This invention provides a method for preventing or treating type I diabetes in a mammal comprising administering the mammal an effective amount of at least one compound of the formula I: ##STR1## The invention also provides pharmaceutical preparations useful for the prevention and/or treatment of type I diabetes comprising an effective amount of at least one compound of the formula previously set forth and a pharmaceutically acceptable carrier.

Diabetes mellitus and its complications are now considered to be the third leading cause of death in Canada and the United States, trailing only cancer and cardiovascular disease. According to a report issued by the National Commission on Diabetes, as many as 10 million North Americans may have diabetes, and the incidence is increasing yearly. Although the acute and often lethal symptoms of diabetes can be controlled by insulin therapy, the long-term complications reduce life expectancy by as much as one third. Compared with rates of incidence in nondiabetic normal persons, diabetic patients show rates which are increased 25-fold for blindness, 17-fold for kidney disease, 5-fold for gangrene, and 2-fold for heart disease.
There are 2 major forms of diabetes mellitus. One is type I diabetes, which is also known as insulin-dependent diabetes mellitus (IDDM), and the other is type II diabetes, which is also known as noninsulin-dependent diabetes mellitus (NIDDM). Most patients with IDDM have a common pathological picture: the nearly total disappearance of insulin-producing pancreatic beta cells which results in hyperglycemia.sup.1-7.
Considerable evidence has been accumulated showing that most IDDM is the consequence of progressive beta-cell destruction during an asymptomatic period often extending over many years.sup.1-7. The prediabetic period can be recognized by the detection of circulating islet-cell autoantibodies and insulin autoantibodies. The hypothesis that IDDM is an autoimmune disease has been considerably strengthened by studies on the nonobese diabetic (NOD) mouse.sup.8-12 and the BioBreeding (BB) rat.sup.13-27. Both of these animals develop IDDM spontaneously and their diabetic syndromes share many pathological features with that of humans with IDDM.
Diabetes research has been directed toward prevention and cure of IDDM. To date, therapy of IDDM in humans by methods designed to suppress the autoimmune response has proved to be largely unsuccessful. Immunosuppressive therapy utilizing glucocorticoids and cyclophosphamide did not alter the course of the disease. Although studies on the use of cyclosporin A in diabetes appear to be encouraging, generalized immunosuppression involves potential complications including infections and drug-induced kidney and liver damage.
There is a need for a compound which would be nontoxic and have no side effects but which would prevent clinical IDDM completely. A preferred drug would be administered noninvasively, such as an orally administered solution or tablet.

University Technologies International, Inc.


A control circuit and method for a single coil magnetic latching relay is provided in the present disclosure. The circuit includes: a first control circuit (21) and a first single coil magnetic latching relay coil (22). The first control circuit (21) includes: a first transistor (211), a first diode (212), a second diode (213), a first capacitor (214), a second capacitor (215), a first resistor (216) and a second resistor (217) and the first control circuit (21) is configured to control the first single coil magnetic latching relay coil (22) to enter a preset state and/or maintain the preset state.

A single coil magnetic latching relay, like other electromagnetic relays, can automatically turn a circuit on and off. The difference is that the closed and open states of the single coil magnetic latching relay completely depends on a permanent magnet, and the switching between on and off states of the single coil magnetic latching relay is triggered by an electric pulse signal of a certain width. Generally, the open and close states of the contact of the single coil magnetic latching relay are maintained by a magnetic force of the permanent magnet. When the contact of the single coil magnetic latching relay needs to be opened or closed, only a positive (negative) direct current pulse voltage is required to excite its coil and the single coil magnetic latching relay switches between the on and off states instantly. Generally, when the contact is maintained open or closed, the coil does not need to be continuously powered and the magnetic force of the permanent magnet can maintain the state of the relay unchanged, thereby reducing power consumption and preventing the coil from generating heat due to being powered for a long time.
A conventional single coil magnetic latching relay generally uses a bridge drive circuit or a silicon controlled drive circuit which have relatively complicated control circuits and high costs.
FIG. 1 is a schematic diagram of a control circuit for a single coil magnetic latching relay in the related art. As shown in FIG. 1, the circuit includes an H-bridge drive circuit composed of two NPN transistors and two PNP transistors. One end of the H-bridge drive circuit is connected to a power supply and the other end is grounded. The circuit further includes a first switching transistor Q305 and a second switching transistor Q306. A base electrode of the first switching transistor Q305 is connected to a first signal terminal RLY-ON, and a collector electrode and an emitter electrode of the first switching transistor Q305 are connected in series between one drive end of the H-bridge drive circuit and the ground. A base electrode of the second switching transistor Q306 is connected to a second signal terminal RLY-OFF, and a collector electrode and an emitter electrode of the second switching transistor Q306 are connected in series between the other drive end of the H-bridge drive circuit and the ground.
It can be seen that when a bridge drive is adopted in the related art, the number of used transistors is large and two independent signals are required to set and reset the single coil magnetic latching relay, resulting in a complicated control circuit.

Single coil magnetic latching relay control circuit and method


A silica based glass waveguide having almost the same optical characteristics as designed value and an optical module using a silica based glass waveguide having excellent optical characteristics and reduced connecting loss are provided. A silica based glass waveguide is comprising a core waveguide and a clad, a core waveguide is formed rectangular in cross section and of SiO2—TiO2 group glass on a synthetic silica glass substrate, and a clad is formed of SiO2—B2O3—P2O5 group glass or etc. on a synthetic silica glass substrate and a core waveguide. A synthetic silica glass substrate is formed of pure SiO2 and having birefringence quantity less than 10 nm/cm.

1. Field of the invention
The present invention relates to a silica based glass waveguide and an optical module using the same, and more specifically to a silica based glass waveguide and an optical module using the same for use in large-capacity optical transmission system.
2. Prior Art
Recently, accompanied with propagation of technology such as internet and high speed communication between computers, developments and improvements of long distance high speed large-capacity transmission system using dense wavelength division multiplexing (DWDM) method are advancing rapidly in the worldwide scale.
In DWDM transmission system, large capacity transmission is performed by multiplexing different wavelength optical signals of 1.55 μm band width to an optical fiber by using an optical multiplexer/demultiplexer, then amplify this multiplexed optical signal collectively with an optical fiber amplifier. As a key component of this DWDM transmission system, an optical multiplexer/demultiplexer which multiplexes or demultiplexes different wavelength optical signals is indispensable.
As an optical multiplexer/demultiplexer, three types of dielectric multilayer film filter type, fiber brag grating type and arrayed waveguide grating (AWG) are put in practical use. Among them, AWG type optical multiplexer/demultiplexer comprising silica based glass waveguide is excellent with respect to mass productivity, cost and multi channeling, because it is manufactured by applying semiconductor process and optical fiber producing technique.
As shown in FIG. 1, this silica based glass waveguide is manufactured as follows. A core glass film (not shown in the figure) is formed on a silica glass substrate 61. A core waveguide 63 is formed by processing such as etching to the core glass film. After a plurality of optical waveguide are formed collectively on the silica glass substrate 61 by forming a clad 65 on the surface of the silica glass substrate 61 and the core waveguide 63, they are cut off for every waveguide.
However, in the conventional silica based glass waveguide 60 shown in FIG. 1, because slight unevenness of various kinds of parameters occurs in practical production process, designed optical characteristics (designed value) and actually obtainable optical characteristics (measured value) are often different slightly. Even thought by considering the core width variation which arise under manufacturing and the small sway of refraction index which arise at the core or at the clad film neighboring the core, the measured value is largely different from the designed value, and obtained each silica based glass waveguide are uneven respectively in optical characteristics, the yield rate is not satisfactory. Accordingly, there were problems in reliability, uniformity of products and yield rate under manufacturing.
Further, there was problem that connecting loss increases when an optical module was constituted by connecting an optical fiber (not shown in the figure) to at least one end of the core waveguide 63 of the silica based glass waveguide 60.

Silica based glass waveguide and optical module using the same


Aspects described herein relate to receiving, from a serving cell, a configuration for performing conditional handover to one or more target cells, establishing, based on detecting a condition from the configuration, a connection with a target cell for performing handover to the target cell, and transmitting, based on establishing the connection with the target cell and based on determining that the conditional handover is of a type where a source connection with the source cell remains, a notification to the serving cell.

