionally, these components of the door have been assembled at the same time and place. To decrease the time and complexity of assembling the entire door, recent proposals have been made to construct some of the hardware as a unitary subassembly. This subassembly can then be joined with the remainder of the door at any given place and time.
U.S. Pat. No. 5,355,629 to Kimura et al., for example, shows a door for a vehicle that is assembled by joining three modules together to facilitate the assembly process. U.S. Pat. No. 4,648,208 to Baldamus et al. shows an automobile door with a unit carrier on which built-in units, especially a complete window winder with window pane, can be preassembled. U.S. Pat. No. 4,882,842 to Basson et al. shows a modular trim panel unit with the preassembly of the interior trim panel for the door including one or more basic mechanical and/or electrical components.
However, it has remained a goal to develop a design which decreases the time and complexity of the automotive door assembly process.


A method for determining the concentration of acid-gases in an amine-regeneration system, such as is typically found in a natural gas refining plant, having a device for measuring the pH of the system from which the concentration of the acid-gases complexed and the amine can be calculated using an empirically-derived relationship between acid-gas concentration and pH. The invention also includes a system for controlling amine regeneration based upon the above described determining method.

1. Technical Field of the Invention
The present invention relates to the operation and control of an amine-regeneration system, for instance, subsumed within a natural gas refinery plant. More specifically, the invention relates to a method for in situ monitoring of the concentration of acid gases, such as CO.sub.2 and H.sub.2 S, sorbed or complexed to the amine used to remove these acid-gases from natural gas. The method relies upon measuring the pH of the amine stream, whether rich or lean, from which acid-gas loading can be calculated.
2. Description of the Prior Art
Natural gas is a ubiquitous fuel having a variety of applications in both commercial and residential settings. Yet, before natural gas can be used for virtually any application, it must be refined. The most significant refining step is removal of waste or corrosive acid-gases, such as carbon dioxide (CO.sub.2), and hydrogen sulfide (H.sub.2 S). These gases are known in the industry as "acid-gases," because they lower the pH when dissolved in water. For example, hydrogen sulfide is highly toxic, even at trace levels, and therefore must be removed. Carbon dioxide reduces the heating value of natural gas, hence it must also be removed. The primary means by which acid-gases are removed from natural gas is by contact with a suitable base, which reacts with the acid(s) to form a salt. A preferred family of bases in the natural gas refining industry is a family of compounds known as alkanolamines. Alkanolamines are desirable because they react sufficiently well with the acid-gases, yet can be regenerated; that is, the acid-gases can be later removed in a separate step so that the same alkanolamine can be recycled through the system. Other parameters relevant to the selection of a compound for acid-gas removal from natural gas include: (1) loading (e.g., moles CO.sub.2 /moles reactant); (2) water solubility (the greater the solubility of the base, the more of it that can be used in the system; and (3) low corrosivity. Furthermore, an organic base, such as alkanolamine is preferred because, the organic portion of the amine has a greater affinity for the acid-gases (because of the greater polarity of the amine compared with the natural gas), hence the alkanolamine(s) adsorbs the acid-gases from the natural gas. Examples of typical alkanolamines used in the industry are monoethanol amine, diglycolamine, diethanolamine, diisopropanolamine, triethanolamine, and N-methyldiethanolamine. Finally, it should be noted that one recent trend in the industry is to select compounds which rather than "react" with the acid-gas, simply remove the acid-gases from the natural gas by relying upon the solvents' greater affinity for the acid-gases. Selexol and Rectisol are suitable exemplars of such physical solvents. "Mixed" solvents--i.e., solvents that rely both upon physical adsorption and chemical reaction to remove acid-gases--are also utilized.
Naturally, the capacity of a given quantity of amine to remove acid-gases from natural gas is limited. The quantity of acid-gas adsorbed onto a given quantity of amine is referred to as the "acid-gas loading," and represents the moles of acid-gas removed per mole of amine. In most systems currently practiced, the amine stream is continuously cycled through the system. Here, after loading, the amine must be regenerated--i.e., the acid-gases must be removed from amine (called "stripping"), so that the amine can be recirculated within the system. While the goal of the regeneration process is to remove completely the adsorbed acid-gases, the stripping process is incomplete, which means that the acid-gases are not completely removed from the amine. This, of course, reduces the efficiency of the amine (on a per-unit-of-amine basis) to remove acid-gases from the natural gas. Hence, in order to maximize the efficiency of the removal of acid-gases from the natural gas, the amine-regeneration process must be as effective as possible, i.e., it must return as much "lean" amine upstream where it contacts the natural gas, as possible. To accomplish this, the process variables that control acid-gas stripping from the amine stream must constantly be readjusted. Before this can be accomplished, the system operator must know the concentration of CO.sub.2 adsorbed by the amine (the "acid-gas loading") at various points in the system, particularly at the point at which the regenerated amine is returned upstream to react with the natural gas.
Most of the currently available methods for monitoring acid-gas loading are quite old--they involve traditional wet-chemistry techniques well known in the chemical art. Essentially, an aliquot of amine solution is obtained from the system. This aliquot is added to a solution of predetermined pH. This solution is then titrated until the pH returns to the predetermined pH. From the concentration and volume of the titrant needed to restore the pH, the concentrations of CO.sub.2 and H.sub.2 S, and their respective species, can be readily calculated.
This method is overwhelmed with difficulties. For one thing, it is expensive and time-consuming. A laboratory technician must collect the samples, and then perform the analyses in a laboratory. Besides the possibility of human error since the acid-gas loading must be determined manually (i.e., by titration), and besides the accumulation of hazardous wastes (e.g., potassium hydroxide and organic amines), which must be disposed of, there are other more significant reasons that these measurements may lack reliability. Measurements obtained by this way are static measurements, at best; they can be performed only periodically, or intermittently. This is highly problematic since a typical natural gas refining/amine-regeneration system is quite often not in equilibrium, due the constant addition of amine, water, etc. which causes "slug flow" in the system, or points of local disequilibria within the system. Hence what is needed is a method for the in situ monitoring of concentrations of acid gases, and which will allow continuous, real-time monitoring of acid-gas loading. Unfortunately, no such method exists to quickly and accurately measure dissolved gases in a dynamic system that would be suitable for use in a natural gas refining/amine-regeneration system. Dissolved gases are notoriously difficult to measure, particularly so in a system under pressure.
Hence the instant invention is directed towards such an in situ process for determining acid-gas loading by indirect measurement of another more easily determined solution parameter, which then acts as a proxy for acid-gas loading. Other systems are known in the art for determining some desired parameter by direct measurement of a different parameter. U.S. Pat. Nos. 5,208,164 and 5,162,084, issued to Cummings and Cummings et al., respectively, are directed to a process for determining the concentration of various anions (e.g., SCN.sup.-, Cl.sup.-, HCO.sub.2.sup.-) in an alkanolamine solution, by directly measuring electrical conductivity. Similarly, U.S. Pat. Nos. 5,196,345 and 4,273,146, issued to Cooper et al. and Johnson, respectively, measure pH and electrical conductivity to infer the concentration of acidic metal hydrides present in organic liquids, and the concentrations of various salts (e.g., NaCl), respectively. U.S. Pat. No. 4,323,092 issued to Zabel discloses a method to determine free chloride ion ("Cl.sup.- ") concentration by measuring total dissolved chlorine. U.S. Pat. Nos. 4,172,880 and 3,844,303, issued to Tzavos and Moon et al., respectively, disclose processes in which electrical conductivity is measured to infer total acidity and alkalinity, respectively. U.S. Pat. No. 4,277,343, issued to Paz discloses a method for determining alkalinity by measuring the partial pressure of CO.sub.2. U.S. Pat. No. 4,877,489, issued to Lloyd discloses a system for measuring electrical conductivity, and from these values the level of entrained bubbles is determined. Finally, U.S. Pat. No. 5,398,711, issued to Ardrey, Jr. discloses a general method for measuring various solution parameters such as conductivity or pH, and from those, inferring levels of the same or other solution components for the purpose of determining if a corrective response is needed.

System and method for determining acid-gas (CO.sub.2, H.sub.2 S) loadings in an alkanolamine system


The structures of this invention comprise a plurality of panels. Rod formations are associated with the panels along at least some edges thereof. Joining devices consisting of elongated frame members are provided with openings for removably receiving the rod formations with the associated panel edges. Connectors are utilized for receiving the respective ends of the frame members. By providing a plurality of openings in the connectors for receiving different rod ends, and by providing a plurality of such connectors, numerous temporary structural configurations can be achieved.

