To cancel a delay time that occurs in a delay circuit due to temperature and voltage changes. The delay circuit includes a plurality of first and second inverters that are each composed of an N-channel first transistor and a P-channel second transistor connected in series, and P-channel third transistors that are connected between a first power supply wiring and the input nodes of the second inverters. According to the present invention, the presence of the third transistors cancels characteristic variations of the second transistors included in the respective plurality of inverters even if there are changes in temperature, voltage, etc. Consequently, when temperature, voltage, or the like changes, variations in the amount of delay of the entire delay circuit can be regarded as resulting from characteristic variations of the first transistors.

1. Field of the Invention
The present invention relates to a delay circuit, and more particularly to a delay circuit that includes a plurality of delay elements connected in series.
2. Description of Related Art
Semiconductor devices may have a delay circuit for adjusting the timing of a control signal inside. For example, Japanese Patent Application Laid-Open No. 2003-273712 describes an example of using inverters as delay elements, which are connected in series to constitute a delay circuit.
In the case of the delay circuit described in Japanese Patent Application Laid-Open No. 2003-273712, when an input signal changes from a low level to a high level, the odd-numbered inverters output a low level and the even-numbered inverters output a high level. Here, N-channel MOS transistors turn ON in the inverters that output the low level, and P-channel MOS transistors turn ON in the inverters that output the high level. Given 2N stages of inverters, the total delay time is N×Tp+N×Tn, where Tn is the time needed for an N-channel MOS transistor to pull down the inverter output, and Tp is the time needed for a P-channel MOS transistor to pull up the inverter output.
Since the driving capability of a transistor depends on temperature, voltage, and the like, the foregoing values Tn and Tp also vary with temperature and voltage. As a result, the delay time of the entire delay circuit varies with temperature, voltage, etc. Variations in the delay time of the entire delay circuit due to changes in temperature, voltage, and the like include both the variation components of Tn and the variation components of Tp. It is therefore not easy to evaluate variations in the delay time of the entire delay circuit.
For example, a state where the N-channel MOS transistors have a low threshold voltage (perform switching at high speed) will be referred to as nL, and a state where the N-channel MOS transistors have a high threshold voltage (perform switching at low speed) will be referred to as nH. A state where the P-channel MOS transistors have a low threshold voltage (perform switching at high speed) will be referred to as pL, and a state where the P-channel MOS transistors have a high threshold voltage (perform switching at low speed) will be referred to as pH. There are four possible cases of variations in the delay time of the entire delay circuit, including nLpL, nLpH, nHpL, and nHpH.
Consequently, if the output signal of the delay circuit needs to be activated in synchronization with the operation timing of a predetermined circuit, it is difficult to make a change in operation timing occurring in the predetermined circuit due to variations in temperature, voltage, and the like coincide with a change in delay time occurring in the delay circuit due to variations in temperature, voltage, etc.


Controlling execution of application-specific hardware pipelines includes detecting, using computer hardware, a loop construct contained in a function within a design specified in a high-level programming language, extracting, using the computer hardware, the loop construct from the function into a newly generated function of the design, and generating, using the computer hardware, a state transition graph corresponding to the loop construct. The state transition graph can be pruned by relocating operations from the function entry state and the function exit state into the loop region. A circuit design defining, at least in part, a pipeline hardware architecture implementing the loop construct can be generated using the computer hardware based, at least in part, on the pruned state transition graph.

High-Level Synthesis (HLS) refers to a technology that converts a design specified in a high-level programming language, e.g., as source code, into a circuit design specified in a hardware description language. The circuit design may then be realized within an integrated circuit (IC). In one aspect, the IC may be a programmable IC. In generating the circuit design, particular programming constructs of the high-level programming language such as loops lend themselves to hardware pipelining. Recognizing loop constructs and such constructs as hardware pipelines can increase the data throughput and performance of the resulting hardware. As such, hardware pipelining is an important design technique for generating high-performance circuit designs in HLS.
A pipeline hardware architecture is typically designed to include a control circuit and a pipeline circuit. The control circuit and the pipeline circuit are designed in a manner that closely tracks the flow control of the loop construct and the data path execution of the original high-level programming language of the design. As a result, each pipeline hardware architecture is, in effect, an application-specific implementation of the loop construct having a customized control circuit. This process can be complex, time-consuming, and error prone.

Application-specific hardware pipeline implemented in an integrated circuit


A purifier of a noxious gas is provided with structure for supplying a gas containing a noxious gas component, a buffer using a liquid which dissolves the noxious gas component in the supplied gas temporarily and later releases the dissolved noxious gas component, and structure for purifying the noxious gas component in the gas supplied from the buffer means. The liquid in the buffer dissolves the noxious gas component when the concentration of the noxious gas component in the supplied gas is high and releases the noxious gas component dissolved thus far when the concentration is low. When the noxious gas is ethylene oxide, water is used as the liquid.