Aspects of the present disclosure relate generally to wireless communication systems, and more particularly, to configuring and/or performing conditional handover among cells.
Wireless communication systems are widely deployed to provide various types of communication content such as voice, video, packet data, messaging, broadcast, and so on. These systems may be multiple-access systems capable of supporting communication with multiple users by sharing the available system resources (e.g., time, frequency, and power). Examples of such multiple-access systems include code-division multiple access (CDMA) systems, time-division multiple access (TDMA) systems, frequency-division multiple access (FDMA) systems, and orthogonal frequency-division multiple access (OFDMA) systems, and single-carrier frequency division multiple access (SC-FDMA) systems.
These multiple access technologies have been adopted in various telecommunication standards to provide a common protocol that enables different wireless devices to communicate on a municipal, national, regional, and even global level. For example, a fifth generation (5G) wireless communications technology (which can be referred to as 5G new radio (5G NR)) is envisaged to expand and support diverse usage scenarios and applications with respect to current mobile network generations. In an aspect, 5G communications technology can include: enhanced mobile broadband addressing human-centric use cases for access to multimedia content, services and data; ultra-reliable low-latency communications (URLLC) with certain specifications for latency and reliability; and massive machine type communications, which can allow a very large number of connected devices and transmission of a relatively low volume of non-delay-sensitive information.
In some wireless communication technologies, a source cell can configure a user equipment (UE) to perform conditional handover to one or more target cells. The source cell can transmit the configuration to the UE before the handover event, where the configuration can specify parameters for performing the handover and one or more conditions for the UE to detect for performing the handover. The UE can accordingly attempt to detect the one or more conditions, and can initiate handover to the one or more corresponding target cells, without further instruction from the source cell, when the one or more conditions are detected.

Techniques for performing conditional handover in wireless communications


The present invention relates to network communication systems for managing client/server connections in a wireless environment. In accordance with the invention, a mobile communication unit (i.e., client), deploys keepalive packets at selected times in order to reset a keepidle timer of a server (e.g., host computer). By periodically resetting the keepidle timer a current connection between the mobile communication unit and server can be maintained as long as desired even when the mobile communication unit is in a power suspend mode. When in a power suspend mode, the mobile communication unit can briefly awake long enough to activate its transmitter and send a keepalive packet to the server to maintain the current connection. In this manner, the mobile communication unit can obtain the power savings of being in primarily a power suspend mode, but still prevent the current connection from timing out.

In recent years, the use of communication systems having wireless mobile communication units which communicate using an optical or radio link with a hardwired network, such as a local area network (LAN), has become quite widespread. Retail stores and warehouses, for example, may use such systems to track inventory and replenish stock. Employees may enter inventory information using a hand held or portable communication unit which can be carried through the store or warehouse. In manufacturing facilities, such systems are useful for tracking parts, completed products and defects. In a medical environment, these systems can reduce the time needed to fill out forms and eliminate inaccuracies by allowing medical personnel to transmit data directly from a mobile communication unit carried by the medical personnel.
A conventional communication system generally includes a number of fixed base stations (i.e., access points) interconnected by a medium to form a network backbone. The network backbone may be wireless in nature or be a hardwired connection formed using a twisted pair cable or shielded coaxial cable for fiber optic lines, for example. Each base station has a service area or cell surrounding the base station within which it has the ability to transmit and to receive relatively error-free data from a mobile communication unit within the area.
In such a network, a mobile communication unit must initially register itself with a base station and then attempt to begin a session with a host computer whereby the host computer allows communication to occur between itself and the particular mobile communication unit. More particularly, when a mobile communication unit is powered up, it "registers" with a base station. However, as the location of this mobile communication unit changes, the mobile communication unit may register with another base station, thereby resulting in a deregistration with the previous base station. Furthermore, deregistration will sometimes occur if there is no communication between the mobile communication unit and its corresponding base station within a predetermined period of time. Thus, in such communication systems, mobile communication units register and deregister frequently as the mobile communication units are moved about.
Each mobile communication unit within the communication system must also begin a connection with a server such as a host computer (or other device which provides application or information based services) once it has registered with a base station. A connection is established to allow the mobile communication unit and server to communicate using a known protocol such as TCP/IP. Following a connection being established, a user of the mobile communication unit is typically prompted to login and begin a session with that particular server. A session is typically only initiated once at start up by each mobile communication unit and is active until such time as the mobile communication unit or server ends the session regardless of the number of registrations and deregistrations which may have taken place with respect to base stations during this period. In order for the mobile communication unit to enter into the system and begin a session with the server, the mobile communication unit must have a unique network identification code (ID). The ID allows the server or other device on the backbone handling session requests to recognize and distinguish each mobile communication unit.
One widely accepted computer architecture, developed specifically to accommodate the above-mention distributed computing environment is the client-server model. The client-server system in general consists of the server which services the requests of a large number of smaller computers (e.g., mobile communication units), or clients, that connect to it. The mobile communication units do not typically communicate with each other, but rather only exchange data with the server, which thereby acts as a clearinghouse for mobile communication unit requests and inter mobile communication unit communications.
In order to ensure proper routing of messages between the server and an intended mobile communication unit, the messages are initially broken up into data packets, each of which receive a destination address according to a consistent protocol, and which are reassembled upon receipt by the target computer. The exchange of information between endpoints in a packet network is achieved via a "protocol." A commonly accepted protocol for this purpose is the Internet Protocol (IP), which provides for networking. Used in conjunction with the IP may be a Transmission Control Protocol (TCP) which provides for a reliable stream delivery of messages or a User Datagram Protocol (UDP) which allows for distinguishing messages among multiple destinations with a given host computer.
More specifically, the TCP protocol is a popular connection-oriented transport layer protocol that is used around the world. The TCP protocol offers a full duplex reliable virtual end-to-end connection for transporting information between endpoints by using one or more of the packets, each of which comprises both control information and data.
The mobile communication units (e.g., wireless terminals) that perform client-server communications (e.g., terminal emulation) establish a TCP connection with the server. Then, they use the connection to establish the session.
When a connection is established between a client (i.e., mobile communication unit) and a server (i.e., host computer) the two machines dedicate a portion of their resources to the connection. People who use mobile communication units frequently power them OFF without logging out or move them out of communication range, an action that would inform the server that the connection will not be used and permit it to recover the resources that it has dedicated to the connection. To avoid this problem, servers (i.e., host computers) are often configured to employ a mechanism deemed a "keepalive" probe." The keepalive probe consists of several IP packets, sent in a burst, by the server. The probe determines if the client (mobile communication unit) is still connected to the LAN and operational. The IP packets of keepalive probes differ from ordinary IP packets in that they do not increment a sequence number that synchronize the transfer of bytes in a data stream between the two end points as a convention packet using the TCP protocol would. In this manner, such IP packet is 'invisible' or 'transparent'. Generally, the IP packet sequence number is one less than the number that the receiving node expects to receive. This has two effects: (1) the receiving node will immediately return an acknowledgment packet to the sender; and (2) the IP packet does not advance the sequence number of the receiving node and therefore it does not change the synchronization state between the two end points.
When a server, that has activated the keepalive feature, does not receive a data packet for a period of time called the "keepidle time," it will send a keepalive probe to the mobile communication unit to assess continued activity. Upon receiving a keepalive message, the mobile communication unit, if active, returns an acknowledgment packet. The server is configured to end its connection with the mobile communication unit when none of the packets in the keepalive probe are acknowledged. Of course the mobile communication unit will not realize the server ended this connection until the mobile communication unit next attempts to communicate with the server.
If the mobile communication unit acknowledges one of the packets in the probe, the server will determine that the mobile communication unit is still active and reset its keepidle timer, thus maintaining the current connection. However, if none of the packets in the keepalive burst are acknowledged, the server will terminate the connection. This typically causes an application program running on the server to end its session with the mobile communication unit.
However, oftentimes workers using mobile communication units (i.e., clients) lay down the mobile communication unit in order to perform another activity or simply place the mobile communication unit in a sleep state in order to conserve battery power. In many of these situations, the worker still desires to maintain the current session so that when he returns to the mobile communication unit or reactivates it, he/she can immediately continue the session he/she was engaged in. Further, in many instances the mobile communication unit may inadvertently or purposefully be taken out of communication range of any access point which establishes a communication link to the server. Unfortunately, as mentioned above, the server will drop the current connection and session if it sends a keepalive probe to the mobile communication unit and it doesn't receive any acknowledgments. When the mobile communication unit is placed in a sleep mode or is out of range, it is unable to receive and acknowledge the keepalive probe, and therefore the current session may be prematurely ended. In many existing systems, the amount of time a server allows before ending a connection may be relatively short as the server was not configured to handle the problems now encountered with mobile communication units.
In light of the above, there is a strong need in the art for a way to maintain a connection and session between the server and the mobile communication unit when the mobile communication unit is in a low power (i.e., sleep) mode or out of range. In particular, there is a strong need in the art for a mobile communication unit which is able to prevent the host computer from prematurely ending the current connection and session while the mobile communication unit is in a sleep mode and increase the amount of time the mobile communication unit can be out of communication range with the server prior to the connection and session being dropped.

This patent is subject to a terminal disclaimer.


A method for testing catalysts in a fluidized bed reactor comprises enclosing catalyst material in capsules having pores or holes smaller than the catalyst material, inserting the capsules filled with catalyst material to into a port of the fluidized bed reactor and recovering at least a portion of the catalyst capsules from the fluidized bed reactor after use through an additional port of the fluidized bed reactor, wherein the capsules move with a flow of uplifted fluid and gas in the fluidized bed reactor.