This invention relates to a temporary structure, that is, a structure which can be assembled and dismantled at will. Although many applications are possible, a contemplated use of the invention is for the amusement of children.
For many years, popular children's toys have included Erector sets, Tinker Toys, Lincoln Logs, and variations thereof which permitted children to assemble structures of various kinds. It is also well known that children enjoy larger scale structures that they can enter and play in, including tent-like and house-like structures.
Particularly in connection with such larger scale structures, it is highly desirable to achieve parts which are fairly easy to assemble but which, at the same time, represent something of a challenge to the skill and imagination of children.


A system for insulating a building comprising a first layer of rolled insulation disposed atop a longitudinally extending upper chord of a roof truss, a purlin or a girt of a wall. Discrete insulating spacer members are intermittently disposed atop the first insulation layer and along the longitudinally extending chord, purlin or girt. A three sided bridge with a plurality of tab elements overlaying and contiguous with the insulating spacer members. A second layer of rolled insulation disposed atop the bridge and panel clips secured with a fastener extending through each of the second layer of insulation, bridge, insulating spacer member, first layer of insulation and upper chord.

For decades insulation has been used in metal buildings to retard thermal transfer through the roof as well as the wall structures. Typical roof and wall insulation configurations use blanket insulation. The thermal resistance offered by the insulation is compromised when it is compressed or packed down. In conventional metal roof and wall insulation systems, when the roof structure is applied to the tops of the roof purlins, or the wall structure is applied to the gifts, the thick layer of blanket insulation is compressed, thus reducing the thermal resistance of the insulation system. In some areas of the conventional roof and wall systems, the compression of the insulation is so severe that a thermal short is created, thus substantially degrading the insulation properties of the insulation system.
The above references to the background art do not constitute an admission that the art forms part of the common general knowledge of a person of ordinary skill in the art. The above references are not intended to limit the application of insulating systems as disclosed herein.

This patent is subject to a terminal disclaimer.

System for enhancing the thermal resistance of roofs and walls of buildings


An apparatus and method for extending digital data transmission link distances provide a mechanism in which data is transmitted over relatively long distances using a repeater to provide data buffering and handle the flow control. The repeater function incorporates large virtual lane receiver buffers in its long distance ports. Enough virtual lanes are implemented so that service level to virtual lane mapping is not required, allowing the repeaters to be made invisible to Subnet Management.

In a System Area Network (SAN), such as an InfiniBand (IB) network, the hardware provides a message passing mechanism that can be used for Input/Output devices (I/O) and interprocess communications (IPC) between general computing nodes. Processes executing on devices access SAN message passing hardware by posting send/receive messages to send/receive work queues on a SAN channel adapter (CA). These processes also are referred to as 'consumers.'
The send/receive work queues (WQ) are assigned to a consumer as a queue pair (QP). The messages can be sent over five different transport types: Reliable Connected (RC), Reliable Datagram (RD), Unreliable Connected (UC), Unreliable Datagram (UD), and Raw Datagram (RawD). Consumers retrieve the results of these messages from a completion queue (CQ) through SAN send and receive work completion (WC) queues. The source channel adapter takes care of segmenting outbound messages and sending them to the destination. The destination channel adapter takes care of reassembling inbound messages and placing them in the memory space designated by the destination's consumer.
Two channel adapter types are present in nodes of the SAN fabric, a host channel adapter (HCA) and a target channel adapter (TCA). The host channel adapter is used by general purpose computing nodes to access the SAN fabric. Consumers use SAN verbs to access host channel adapter functions. The software that interprets verbs and directly accesses the channel adapter is known as the channel interface (CI).
Target channel adapters (TCA) are used by nodes that are the subject of messages sent from host channel adapters. The target channel adapters serve a similar function as that of the host channel adapters in providing the target node an access point to the SAN fabric.
Channel adapters may be either directly connected together or can be connected through the SAN fabric. The SAN fabric comprises one or more switches and/or one or more routers. In any case, the links between the channel adapter ports, switch ports, and router ports are point to point and have separate conductors in each direction. Each of the two ports connected by a link has multiple virtual lanes (VL). Virtual lanes provide a mechanism for creating multiple virtual links on a single physical link. Associated with each virtual lane is a virtual lane buffer which is used to control the flow of packets. The flow control is credit based which means that the transmitter sends packets only if there is sufficient empty space in the receiving virtual lane buffer.
Some of the virtual lane buffer space at the receiver accommodates the round trip delay on the link. As links get longer, the round trip delay increases and larger virtual lane buffers are required to keep the link going at full speed. With a given size of virtual lane receiver buffers, at some distance the round trip link delay is enough that the cerdits do not arrive at the transmitter quickly enough to keep the link going at full speed.
Implementations of channel adapters, switches, and routers limit the virtual lane buffering to the amount anticipated by the configuration, and most configurations limit the links to less than 300 meters. What is needed is a way to extend links to many kilometers while maintaining the full link speed without adding large virtual lane buffers to every channel adapter, switch, and router port. By introducing a repeater that has large virtual link buffers, very long distances can be achieved. At some point, the format of the flow control packets must be expanded to accommodate the larger buffers. The repeater may or may not be visible to the various layers of link management software and firmware, and making the repeater invisible requires further changes to the flow control process.
The repeater function could either be incorporated into switch or router ports or it could be a stand alone device in which case it looks like a two port switch. Additionally, the repeater function could be constructed to be transparent to management software and firmware.

Long distance repeater for digital information

International Business Machines Corporation


A method of calibrating a non-invasive blood glucose measurement instrument to a diabetic test subject employs targeted glycemic profiles in anti-correlated pairs. During calibration, reference blood glucose determinations are made using conventional invasive sampling methods. Concurrently, noninvasive spectral measurements are made using the noninvasive glucose monitor. Through controlled oral ingestion by the subject of calculated amounts of carbohydrate, the subject""s blood glucose level is manipulated to mimic the patterns of the targeted profiles. During a first visit, a first profile of a pair is induced; during a second visit the inverse of the first profile is induced. The targeted profiles produce reference blood glucose values in which correlation to sampling factors is reduced or eliminated, thus the resulting calibration is correlated to glucose, and not to other analytes, sampling factors or environmental factors. A formula is provided for calculating the required amount of carbohydrate to ingest to induce a targeted glycemic profile in a test subject.