The present invention relates to a purifier of a noxious gas containing all kinds of hazardous components or malodorous components.
There are noxious gases containing hazardous components or malodorous components such as ethylene oxide gas used for sterilization procedure in hospitals or the like, carbon monoxide or hydrocarbon etc. exhausted from e.g. combustion equipment or from drying equipment for organic solvents. These hazardous components and these malodorous components should be purged from noxious gases before the noxious gases are released to the atmosphere. One approach to purify a noxious gas is to pass the noxious gas through an oxidation catalyst. The use of an oxidation catalyst can accelerate the oxidation reaction of ethylene oxide gas, carbon monoxide, hydrocarbon or the like at a lower temperature (for example, 200 to 400xc2x0 C.) than that for burning directly, so that the noxious gas can be changed into innocuous carbon dioxide or water vapor.
Such a gas purifier has, depending on e.g. the amount of catalyst stored inside, limitations with respect to the quantity of noxious gas components to be purified per unit of time (hereinafter referred to as xe2x80x9cprocessing capabilityxe2x80x9d). If a noxious gas in excess of the upper limit of this processing capability (concentration or gas volume) is supplied to the purifier, the noxious gas is exhausted without being sufficiently purified. In using this type of gas purifier, it is therefore important to prevent the supply quantity of noxious gas components, even temporarily, from exceeding the processing capability of the purifier.
However, a noxious gas is not always produced in a constant quantity and in a constant concentration. It is rather common that the quantity and the concentration of gas produced fluctuate to a large extent. Moreover, depending on the release source, a noxious gas is often produced intermittently. In such a case where the quantity and the concentration of noxious gas fluctuate, the installation of a purifier with processing capability covering the peak quantity of noxious gas is not an economical solution from the viewpoint of cost of the device and space to be occupied by the device.
Thus, consideration has been given to equipping a purifier with a cushioning device (buffer), which supplies the noxious gas to the purifier after the changes of quantity and concentration of a noxious gas have been smoothed, namely reduced, as much as possible. The simplest example of such a buffer is the use of a variable-volume container such as a plastic bag. In this case, the produced noxious gas is gathered temporarily in a plastic bag and then fed in an almost constant quantity into a purifier by the operation of a suction fan or the like of the purifier.
However, even if the use of a variable-volume container as a buffer can reduce fluctuations in the quantity of the supplied noxious gas, fluctuations of noxious gas concentration cannot be controlled. In other words, it is not possible to prevent the concentration of noxious components (components to be purified) contained in a noxious gas from fluctuating. Furthermore, although a plastic bag is inexpensive, this plastic bag needs to have a considerably large size for demonstrating sufficient buffer effects. As a result, a large space is required for installation, and the installation method is also not easy. Additionally, for safety reason, the plastic bag may have to be placed inside a casing having a certain degree of mechanical strength, which forms a dual structure resulting in higher cost. There are also inflammable gases and explosive gases included in noxious gases, so that this aspect should be taken into account as well.
Accordingly, it is an object of the present invention to provide a purifier of a noxious gas equipped with a buffer means for purifying the noxious gas economically and safely when the quantity or the concentration of the noxious gas fluctuates.
In order to accomplish the above object, a purifier of a noxious gas of the present invention is provided with means for supplying a gas containing a noxious gas component, buffer means using a liquid which dissolves the noxious gas component in the supplied gas temporarily and later releases the dissolved noxious gas component, and means for purifying the noxious gas component in the gas supplied from the buffer means.
According to the purifier using such a liquid, the noxious gas component can be supplied to the purification means after having been reduced at least to a certain value. Furthermore, there is no need to install a special apparatus or facility for carrying out this process. The size of the device itself can be determined appropriately according to the required processing capability and will not be unnecessarily large. Furthermore, if a noncombustible and inactive liquid is chosen as the liquid to be used for the buffer means, even inflammable and explosive noxious gases can be treated safely.
Apart from the present patent application, the applicant of the present invention has filed another patent application of a purifier equipped with buffer means using a gas adsorbent such as activated carbon (Japanese Patent Application (Tokugan Hei) 9-250245). According to this device, the noxious gas can be supplied to the purification means after the concentration is controlled at least to a certain value. And the same with the purifier of the present invention, the device in the aforementioned other application also demonstrates excellent cost performance. However, a certain kind of noxious gas such as ethylene oxide generates heat (ca. 70 to 80xc2x0 C.) when adsorbed to activated carbon etc., so that the noxious gas may not be purified successfully. On the other hand, the purifier of the present invention has the advantage of solving this problem of heat generation by using a liquid for the buffer means.
In the present invention, a noxious gas implies not only a gas which is hazardous for organisms including human beings or harmful to the environment, but also to all kinds of gases that preferably are removed, such as a hazardous gas of inflammable or explosive nature, an unpleasant gas with offensive odor, and a gas containing this kind of hazardous and unpleasant gas. The gas may be inorganic or organic. As examples of noxious gases, there are a volatile organic compound gas such as above-mentioned ethylene oxide, toluene, and acetone etc., and an inorganic compound gas etc. such as ammonia or the like. Gases containing a noxious gas can be listed, for example, emission gas of a sterilization apparatus used for sterilizing medical instruments (ethylene oxide-containing gas), emission gas of an incinerator, emission gas of a plant, exhaust gas of an organic solvent dryer, exhaust gas of an incinerator, exhaust gas of a draft chamber, and exhaust gas of a paint booth.
In the purifier of the present invention, it is preferable that the liquid in the buffer means dissolves the noxious gas component when the concentration of the noxious gas component in the supplied gas is high and releases the noxious gas component dissolved thus far when the concentration is low. Accordingly, the noxious gas component can be supplied to the purification means in a constant concentration, and the purification can be carried out efficiently. Such a function originally should be given to the liquid itself. However, if this function is not carried out sufficiently, as will be described later, a gas containing a noxious gas or a clean gas may be blown into the liquid to force dissolution or release.
It is preferable that the purifier of the present invention includes means for supplying a clean gas, with which the clean gas is supplied into the liquid in the buffer means. By supplying the clean gas into the liquid in the buffer means, the noxious gas dissolved in the liquid can be released even more. As a result, this liquid is purified and can be used once again for dissolving a noxious gas with high concentration.
There are two ways of supplying a clean gas into the liquid in the buffer means. The first embodiment is to supply a gas containing a noxious gas and a clean air by turns, and the second embodiment is to supply a gas containing a noxious gas and a clean gas at the same time. Depending on the configuration of the device and so forth, it is possible to choose one or the other embodiment appropriately, but the second embodiment is preferable. This is because when a gas containing a noxious gas and a clean gas are supplied simultaneously into the liquid in the buffer means, the dissolution and the release of the noxious gas occur simultaneously. Thus, the liquid can demonstrate the buffer effect and control the concentration of the noxious gas to be supplied into the purification means at least to a certain value. Moreover, the processing time can be reduced considerably from that required for the above first embodiment.
In the purifier of the present invention, it is preferable that the buffer means includes means for bringing a gas released from a liquid once again into contact with the liquid. This configuration enhances the buffer effect, since the noxious gas contained in the released gas dissolves once again in the liquid.