Ebullated-bed reactors are one of the types of reactors currently used in hydrocracking of heavy oils and other chemical processing. The ebullated-bed reactor is a fluidized-bed three phase system in which back-mixing of both the reactor liquid composition and the catalyst particles occurs. The catalysts used in the ebullated-bed reactor are kept in a fluidized state through the upward lift of liquid reactants and gas (feed oil plus recycled products) which enter the reactor and are distributed across the bed through a distributor and grid plate. Fresh catalyst can be added and spent catalyst withdrawn to control the level of catalyst activity in the reactor. FIG. 1 is a cross-sectional view of an exemplary ebullated-bed reactor (as known in the art). As shown, the ebullated-bed reactor 100 includes a generally cylindrical housing 105 with a feedstock port 108 arranged at the bottom of the housing and a catalyst feed port 110 arranged at the top. Feedstock (e.g., oil) is recycled through a recycling path 115 and catalyst can be withdrawn and recovered from the bottom of the reactor via a withdrawal port 118. A grid plate 120 is positioned near the bottom of the reactor. The level indicators in FIG. 1 show that the catalyst input to the reactor mixes with the liquids and gases in the reactor and expands from a "settled catalyst level" to an "expanded catalyst level" in the reactor through uplift.
Ebullated-bed reactors have several advantages over fixed-bed reactors: the ebullating bed does not get plugged by solids present in some heavy feeds; the liquid recycle provides a high magnitude of mixing within the reactor, thus ensuring that temperature gradients are minimized; and catalysts can be added and withdrawn continuously, allowing long operating runs without shutting down the reactor. The catalyst pellets should be small enough to facilitate suspension by the liquid phase in the reactor. The rate of catalyst addition and withdrawal is set in order to maintain constant conversion. It is noted that slurry-bed reactors have similar advantages to the aforementioned advantages of ebullated-bed reactors.
Catalyst testing containers for fixed reactor beds are not designed optimally for ebullated-bed reactors. For example, catalyst baskets described in commonly-assigned U.S. Pat. No. 9,802,173 (by the present inventor) are designed to be loaded with large amounts of catalysts, on the order of 100 cubic centimeters to 10 liters, and for use at a fixed location in a fixed-bed reactor. Such catalyst baskets cannot be applied in reactors in which catalysts are mobile and are replaced daily.

Method of providing catalysts for a fluidized bed reactor


A method of operating a spectrum system includes issuing communicating transmitter commands to a spectrum operator system from the spectrum system. The spectrum operator system is in communication with a transmitter. The method also includes instructing, using a computing processor, the spectrum operator system to identify a set of wireless terminals associated with the transmitter, instruct the set of wireless terminals or a subset of the wireless terminals associated with the transmitter to return network measurements to the spectrum system, and instruct different subsets of wireless terminals associated with the transmitter over time to return network measurements to the spectrum system.

Wireless communications continue to gain in popularity, but wireless communications are constrained due to a lack of available, interference free spectrum that may be used for reliable communications within a geographic area. A leading cause of the lack of available spectrum is the manner in which spectrum has been historically allocated. Since the early days of radio and telegraph transmission, the available radio spectrum in the United States and other jurisdictions has been carved up by regulatory agencies into discrete bands or channels. Use of spectrum bands has been restricted to certain types of users or certain licensees. Because many of these bands were allocated at a time when technology was very primitive and data rate requirements were very low, the bands were not allocated in an efficient manner for current demands.
The US President's Council of Advisors on Science and Technology (PCAST) has indicated that traditional practice of clearing federal spectrum by relocating federal users and subsequently auctioning the spectrum for commercial use is impractical and unsustainable. The costs and the timelines involved in relocating Federal users and equipment are daunting, and in some cases, simply impractical. At the same time, there are various Federal spectrum bands that are currently used in a sporadic and low duty-cycle manner, both geographically and in time. PCAST recognizes the need to implement a Spectrum Access System (SAS) that securely facilitates commercializing Federal spectrum without impeding Federal users, and also provide for temporary or permanent revocation of the commercial rights and pre-emption in favor of Federal Users.

Augmenting spectrum sharing using network measurements


This invention concerns improvements relating to a deformable-mirror holder for holding a mirror in a desired position, to within accepted tolerances, even whilst the mirror is deforming or in a deformed state. More particularly but not exclusively, this invention relates to a holder for a bimorph mirror. A deformable mirror holder (31) is provided comprising a body with a receiving portion for receiving a deformable mirror (30), and wherein the receiving portion is defined by a passive flexible support structure (41) such that, in use, to the support structure provides a supporting surface to the mirror. This invention extends to a deformable mirror and a deformable mirror holder as described above.

Deformable mirrors are often used in the field of adaptive optics. For example, phase distortions in a signal may be sensed by a wavefront sensor and these distortions may be corrected for by an adaptive mirror. Such adaptive mirrors may be employed in numerous fields, including:                imaging, for example adaptive mirrors are used in astronomy to improve the resolution of earth-based telescopes that are otherwise affected by atmospheric distortions;        laser sensing, where the amount of laser light that can be delivered onto a target is significantly increased by using an adaptive mirror to correct for atmospheric distortions—this enables either better information to be obtained or objects to be identified at a greater range; and        laser generation, where an adaptive mirror can be used intracavity within a high power laser to counter the thermal blooming that can be otherwise induced by the high concentration of laser light inside the cavity.
Bimorph deformable mirrors have been proposed as low cost adaptive mirrors. The two main operational parameters of a bimorph mirror are its bandwidth and its stroke. Bandwidth determines how quickly the mirror can be deformed and hence, for example, how quickly the mirror can respond to the variations in atmospheric turbulence. Stroke corresponds to the maximum displacement of the mirror when deformed and this determines, for example, the level of turbulence that can be corrected. Ideally, both bandwidth and stroke would be maximised. However, conventional designs mean that there is a reciprocal relationship between these two parameters, and one parameter can only be improved at the expense of the other. Therefore, to date, designers have always looked for ways to improve either the resonant frequency or the stroke independently from each other.
Conventionally, deformable mirrors are supported rigidly around their edge, for example an annular ring overlapping the periphery of the mirror is used to hold the mirror firmly in position. Such an arrangement benefits from being simple yet rugged. However, it has an inherent disadvantage in that it creates a dead space around the mirror's edge. This corresponds both to the area of the mirror held firmly under the annular ring and also to the adjacent area. This is because the useable area of the deformable mirror (the active area) must bend to adopt a desired profile, for example either a concave or a convex shape. The annular area between the active area and the annular ring must bend in the opposite sense and so forms an area of inflexion that has undesirable optical properties. Hence the active area occupies only a central portion of the whole mirror. This is illustrated in FIGS. 1 to 3, albeit with the deformation of the mirror exaggerated for the sake of clarity.
One way of alleviating this problem is to clamp the mirror at only three positions, such that the mirror edge can twist. However, this arrangement is to the detriment of ruggedness and the twisting introduces unwanted distortions leading to an optically inferior performance.
It is also known that for smaller mirrors, bonded piezoelectric elements (e.g. bimorph deformable mirrors) are preferred due to their relatively low cost. Such mirrors provide an adequate balance between bandwidth and stroke. However, the balance between bandwidth and stroke is especially important when looking to make larger mirrors e.g. mirrors with active apertures greater than 10 to 15 cms. In order to keep the resonant frequency and thus the bandwidth of the mirror constant, the thickness of the substrate must also increase. For the larger mirrors this will adversely affect the minimum curvature available from the mirror. For this reason, larger mirrors have historically been zonal mirrors. The fact that the substrate is supported by a large number of actuators means that the resonant frequency, and therefore bandwidth, is no longer directly linked to the mirror diameter. However, the overriding issue with this type of deformable mirror is the cost. Although there are a number of different actuator technologies available, none of them are cheap. This makes large mirrors expensive because as many as 300 actuators may be required. For a bonded piezoelectric element mirror, although a large piezoelectric element will be more expensive than a smaller one, the cost differential will not be as great. A second issue is that it is not always possible to place discrete actuators as close to each other as required because of their fairly large size.
Against this background, the Applicant has filed a UK patent application (No. 0309976.9, 30 Apr. 2003 filing date) directed to a deformable mirror comprising a reflective surface provided on a substrate and a layer of deformable material attached to the substrate that is operable to deform the mirror and wherein the substrate is supported by an actuator that is operable to deform the mirror. The actuator can be used to provide the basic deformation required of the mirror (e.g. focus), while the deformable material can be used to provide fine tuning of the mirror shape.
Additionally, against this background, the Applicant has filed a UK patent application (No. 0309979.3, 30 Apr. 2003 filing date) directed to a deformable mirror holder that simply supports the mirror uniformly around the edge.

Mirror structure having piezoelectric element bonded to a mirror substrate


An information processing device processes information based on a plurality of chromatograms obtained by analyzing a plurality of samples. A determination processing unit determines presence or absence of each of a plurality of target components in each sample based on the plurality of chromatograms. A list generation processing unit generates a list associating the plurality of target components with each sample and indicating the presence or absence of each of the plurality of target components in each sample determined by the determination processing unit. Checking the list enables prompt confirmation of the presence or absence of the target components in each of the plurality of samples.