1. Field of the Invention
The invention relates to non-invasive measurement of blood analyte levels. More particularly the invention relates to a process for calibrating a NIR spectrometer to a test subject using targeted glycemic profiles to obtain a wide range of reference blood glucose values, thereby increasing the robustness of the calibration and minimizing the possibility that the calibration is correlated to variables other than glucose.
2. Description of Related Art
NIR (near-IR) spectroscopy has long been studied for use in measurement of blood analytes, particularly glucose. The degree of physiologic and anatomical variation encountered in the general population has rendered it exceedingly difficult to develop an instrument that can be used to make blood glucose measurements on any subject. However, calibration of an instrument to a single individual is possible, and it produces measurements with sufficient accuracy to make the instrument clinically valuable. In general, the calibration process involves acquiring invasive glucose samples for reference values and concurrently making noninvasive spectral measurements. After the reference values and spectral data have been divided into a multivariate calibration set and a test set, used to insure accuracy of the calibration, a mathematical algorithm is developed that makes a blood glucose prediction from a new spectral sample.
It is desirable that the spectra making up the calibration set and test set, and subsequent sample spectra, be as free of noise from sampling factors as possible. For example, P. Cooper and T. Barker, Individual calibration of blood glucose for supporting noninvasive self-monitoring blood glucose (sic), PCT Application Ser. No. WO98/37805 (Feb. 26, 1997) teach a procedure for calibrating a noninvasive glucose monitor to an individual for self-monitoring of blood glucose levels. Spectroscopic samples are gathered at the subject""s skin surface using a noninvasive glucose monitor. During sampling, the skin surface is repeatedly moved relative to the sampling probe, so that several samples are gathered, each from a slightly different measurement site. Then, a mean spectrum is calculated from the samples taken at the various sites. Thus, the influence on the spectral measurement of skin variability is minimized. At the same time, the subject""s blood glucose level is measured using an invasive blood glucose-monitoring instrument. During the data-gathering phase of the calibration procedure, a glucose excursion is induced. Subsequently, blood sugar level is restored to basal level through the administration of exogenous insulin.
Moreover, it is essential that the reference glucose values do not correlate to any other sampling factor; for example skin temperature, skin humidity, room temperature, time, or other blood analytes. Cooper, et al. decorrelate to the various sampling factors by selecting a small fraction of up to sixty days worth of data with correlation constraints. While the teachings of Cooper, et al. recognize the importance of minimizing noise in the spectral data from various sampling factors, and provide strategies for such control, they do not address the need for an efficient calibration regimen, that can be accomplished in a short period of time.
Glucose excursions are often induced through the intravenous administration of dextrose, a disaccharide composed of two glucose subunits, during procedures commonly known as euglycemic insulin clamp techniques. Over the course of a procedure of this type, exogenous insulin may be infused at a rate that maintains a constant plasma insulin level above a fasting level. The glucose infusion is delivered via an indwelling catheter at a rate based on plasma glucose measurements done at five-minute intervals. When the plasma glucose level falls below basal level, the glucose infusion rate is increased to return plasma to basal levels. Conversely, glucose infusion is decreased or the insulin infusion increased when plasma glucose exceeds basal levels. The total amount of glucose infused over time, or the M value, comprises an index of insulin action on glucose metabolism. See Consensus development conference on insulin resistance, Diabetes Care, vol. 21 (2) p. 310 (1998). A typical profile resulting from this procedure would resemble a straight line, but a stepped increase or decrease in blood glucose may also be obtained. See Preservation of physiological responses to hypoglycemia two days after antecedent hypoglycemia in patients with IDDM, Diabetes Care, vol. 20 (8) p. 1293 (1997). Although euglycemic clamp studies are effective for quantifying the amount of insulin required to achieve a particular glycemic pattern, they suffer the disadvantage of being highly impractical in clinical settings. Additionally, they entail a significant amount of risk to the patient, and they generally meet with poor patient acceptance.
There exists, therefore, a need in the art for an efficient, low-risk method of calibrating a noninvasive glucose monitor to an individual patient that minimizes or eliminates correlation of reference glucose data to sampling factors such as skin temperature, skin humidity, room temperature, time, or other blood analytes. It would be advantageous to provide targeted, information rich, glycemic profiles for use in calibrating the noninvasive glucose monitor to individual subjects. It would be further advantageous to provide such glycemic profiles in pairs, in which one of the pair is anti-correlated to the other, so that the anti-correlated profiles are mirror images of each other. It would be a great advantage to provide a method of calibrating a noninvasive glucose monitor to a subject in which the subject""s blood glucose level is dynamically manipulated through the controlled oral ingestion of calculated amounts of carbohydrate in such a manner as to reproduce the patterns of the anti-correlated profiles; during which time, noninvasive spectral measurements and determinations of blood glucose level would be made at regular intervals, thus degrading ancillary correlations to glucose and providing uncorrelated reference values for the calibration. Furthermore, it would be useful to provide a formula for reliably calculating the required amount of carbohydrate to produce a targeted glycemic profile in a test subject.
The invention provides a low-risk method of calibrating a noninvasive glucose monitor to an individual subject that minimizes or eliminates correlation of reference glucose data to sampling factors such as skin temperature, skin humidity, room temperature, time, or other blood analytes. Anti-correlated pairs of targeted glycemic profiles are provided, in which one profile of the pair is the inverse of the other. A formula is provided for calculating the amount of carbohydrate a subject must ingest orally in order to produce a glucose excursion that reproduces that of one of the target profiles. Advantageously, the formula employs a numerical index of a subject""s sensitivity to carbohydrate challenges. Rapid-acting insulin is administered to lower blood glucose levels at a rate that duplicates that of a target profile. On successive calibration visits, first one profile of a pair and then the inverse profile are produced in a subject. Throughout the course of a visit, noninvasive spectral measurements are made at predetermined intervals. Concurrently, blood glucose levels are measured with a conventional, invasive blood glucose monitor. After the reference values and spectral data have been divided into a multivariate calibration set and a test set, used to insure accuracy of the calibration, a mathematical algorithm is developed that makes a blood glucose prediction from a new spectral sample. Thus, a calibration is provided that avoids correlating glucose to sampling factors.
In a preferred embodiment of the invention, anti-correlated target profiles are provided that include a single glucose excursion within a predetermined time period. In a second, equally preferred embodiment of the invention, each target profile includes multiple glucose excursions within a predetermined time period.
In addition, the calibration visits provide a valuable educational experience for diabetic subjects, providing them with a greater awareness of the impact of carbohydrate on blood glucose levels. Furthermore, since the invented formula reliably calculates the amount of carbohydrate required to produce a targeted response in a subject""s blood sugar level, it serves as an important tool for dietary management of various disease conditions, such as diabetes and hypoglycemia.

Use of targeted glycemic profiles in the calibration of a noninvasive blood glucose monitor


An improved positive control non-return valve assembly which is mounted on the front end of a helical plasticating screw of an injection molding machine. The valve assembly comprises a thread retainer with means for attachment to the plasticating screw. The valve assembly also comprises a distribution chamber that has an annular shaped flow gap and a cylindrical passageway that leads to a plurality of discharge ports. The non-return valve assembly forms a seal, builds pressure, and displaces molten plastic fluid from the distribution chamber through a discharge chamber passageway, and into a mold.