In the purifier of the present invention provided with the means for conducting the repetitive contact mentioned above, in the case where the process of contacting once again and the process of supplying a clean gas into the liquid both are carried out in the same container, the clean gas should not be supplied into the liquid when the gas released from the liquid is brought once again into contact with the liquid. On the other hand, it is preferable to supply the clean gas into the liquid at the time when the gas released from the liquid is not brought once again into contact with the liquid.
In the purifier of the present invention provided with the means for conducting the repetitive contact mentioned above, it is preferable that the buffer means includes a dissolution section for dissolving a noxious gas into the liquid, a purification section for cleaning the liquid containing the dissolved noxious gas with a clean gas, and means for bringing the gas released from the liquid in the dissolution section into contact with the liquid cleaned in the purification section Accordingly, the gas containing the noxious gas can be supplied simultaneously with the clean gas, so that the processing time and the processing efficiency are improved significantly. In the buffer means of this purifier, it is preferable that the liquid circulates between the dissolution section and the purification section, and that the gas containing the noxious gas is fed into the purification means from at least the purification section of the two aforementioned sections. Consequently, the processing time and the processing efficiency are improved even more.
When the gas released from the liquid and the liquid are brought into contact once again, the purifier of the present invention preferably is equipped with means for increasing at least either the contact area or the contact time. This is because the re-dissolution process of the noxious gas with the liquid can be carried out even more efficiently.
For increasing the above contact area or the above contact time, it is preferable to use, for example, means to shoot the liquid in the form of fog or shower, or means to let the liquid run along the surface of a member. This member should have a large surface area, for example, a horseshoe-shaped (U-shaped) member made of ceramics, metals, or resin etc. By placing a large number of such members and by pouring the liquid over these members, the liquid runs along the surfaces of these members, thereby contacting and dissolving the noxious gas. This kind of member is generally available on the market as a member used for increasing a gas-liquid contact area. Besides the aforementioned horseshoe shape, there are other forms such as Raschig ring, partition ring, primtriangle or the like. Not only these members but also a member with a large surface area such as a porous member, a member made of fiber, or the like can be used. Preferably, the members used here should have a small pressure loss, that is, good permeability.
It is preferable in the purifier of the present invention that the purification section mentioned above cleans the noxious gas component by means of a catalyst. In comparing with the method for purifying a noxious gas by burning, the use of catalyst has not only the advantage of reduction in energy costs but also of superiority in safety. As for the catalyst mentioned above, for example, oxidation catalysts can be used. To name some concrete examples, precious metal catalysts such as platinum and palladium, magnesium oxide, and copper oxide can be used. Furthermore, these catalysts usually are supported by a carrier, for example, by calcium aluminates. A carrier generally is formed e.g. in a honeycomb construction with permeability, and a catalyst is supported by the carrier through impregnation and adhesion. The present invention prefers to use a platinum catalyst supported by calcium aluminates of honeycomb construction. Moreover, the amount of catalyst used etc. is not particularly limited and can be decided appropriately depending on the intended processing capability and other conditions.
It is preferable that the purification section mentioned above includes means for detecting a catalytic temperature and means for controlling the quantity of a noxious gas to be supplied into the purification means based on the temperature detected by the detection means of catalytic temperature. If the concentration of a noxious gas increases, the catalytic temperature may rise due to the accelerated catalytic reaction, and the aforementioned means are provided to prevent this from occurring.
In the present invention, the liquid used for the above buffer means preferably has low volatility, less harmfulness, and small heat release when burned. Examples of the above liquid are: aqueous solvents such as water and sodium hydroxide aqueous solution; organic solvents such as alcohols, e.g. methyl alcohol, ethyl alcohol, and polyalcohol derivatives etc., e.g. ethylene glycol. The above liquid may be used individually or in combinations of two or more different kinds. When two or more different kinds of liquid are used, they may be used in a mixed form or separately. These liquids are selected appropriately according to the kind of noxious gas and so forth. For instance, water is preferably used for ethylene oxide, methyl ethyl ketone, isopropyl alcohol or the like. While alcohols are used preferably for xylene, toluene, methyl isobutyl ketone or the like, ethylene glycol is used preferably for acetone.
In the present invention, if a noxious gas to be purified is ethylene oxide, water should be used as the above liquid for the reason described above. Additionally, if a noxious gas to be purified is ethylene oxide, the concentration of ethylene oxide contained in a gas supplied from buffer means to purification means is preferably controlled to be 20000 ppm or less. The lowest critical concentration of explosion is 3% for ethylene oxide, so that the concentration of 20000 ppm or less does not cause a safety problem. For other noxious gases, the lowest concentration of supply to the purification section is determined appropriately by the nature of the gas etc. For example, the concentration for methyl ethyl ketone is 1.8%, 2.0% for isopropyl alcohol, 1.0% for xylene, 1.2% for toluene, 1.4% for methyl isobutyl ketone, and 2.15% for acetone.
In the present invention, the above clean gas should be an inert gas, and for the reasons such as application and cost, it is preferable to use clean air. In the present invention, a clean gas implies a gas that substantially does not contain a noxious gas to be purified, and the use of a filter etc. for collecting dust is not particularly necessary. However, it is preferable to use a gas that has passed through a dust collecting filter for durability of the device or with respect to catalytic activity and so forth.
In the present invention, the means for supplying a gas into the liquid is preferably operated by blowing the gas into the liquid and producing a large quantity of bubbles. It is because this method improves the solubility of the gas into the liquid. One example of this means for producing bubbles is blowing the gas into the liquid through a porous member.
In the present invention, when a water-sealed vacuum pump is used for supplying a gas containing a noxious gas together with water, it is preferable that the water circulates between the water-sealed vacuum pump and the buffer means. This system can utilize the water of the water-sealed vacuum pump effectively.
This purifier preferably is configured such that, when an abnormal state breaks out, the water and the gas containing a noxious gas supplied from the water-sealed vacuum pump are not supplied into the buffer means but instead released to the outside of the purifier. Furthermore, it is preferable to store the released water and the released gas containing a noxious gas temporarily in a storage tank. After the purifier has returned to a normal state, the water and the gas to be purified are supplied from the storage tank into the buffer means and then cleaned by the purification means.
Next, the present invention provides a method for purifying a noxious gas by which a gas containing a noxious gas component is purified. The method includes the steps of: passing the gas through buffer means using a liquid that dissolves the noxious gas component temporarily and releases the dissolved component later, and supplying the above gas into purification means. Here, the gas supply is intermittent, or the concentration of the noxious gas component becomes intermittently higher. With this method, the gas is supplied to the purification means after the peak concentration value of the noxious gas component in the gas is reduced. This method can be carried out with the use of the purifier of the present invention described above. Due to the reasons mentioned above, it is preferable in this method to supply the gas containing the noxious gas and the clean gas simultaneously into the liquid in the buffer means.