In order to quantify a target component contained in a sample, analysis using a high performance liquid chromatograph may be performed. For example, since mycotoxins having toxicity to humans or animals may be produced in food and beverages (e.g., see Patent Document 1 below), when each component of mycotoxin is analyzed as a target component by the high performance liquid chromatograph, each target component can be quantified based on the obtained chromatogram.
When the chromatogram is to be used for quantification of the target component, a calibration curve is prepared by measuring a standard sample of the target component, and based on the calibration curve and the chromatogram obtained by measuring the sample, the concentration of the target component contained in the sample is calculated. In this manner, the chromatogram is generally used for quantification of a target component and is not used for qualitative analysis of the target component.
Patent Document 1: Japanese Unexamined Patent Application Publication No. 2015-25680

Information processing device, information processing method, and information processing program


A power control device for a construction machine of the present invention is characterized by including an engine, an actuator adapted to be driven with power of the engine, an engine controller for stopping the engine automatically when it is not necessary to drive the actuator, and an air conditioner for conditioning the air in an interior of a cab of the construction machine, and in which when an air conditioner operation detecting unit detects that the air conditioner is in operation and even when an engine power necessity determining unit determines that the power of the engine is not necessary, automatic stop of the engine by the engine controller is prevented.

In Japanese Patent Laid-Open Nos. 2000-96627 and 2001-41069, there is disclosed a construction machine having an auto-stop function for stopping an engine automatically upon establishment of preset auto-stop conditions (e.g., a state in which a gate lever for opening and closing a gateway for operator is opened and a lever for operating a working actuator is not operated).
However, in the construction machine having such an auto-stop function and with an air conditioner installed within a cab, since a compressor of the air conditioner is directly connected to the engine, the compressor becomes unable to be driven upon automatic stop of the engine and a cooling capacity of the air conditioner is eventually lost. Therefore, for example in the summer season, when the operator leaves the construction machine without turn-off of an ignition key and returns after a while, an interior of the cab may be no longer comfortable because of a rise in internal temperature, thus making it impossible for the operator to enter the cab and resume operation, with consequent deterioration of a working efficiency.

Power control device for construction machine

Kobelco Construction Machinery Co., Ltd.


A method, system, and computer program product for reconstructing a data stream are provided. The method includes listening to an original data stream, and extracting messages from the original data stream. The method further includes determining statistical data from the extracted messages, and creating a reconstructed data stream using the statistical data.

This invention relates generally to data modeling, and more particularly to a method, system, and computer program product for reconstructing a data stream.
The ability to reconstruct data from an original data source is useful in a variety of applications and may assist in achieving various goals. Data reconstruction may be used on projects that involve data conversion, storage, or analysis. Data reconstruction may be useful in support of reverse engineering of a system, and may also enable the development of a model of a data consumer or producer to support system testing. Reconstructed data may be used to playback a data stream into a system for simulation purposes. Reconstructed data may also be used to supplement native data traffic on a networked system, or may assist in tilling gaps to replace missing data packets in a transmission.
In developing techniques to reconstruct data, accuracy in the reconstruction is important. An inaccurate reconstruction may appear as noise in the system, leading to poor system performance, while accurate data reconstruction may appear transparent to a consumer of the reconstructed data.
Although data capture, replay, storage, and conversion algorithms have been contemplated for various application specific solutions, such solutions fail to support a broad range of message types that may exist in a heterogeneous enterprise IT architecture. A heterogeneous enterprise IT architecture may contain a variety of computing systems, and employ multiple industry standard communication protocols. Furthermore, a heterogeneous enterprise IT architecture may be reconfigured dynamically, with components using a variety of communication protocols being added or removed from the system in an unpredictable manner. Application specific solutions for reconstructing data streams fail to meet the needs of a heterogeneous enterprise IT architecture in that they target only specific applications or protocols without providing robust support for multiple industry standard communication protocols.
Accordingly, there is a need for a method for reconstructing a data stream using industry standard communication protocols.

Method, system, and computer program product for reconstructing a data stream

International Business Machines Corporation


Disclosed is a method of removing an acid halide, anhydride, or ester impurity from a mixture with a desired product with which it codistills. At least about a stoichiometric amount of a primary or secondary amine having a boiling point at least 10.degree. C. higher or lower than the boiling point of said desired product is added to the mixture. The desired product is not an acid halide, anhydride, or ester and does not react with the amine. The amine forms a reaction product with the impurity that has a boiling point at least 10.degree. C. higher or lower than the boiling point of the desired product. The mixture is distilled to isolate the desired product.

This invention relates to a method of removing an acid halide, anhydride, or ester from a mixture with a compound with which it codistills. In particular, it relates to reacting the acid halide, anhydride, or ester with an amine to form a higher or lower boiling compound, followed by distillation.
Parachlorobenzonitrile (PCBN) can be used to make pigments, pharmaceuticals, and agricultural products. It is made by reacting parachlorobenzoic acid with parachlorobenzotrichloride (PCBTC) and ammonium chloride (see U.S. Pat. No. 5,866,709, herein incorporated by reference). In making PCBN, various side products and unreacted starting material can end up in the product mixture. Most of these impurities can be separated by distillation, but the boiling point of one side product, parachlorobenzoyl chloride (PCBOC), is only 2.degree. C. less than the boiling point of PCBN(223.degree. C.),so it codistills with the PCBN. The presence of PCBOC in the PCBN is not acceptable to some users of PCBN as it lowers the quality of the products made from PCBN. While separation could be accomplished by crystallation or further distillation, those processes are not cost effective.

Removal of an impurity from a mixture with a codistillant


Systems and methods are disclosed for matching of individuals to one another using a matching model. The matching model matches social network users based on ratings given by users one to another, as well as, as appropriate and available, explicit attributes indicated by users and other data such as location data and system usage data.

1. Field
This disclosure relates to matching of individuals one to another through online systems or through use of mobile, wireless, and/or electronic devices.
2. Description of the Related Art
Social network services have been in existence for a number of years. Social network services typically consist of online communities of individuals who share common background, attributes, interests and/or activities, and who are interested in meeting and/or interacting with other individuals in the network. Most social network services are web based and provide a variety of ways for users to interact, such as e-mail, instant messaging, posting blogs, and posting comments on each other's social network profile pages. A number of social network services have developed solutions to accommodate users participating in social networks through use of wireless devices, and other portable electronic devices.
Conventional social networking solutions, such as online social networks, typically require a user who wants to find other members that share similar interests to designate the specific attributes sought at the same time as the user wants to find these members. It is often difficult to find users with desired qualities because conventional social networking solutions typically have many users, and entering desired attributes often returns too many potential matches. Searching for other members that a user would find of interest oftentimes requires sorting through the profiles and data of many other members and/or performing multiple searches to find individuals of interest.
Users of many conventional social networks may also search for individuals that one may have interest in by scanning though the profiles and data of users associated with already-known members. In some instances, meeting individuals who have an established relationship with an already-known individual may require a user to request permission from a user's already-known contact, the person of interest, or both. This results in a delay for the user before the user can meet the person of interest as well as additional user effort.
Further, although a user may find another member in a social network desirable and may want to interact with that individual, it is often difficult to determine if the user himself or herself has attributes that the other individual would find desirable.


For the purpose of compensating for a variation in the static magnetic field of an MRI apparatus, RF probes 1P1 and 1P2 are placed and a reference static magnetic field is measured as a reference frequency in the beginning; the static magnetic field is measured at an appropriate time as a frequency to determine the amount of static magnetic field variation from their difference; and the transmission frequency of an RF pulse and the receiving detection frequency of an NMR signal are corrected or the gradient current for a gradient coil is corrected so as to compensate for the amount of the magnetic field variation.