The invention relates to the injection molding process, blow molding process or the like and in particular to a positive control non-return valve that controls the flow of molten plastic fluids. More specifically, the invention relates to an improved non-return valve assembly that allows the proper flow through said valve in one direction and positively stops the reverse flow of material therethrough.
The manufacturing process of injection molding is a primary form of manufacturing of plastic products in the world today. The demands of high molded part tolerances, dimensional stability, and shot-to-shot repeatability are increasing and better controls and mechanical components of the injection machines are required to meet the demands. A major component that contributes to this process of improvement is the plasticating unit and specifically, the non-return valve which is one of the components of the assembly. The non-return valve controls the volume of molten plastic material that is injected into the mold. Any imperfection in the operation of this component is reflected in the molded part. Imperfect molded parts cost the industry billions of dollars per year. An improvement in the non-return valve is needed to eliminate imperfect molded parts.
Injection Molding machines of the type in which the invention pertains to generally comprises an elongated helical plasticating screw which rotates and recripicates axially in a cylindrical bore of an elongated heated barrel for moving heated plastic material along the helical flight channels of the screw, from an inlet port to a discharge port where it is injected from a distribution chamber, through a nozzle and into a mold. The flow of the molten plastic material into the distribution chamber for subsequent discharge through the nozzle is controlled by the non-return valve.
A review of the prior art illustrates two primary methods/designs for controlling this process. The first is a sliding ring non-return valve which is illustrated in FIGS. 2A and 2B. The second is the ball check non-return valve which is illustrated in FIG. 2C. There of course are various alterations that change the performance slightly such as U.S. Pat. No. 5,151,282 to Dray, and my own U.S. Pat. No. 5,164,207, but none embody the changes necessary to correct the problems that plague the device as well as this invention does.
With the sliding ring design, FIG. 2A, U.S. Pat. No. 4,105,147 (1977), U.S. Pat. No. 4,643,665 (1985), U.S. Pat. No. 5,112,213 (1991), U.S. Pat. No. 4,850,851 (1989), U.S. Pat. No. 4,681,528 (1987) as examples, the sliding ring 88, becomes the shutoff mechanism which when the helical screw 10, moves foreword to displace plastic into the mold 42, engages with and forms a seal with the rear seat 92. The ring, hereby referred to as the shutoff mechanism, is free to float and is not connected to the helical screw or fluted retainer 90. This shutoff mechanism forms a fit within close proximity to barrel 12, to form a gap 48. Having a free floating unattached shutoff mechanism that is not connected to and does not rotate with either the helical screw or retainer and that is the component that forms the gap, is desirable for precise valve operation.
With the ball check valve design FIG. 2B, U.S. Pat. No. 5,097,864 (1992), the ball 98, becomes the shutoff mechanism upon screw forward movement, forming a seal with seat 102, thereby not allowing molten plastic back flow. Although this ball shutoff mechanism is free floating, it does not comprise the gap 48. The body 94, which is in close proximity to the barrel wall, rotates with the screw and acts as a bearing surface, creating frictional heat and causing adhesive wear problems between the outside diameter of the valve and the inside diameter of the barrel. This frictional heat and potential wear problem is undesirable. Even the Dray design and my own patent xe2x80x9cThe Auto-shutxe2x80x9d valve rotate with the screw.
Common problems associated with non-return valves of this type are; a) the passage ways allowed for material flow is restricted, not allowing for ample area for which to pass which reduces the throughput, slowing down the injection molding cycle. Also, a mechanical shearing action is exerted on the material which creates frictional heat for the material, sometimes exceeding it""s capacity. b) The sealing surfaces in either the ring type, ball type or Auto-shut design can become exposed to unmelted or partially melted polymeric material, inhibiting a good seal, which allows for material migration back through the valve. This lost volume of material will cause an imperfect product to be formed in the mold. Imperfect products require significant inspection costs for the manufacturer. c) The retaining areas that are designed to govern the forward movement of the shutoff mechanism during screw rotate, are forced against each other with a combination of hydraulic pressure and high rotational speeds causing them to wear adhesively. As wear occurs, the functionality of the valve begins to diminish, creating more imperfect products. d) The inability of the non-return valve and specifically, the shutoff mechanism to shutoff completely over a range of viscosity""s that is normally seen in a day-to-day operation of an injection molding plant. It is not uncommon for a injection molder to process a multitude of polymers each day on the same machine requiring a valve that can operate efficiently over this wide range of viscosity""s. It is our opinion that the major cause for valve shutoff failure is the differential of surface area of the shutoff mechanism from the proximal end to the distal end. The greater the differential in the positive direction, the greater the closing force, which is directly related to molded part quality. A lack of significant differential exists on most valves today, making them in-effective to operate with a range of viscosity""s. When this occurs, a change of components is necessary or a change in the entire assembly is necessary which creates downtime and labor costs.
Accordingly, several objects and advantages of the invention are listed herein including but not excluding:
a) to provide a non-return valve that uses mathematical and Theological analysis to calculate not only cross sectional area but polymeric shear rates when designing the stroke of the body and volumetric passageways through the valve. During the screw recovery phase of the injection molding cycle the molten plastic fluid is pumped along the flight channels until it engages the proximal end of the body, urging it forward and providing an annular passageway for the fluid to flow. The annular passageway leads to a cylindrical geometry that leads to a conical portion that leads to a plurality of cylindrical ports that leads through the valve exiting to the discharge chamber. Generous radii are provided along with smooth passageways so as not to induce shear concentration points. The design lends itself to ease of manufacturing;
b) to provide a non-return valve that through it""s design offers a significant mechanical advantage during the most critical shutoff phase of the injection molding cycle. By virtue of the inventions significant frontal area specifically the differential between the frontal area and the rearward area of the shutoff mechanism, the large mass and increase in the length of engagement, which all contribute to the valves closing force, the performance is significantly improved over the industry standard components. This significant increase in the closing force equates to energy that is used to finish melting the partially melted polymer and assure more consistent shutoff performance,
c) to provide a non-return valve that has a improved design of the retaining members that govern the forward movement of the shutoff mechanism. The invention""s design incorporates a large spherical seat area constructed of high wear resistant materials. The spherical geometry assures that there will be uniform and equal contact between the two mating components even though the axis of the body does not remain the same as the axis of the spherical retainer when the molten plastic fluid is being pumped through the valve. Perpendicular surfaces or conical surfaces which are commonly used do not assure even surface contact and hence lead to high stress concentration areas and premature wearing of the components. In addition, the significant frontal area of the shutoff mechanism that is forward of the discharge plane acts as a counter force which lessens the total force being applied between the two mating sealing areas, thereby extending the wear life. This fact is believed to be unique amongst the industry standard designs;
d) to provide a non-return valve whose member that is attached to, and rotates with, the plasticating screw, has a geometry that offers little torsional resistance to the molten plastic fluid and occasional solid phase polymeric material so as not to have the tendency to break or fail torsionally. The inventions rotating attached member, 70,80, is cylindrical in nature with a generally inscribed polygon installed for ease of removal. The polygon that is close in proximity to the diameter of the shaft is significantly less likely to resist the flow of the polymeric material than the industry standard non-return valves, thus transmitting torque to the shaft that ultimately leads to torsional failure;
e) to provide a non-return valve that has a significant mechanical advantage during the shutoff or closing phase of the injection molding cycle that allows it to operate over a wider range of viscosity""s, delivering shutoff performance that is unmatched with the known existing technology. By virtue of the inventions significant frontal area, specifically the differential between the frontal area and the rearward area of the shutoff mechanism, the large mass and increase in the length of engagement, which all contribute to the valves closing force, the performance is significantly improved over the industry standard components. The magnitude of difference in closing force is enough to supply shutoff performance over the wide range of viscosity""s that are encountered in the injection molding process, thereby eliminating the need to modify or replace the non-return valve.

Positive control non-return valve for an injection molding machine


A magnetic recording medium is provided, which has a recording layer formed in a concavo-convex pattern and makes it possible to obtain the stable flying characteristics of a head. In the magnetic recording medium, concave portions between recording elements are filled with a non-magnetic material. Thus, the surface of the magnetic recording medium takes a concavo-convex shape which is different from the concavo-convex pattern of the recording layer. Also, the arithmetical mean deviation of the assessed profile of the concavo-convex shape in the surface is restricted to 1 nm or less.

1. Field of the Invention
The present invention relates to a magnetic recording medium which has a recording layer formed in a concavo-convex pattern.
2. Description of the Related Art
Conventionally, a magnetic recording medium such as a hard disc has been significantly increased in areal density by means of improvement such as fining magnetic particles forming a recording layer, material changes, and increased precision in the processing of heads. Further increase in the areal density is expected in the future.
However, problems such as a limitation in the processing of the head, side fringes due to the spread of a magnetic field, and crosstalk have become revealed, so that improvements in the areal density by a conventional improvement method has reached their limitations. Thus, a magnetic recording medium such as a discrete track medium and a patterned medium has been proposed as a candidate for a magnetic recording medium which can realize further increase in the areal density (refer to, for example, Japanese Patent Laid-Open Publication No. Hei 9-97419). In such a magnetic recording medium, a recording layer is formed in a predetermined concavo-convex pattern.
Namely, since information is recorded on convex portions of the concavo-convex pattern, it is possible to restrain a side fringe, crosstalk, and the like between a convex portion and another convex portion adjacent thereto. Forming the recording layer in the concavo-convex pattern also has the effect of preventing a magnetic head from adhering to the surface of the magnetic recording medium.
When the surface of the medium is in the concavo-convex pattern, on the other hand, there are cases where recording and reproducing characteristics become worse because of the instability of the flying height of the head. Accordingly, it is considered to deposit a non-magnetic material over the recording layer in the concavo-convex pattern for the purpose of filling concave portions with the non-magnetic material. Then, an excess part of the non-magnetic material above the recording layer is removed to flatten the surface of the magnetic recoding layer.
A method of dry etching is available as a method for processing the recording layer into the concavo-convex pattern. A deposit technology such as sputtering, which is used in the field of semiconductor manufacturing, is available as a method for depositing the non-magnetic material. Also, a processing technology such as CMP (chemical mechanical polishing), which is used in the field of semiconductor manufacturing, is available as a method for removing the excess part of the non-magnetic material above the recording layer to flatten the surface.
It is difficult, however, to completely flatten the surface even if the CMP method or the like is used. A concavo-convex shape in which the concavo-convex pattern of the recording layer is reflected is formed in the surface. In the CMP method, for example, it is difficult to precisely control the amount (thickness) of processing in the order of nanometers. Thus, there are cases where after the non-magnetic material above the recording layer is removed, a part of the recording layer is removed together with the non-magnetic material, and hence difference in the height of the concavo-convex shape in the surface, in which the concavo-convex pattern of the recording layer is reflected, contrarily increases due to difference in the speed of processing of both.
There are cases that the stable flying characteristics of the head cannot be obtained due to such a concavo-convex shape in the surface.


A news-printing photoengraving machine of this invention increases photoengraving speed without unduly increasing size or manufacturing costs of a CPT-type photoengraving machine by decreasing waiting time for form plates transferred from a plate feed section. The machine comprises a plate feed section, an exposure section, a plate discharge section, and a development section to make a drawing on a form plate at the exposure section in accordance with a signal output from a computer. The form-plate feed section has a stocker case for storing form plates and a transfer unit set above the stocker case to be vertically movable for transferring form plates along a guide rail. The exposure section has at least two exposure barrels arranged at intervals, a laser-beam scanning head, a first table on a side of each exposure barrel toward the form-plate feed section, and a second table on a development-section side of each exposure barrels. The plate discharge section has a discharge table on an exposure- section side of the development section.