Purifier of noxious gas and method for manufacturing the same


An embodiment of the invention may include a method of forming and a resulting multiply-and-accumulate device. The device may include a capacitor in a second region. The capacitor comprises a dielectric located between a first metal contact and a second metal contact. The device may include a stacked nanosheet device in the first region from the nanosheet. The stacked nanosheet device may include a top transistor and a bottom transistor in contact with the first metal contact. The device may include a nanosheet device in the third region, wherein a source/drain of a transistor of the nanosheet device is in contact with the first metal contact.

The present invention relates to semiconductor device fabrication, and more specifically, to stacked FET gates.
Stacked nanosheet designs provide a significant gain for both logic and memory device structural scaling by stacking FETs above one another. The stacked nanosheet device allows for 2 n-FETs, 2 p-FETs, or a combination of n-FET and p-FET devices located in the same footprint of a nanosheet.

Stacked FET multiply and accumulate integrated circuit

International Business Machines Corporation


Method for forming dielectric isolation region and SiGe channels for CMOS integration of nanosheet devices generally includes epitaxially growing a multilayer structure including alternating layers of silicon, silicon germanium having a germanium content of x atomic percent and silicon germanium having a germanium content of at least 25 atomic percent greater than x. The alternating layers can be arranged and selectively patterned to form a nitride dielectric isolation region, silicon nanochannels in the NFET region, and silicon germanium nanochannels in the PFET region.

The present invention relates in general to integrated circuit device structures and their fabrication. More particularly, the present invention relates to dielectric isolation and SiGe formation for integration in complementary metal oxide semiconductor (CMOS) nanosized channel devices.
In an integrated circuit, each metal oxide semiconductor field effect transistor (MOSFET) has a source and a drain that are formed in an active region of a semiconductor layer by implanting n-type or p-type impurities in the layer of semiconductor material. Disposed between the source and the drain is a channel (or body) region. Disposed above the body region is a gate electrode. The gate electrode and the body are spaced apart by a gate dielectric layer. Complementary metal oxide semiconductor (CMOS) is a technology that uses complementary and symmetrical pairs of p-type and n-type MOSFETs to implement logic functions. The channel region connects the source and the drain, and electrical current flows through the channel region from the source to the drain. The electrical current flow is induced in the channel region by a voltage applied at the gate electrode.
Non-planar MOSFET architectures, such as nanosheet (or nanowire) transistors, can provide increased device density and increased performance over planar transistors. Nanosheet transistors, in contrast to conventional planar FETs, include a gate stack that wraps around the full perimeter of multiple nanosheet channel regions for improved control of channel current flow. Nanosheet transistors enable fuller depletion in the nanosheet channel regions and reduce short-channel effects.

Dielectric isolation and SiGe channel formation for integration in CMOS nanosheet channel devices

INTERNATIONAL BUSINESS MACHINES CORPORATION


A multi-faceted intake filter for an aquarium includes a top surface portion, a bottom surface portion and a plurality of side surface portions that collectively define a filter body is formed from a compressible foam. The intake filter also includes a bore that extends along a longitudinal axis of the filter body. The bore includes a first end exposed at the top surface portion that leads to a second end which terminates prior to the bottom surface portion. The bore is designed to receive an intake portion of an aquarium filter tube. Preferably, the bore is off-set from a central axis of the filter body. The off-set bore allows the intake filter to be placed in a wide range of aquarium configurations, with at least one of the side surface portions abutting a wall of the aquarium.

1. Field of the Invention
The present invention pertains to the art of aquariums and, more particularly, to an intake tube filter for an aquarium.
2. Discussion of the Prior Art
At present, aquarium filters are of two general types. The first type constitutes under-gravel filters which are placed on a bottom of an aquarium and filtered with gravel so that the entire floor of the aquarium acts as a filter. The second type is defined by above gravel filters which function to draw in fluid from above the bottom of the aquarium and subsequently pass the fluid through a filter prior to re-introducing the fluid back into the aquarium. For instance, it is known to draw in fluid through an intake tube of a filter that is suspended above the bottom of the aquarium. The fluid is then directed through an enclosure arranged outside the aquarium prior to being sent back to the aquarium. The enclosure is packed with a filter medium, such as charcoal, synthetic floss or the like, to cleanse the fluid.
Above gravel filters possess certain drawbacks. More specifically, external filters typically employ a filter tube having an intake provided with a strainer or the like that prevents fish from being drawn into the filter. However, strainers are designed to keep out larger fish, not smaller fish. For instance, fry and other small fish can often pass through the strainer and wind up in the filter. To address this problem, while also providing an additional degree of filtration, it has been proposed to place a filter over the intake. Unfortunately, available intake filters are essentially only fit to a particular intake tube, rather than to the tank. This creates a serious concern as fish can become trapped between the intake filter and a wall of the aquarium. Unless this condition is discovered quickly, the fish may be fatally harmed.
Based on the above, there exists a need for a filter for an intake tube wherein the filter is specifically designed to protect fish from being undesirably trapped between the filter tube and a wall of an aquarium. More specifically, there exists a need for a filter that can be universally fit to a wide variety of filter tubes, while preventing the ingestion of smaller fish or fry and, at the same time, ensuring that fish are not caught and trapped between the filter and a wall of the aquarium. In addition, there exists a need for an intake tube filter which is capable of performing at least a substantial portion of the filtering function.

Multi-faceted intake filter for an aquarium


A readily dissolvable carrier material having sufficient rigidity for administration of drugs, nutrients, vitamins, biologically-active materials, foodstuffs and combinations thereof capable of rapid dissolution by saliva, bodily fluids or other liquid comprising an interim skeletal structure of a water-soluble, hydratable gel or foam forming material, preferably a proteinaceous material, such as gelatin, that has been hydrated, rigidified, such as with maltodextrin, in the hydrated state and dehydrated to leave spaces in place of hydration water. On dissolution by saliva, bodily fluids or other liquids. The composition becomes a liquid system. While the oral route is preferred, other routes may be used to administer the compositions of this method.