The present invention relates to a magnetic field variation measuring method and magnetic field variation compensating method for an MRI (magnetic resonance imaging) apparatus, and an MRI apparatus, and more particularly to a magnetic field variation measuring method for measuring a variation in a static magnetic field of an MRI apparatus, a magnetic field variation compensating method for compensating a variation in a static magnetic field of an MRI apparatus, and an MRI apparatus capable of implementing such methods.
The static magnetic field of an MRI apparatus should be constant, but when a metal mass (e.g., an automobile) moves near the MRI apparatus or the environment changes (e.g., the temperature changes), the static magnetic field may be undesirably varied.
In the past, measures for dealing with such variation in the static magnetic field have focused on restraining the cause of the variation, such as by magnetically shielding the MRI apparatus or air-conditioning the room where the MRI apparatus is installed.
However, a variation in the static magnetic field sometimes occurs even after the measures have been taken, and in this case, a problem arises in that the image quality is undesirably degraded.
It is therefore a first object of the present invention to provide a magnetic field variation measuring method that can measure a variation in the static magnetic field of an MRI apparatus.
Moreover, it is a second object of the present invention to provide a magnetic field variation compensating method that can compensate for a variation in a static magnetic field of an MRI apparatus.
Furthermore, it is a third object of the present invention to provide an MRI apparatus that can suitably implement the magnetic field variation measuring method and magnetic field variation compensating method.
In accordance with its first aspect, the present invention provides a magnetic field variation measuring method characterized in: placing I (wherein Ixe2x89xa71) RF probes, each of which has a combination of a small phantom capable of emitting an FID (free induction decay) signal and a small coil, in proximity of an imaging region of an MRI apparatus; transmitting RF pulses from said RF probes at a time when a reference magnetic field is to be measured, and receiving FID signals to determine reference frequencies fir (wherein i=1xe2x88x92I) from said FID signals; transmitting RF pulses from said RF probes at times when a magnetic field variation is to be measured, and receiving FID signals to determine frequencies fi from said FID signals; and determining a j-th order magnetic field variation xcex1j by solving the following equation:                     f        i            -              f        ir              =                  ∑                  j          =          0                          I          -          1                                            α          j                ·                  r          i          j                      ,
wherein the position of each RF probe is represented by rj.
In the magnetic field variation measuring method of the first aspect, RF probes are placed and a reference static magnetic field is measured as a reference frequency in the beginning, and the static magnetic field is measured at appropriate times as a frequency, to determine the amount of a static magnetic field variation from their difference. If the RF probes are fixed, up to an (Ixe2x88x921)-th order magnetic field variation can, in general, be determined.
In accordance with its second aspect, the present invention provides the magnetic field variation measuring method of the aforementioned configuration, characterized in that I=2, and a zeroth-order magnetic field variation xcex10 and a first-order magnetic field variation xcex11 are determined.
In the magnetic field variation measuring method of the second aspect, the RF probes are fixed, and zeroth- and first-order magnetic field variations can be determined.
The zeroth-order magnetic field variation is a magnetic field variation that is independent of position, and the first-order magnetic field variation is a magnetic field variation that is a linear function of position.
In accordance with its third aspect, the present invention provides a magnetic field variation measuring method characterized in: placing two RF probes, each of which has a combination of a small phantom capable of emitting an FID signal and a small coil, across an imaging region of an MRI apparatus; transmitting RF pulses from said RF probes at a time when a reference magnetic field is to be measured, and receiving FID signals to determine reference frequencies f1r and f2r from said FID signals; transmitting RF pulses from said RF probes at times when a magnetic field variation is to be measured, and receiving FID signals to determine frequencies f1 and f2 from said FID signals; and determining a zeroth-order magnetic field variation xcex10 and a first-order magnetic field variation xcex11 by solving the following equations:             α      0        =                            (                                    f              1                        -                          f                              1                                r                                              )                +                  (                                    f              2                        -                          f                              2                                r                                              )                    2                  α      1        =                                        (                                          f                1                            -                              f                                  1                                    r                                                      )                    -                      (                                          f                2                            -                              f                                  2                                    r                                                      )                          2            .
In the magnetic field variation measuring method of the third aspect, the RF probes are fixed, and zeroth- and first-order magnetic field variations can be determined.
In accordance with its fourth aspect, the present invention provides the magnetic field variation measuring method of the aforementioned configuration, characterized in that the time when the reference magnetic field is to be measured is immediately before the beginning of a pulse sequence for imaging a first view, and the times when the magnetic field variation is to be measured are immediately before the beginnings of pulse sequences for imaging second and later views.
In the magnetic field variation measuring method of the fourth aspect, when an imaging pulse sequence is repeated to collect data filling a k-space, a magnetic field variation is measured before the beginning of the imaging pulse sequence each time, and therefore a magnetic field variation when a metal mass moves near the MRI apparatus can be dealt with.
Particular examples of the imaging pulse sequence include pulse sequences that observe a gradient echoes, such as one according to GRASS (gradient recalled acquisition in the steady state) or SPGR (spoiled GRASS).
In accordance with its fifth aspect, the present invention provides the magnetic field variation measuring method of the aforementioned configuration, characterized in that the time when the reference magnetic field is to be measured is at startup of the MRI apparatus, and the times when the magnetic field variation is to be measured are at regular time intervals after the startup of the MRI apparatus.
In the magnetic field variation measuring method of the fifth aspect, since the magnetic field variation is measured at startup of the MRI apparatus and at regular time intervals after the startup, a magnetic field variation when the environment changes can be dealt with.
In accordance with its sixth aspect, the present invention provides the magnetic field variation measuring method of the aforementioned configuration, characterized in that the MRI apparatus is an open-type MRI apparatus that generates a static magnetic field in the vertical direction, and the RF probes are disposed above and below the imaging region.
In the magnetic field variation measuring method of the sixth aspect, a variation in the static magnetic field of an open-type MRI apparatus, in which homogeneity of the magnetic field is achieved by mechanical shimming or by adding a plurality of small pieces of magnet or iron, can be suitably measured.
In accordance with its seventh aspect, the present invention provides a magnetic field variation compensating method characterized in correcting the transmission frequency of an RF pulse and the receiving detection frequency of an NMR signal based on the zeroth-order magnetic field variation xcex10 measured by the magnetic field variation measuring method of the aforementioned configuration.
In the magnetic field variation compensating method of the seventh aspect, the zeroth-order static magnetic field variation can be compensated for by correction of the transmission frequency of an RF pulse and the receiving detection frequency of an NMR signal.
In accordance with its eighth aspect, the present invention provides a magnetic field variation compensating method characterized in correcting the gradient current based on the first and higher order magnetic field variations xcex1j measured by the magnetic field variation measuring method of the aforementioned configuration.
In the magnetic field variation compensating method of the eighth aspect, the first and higher order static magnetic field variations can be compensated for by correction of the gradient current.
In accordance with its ninth aspect, the present invention provides an MRI apparatus characterized in comprising: I (where Ixe2x89xa71) RF probes, each of which consists of a combination of a small phantom capable of emitting an FID signal and a small coil, disposed in proximity of an imaging region; reference frequency acquiring means for transmitting RF pulses from said RF probes at a time when a reference magnetic field is to be measured, and receiving FID signals to determine reference frequencies fir (wherein i=1 to I) from said FID signals; frequency acquiring means for transmitting RF pulses from said RF probes at times when a magnetic field variation is to be measured, and receiving FID signals to determine frequencies fi from said FID signals; and magnetic field variation calculating means for determining a j-th order magnetic field variation xcex1j by solving the following equation:                     f        i            -              f        ir              =                  ∑                  j          =          0                          I          -          1                                  j        ·                  r          i          j                      ,
wherein the position of each RF probe is represented by ri.
In the MRI apparatus of the ninth aspect, the magnetic field variation measuring method of the first aspect can be suitably implemented.
In accordance with its tenth aspect, the present invention provides the MRI apparatus of the aforementioned configuration, characterized in that I=2, and a zeroth-order magnetic field variation xcex10 and a first-order magnetic field variation xcex11 are determined.
In the MRI apparatus of the tenth aspect, the magnetic field variation measuring method of the second aspect can be suitably implemented.
In accordance with its eleventh aspect, the present invention provides an MRI apparatus characterized in comprising: two RF probes, each of which consists of a combination of a small phantom capable of emitting an FID signal and a small coil, disposed across an imaging region; reference frequency acquiring means for transmitting RF pulses from said RF probes at a time when a reference magnetic field is to be measured, and receiving FID signals to determine reference frequencies f1r and f2r from said FID signals; frequency acquiring means for transmitting RF pulses from said RF probes at times when a magnetic field variation is to be measured, and receiving FID signals to determine frequencies f1 and f2 from said FID signals; and magnetic field variation calculating means for determining a zeroth-order magnetic field variation xcex10 and a first-order magnetic field variation xcex11 by solving the following equations:             α      0        =                            (                                    f              1                        -                          f                              1                                r                                              )                +                  (                                    f              2                        -                          f                              2                                r                                              )                    2                  α      1        =                                        (                                          f                1                            -                              f                                  1                                    r                                                      )                    -                      (                                          f                2                            -                              f                                  2                                    r                                                      )                          2            .
In the MRI apparatus of the eleventh aspect, the magnetic field variation measuring method of the third aspect can be suitably implemented.
In accordance with its twelfth aspect, the present invention provides the MRI apparatus of the aforementioned configuration, characterized in that the time when the reference magnetic field is to be measured is immediately before the beginning of a pulse sequence for imaging a first view, and the times when the magnetic field variation is to be measured are immediately before the beginnings of pulse sequences for imaging second and later views.
In the MRI apparatus of the twelfth aspect, the magnetic field variation measuring method of the fourth aspect can be suitably implemented.
In accordance with its thirteenth aspect, the present invention provides the MRI apparatus of the aforementioned configuration, characterized in that the time when the reference magnetic field is to be measured is at startup of the MRI apparatus, and the times when the magnetic field variation is to be measured are at regular time intervals after the startup of the MRI apparatus.
In the MRI apparatus of the thirteenth aspect, the magnetic field variation measuring method of the fifth aspect can be suitably implemented.
In accordance with its fourteenth aspect, the present invention provides the MRI apparatus of the aforementioned configuration, characterized in that the MRI apparatus is an open-type MRI apparatus that generates a static magnetic field in the vertical direction, and the RF probes are disposed above and below the imaging region.
In the MRI apparatus of the fourteenth aspect, the magnetic field variation measuring method of the sixth aspect can be suitably implemented.
In accordance with its fifteenth aspect, the present invention provides the MRI apparatus of the aforementioned configuration, characterized in comprising RF frequency correcting means for correcting the transmission frequency of an RF pulse and the receiving detection frequency of an NMR signal based on the measured zeroth-order magnetic field variation xcex10.
In the MRI apparatus of the fifteenth aspect, the magnetic field variation compensating method of the seventh aspect can be suitably implemented.
In accordance with its sixteenth aspect, the present invention provides the MRI apparatus of the aforementioned configuration, characterized in comprising gradient current correcting means for correcting the gradient current based on the measured first and higher order magnetic field variations xcex1j.
In the MRI apparatus of the sixteenth aspect, the magnetic field variation compensating method of the eighth aspect can be suitably implemented.
According to the magnetic field variation measuring method for an MRI apparatus of the present invention, the amount of a variation in a static magnetic field caused by a metal mass (e.g., an automobile) moving near the MRI apparatus or an environment change (e.g., a change in temperature) etc. can be measured.
Moreover, according to the magnetic field variation compensating method for an MRI apparatus of the present invention, a variation in the static magnetic field of an MRI apparatus can be compensated for.
Furthermore, according to the MRI apparatus of the present invention, the magnetic field variation measuring method and magnetic field variation compensating method can be suitably implemented.
Further objects and advantages of the present invention will be apparent from the following description of the preferred embodiments of the invention as illustrated in the accompanying drawings.