1. Field of the Invention
The present invention relates to improvements of so-called CTP (Computer to Plate) machines for directly forming desired drawings on form plates by operating laser-beam scanning heads with drawing image signals sent from computers; which CTP machines are used to make printing plates for newspaper printing and the like.
2. Prior Art
Because use of computers in the information processing art, or image processing art, has increased in recent years, a printing plate making machine for a CTP-system for making printing plates for newspaper printing has been developed and put to practical use. This printing-plate-making machine forms a drawing directly on a plate with a laser beam in accordance with drawing image signals sent from a computer.
For news printing however, it is very important to improve printing efficiency because it is often required that great numbers of newspapers be printed in short times. In order to print a great number of newspapers in a short time, in accordance with such requirements, it is necessary to further decrease a time of "stop of operation" of a rotary press for carrying out so-called printing plate replacement. For example, it is necessary to decrease a number of printing plates to be replaced by increasing the size of the printing plates. Thus, the time required for printing-plate setting can be decreased by decreasing the number of printing plates to be replaced.
However, if the size of the plates is increased, for example the plate equivalent of one page of newspaper (lateral width W.times.length L) could be changed to be a plate equivalent of two pages of newspaper (lateral width W.times.length 2L), the required time for producing one printing plate is increased from approximately 4 minutes (in the case of one page) to approximately 5 minutes 30 seconds (in the case of two pages) because the drawing area of the plate increases.
As a result, even if the printing plate setting time required for printing-plate replacement can be approximately halved by increasing the size of printing plates (e.g. double size), supplying the printing plates is restricted due to speed restrictions in producing the printing plates and therefore, the problem occurs that equipment for producing the printing plates must be greatly enlarged.
To solve the above problems, the present applicant previously developed the machine shown in FIGS. 9-11 and a method disclosed in Japanese Patent Application No. 222141/1995 for producing printing plates for newspaper printing.
FIG. 9 is an exterior view of a machine for producing printing plates for newspaper printing in which a dark-room section F, a plate feed section A, an exposure section B. a plate discharge section C, a development section D, and a printing plate storage section E are basically provided along a longitudinal direction of a machine body K. Moreover, though not illustrated, laser-beam scanning heads are operated with so-called image signals sent to the exposure section B from a computer provided at a separate control section and laser scanning corresponding to the image signals is applied to OPC layers of OPC (organic Photo Conductor) plates, and thereby image-signal drawings are drawn on plate surfaces as electrostatic latent images.
FIGS. 10 and 11 are respective top and side views showing outlines of the arrangement of the plate feed section A, the exposure section B, and the plate discharge section C of the machine of FIG. 9 for producing printing plates for newspaper printing.
The plate feed section A comprises a stocker case 1, a vacuum-type sucker 2, a transfer unit 3, and a guide rail 4. OPC plates P, each provided with an organic photo conductor layer and being stored in the stocker case 1, are transferred to the exposure section B by the transfer unit 3 one by one.
A plurality of plates P are superposed on one another, being packed with slip sheets for protecting surfaces of the form plates between them. The packed plates P are unpacked in the dark-room section F and the slip sheets are removed from between them and thereafter, only the plates P are superposed in the stocker case 1. The stocker case 1, in which the form plates P are superposed, is at a predetermined position in the plate feed section A relative to the dark-room section F.
The exposure section B (there are actually two sub-exposure sections B1 and B2), comprises a table 5 (5a and 5b), an exposure barrel 6 (6a and 6b), a roller 7 (7a and 7b), and a laser-beam scanning head 8 (8a and 8b). In the case of this machine H for producing the printing plates for newspaper printing, the two sub-exposure sections B1 and B2 are provided to expedite production of the printing plates, the two sub-exposure sections being spaced an interval along the longitudinal direction of the machine body K from one another, the exposure barrel of each being rotatable about its laterally positioned axis.
Moreover, two laser-beam scanning heads 8 (8a1, 8a2 and 8b1, 8b2) are arranged at each sub-exposure section B1 and B2. By synchronously operating these two laser-beam scanning heads, a drawing is formed on the plates P at a speed two times higher than when only one laser-beam scanning head 8 is used.
The plate discharge section C comprises a discharge table 9 provided between the exposure section B and the development section D. Exposed plates P transferred from each sub-exposure section B1, B2 by the transfer unit 3 are discharged onto the plate discharge section C and subsequently sent to the development section D.
In FIG. 11, a plate P transferred onto the table 5a via a route R.sub.1 by the transfer unit 3 is wound about the first exposure barrel 6a by a counterclockwise rotation of the roller 7a and a clockwise rotation of the first exposure barrel 6a and then, the laser-beam scanning head 8a is operated, thereby making a drawing corresponding to a drawing image signal output from the computer section (not shown)
When predetermined laser-beam scanning is completed, the roller 7a and the first exposure barrel 6a are respectively rotated in opposite directions, and the exposed plate P is discharged temporarily onto the table 5a. Then, the exposed plate P is transferred onto the discharge table 9 by the transfer unit 3 via a route R.sub.2 and the transfer unit 3, having released the plate P, is returned to the stocker case 1 via a route R.sub.3.
The same operation is also performed at the second exposure barrel 6b, with a new plate P being transferred onto the table 5b via a route R.sub.4 while a drawing on the plate P is being made at the first exposure barrel 6a. When a drawing at the second exposure barrel 6bis completed, the exposed form plate P is transferred onto the discharge table 9 from the table 5b via a route R.sub.5. Operations of the first exposure barrel 6a, the second exposure barrel 6b and the transfer unit 3 are sequentially performed in accordance with a predetermined timing program and the exposed plates P are thus alternately sent into the development section D from the exposure barrels 6a and 6b.
Problems to be Solved by the Invention
The machine for making the printing plates for newspaper printing shown in FIGS. 9-11 requires the following time to process a plate P for one page of newspaper with one operating laser-beam scanning head.
______________________________________ Time for drawing by rotation Approximately 153 sec. of exposure barrel Time for placing the plate Approximately 13 sec. on the exposure barrel Time for removing the plate Approximately 13 sec. from exposure barrel Time for transferring the Approximately 15 sec. plate (Route R.sub.1) Time for transferring the Approximately 15 sec. exposed plate (Route R.sub.2) Time for allowing transfer Approximately 15 sec. unit to return (Route R.sub.3) ______________________________________
That is, because the tables 5a and 5b are used to hold the plates P before their engagement with the exposure barrels 6a and 6b and also to hold the plates P after their removal from the exposure barrels 6a and 6b, it is impossible to transfer new plates P to the exposure barrels 6a and 6b until the old plates P, which have been removed from the exposure barrels 6a and 6b have been transferred from the tables 5a and 5b to the discharge table 9. As a result, an amount (approximately 45 seconds) of the total operation time of the transfer unit 3 in the preceding exposure operation for one exposure barrel 6 is so-called waiting time in which operation of the exposure barrel 6 is suspended. Even if drawing time is shortened by using a plurality of laser-beam scanning heads 8, there remains the problem that it is impossible to greatly shorten the overall time for making printing plates because the time for waiting for new (or next) plates P is relatively long and it is impossible to quickly feed the next plates P.
It is an object of the present invention to solve the above problem of the machine shown in FIGS. 9 to 11 for making printing plates for newspaper printing and to provide a machine for making printing plates for newspaper printing which, without an increase in size and manufacturing costs of the machine, can greatly increase the speed of making the printing plates.