The method and compositions of the present invention are directed to an alternative method of drying drug and nutrient carriers that produce solid, rigid, but rapidly dissolvable drug and nutrient carriers capable of rapid liberation of the active component to the body in a method that yields new and unexpected results over extant methods of freeze drying.
In accordance with an important feature of the present invention, a composition of (1) a hydrogel or foamed, non-toxic, edible solid carrier material, such as a proteinaceous material, particularly gelatin or a gelatin derivative, e.g., gelatin; gelatin A; gelatin B, modified fluid gelatin, albumin, and the like; or hydrogels formed from materials such as acacia, tragatanth, and/or guar gum; or aqueous foams formed with any anionic, cationic or amphoteric surfactant, either synthetic or natural (biosurfactants) e.g., lecithin; together with (2) a non-toxic, edible, polysaccharide, capable of rigidifying the hydrogel or foam substance during dehydration thereof, for example, dextrin or a dextrin derivative, such as maltodextrin, can be dried in accordance with the present invention to leave a porous skeleton carrier, preferably of a proteinaceous material, capable of absorbing and/or adsorbing many times its weight in a drug and/or nutrient and the like.
In accordance with one important embodiment of the present invention, the solid, porous, skeletal carrier is formed by drying the fully hydrated gel or foam material from the gel or foamed state by transfer of water from the hydrated material to an alcohol solution, when both the hydrated gel or foam material and the alcohol are frozen or near freezing, without necessitating vacuum conditions, as needed for lyophilization.
A literature search of Chemical Abstracts 1975 to 1988 failed to reveal any reference which anticipates or suggests the water removal methods of this invention or the products produced by such methods.
Reference texts such as Remington's Pharmaceutical Sciences, 15th Edition, 1976, and Lachman et al, The Theory And Practice Of Industrial Pharmacy, Lea & Febiger, 1978, describe the process of lyophilization as a method to stabilize water and heat-sensitive drugs.
Patent references which include lyophilization in their respective methods are exemplified by Alexander U.S. Pat. No. 4,537,883; Lafon U.S. Pat. No. 4,537,883; Vendel U.S. Pat. No. 3,496,267 and Saferstein, et al U.S. Pat. No. 4,752,466. In each of these patents a method involving lyophilizing or freeze drying under vacuum conditions of unstable compositions is disclosed.
Aside from the common use of low temperature, the low temperature drying method of the present invention has very little similarity to the process of lyophilization. The differences of method and product between this invention and the well known lyophilization process will become more apparent hereinafter.
Lyophilization involves the use of mechanical equipment and control of vapor pressure to produce stabilized drugs. In contrast, the method of the present invention includes the use of an organic solvent and is based on the chemical processes of solubilization and dissolution to produce drug and nutrient delivery compositions, preferably under ambient pressure conditions.

Freeze dry composition and method for oral administration of drugs, biologicals, nutrients and foodstuffs


The process for the production of the carboxylic acid chlorides of the aromatic nitrogen heterocycles of the series of the compounds of the general formulas: ##STR1## The hydroxy carboxylic acids of the aromatic nitrogen heterocycles from the series of the compounds of the general formulas: ##STR2## In the general formulas I to VI, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are the same or different and each is a hydrogen atom or a halogen atom. The chlorination is performed with a solution of phosphorous pentachloride in phosphoroxy chloride. The excess phosphorous pentachloride is converted into phosphoroxy chloride either with a C.sub.1 -C.sub.4 -carboxylic acid or with a silane of the general formula: EQU (CH.sub.3).sub.3 --Si--OR.sub.9 VII. Then the product according to one of the general formulas I to III is isolated.

1. Field Of The Invention
The invention relates to a new process for the production of carboxylic acid chlorides of aromatic nitrogen heterocycles of the series of compounds of general formulas: ##STR3## by chlorination of the corresponding hydroxy carboxylic acids of aromatic nitrogen heterocycles from the series of compounds of the general formulas: ##STR4## In the above general formulas I to VI, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are the same or different and each is a hydrogen atom or a halogen atom.
These carboxylic acid chlorides of aromatic nitrogen heterocycles, such as, 6-chloropicolinic acid chloride, are important intermediate products for the production of herbicides [European Published Patent Application No. 447,004].
2. Background Art
The direct reaction of 6-hydroxypicolinic acid to 6-chloropicolinic acid chloride has not yet been described in the literature. Only the chlorination of 6-hydroxypicolinic acid to 6-chloropicolinic acid with phosphorous pentachloride in phosphoroxy chloride is known [Ber. D. Chem. ges., 45, (1912), page 2461]. 6-Chloropicolinic acid chloride can then be produced only by another chlorination of 6-chloropicolinic acid with, for example, thionyl chloride. A drawback of this process is the fact that under these conditions the product can only be produced by a 2-stage synthesis and that large amounts of phosphoric acid accumulate in the first stage as waste product in the working-up of 6-chloropicolinic acid as the intermediate product.
Also, the production of 6-chloropicolinic acid chloride, starting from 6-chloro-2-methylpyridine, is known [European Published Patent Application No. 032516]. A great drawback of this process is the fact that the feedstock 6-chloro-2 -methylpyridine must first be oxidized in a first stage with potassium permanganate to 6-chloropicolinic acid, the latter compound is then converted with thionyl chloride in the second stage into 6-chloropicolinic acid chloride, and the product is obtained in a moderate yield.

Process for the production of carboxylic acid chlorides of aromatic nitrogen heterocycles


A driveshaft misalignment measurement system for a drivetrain of an aircraft includes a driveshaft having a first end forming a driveshaft spline and a drivetrain subsystem including a spline adapted to connect to the driveshaft spline to form a splined connection. Rotational energy is transferred between the drivetrain subsystem and the driveshaft via the splined connection. The driveshaft misalignment measurement system also includes accelerometers coupled to the drivetrain configured to detect acceleration data and a flight control computer configured to measure misalignment at the splined connection using the acceleration data.

Driveshafts, or torque shafts, are used to transmit torque in an aircraft drivetrain. For example, driveshafts in a rotorcraft drivetrain transmit rotational energy from an engine or motor to a rotor via a gearbox. Driveshafts are subject to different types of misalignments that can reduce or prevent the efficient transmission of torque in the drivetrain. For example, static misalignment of a driveshaft can occur as a result of flight loads experienced during flight maneuvers. Installation stackup misalignment of a driveshaft may be caused by improper assembly or installation of drivetrain components. Driveshafts are also subject to oscillatory misalignment caused by rotor harmonics or other oscillatory vibrations that occur during flight. One example in which oscillatory driveshaft misalignment can be observed is in tiltrotor aircraft with hard-mounted drivetrains that experience high levels of rotor harmonics, aeroelastic phenomena and other vibrations.
Flex-coupling driveshafts are employed by current helicopters to combat driveshaft misalignment. Measuring oscillatory driveshaft misalignment in flex-coupling driveshaft systems, however, requires an exposed driveshaft since misalignment is typically measured directly at the driveshaft. Also, while driveshaft flex-couplings can reduce driveshaft misalignment, they are not feasible for all types of aircraft. For example, the nacelles of tiltrotor aircraft often use hard-mounted drivetrain components, the driveshafts of which are often obscured by a driveshaft housing that precludes direct misalignment measurements. For aircraft with hard-mounted driveshafts, the connections on either end of the driveshaft may have small misalignment limits, which if exceeded can fail or cause damage to the connection or driveshaft. Accordingly, a need has arisen for driveshaft misalignment measurement systems and methods that are effective across a wider variety of aircraft with different types of drivetrains.