Magnetic field variation measuring method and magnetic field variation compensating method for MRI apparatus, and MRI apparatus

GE Medical Systems Global Technology Company, LLC


The present invention is directed to a synthetic peptide having a length of not more than 30 amino acids comprising a divalent cation binding site. Such a peptide according to the present invention is part of a composition for nucleic acid amplification and provides for a so-called hot start effect.

A major problem with nucleic acid amplification and more especially with PCR is the generation of unspecific amplification products. In many cases, this is due to an unspecific oligonucleotide priming and subsequent primer extension event prior to the actual thermocycling procedure itself, since thermostable DNA polymerases are also moderately active at ambient temperature. For example, amplification products due to eventually by chance occurring primer dimerization and subsequent extension are observed frequently. In order to overcome this problem, it is well known in the art to perform a so called "hot start" PCR, wherein one component essential for the amplification reaction is either separated from the reaction mixture or kept in an inactive state until the temperature of the reaction mixture is being raised for the first time. Since the polymerase cannot function under these conditions, there is no primer elongation during the period when the primers can bind none specifically. In order to achieve this effect, several methods have been applied:
Physical Separation of the DNA Polymerase
The physical separation can be obtained for example by a barrier of solid wax, which separates the compartment containing the DNA polymerase from the compartment containing the bulk of the other reagents. During the first heating step the wax is then melting automatically and the fluid compartments are mixed (Chou, Q., et al., Nucleic Acids Res 20 (1992) 1717-23, U.S. Pat. No. 5,411,876). Alternatively, the DNA polymerase is affinity immobilized on a solid support prior to the amplification reaction and only released into the reaction mixture by a heat mediated release (Nilsson, J., et al., Biotechniques 22 (1997) 744-51). Both methods, however are time consuming and inconvenient to perform.
Chemical Modification of DNA Polymerase
For this type of hot start PCR, the DNA polymerase is reversibly inactivated as a result of a chemical modification. More precisely, heat labile blocking groups are introduced into the Taq DNA polymerase which renders the enzyme inactive at room temperature (U.S. Pat. No. 5,773,258). These blocking groups are removed at high temperature during a pre-PCR step such that the enzyme is becoming activated. Such a heat labile modification, for example can be obtained by coupling Citraconic Anhydride or Aconitric Anhydride to the Lysine residues of the enzyme (U.S. Pat. No. 5,677,152). Enzymes carrying such modifications are meanwhile commercially available as Amplitaq Gold (Moretti, T., et al., Biotechniques 25 (1998) 716-22) or FastStart DNA polymerase (Roche Molecular Biochemicals). However, the introduction of blocking groups is a chemical reaction which arbitrarily occurs on all sterically available Lysine residues of the enzyme. Therefore, the reproducibility and quality of chemically modified enzyme preparations may vary and can hardly be controlled.
Recombinant Modification of DNA Polymerase
Cold sensitive mutants of Taq Polymerase have been prepared by means of genetic engineering. These mutants differ from the wildtype enzyme in that they lack the N-terminus (U.S. Pat. No. 6,241,557). In contrast to native or wild type recombinant Taq Polymerase, these mutants are completely inactive below 35° C. and thus may be used in some cases for performing a hot start PCR. However, the N-terminal truncated cold sensitive mutant form requires low salt buffer conditions, has a lower processivity as compared to the wild type enzyme and thus can only be used for the amplification of short target nucleic acids. Moreover, since the truncated form lacks 5′-3′ exonuclease activity, it can not be used for real time PCR experiments based on the TaqMan detection format.
DNA Polymerase Inhibition by Nucleic Acid Additives
Extension of non-specifically annealed primers has been shown to be inhibited by the addition of short double stranded DNA fragments (Kainz, P., et al., Biotechniques 28 (2000) 278-82). In this case, primer extension is inhibited at temperatures below the melting point of the short double stranded DNA fragment, but independent from the sequence of the competitor DNA itself. However, it is not known, to which extent the excess of competitor DNA influences the yield of the nucleic acid amplification reaction.
Alternatively, oligonucleotide Aptamers with a specific sequence resulting in a defined secondary structure may be used. Such Aptamers have been selected using the SELEX Technology for a very high affinity to the DNA polymerase (U.S. Pat. No. 5,693,502, Lin, Y., and Jayasena, S. D., J Mol Biol 271 (1997) 100-11). The presence of such Aptamers within the amplification mixture prior to the actual thermocycling process itself again results in a high affinity binding to the DNA polymerase and consequently a heat labile inhibition of its activity (U.S. Pat. No. 6,020,130). Due to the selection process, however, all so far available Aptamers can only be used in combination with one particular species of DNA polymerase.
Taq DNA Antibodies
An alternative approach to achieve heat labile inhibition of Taq DNA polymerase is the addition of monoclonal antibodies raised against the purified enzyme (Kellogg, D. E., et al., Biotechniques 16 (1994) 1134-7; Sharkey, D. J., et al., Biotechnology (N Y). 12 (1994) 506-9). Like the oligonucleotide Aptamers, the antibody binds to Taq DNA polymerase with high affinity at ambient temperatures in an inhibitory manner (U.S. Pat. No. 5,338,671). The complex is resolved in a preheating step prior to the thermocycling process itself. This leads to a substantial time consuming prolongation of the amplification as a whole, especially if protocols for rapid thermocycling are applied (WO 97/46706).
U.S. Pat. No. 5,985,619 discloses a specific embodiment for performing PCR using a hot start antibody, wherein besides Taq polymerase, e.g. Exonuclease III from E. coli is added as a supplement to the amplification mixture in order to digest unspecific primer dimer intermediates. As disclosed above, Exonuclease III recognizes double-stranded DNA as a substrate, like, for example, target/primer- or target/primer extension product hybrids. Digestion is taking place by means of cleavage of the phosphodiester bond at the 5′ end of the 3′ terminal deoxynucleotide residue. Since this type of exonuclease is active at ambient temperatures, all unspecifically annealed primers and primer extension products therefore are digested. This results in some embodiments in an even enhanced specificity of the amplification reaction. Yet, digestion of the unspecific primers dependent on the duration of the preincubation time may lead to a substantial and uncontrolled decrease in primer concentration, which in turn may affect the amplification reaction itself.
Usage of Modified Primers Alone or in Combination with Exonucleases
EP 0 799 888 and GB 2293238 disclose an addition of 3′ blocked oligonucleotides to PCR reactions. Due to the 3′ block, these oligonucleotides can not act as primers. The blocked oligonucleotides are designed to compete/interact with the PCR primers which results in reduction of non-specific products.
Another alternative is the use of phosphorothioate oligonucleotide primers in combination with an exonuclease III in the PCR reaction mixes (EP 0 744 470). In this case, a 3′ exonuclease, which usually accepts double stranded as well as single stranded DNA substrates, degrades duplex artifacts such as primer dimers as well as carry over amplicons, while leaving the single stranded amplification primers undegraded. Similarly, the usage of primers with a basic modified 3′ ends and template dependent removal by E. coli Endonuclease IV has been suggested (U.S. Pat. No. 5,792,607).
A particular embodiment of the general idea is found in EP 1 275 735. Its specification discloses a composition for performing a nucleic acid amplification reaction comprising (i) a thermostable DNA-Polymerase, (ii) a thermostable 3′-5′ Exonuclease, and (iii) at least one primer for nucleic acid amplification with a modified 3′ terminal residue which is not elongated by said thermostable DNA-Polymerase as well as methods for performing a PCR reaction using this composition. Furthermore, the method is directed to kits comprising such a composition.
However, it is major drawback of the disclosed alternatives that for each PCR reaction, modified primers are required, which lead to increased requirements regarding increase the cost for each individual assay.
Other PCR Additives
Other organic additives known in the art like DMSO, betaines, and formamides (WO 99/46400; Hengen, P. N., Trends Biochem Sci 22 (1997) 225-6; Chakrabarti, R., and Schutt, C. E., Nucleic Acids Res 29 (2001) 2377-81) result in an improvement of amplification of GC rich sequences, rather than prevention of primer dimer formation. Similarly, heparin may stimulate in vitro run-on transcription presumably by removal of proteins like histones in order to make chromosomal DNA accessible (Hildebrand, C. E., et al., Biochimica et Biophysica Acta 477 (1977) 295-311).
It is also known that addition of single strand binding protein (U.S. Pat. No. 5,449,603) or tRNA, (Sturzenbaum, S. R., Biotechniques 27 (1999) 50-2) results in non-covalent association of these additives to the primers. This association is disrupted when heating during PCR. It was also found that addition of DNA helicases prevent random annealing of primers (Kaboev, O. K., et al., Bioorg Khim 25 (1999) 398-400). Furthermore, poly-glutamate (WO 00/68411) in several cases may be used in order to inhibit polymerase activity at low temperatures.
Moreover, it is known that polyanionic polymerase inhibitors may control the activity of thermostable DNA polymerases dependent on the applied incubation temperature. U.S. Pat. No. 6,667,165 discloses a hot start embodiment, characterized in that inactive polymerase-inhibitor complexes are formed at temperatures below 40° C. Between 40° C. and 55° C., the inhibitor competes with the template DNA for binding to the Taq Polymerase, whereas at temperatures above 55° C., the inhibitor is displaced from the polymerase active site. Yet, the inhibitor tends to reduce the obtainable product yield, when primers with lower annealing temperatures are used.
Magnesium Sequestration
Since thermostable polymerases are known for a long time to be active only in presence of Mg2+ cations, a sequestration of magnesium prior to the start of the thermocycling protocol has been attempted in order to avoid mispriming and unspecifying primer extension. As disclosed in U.S. Pat. No. 6,403,341, Mg2+ may be present in form of a precipitate and thus unavailable at the beginning of the amplification reaction. Upon temperature increase during the first round of thermocycling, the precipitate dissolves and Mg2+ becomes fully available within the first 3 cycles. Such a solution has been shown to be fairly applicable and capable of providing good hot start results. On the other hand, such a solution does not allow the preparation of mastermixes containing all reagents except primer and target nucleic acid which are necessary to perform a nucleic acid amplification reaction. As a consequence, inter-assay data reproducibility and data comparisons are complicated.
In view of the outlined prior art it was an object of the invention to provide an improved alternative composition and method for hot start PCR, which allows for an inhibition of unspecific priming and primer extension not only prior to the amplification process itself but also during the thermocycling process. More precisely, it was an object of the invention to provide an alternative composition and method for hot start PCR, where no extension of unspecifically annealed primers can take place.