Machine for simultaneously making two printing plates for newspaper printing

Kabushiki Kaisha Kaneda Kikai Seisakusho


The present invention relates to a rodent serum marker for prostate cancer comprising b-microseminoprotein (PSP94) and diagnostic methods thereof. The present invention also relates to a recombinant sequence to raise a ligand of a specific binding affinity to a rodent serum marker for prostate cancer, which comprises the following amino acid sequence:

There were an estimated 220,900 new cases of prostate cancer (CaP) and 28,900 deaths in the US in 2003. Prostate cancer remains the most frequently diagnosed malignancy among North American males, and is second only to lung cancer in mortality. Genetics, diet, and lifestyle are just some of the factors that contribute to the development of prostate cancer. Prostate specific antigen (PSA) is the only prostate cancer marker widely used for population screening, diagnosis, and monitoring of prostate cancer (prostate cancer). The use of PSA as a serum marker has increased our ability to detect Prostate cancer, select therapy and to monitor outcomes.
Prostate cancer has proven to be a complicated disease due to its heterogeneous and multifocal nature. Consequently, much research has been devoted to elucidating the mechanisms of the disease. This has led to the construction of genetically engineered mouse models of prostate cancer utilizing transgenic and knock-out techniques that attempt to model the human clinical situation in all aspects. Rat probasin gene-based transgenic adenocarcinoma prostate (TRAMP) and LPB-SV40 tag (LADY) models are currently the most prevalent murine prostate cancer models.
Unlike in humans, murine models of prostate cancer currently lack established biomarkers for the disease, specifically serum biomarkers. Current prostate cancer (CaP) research in both basic and pre-clinical trial studies employ genetically engineered (GE) mouse models, since CaP does not occur naturally in rodents.
A serum biomarker in genetically engineered (GE)-CaP is valuable in four ways: it enables the non-invasive detection of cancer stage/progression; it can be used to assess effectiveness of treatments; it can monitor disease recurrence/disease-free state; and it is a much more affordable alternative than expensive molecular/micro-imaging techniques. The ability to non-invasively quantify tumor burden in living conditional tumor model mice will ultimately lead to the development of more accurate models of human cancer that are better suited to evaluating and optimizing preclinical cancer therapy.
Since mice do not produce and express a human PSA analog, the search begins for other equals in mice. Prostatic secretory protein of 94 amino acids (PSP94), also known as β-microseminoprotein (β-MSP) (Hara, M. and Kimura, H., J Lab .Clin. Med, 113: 541-548, 1989; Abrahamsson, P.-A. et al., The prostate, 12: 39-46, 1988; Hyakutake, H. et al., The prostate, 22: 347-355, 1993), is one of the three most abundantly secreted proteins from the prostate gland (the others being PSA and PAP [prostatic acid phosphatase]). Though PSP94 is an abundant protein, little is known about its real biological function. As with PSA, much research has investigated the utility of PSP94 as a prostate cancer marker in humans in terms of serum bound/free forms, urine levels and tissue expression. Furthermore, PSP94 expression in prostate tissue has been demonstrated as having statistical association with histological grade. In most cases this association is inversely correlated—that is, as tumor grade advances PSP94 expression decreases (Hyakutake, H. et al., The prostate, 22: 347-355, 1993)—the same as in PSA (Grande, M. et al., Clin. Cancer Res., 6: 1790-1795, 2000; Stege, R. et al., Clin. Cancer Res., 6: 160-165, 2000).
It would be highly desirable to be provided with a serum marker in rodent prostate cancer models.

Serum tumor marker in rodent prostate cancer models

Abstract: (SEQ ID NO: 1)MGGSHHHHHHGMASMTGGGGMGRNTRYDDDDKDRWGSWVCSIENREIFPNQMSDDCMDADGNKHFLNTPKKNCTWCSCDKTSITCCTNATPLSYDKDNCDVQFHPENCTYSVVDRKNPGKTCRVDSWTM.

London Health Sciences Centre Research Inc.


An outer retainer includes a pair of annular portions facing each other in an axial direction and a plurality of column members connecting the annular portions. A plurality of window portions is formed by the annular portions and the column members, and an outward flange is provided at one side end thereof. The column member between window portions in predetermined positions is cut and the cut portion on the outward flange side is bent radially outward to be an elastic member. Paired cut-away portions are formed in predetermined portions of the outward flange with the elastic member disposed between the paired cut-away portions. In the thus-configured outer retainer, at least three window portions are disposed between the elastic member and the cut-away portion adjacent to the elastic member in the peripheral direction. Column members between paired cut-away portions are bent outward in the radial direction to be enlarged in diameter.

1. Field of the Invention
The present invention relates to an outer retainer for a one-way clutch that is employed for an automatic transmission and the like of a vehicle.
2. Related Background Art
The automatic transmission and the like of the vehicle involves using the one-way clutch that transmits rotary force on a driving side in one direction but does not transmit the rotary force in the opposite direction.
A conventional sprag type one-way clutch is constructed of an inner race and an outer race that are concentric and make relative rotations and of a one-way clutch mechanism interposed between the inner race and the outer race. The one-way clutch mechanism is built up by a plurality of sprags defined as torque transmitting members, a spring member that biases the sprags in an engaging direction, a cylindrical inner retainer and an outer retainer which hold the sprags and restrain an excessive inclination thereof, and a pair of end bearings that ensure operations of the sprags by retaining these two retainers at a predetermined interval.
The outer retainer is constructed of two annular portions facing each other in an axial direction and a plurality of column members connecting these annular portions and provided at a predetermined interval in a peripheral direction. The outer retainer has a plurality of window portions each configured by the neighboring column members and the two annular portions at a predetermined interval in the axial direction. Further, one annular portion is formed with an outward flange directed outward in a radial direction at an end on the opposite side to the other annular portion in the axial direction, i.e., at an end of the outer retainer in the axial direction. The outward flange engages with an engagement groove formed in an inner peripheral face of the outer race, thereby positioning and supporting the outer retainer with the outer race.
The inner retainer and the outer retainer have substantially the same configuration, however, a flange of the inner retainer formed at an end in the axial direction is an inward flange directed inward in the radial direction.
In the thus-constructed one-way clutch, in the case of transmitting torque with the outer race serving as a driving race for applying rotary force to sprags, it is required to apply proper drag torque to between the outer retainer and the inner peripheral face of the outer race in order to surely transmit an operation to the sprags such as when an abrupt operation is applied to the outer race.
A known means for obtaining the drag torque is a means that forms a shaped portion called a T-bar or an i-bar in the outer retainer, gets the shaped portion deformed and thus brings the shaped portion into contact with the inner peripheral face of the outer race. The T-bar is formed by a portion of the annular portion on the side of the outward flange cut away at two portions thereof defining respectively two window portions neighboring each other and the column member between the window portions neighboring each other. In other words, this T-bar forming means configures a T-bar defined as a T-shaped portion by the column member between the neighboring window portions and the divided outward flange-sided annular portion between the two cut-away portions. A plurality of thus-formed T-bars are provided at a predetermined interval, and the column members of these T-bars are bent outward in the radial direction by a predetermined quantity. The divided and radially outward flange of the T-bar engages with an engagement groove formed in an inner peripheral face of the outer race. The flange engaging with the engagement groove serves as a mechanism for preventing a removable of the outer retainer after being assembled to the outer race.
Moreover, the i-bar defined as an i-shaped portion is formed by cutting a part of one column member, closer to the annular portion, between the neighboring window portions so as to separate the column member into two column portions. A scheme is that a plurality of the thus-configured column members are provided at a predetermined interval, one of the separated column portions of each thus-configured column member, is bent outward in the radial direction into an elastic member, the outer retainer is held on the inner peripheral face of the outer race by dint of spring action of the elastic member, and the elastic member abuts on the inner peripheral face of the outer race, thereby obtaining the drag torque.
Japanese Utility Model Laid-Open Publication No. 63-115637 discloses an outer retainer having a connected T-bar structure in which the T-bars are formed so as to be connected in the peripheral direction, and peripheral rigidity of the T-bar is thus improved.
Further, U.S. Pat. No. 5,000,303 discloses an outer retainer having a configuration that an i-bar is, as illustrated in FIG. 4, built up by providing a column member 1122 with a cut portion 1181 in an outer retainer 103, the i-bar serving as an elastic member 1161 being slid on an inner peripheral face of an outer race, and further cut-away portions 1171, 1172 are formed by cutting through annular portions 110b on the side of an outward flange 113, at portions where window portions 1151, 1154 on both sides of window portions 1152, 1153 adjacent to the elastic member are provided with the column member 1122 formed with the elastic member 1161 being centered. The portion of the annular portion 110b between the cut-away portions 1171 and 1172 get deformed to open in the peripheral direction, that is, enlarge outwardly in the radial direction. Thus, the outer retainer is deformed, whereby an outer diametrical face of the outward flange is slid on the inner peripheral face of the outer race.
As in the outer retainer illustrated in FIG. 4, however, if an interval in the peripheral direction between the cut-away portion formed in the annular portion on the outward flange side and the column member formed with the elastic member, is small, namely, if the cut-away portions are provided at the window portions existing on both the sides of the window portions adjacent to the elastic member with this elastic member being centered, the outer retainer is easy to be broken due to a stress. That is, in the case of the one-way clutch used for a starter etc, there is a sharp fluctuation in rotations as when an engine abruptly starts up, and there is the increased amplitude of the stress applied to the retainer due to centrifugal force. Consequently, if a position of the elastic member acting to support the outer retainer on the inner peripheral face of the outer race is close to a position of the cut-away portion provided at the annular portion on the side of the outward flange, a corner part (depicted by, e.g., an ellipse in FIG. 4) of the window portion is easy to be broken due to the amplitude of the stress in the annular portion on the side of the outward flange configuring the window portion formed with the cut-away portion or in the annular portion on the side having none of the outward flange. Namely, a distance from the column cut and deformed to be the elastic member to the cut away portion of the annular portion on the side of the outward flange is shorter, the amplitude of the stress is larger, and both of the corners of the window portions formed with the cut-away portion are easy to be broken.
Further, in the case of forming the cut-away portion and the elastic member simultaneously, if the interval between the cut-away portion and the elastic member is small, i.e., if the distance therebetween is short, the working apparatus itself comes to have a complicated mechanism, resulting in a rise in costs.