Driveshaft misalignment measurement systems and methods


Processes for preparing an oral care composition having improved taste, color, odor and/or clarity, wherein said processes comprise the steps of: providing an unfiltered dentifrice component selected from unfiltered alkyl phosphate surfactants, alkyl phosphate ethoxylated surfactants, lauryl sulfate surfactants, betaine surfactants, antibacterial agents, cetyl pyridinium chloride, metal Salts, phytic acids, or mixtures thereof; filtering the unfiltered dentifrice component with an adsorbent to form a filtered dentifrice component; and incorporating the filtered dentifrice component into the oral care composition. In one such process, activated carbon with a median particle size of less than or equal to about 30 μm, optionally a macro-mesoporous:microporous ratio about 0.9 or higher and optionally a BET per Total Volume of equal to or less than about 1600 m^2/g, has been found to remove undesirable contaminants from oral care dentifrice components, such as alkyl phosphate surfactant, alkyl phosphate ethoxylated surfactant, lauryl sulfate surfactant, betaine surfactants, antibacterial agents, cetyl pyridinium chloride, metal salts, or phytic acid.

Traditionally, much effort has been expended to improve the taste, color, odor or clarity of oral care compositions such as dentifrice (toothpaste), mouth rinse, and the like. Because of the nature of such compositions, the taste of a product may often be of more importance to consumers than the actual efficacy. Since many efficacious oral care components have undesirable taste, color, odor or clarity, efforts to improve these characteristics are common in the art. For taste, one way to remedy an undesirable product taste is to add additional components, such as flavors, that will improve the overall taste experience for the consumer. However, such remedies can be expensive and it may be difficult to entirely mask an undesirable taste. Improvement of color or clarity through dyes or other additives has similar issues.
Activated carbons are generally known in the art as useful for filtering/purifying water (due to their adsorbent behavior and large surface area) by removing undesirable constituents, such as chlorine, sediment, organics, viruses, and volatile organic compounds. They have also been utilized in chemical processing to reduce or eliminate undesirable by-products or contaminants. Activated carbons are known to be less effective at removing minerals, salts, and dissolved inorganic compounds.
In JP 2004107270, activated carbon was also taught to be used to remove odiferous and discoloring species from a phosphate ester surfactant.
Therefore, there is still an interest in finding ways to improve the overall taste, color, odor and/or clarity of food-grade materials such as those used in an oral care composition that are efficacious, cost-effective, and desirable to consumers.

Process for making improved oral compositions


A method of manufacturing a shaped polymeric article is provided. A sheet of extruded hot polymeric material is provided and disposed onto a rotating belt. The rotating belt includes a mold impression therein and a plurality of apertures therethrough. The mold impression resembles a plurality of adjacent shingle impressions of substantially the same length. Each of the shingle impressions includes a bottom edge where at least one of the bottom edges is beveled to give the appearance of shingles having different lengths. Vacuum pressure is applied to the hot polymeric material through the belt, so as to draw the sheet into intimate forming contact with the mold impression to form a patterned central portion. The patterned central portion is cooled below the heat deflection temperature of the polymeric material. A length of the sheet is severed to produce a shaped polymeric article.

This invention relates to the continuous manufacture of shaped articles, such as siding panels having the appearance of real wood, such as cedar shake.
Continuous and semi-continuous processes for creating patterns on extruded plastic sheets have been used in the building components industry for a number of years. Some prior systems have disclosed rigid linked patterns for forming shaped impressions in an extruded sheet material. Unfortunately, such rigid shaped patterns tend to form unsightly horizontal seams in the material. Other systems have used pattern forms on rotating cylindrical drums. Although these processes are continuous, and do not produce horizontal seams, they often require expensive additional equipment and instrumentation to align the arcuate surface of the pattern with the relatively flat surface of the product, and to avoid, or correct, unwanted bowing of the product.
Because of the limitations on prior continuous processes, some manufacturers have opted for injection or blow molding such products one at a time. While this technique can provide the desired detail in texture and surface finish, it is limited to product sizes of about 4-5 feet in length and provide product thicknesses which are practically limited to greater than about 0.080 inches. This is generally because of the difficulty associated with flowing hot viscous polymer through thin cross-sectional profiles in steel molds. Additionally, because of the known size limitations, the randomness of individual features on the surface of a molded product is limited. This is because only a relatively small number of pattern elements, such as shingles, can be molded into the relatively small surface area. When several of these products are aligned side by side on a wall of a building, for example, it is sometimes obvious to see the pattern repeated over and over again.
One solution to these problems is disclosed in Bosler, U.S. Pat. No. 5,314,325 dated May 24, 1994. Bosler""s invention provides a continuous vacuum forming process which uses a resilient mold belt for providing semi-continuous production of almost unlimited lengths of shaped polymeric articles. He further teaches a single cooling step whereby the entire width of the product is brought below the heat deflection temperature of the polymeric material.
It has now been determined, however, that a single cooling step reduces the temperature of the edge portions below a comfortable range for subsequent sizing and forming. Accordingly, there remains a need for providing for the separate formation of edge portions, such as butt-edges and nail edges customarily used in the fabrication of siding panels.
The present invention provides an extruded siding panel, and method of making the same, comprising a sheet of polymeric material. The sheet includes a molded central portion comprising a plurality of adjacent shingle impressions of substantially the same length. Each of the shingle impressions includes a bottom edge. At least one of the bottom edges of the shingle impressions is beveled to give the appearance of shingle impressions having different lengths.
The siding panel embodiments, described herein, provide the appearance of shingles having different lengths without the need to form shingle impressions having different lengths. This feature promotes the appearance of a miscellaneous selection of individual shingles on any wall covered with the siding pattern. The formation of the beveled edges is also easily incorporated into a continuous extrusion process and in a pattern that provides the aforementioned appearance of miscellaneous shingle selection. The above and other features of the present invention will be better understood from the following detailed description of the preferred embodiments of the invention that is provided in connection with the accompanying drawings.