PCR hot start by magnesium sequestration


Provided is an implantable RFID-enabled micro-electronic neurostimulator system for treating obstructive sleep apnea, comprising an implant having a top and a bottom layer, the bottom layer serving as an attachment mechanism such that the bottom layer of the implant encompasses the hypoglossal nerve and attaches to the top layer of the implant; a printed circuit board (PCB) attached to the top layer of the implant, the PCB having a first and a second opposing sides; a neural interface attached to the second side of the PCB; a core subsystem (CSS) attached to the first side of the PCB and electrically connected to the neural interface; and a radio frequency (RF) interface attached to the first side of the PCB and electrically connected to the CSS, wherein the implant is powered and controlled by an external programmable controller.

Sleep apnea is a physiological condition affecting millions of people worldwide. It is described as an iterated failure to respire properly during sleep. Those affected by sleep apnea stop breathing during sleep numerous times during the night. There are two types of sleep apnea, generally described in medical literature as central sleep apnea and obstructive sleep apnea. Central sleep apnea is a failure of the nervous system to produce proper signals for excitation of the muscles involved with respiration. Obstructive sleep apnea (OSA) is cause by physical obstruction of the upper airway channel (UAW).
Obstruction of the upper airway is associated with a depression of the respiratory system caused by a loss of tone of the oropharyngeal muscles involved in maintaining UAW patency. As those muscles lose tone, the tongue and soft tissue of the upper airway collapse, blocking the upper airway channel. Blockage of the upper airway prevents air from flowing into the lungs. This creates a decrease in blood oxygen level, which in turn increases blood pressure and heart dilation. This causes a reflexive forced opening of the UAW until the patient regains normal patency, followed by normal respiration until the next apneic event. These reflexes briefly arouse the patient from sleep (microarousals).
Current treatment options range from non-invasive approaches such as continuous positive applied pressure (CPAP) to more invasive surgical procedures such as uvulopalatopharyngoplasty (UPPP) and tracheostomy. In both cases patient acceptance and therapy compliance is well below desired levels, rendering the current solutions ineffective as a long term solution-for therapeutic treatment of OSA.
Implants are a promising alternative to these forms of treatment. Pharyngeal dilation via hypoglossal nerve (XII) stimulation has been shown to be an effective treatment method for OSA. The nerves are stimulated using an implanted electrode. In particular, the medial XII nerve branch (i.e., in genioglossus), has demonstrated significant reductions in UAW airflow resistance (i.e., increased pharyngeal caliber).
Reduced UAW airflow resistance, however, does not address the issue of UAW compliance (i.e., decreased UAW stiffness), another critical factor involved with maintaining patency. To this end, co-activation of both the lateral XII nerve branches (which innervate the hypoglossus (HG) and styloglossus (SG) muscles) and the medial nerve branch has shown that the added effects of the HG (tongue retraction and depression) and the SG (retraction and elevation of lateral aspect of tongue) result in an increased maximum rate of airflow and mechanical stability of the UAW.
While coarse (non-selective) stimulation has shown improvement to the AHI (Apnea+Hypopnea Index) the therapeutic effects of coarse stimulation are inconclusive. Selective stimulation of the functional branches is more effective, since each branch-controlled muscle affects different functions and locations of the upper airway. For example, activation of the GH muscle moves the hyoid bone in the anterosuperior direction (towards the tip of the chin). This causes dilation of the pharynx, but at a point along the upper airway that is more caudal (below) to the base of the tongue. In contrast, activation of the HG dilates the oropharynx (the most commonly identified point of collapse, where the tongue and soft palate meet) by causing tongue protrusion. Finally, the tongue retractor muscles (HG and SG) do not themselves generate therapeutic effects, but they have been shown to improve upper airway stability when co-activated with the HG muscle.
While electrical stimulation of the hypoglossal nerve (HGN) has been experimentally shown to remove obstructions in the UAW, current implementation methods require accurate detection of an obstruction, selective stimulation of the correct tongue muscles, and a coupling of the detection and stimulation components. Additionally, attempts at selective stimulation have to date required multiple implants with multiple power sources, and the scope of therapeutic efficacy has been limited. A need therefore exists for an apparatus and method for programmable and/or selective neural stimulation of multiple implants or contact excitation combinations using a single controller power source.

RFID-based apparatus, system, and method for therapeutic treatment of obstructive sleep apnea


Provided is a high-voltage complementary metal-oxide semiconductor (CMOS) charge pump. The high-voltage CMOS charge pump includes a first Dickson charge pump for doubling a supply voltage based on an input clock signal and a complementary input clock signal with reversed phases to each other; a level shifter for doubling voltage levels of the input clock signal and the complementary input clock signal based on an output signal and a complementary output signal of the first Dickson charge pump as power sources, to thereby output a doubled-output clock signal and a doubled-output clock signal; and a second Dickson charge pump for doubling voltage levels of the output signal and the complementary output signal based on the doubled-output clock signal and the doubled-complementary output clock signal from the level shifter.