A method of identifying at least one resource in a distributed computing system which is a potential root cause of performance degradation of the system includes the steps of: computing operational bounds for the system and operational bounds for at least one resource in the system; comparing current end-to-end system performance with the operational bounds for the system; when the current end-to-end system performance is outside of the operational bounds for the system, comparing current performance of the at least one resource in the system with the operational bounds for the at least one resource; and generating at least one output identifying the at least one resource in the system which is a potential root cause of performance degradation of the system.

One of the major challenges for administrators of distributed information technology environments is maintenance of service level objectives, or SLOs. In accomplishing this goal, it is important that the administrator pinpoint the potential root cause of a system fault as soon as user transaction performance begins to degrade so that corrective action can be taken before an SLO violation occurs, such as the user perceiving major service degradation and/or disruption.
Existing methods for application-level root cause prediction primarily focus on either performance predictions based on historical data or solving queuing network models with the goal of either provisioning the system appropriately or limiting the traffic access in order to satisfy the SLO for incoming traffic. These methods, however, do not take into account system failures which can result in unexpected performance values and thus jeopardize capacity planning estimations and the limits imposed on the arriving traffic.
Existing methods for network failure prediction are typically based on either transmission control protocol (TCP) related data or management information base (MIB) variables, both of which present highly non-stationary characteristics making it difficult to accurately model the dynamics of the system without large amounts of information and processing.
Accordingly, there exists a need for techniques for predicting root cause performance degradation and failure in a distributed computing system while avoiding the complexity and inefficiency found in conventional techniques for predicting network degradation and failure.

Performance degradation root cause prediction in a distributed computing system


A transformer system is provided that includes four magnetically coupled coils having fixed spacing geometry. The four magnetically coupled coils include a drive coil that produces magnetic fields and a load coil. A first resonant coil is magnetically coupled to the drive coil producing energy that is stored by the first resonant coil. A second resonant coil is magnetically coupled to the first resonant coil to propagate the energy stored in the first resonant coil to the second resonant coil without using a magnetic core. The second resonant coil is then magnetically coupled to the load coil where the energy is transferred to the load coil.

The invention relates to the field of power transformers, and in particular to coreless power transformers.
The transformer has been a pivotal device in the large-scale transmission and delivery of electrical energy since its commercial success in the late 1800s. Its official conception dates back to May 1885, when three young engineers of the Hungarian Ganz factory, Zipernowsky, and associates, demonstrated what is generally considered to be the prototype of today's lighting systems. They were able to illuminate the Industrial Exhibition of Budapest—1,067 60 V incandescent lamps—via 75 toroidal, iron core transformers connected in parallel to a 1350 V AC generator. Shortly after, William Stanley modified the Hungarian design for ease of manufacturing and costs and founded the "Stanley Transformer," which demonstrated step-up/step-down capabilities and electrified downtown Great Barrington, Mass. What followed were decades of expansion in AC electric power systems through the 20th century as electricity and transformers became a critical part of the economic infrastructure of most industrialized nations. Transformers increased in size and power rating, with large units used for the power transmission grid and vastly more, smaller units used in the electric power distribution system.
The basic physical principles of transformers remain the same today as they were 130 years ago, though efficiency, costs, weight, versatility, and dimensions have drastically improved. Today's transformers can operate up to the megavolt level and handle more than a million kVA with lifetimes of 25-40 years. However, transformers present a considerable expense to power companies due to their high costs and weight associated with their required steel core and copper windings. Additionally, the U.S. has spent an average of $800 million in importing large power transformers per year in the last five years. Therefore, although the steel core has been a staple in transformer engineering for years, perhaps a radically different design could mitigate the climbing costs of these indispensable devices.


The present invention belongs to the field of active polymer materials. Specifically, it relates to an active polystyrene film that has antimicrobial or antioxidant activity and the method of production of said film. It also refers to wrappers, packages and slice separators (interleavers) that comprise said film.

In order to improve the oxidative and microbial stability of food products and thus prolonging their shelf life, antioxidant and antimicrobial agents, respectively, are used as additives that are added directly to the products.
Thus, it is common practice that antioxidant agents or antimicrobial agents are directly added, in relatively high amounts, during the processing or before the packaging of food products, in order to protect them for a long time. During storage and marketing, that initial amount gradually decreases as it exerts its antioxidant or antimicrobial effect and eventually runs out. This is the moment when oxidation reactions start and the product begins to deteriorate, or when the microorganisms present in the product begin to grow.
Oxidation reactions in packaged food products start on the surface, particularly in the portion that first receives oxygen or light that diffuses through the wall of the packages, so systems have been developed where the package is used as a vehicle for the application of antioxidant agents.
Likewise, the part of a packaged food that is most vulnerable to microbial contamination is its surface and different systems have been described where the package is used as a vehicle for the application of antimicrobial agents.
Producers of films and packaging for food products have spent decades trying to develop films and packaging with antioxidant or antimicrobial properties. Various products have been described in the literature.
U.S. Pat. No. 8,343,522 B2 describes coated sheets for antimicrobial treatment based on biopolymers, particularly cellulosic and proteinic (e.g. collagen). The sheet is antimicrobial in nature because it is impregnated or coated with at least one α-amino acid ester, where said α-amino acid is covalently linked to the film. Due to said covalent link, the antimicrobial agent is not capable of being released into the medium.
WO 2017/049364 A1 describes a food packaging material comprising a polymeric material and an antioxidant agent. In particular, in the tests shown the polymeric material is polyethylene resin and the antioxidant is a rosemary extract.
US 2012/0276357 A1 describes a packaging material with antioxidant activity comprising at least 89% of a polymeric substance, between 2-10% of tocopherol and between 0.1-1% of a surface modifying agent. In particular, in the tests shown the polymeric substance is low-density polyethylene.
U.S. Pat. No. 8,734,879 discloses a method of preserving a food product through a packaging material having preservative properties. Said packaging material comprises a Nα-lauroyl-L-arginine ethyl ester salt and an acyl monoglyceride comprising glycerol monolaurate incorporated in a polymeric material. Said document shows a synergistic effect on the preservative action only between Nα-lauroyl-L-arginine ethyl ester salt and glycerol monolaurate, there are no tests with other compounds.
To date, the inventors are not aware of the presence of these products on the market. In particular, they have not found any slice polystyrene separators having antioxidant or antimicrobial properties.
Surprisingly, the authors of the present invention have developed a film in which the active substances migrate towards the surface of the film and maintain their functionality despite the film manufacturing process. With this film you can prepare slice separators, wraps and packages for food products with antioxidant or antimicrobial properties. Thus, these separators, wraps and packages provide antioxidant or antimicrobial properties to food products with which they are in contact. This supposes important advantages, between which it is possible to emphasize the prolongation of the useful life of these products.


A medical management system is provided that integrates all aspects of healthcare provider practice management and managed care, including schedule management, patient registration, insurance information, EMR and billing and collections. The system integrates a central framework module, a scheduling module, a registration module, an account management module and an electronic record module to provide a seamless exchange of information. A clinical module provides template builder which allows the users to define a customized template. The custom and standard templates are used by a document builder to generate documents, such as progress notes and H&P notes, which are retained in the patient's electronic chart. The progress note template allows the clinician to record a patient encounter by presenting the clinician with predefined sections and sentences that are easily completed by the clinician during or after the patient encounter. The templates and documents generated are designed to closely resemble a paper chart. Information gathered during patient scheduling and triage are referenced to pre-populate the templates to avoid having the clinician entering redundant information. The documents are relied upon to automatically generate patient superbills and electronic requests are sent to a claims clearinghouse.