Method of manufacturing a shaped polymeric article


A medical imaging device has an emission tomograph, at least one ultrasonic (US) probe for providing images giving real-time information about the location of the internal organs of a subject, a tracking system for spatially locating the at least one ultrasonic probe in relation to the medical imaging device, and an image processing unit in which the location information obtained by the ultrasonic probe is used for attenuation correction of image information obtained by the emission tomograph.

In cardiac and thoracic PET or PET/CT, the image reconstruction procedure requires a good estimate of the attenuation suffered by pairs of emitted photons. In measuring this and converting the measurements to correction factors, it may be particularly important to account for attenuation edges related to the boundaries between lung and soft tissue, including the moving diaphragm and heart wall. It is axiomatic that one may need to correct the PET data with a different pattern of attenuation correction factors at each moment in time, yet this is not done in normal practice. Instead, one makes do with approximate solutions.
Conventional PET scanners make a transmission measurement lasting several minutes, based on a line source orbiting between the patient and the PET scanner's detectors. In that case, one measures the time-averaged attenuation due to the patient as his chest may have moved through many configurations. Arguably, this may result in a good standard for cardiac PET. In the case of PET/CT, attenuation maps are derived either from the "snapshot" provided by a fast CT scan (to use a metaphor from ordinary photography) or from the "time-exposure" obtained in a slow CT scan. Fast CT scanning of the chest fails to represent faithfully the configuration of attenuating tissue, which is in constant motion. Slow CT somewhat averages organ motions in the chest, but the averaging is not identical to the motion that occurs in a PET scan, which typically lasts for many minutes. Still another approach is the time-averaged CT scan. Of these various approaches, the fast static CT has the advantage of a lower radiation burden.
A need exists to measure the attenuation more accurately to give a better calculation of an emission image. This may improve the quality of the image reconstruction procedure and the resulting image.
Besides the continuous quest for improved image quality, it may be desirable to have an efficient and/or sensitive medical device performing PET, PET/CT, SPECT or SPECT/CT. This would allow for a reduction in time for taking images, an improved quality of the images, and/or a reduction of exposure of a subject to the image apparatus.
Additionally, it is desirable to avoid cumbersome and time consuming arrangements or methods, in an economic and technical perspective, for measuring the attenuation accurately.

Ultrasonic imager for motion measurement in multi-modality emission imaging


Bacterial strain Clostridium histolyticum was deposited in CCM (Czech Collection of Microorganisms at Masaryk University, Faculty of Science) under No. CCM 8656. This strain produces proteolytic enzymes including collagenase, elastinase, neutral proteases and clostripain under anaerobic conditions at a temperature from 25° C. to 45° C. The strain is used for the production of a mixture of two collagenases, col 1 and col 2, with molecular weight 116 kDa and 126 kDa, and possibly clostripain. The mixture of the above-mentioned collagenases and possibly clostripain obtained from the above-mentioned strain is used for the isolation of Langerhans islets.