Generally, a charge pump is used to generate an internal voltage, e.g., 2VDD or 4VDD, which is higher than a supply voltage VDD. A Dickson charge pump is widely used as the charge pump.
FIG. 1 is a circuit diagram of a general Dickson charge pump.
As shown in FIG. 1, a first input clock signal IN1 and a second input clock signal IN2 are inputted through inverters, and the first and second input clock signals IN1 and IN2 swing with swing amplitude of VDD. The first input clock signal IN1 is out of phase with the second input clock signal IN2. That is, the second input clock signal IN2 is generated by inverting the first input clock signal IN1.
The Dickson charge pump includes a first NMOS transistor N1, a second NMOS transistor N2, a first PMOS transistor P1, a second PMOS transistor P2, a first flying capacitor C1, and a second flying capacitor C2.
In the first NMOS transistor N1, a drain is coupled to the supply voltage VDD, a source is connected to a node VA, and a gate is connected to a node VB. In the second NMOS transistor N2, a drain is coupled to the supply voltage VDD, a source is connected to the node VB, and a gate is connected to the node VA.
In the first PMOS transistor P1, a source is connected to the node VA, a drain is connected to an output voltage terminal Vout, and a gate is connected to the node VB. In the second PMOS transistor P2, a source is connected to the node VB, a drain is connected to the output voltage terminal Vout, and a gate is connected to the node VA.
The first flying capacitor C1 is connected between the node VA and a first clock input terminal IN1. The second flying capacitor C2 is connected between the node VB and a second input clock terminal IN2.
A load capacitor CL connected between the output voltage terminal Vout and a ground terminal GND. The load capacitor CL is formed by modeling a load capacitance.
FIG. 2 is a diagram showing waveforms at each node of the Dickson charge pump shown in FIG. 1. Hereinafter, operations of the Dickson charge pump will be described referring to FIG. 2.
When a voltage level of a node IN1 is VDD and a voltage level of a node IN2 is GND, a voltage level of the node VA is raised to 2VDD due to a bootstrapping phenomenon. Then, the second NMOS transistor N2 is turn-on, charges the second flying capacitor C2, and thus a voltage level of the node VB becomes VDD. Then, the second PMOS transistor P2 and the first NMOS transistor N1 are turn-off due to the node VB having the VDD, the first PMOS transistor P1 is turn-on and a voltage level of the node VA becomes 2VDD. Consequently, the load capacitor CL connected to the output voltage terminal Vout is charged with 2VDD.
When a voltage level of the node IN1 is GND and a voltage level of the node IN2 is VDD, the voltage level of the node VB having VDD is raised to 2VDD due to the bootstrapping phenomenon. Then, the first NMOS transistor N1 is turn-on, charges the first flying capacitor C1, and thus a voltage level of the node VA becomes VDD. Then, the first PMOS transistor P1 and the second NMOS transistor N2 are turn-off due to the node VA having the VDD level, the second PMOS transistor P2 is turn-on and a voltage level of the node VB becomes 2VDD. Consequently, the load capacitor CL connected to the output voltage terminal Vout is charged with 2VDD.
In other words, when the voltage level of the node VA is 2VDD, the first NMOS transistor N1 is turn-off, the first PMOS transistor P1 is turn-on, the output voltage terminal Vout becomes 2VDD and the node VB is charged with VDD. When the voltage level of the node VB is 2VDD, the second NMOS transistor N2 is turn-off, the second PMOS transistor P2 is turn on, the output voltage terminal Vout becomes 2VDD and the node VA is charged with VDD. Voltage levels of the node VA and the node VB are alternatively raised to 2VDD, the raised voltage charges the load capacitor CL and the output voltage is constantly 2VDD.
The Dickson charge pump is a basic charge pump. The Dickson charge pump generates 2VDD output voltage from the supply voltage VDD by receiving the out-of phase clock signals without a separated controller.
FIG. 3 is a circuit diagram of a general level shifter.
As shown in FIG. 3, the level shifter is a circuit for transforming swing amplitude of the clock signal. The level shifter transforms the first input clock signal IN1 having VDD swing amplitude into a third input clock signal IN3 having 2VDD swing amplitude, and outputs the third input clock signal to a output terminal OUT1.
The level shifter includes a third PMOS transistor P3, a fourth PMOS transistor P4, a third NMOS transistor N3 and a fourth NMOS transistor N4.
In the third PMOS transistor P3, a source is coupled to a second supply voltage VDD2, a drain is connected to a node VC, and a gate is connected to the first output terminal OUT1. In the fourth PMOS transistor P4, a source is coupled to the second supply voltage VDD2, a drain is connected to the first output terminal OUT1, and a gate is connected to the node VC.
In the third NMOS transistor N3, a source is connected to the first clock input terminal IN1, a drain is connected to the node VC, and a gate is coupled to the supply voltage VDD. In the fourth NMOS transistor N4, a source is connected to the GND, a drain is connected to the first output terminal OUT1, and a gate is connected to the first clock input terminal IN1.
FIG. 4 is a diagram showing waveforms at each node of the level shifter shown in FIG. 3. Hereinafter, operations of the level shifter will be described referring to FIG. 4.
When a voltage level of the first input clock signal IN1 is VDD, the fourth NMOS transistor N4 is turn-on and a voltage level of the first output terminal OUT1 is GND. Then, the third PMOS transistor P3 becomes turn-on and the fourth PMOS transistor P4 becomes turn-off due to cross-coupled structure.
On the other hand, when the voltage level of the first input clock signal IN1 is GND, the fourth NMOS transistor N4 is turn-off, the third NMOS transistor N3 becomes turn-on and the fourth PMOS transistor P4 becomes turn-on. Then, when the fourth PMOS transistor P4 is turn-on, third PMOS transistor P3 is turn-off, the third PMOS transistor P3 prevents current flows through the third NMOS transistor N3, and the first output terminal OUT1 becomes VDD2 due to the cross-coupled structure.
As described above, while the first input clock signal swings between VDD and GND, the first output terminal OUT1 swings between GND and the second supply voltage VDD2 in the level shifter.
FIG. 5 is a circuit diagram of a cascade charge pump receiving the supply voltage VDD and generating 4VDD, which is quadruple of the supply voltage. The cascade charge pump is formed by cascading the Dickson charge pump and the level shifter.
As shown in FIG. 5, the cascade charge pump is formed by connecting two Dickson charge pumps 100 and 200 by using the level shifter 300. The Dickson charge pump is called as a cross-coupled doubler.
Structure of each Dickson charge pump 100 and 200 is the same as that of Dickson charge pump shown in FIG. 1, and the detailed description will be omitted.
FIG. 6 is a diagram showing waveforms at each node of the cascade charge pump shown in FIG. 5. Hereinafter, operations of the cascade charge pump will be described referring to FIG. 6.
The cascade charge pump includes a first Dickson charge pump 100, a second Dickson charge pump 200 and the level shifter 300.
The first Dickson charge pump 100 is the same as the Dickson charge pump shown in FIG. 1. That is, the first Dickson charge pump 100 receives input clock signals IN1 and IN2 which are out-of phase for each other and swing between GND and VDD, and generates IN1′ and IN2′ swing between VDD and 2VDD by using flying capacitors C3 and C4. A voltage level of the first output terminal Vout1 is raised to 2VDD by repeatedly outputting IN1′ and IN2′ having 2VDD.
An output voltage of the first Dickson charge pump 100 is used as a power source of the second Dickson charge pump 200 and the level shifter 300. The level shifter 300 receives the output voltage 2VDD of the first Dickson charge pump 100 and the first input clock signal IN1, generates a signal OUT1 having 2VDD swing amplitude, and outputs the signal OUT1 to the second Dickson charge pump 200. The signal OUT1 is inputted to the second Dickson charge pump 200 as a third input clock signal IN3 and a fourth input clock signal IN4 through inverters.
Accordingly, the second Dickson charge pump 200 uses output voltage 2VDD of the first Dickson charge pump 100 as the power source and receives the signal OUT1 having 2VDD swing amplitude from the level shifter 300 as an input signal. Then, the second Dickson charge pump 200 generates a signal IN3′ and a signal IN4′ swing between 2VDD and 4VDD by using flying capacitors C5 and C6. Herein, a voltage level of a second output terminal Vout2 is raised to 4VDD by repeatedly outputting IN3′ and IN4′ having 4VDD.
As described above, the conventional high-voltage CMOS charge pump requires two charge pumps, one level shifter, and four inverters in order to raise the supply voltage VDD up to the quadruple 4VDD of the supply voltage. Therefore, a large layout area is needed to implement the conventional high-voltage CMOS charge pump having a lot of MOS transistors.

Electronics and Telecommunications Research Institute


A method for tracking software code revisions with a checksum data value being automatically appended to source files. The method including assessing via a code management tool a source file containing source code. The method proceeds by appending a checksum data value via the code management tool to the source file. The method concludes by injecting the checksum data value into a binary module for display by a user.

1. Field of Invention
This invention relates in general to software applications, and more particularly to tracking software revisions.
2. Description of Background
Open source development using multiple licenses has made managing source code a serious challenge for corporations. As a result of the proliferation of projects based on open source code, corporations must support customers on unlimited, and somewhat unknown versions of software. Answering the question: "What driver do I need?" and comparing this to: "What driver am I running?" Needless to say, it has become a daunting and frustrating task to determine the necessary driver.
This issue was not present in proprietary operating systems, because vendors could control installation tools and use release numbers to track the version of the source code running on any given system. Since open source developers frequently do not update the release field (even if it is present) the current tools available for managing code levels do not work in this environment.
Specifically, existing code management tools such as a concurrent version system (CVS) tool fail to provide sufficient granularity when tagging files to assist with this problem. For example, today, CVS provides keyword substitution for elements such as:
$Revision: 1.5$
$Id:hello.c. v 1.1 2001/06/01 03:21:13 jrandom Exp qsmith $
$R Csfile:hellow.c, v $
This source code informs a user that the revision number is 1.5 of the driver. However, in Linux, frequently there is a 1.5 version on a developer's A box, that's different from the 1.5 version of the code on developer's B box. The 1.5 shows you some general common origin, but does not uniquely identify the code. The current tools available for discovering what is running on an existing system are to obtain the output from a modprobe-v program.
Thus, there is a need for a source code management system to calculate the checksum of the source file itself and allow the user to tag the file for display by programs such as the modprobe.

Method for tracking code revisions with a checksum data value being automatically appended to source files