Service professionals that regularly schedule patient visits have historically relied upon manual practice management, patient records and managed care (i.e., insurance) techniques. For instance, scheduling patients, tracking prescription orders, and maintaining file documentation are typically performed through paper calendars and files. An office assistant receives and schedules patient appointments on the paper calendar. The service professional then checks the paper schedule for each day.
For purposes of this application, service professionals may include, for instance, healthcare providers such as physicians (MD or DO), dentists, chiropractors, psychologists, and counselors. However, the terms "clinician" or "physician" as used herein are understood to include any service professional or healthcare provider who treats a patient, including for instance physicians, nurses, technicians, therapists, chiropractors, physicians assistant, midwife, psychologists, and counselors.
All information concerning the patient's medical history, such as clinician observations, thoughts, treatments administered, patient history, medication lists, vaccine administration lists, laboratory reports, X-rays, charts, progress notes, consultation reports, hospital reports, correspondence and test results, have traditionally been kept in the paper file. Much of this information is handwritten and signed by the clinician, or transcribed from clinician dictation. Paper-based medical files are typically filed alphabetically by the patient's last name, with the patient's name, date of birth and any known allergies on the outside of the file.
However, manual practice management, patient record and managed care techniques are inefficient since they require a great deal of interaction between the service professional and the office assistant. Last minute scheduling changes often result in lost time for the service professional. In addition, manual tracking is prone to error and the large amounts of paper that is generated take up valuable office space. A small office of 2-3 physicians, for instance, can have approximately 20,000 or more active patients, and therefore anywhere from about 25,000 to 60,000 patient files, depending upon how long they have been in practice.
Since the medical record is paper-based and manually produced, the information needed to bill a patient must be manually entered into the billing application. Clinician orders that often generate billable procedures are difficult to process because they are written by hand and in many cases are omitted from the patient's bill. In addition, handwritten orders for prescriptions have been identified as the number one cause of medical errors resulting in patient death in the United States. Add to these issues the complexity of insurance contracts and procedure fee schedules that govern the amount which clinicians are to be paid for their services, and the result is a very inefficient, labor-intensive process requiring many checks and balances to ensure accurate processing.
In a typical office visit for a medical clinician, the clinician will review his/her schedule for that day or week. In any given day, the clinician may have 20-80 office visits, and up to 2 (or more) medical procedures. Prior to a scheduled examination, the clinician will manually flip through the paper file, which has been retrieved from the central files by the office assistant, to determine the purpose of the office visit and review the patient's relevant medical history.
A typical patient visit or patient encounter takes about 10 minutes, with the physical examination comprising about 2 to 5 minutes. Following the examination, or sometimes during, the clinician will make progress notes about the patient's medical condition, order any necessary tests, give the patient any prescriptions, and advise if follow-up appointments are needed. A clinician will usually spend about 2 to 5 minutes to make progress notes and place them in the patient file.
If tests are performed onsite, the clinician, laboratory technician or nurse, conducts the test. If the test results can be obtained relatively quickly, the clinician might wait for the results before releasing the patient, and review the results with the patient. Some testing, however, may be conducted off-site, and later reported to the clinician. The test results must then be analyzed and reported to the patient after the initial office visit, and follow-up appointments may be scheduled.
The amount of paperwork required has a significant impact on the service professional, which often detracts from the amount of time the service provider can spend with the patient. In the medical arena, every hour of emergency department patient care requires an hour of paperwork. For surgery and inpatient acute care, every hour of patient care results in 36 minutes of paperwork. In skilled nursing care, every hour of patient care results in 30 minutes of paperwork. And, in home health care, every hour of patient care results in 48 minutes of paperwork. A physician can spend 22-38% of his/her time charting on paper.
In today's practice, service professionals, and physicians in particular, have added restraints due to increased government and insurance regulations, liability, working longer hours, less time to spend with patients, all of which result in the practice being less profitable and providing a lower quality of care. Governmental and insurance rules and regulations include, for instance, electronic payment requirements, HIPAA (Health Insurance Portability and Accountability Act) requirements (such as electronic health transaction standards, unique identifiers, privacy and confidentiality standards, and security and electronic signature standards), coding and audit requirements, restricted formularies, clinical pathways, increased malpractice risks from pseudo standards of care and requirements for more structured data.
Accordingly, there is a need for a system that can reduce the amount of time spent by a clinician on activities outside the practice of medicine, such as paperwork, dictation, etc. There is also a need for a system that can reduce the amount of time spent by other workers in the clinician's practice including the administrative or office assistants, nurses, clinician assistant, and laboratory technicians. Those systems must also be able to comply with government and insurance regulations and must also provide data that can be analyzed to develop better care protocols.
Systems have been developed which automate patient tracking, medical documents or billing, such as described in U.S. Pat. Nos. 5,991,730, 5,991,729, 5,946,659, 5,933,809, and 5,899,998 to Lubin et al., Barry et al., Lancelot et al., Hunt et al. and McGauley et al., respectively. However, automated systems have not been well received by the service professional community, with fewer than about 5% of all physicians using some sort of electronic medical record (EMR) system, which is broadly understood to be a medical record system that has the capability to electronically provide all of the functionality and features provided by the paper chart, and data that can be analyzed to develop better care protocols.
Service professionals have resisted those systems since they are unable to keep up with the rapid pace and movement of the service professional during the various tasks which are performed throughout the day. One disadvantage of those systems is that they are technology-driven, as opposed to being user-driven, and therefore difficult to use, especially by those service professionals that have difficulty with computer technology.
In addition, those systems are fragmented in that they individually implement a single activity of practice management and managed care to manage scheduling, patient registration, insurance information, billing and collections. In instances where physicians are using EMR, practice management and managed care applications to manage their practices, the applications are typically stand-alone and run on disparate technology platforms.
The absence of a common technology platform requires multiple custom interfaces to connect the "silos" of information to work together in real-time. The process of developing interfaces between disparate applications by multiple vendors can be expensive and difficult and is usually costly and labor-intensive to maintain. Problems are time-consuming and difficult to identify when they arise. These usually costly and labor intensive interfaces are typically used by larger clinician practice groups (50 or more), integrated delivery networks, and university-based practices.
Consequently, those prior systems do not provide a single system that integrates the features of practice management, patient records and managed care. Further adding to the problem, those systems are not set up to communicate with each other, so that practices that have more than one system need to enter redundant information into each system. The various systems are not well suited for interaction between each other, or to maintain information that would be useful to the other systems.
However, even if those fragmented systems could communicate with one another, the systems would merely be interfaced, as opposed to being integrated. Systems that are interfaced exchange limited data to address practice management, EMR and managed care needs. Interfacing systems also require multi-vendor support and the sharing of limited data across limited system components and multiple databases. Interfacing also leads to inconsistency in system user interfaces and system versioning is difficult to manage.


A secondary battery according to the present invention has a current collector and a positive electrode mixture layer that coats the current collector. The positive electrode mixture layer includes a positive electrode active material, an electrically conductive material, and a binder, and the positive electrode active material is constituted by hollow-structure secondary particles formed by the aggregation of a plurality of primary particles of a lithium transition metal oxide and has a through hole penetrating from outside to a hollow portion. In addition, a particle porosity A1 of the positive electrode active material satisfies 2.0(%)≦A1≦70(%). Furthermore, a DBP absorption A2 of the positive electrode active material satisfies 23 (mL/100 g)≦A2. Moreover, the tap density A3 of the positive electrode active material satisfies 1.0 (g/mL)≦A3≦1.9 (g/mL).

A lithium-ion secondary battery comprises a material (an active material) which reversibly stores and releases lithium ions (Li ions) at positive and negative electrodes, and charging and discharging are realized by the migration of lithium ions between the positive and negative electrodes. Typical examples of an active material used in an electrode (typically, a positive electrode) of such a lithium-ion secondary battery include a complex oxide containing lithium and a transition metal element. For example, a lithium complex oxide (a nickel-containing lithium complex oxide) which at least contains nickel (Ni) as the transition metal element and which has a layered structure is preferably used. Patent Literature 1 is an example of a technical document relating to active materials of lithium-ion secondary batteries.
Patent Literature 1 discloses a positive electrode active material made of lithium-containing complex oxide powder whose DBP liquid adsorption ranges from 20 to 40 ml per 100 g of lithium-containing complex oxide powder weight. In this case, for the DBP liquid adsorption of the powder, a reagent solution of the powder is titrated with a constant-rate burette using an absorptometer, a plastograph, or a plasti-corder in compliance with test method A or test method B for DBP adsorption as defined in JIS K6217 (1997), a change in viscosity characteristics during the titration is measured by a torque sensor and recorded, whereby the DBP liquid adsorption of the powder is defined as an additive amount of the reagent solution corresponding to a torque that is 70% of a maximum generated torque.