Collagenase is a protease which is able to degrade the collagen protein (the basic component of intercellular mass, e.g., in connective tissue). Collagenases are commonly used in research, particularly for the disintegration of intercellular mass to release cells. In this respect, clostridiopeptidase A isolated from Clostridium histolyticum proved to be useful (the name of the bacterium, i.e., histolyticum, reflects its ability to degrade tissues). Enzyme collagenase is not only used for research purposes; it has also found its place in human and veterinary medicine, especially for the treatment of skin diseases. In connection with certain non-specific proteases, the collagenase removes necrotic tissue from wounds and thus accelerates healing and improves epithelialization. Collagenase is used in tissue transplantation and for tissue disintegration. It is also applied for the treatment of (acid) burns of various degrees, decubiti, skin ulcers, scabs, etc. Not only is the epithelialization of skin fast and effective after treatment with collagenase, but also the collagenase treatment prevents formation of keloids (enlarged scars of tumour-like appearance) and hypertrophic growth as a result of the formation of decomposed collagen.
Various strains of microorganisms, cultured under defined conditions, are known to synthesize collagenase. It was found that among all organisms that are able to synthesize collagenase, Clostridium histolyticum is the best producer. MacLennan J. D., Mandl I. and Howes E. I.: Bacterial digestion of collagen. J. Clin. Inv. 32: 1317-1322 (1953) described conditions needed for growth of Clostridium histolyticum. They examined the composition of the liquid environment which mainly consists of proteose peptone, inorganic salts and a vitamin solution. Bacteria are cultured at 37° C. and pH 7.2. Berman S., Lewenthal J. P., Webster M. E., Altieri P. L. and Gochenour R. B.: Factors affecting the elaboration by Clostridium histolyticum of proteinases capable of debriding third degree burn eschars on guinea pigs. J. Bacteriol. 82: 582-588 (1961) also examined growth conditions of Clostridium histolyticum with the aim to produce collagenase. They were successful in culturing of Clostridium histolyticum in medium which did not contain any inorganic salts; it only contained proteose peptone, enzymatically hydrolysed proteins of casein and soya (soya culture medium) and a vitamin solution. Such a composition of culture medium also determined other parameters of conditions required for satisfactory growth and biosynthesis of collagenase, such as the value of pH 8.5 and a temperature 30° C. and higher.
Clostridium histolyticum is an anaerobic bacterium and anaerobic conditions must be ensured for culturing of this bacterium in a liquid environment. Takahashi S. and Seifert S.: J. Appl. Bact. 35, 47 (1972) used the reducing agents sodium thioglycolate and sodium bisulfite in order to achieve the anaerobic conditions necessary for bacterial growth. The optimum results, i.e., the highest yield of collagenase, was achieved when the above-mentioned reducing agents were used in the ratio of 1:1.
Up to the present, a considerable number of procedures using various buffering systems (and mostly including precipitation for the isolation of a functional protein) have been applied for collagenase extraction from different sources (both bacterial and other). However, these procedures are performed at physiological pH 7.4-7.6, which is not optimal for the production of bacterial collagenase and at a low temperature which prevents degradation of the enzyme. The essence is that commonly used physiological pH is not the most suitable for Clostridium. E.g., Yoshida, E. and H. Noda, 1965. Isolation and characterization of collagenase I and II from Clostridium histolyticum. Biochim Biophys. Acta, 10593: 562-574. DOI: 10.1016/S0926-6593(65)80239-9; or Sakamoto, S., P. Goldhaber and M. J. Glimcher, 1972. The further purification and characterization of mouse bone collagenase. Calc. Tis. Res., 10: 142-151. DOI: 10.1007/BF02012544; or Bond, M. D. and H. E. Van Wart, 1984. Characterization of the individual collagenases from Clostridium histolyticum. Biochemistry, 19: 3085-3091. DOI: 10.1021/bi00308 a036; or Matsushita, O., K. Yoshihara, S. I. Katayama, J. Minami and A. Okabe, 1994. Purification and characterization of a Clostridium perfringens 120-Kilodalton collagenase and nucleotide sequence of the corresponding gene. J. Bacteriol., 176: 149-156. PMCID: PMC205026.
Buffers other than Tris-HCl are also used for the purification of collagenase, e.g., sodium bicarbonate, which also should maintain the stability of collagenase. In bicarbonate buffers, a higher pH is used, which is in our case suitable for collagenase from Clostridium histolyticum; however, in such purification protocols, the collagenase is isolated from snails. Indra, D., K. Ramalingam and M. Babu, 2005. Isolation, purification and characterization of collagenase from hepatopancreas of the land snail Achatina fulica. Comparative Biochem. Phys., 142: 1-7. DOI: 10.1016/J.CBPC.2005.02.004.
The amounts of used ions appropriate for stability and effective action of enzymes degrading extracellular components are different in the particular approaches. Klimova, O. A., S. I. Borukhov, N. I. Solovyeva, T. O. Balaevskaya and A. Y. Strongin, 1990. The isolation and properties of collagenolytic proteases from crab hepatopancreas. Biochem. Biophys. Res. Commun., 166: 1411-1420. DOI: 10.1016/0006-291x(90)91024-M.
By combining the use of a specific production strain from an MB Pharma collection and suitable culturing conditions, sufficient production of the required enzymes occurs. A combination of collagenase produced by the specific strain of Clostridium histolyticum and the implementation of optimum conditions of collagenase purification is unique. At first, we stabilize the enzyme through dialysis to a buffer of a higher pH (8), which is more natural for Clostridium histolyticum collagenase than physiological pH in the above-mentioned procedures. Only through gradual dialysis to buffers of a lower pH, fluent transition to physiological conditions more appropriate for clinical practice, is ensured. Crude collagenase enzymes produced up to now lack sufficient efficacy for Langerhans islets (LI) isolation. This can be caused by poor production of individual proteins or incorrect preparation process. For high yield of LI, it is necessary to use highly efficient purified collagenase enzymes and mixtures of these enzymes. Combination of a new production strain CCM 8656 and circumscribed enzyme production procedures (see examples) enables the production of enzymatic mixture that is more efficient than the crude collagenases available and its efficacy is comparable to efficacy of purified collagenases mixture.
The objective of this invention is to provide a specific Clostridium histolyticum strain, the product of which, the collagenase enzyme, is obtained and in its final form can be used for cleavage of connective structures of the pancreas in order to receive vital Langerhans islets which can be used in a transplantation treatment of diabetes. Collagenase is a mixture of up to 12 proteolytic enzymes and other proteins received from a filtrate of Clostridium histolyticum cultures. Pancreas digestion is performed in an isolation chamber which was designed by Dr. Ricordi et al. and which is used in almost all isolation centres (Berková Z., Zacharovová K., Kříž J., Jirák D., Girman P., Dovolilová E., Koblas T., Hájek M., Saudek F.: The impact of islet labeling with superparamagnetic nanoparticles for magnetic resonance imaging on islet vitality; 10th world congress of IPITA, Geneva, Switzerland, 4.-7.5.2005). It is a closed system in which a collagenase solution circulates, and while it is slightly agitated, the cells release gradually.

Bacterial strain clostridium histolyticum and methods of use thereof


An ultrasound imaging apparatus (20) is disclosed, comprising a data interface (30) configured to receive a plurality of different ultrasound data sets (26, 28) resulting from an ultrasound scan of an object (18) in different viewing directions. The ultrasound imaging apparatus further comprises a segmentation unit (32) for segmenting anatomical structures of the object in the different ultrasound data sets and for providing segmentation data of the anatomical structures, and a reference determining unit (34) for determining a spatial reference (48, 50, 52, 54) for the different ultrasound data sets on the basis of the segmentation data. A confidence determining unit (40) is included for determining confidence values (56) for different regions of the received ultrasound data on the basis of the spatial reference.

Ultrasound imaging systems are generally known for examination of anatomical features in human patients. In particular, ultrasound imaging systems are used for prenatal screening examination of the foetal central nervous system. A corresponding ultrasound system is e.g. known from US 2009/0093717 A1.
Due to the physics of ultrasound propagation in tissue, the orientation of the ultrasound probe with respect to the anatomical features and in particular with respect to a foetal skull has a significant influence on the quality of the ultrasound images and in this particular case of the neurosonogram. To overcome this drawback of the ultrasound propagation in tissue, the probe of the ultrasound system is usually disposed at a specific position in order to obtain the most confident view for diagnostic.
A further technique to improve the quality of the ultrasound images is to acquire a series of partially overlapping image frames from independent spatial directions using a transducer array for steering and/or translation of the different image frames.
However, the known ultrasound imaging systems cannot reflect the anatomical structures of all regions within the field of view and may provide artefacts in certain regions of the field of view so that the clinical diagnostic can be negatively affected.


Disclosed herein are methods of using a cell-derived extracellular matrix derived in-vitro from cells isolated from amniotic fluid (AFC-ECM) for the maturation of immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs) in culture forming mature cardiomyocytes. Also disclosed herein is a cell construct comprising a monolayer of these mature cardiomyocytes on an AFC-ECM useful for cardiotoxicity and/or proarrhythmic screening assays of drug compounds. Also disclosed herein are methods for determining the cardiotoxicity and/or proarrhythmic effect of a drug compound in vitro using such cell constructs.

Cardiotoxicity, or the perceived potential for cardiotoxicity, is a leading cause of toxicity related drug attrition during the investigation and selection of new drugs. Cardiac safety testing of new chemical entities that become lead drug candidates is a critical aspect of the drug discovery and development pipeline. A large number of cardiac side effects of cardiac and non-cardiac drugs are caused by drug interaction with one or more cardiac ion channels. Cardiac ion channels regulate cellular excitability, contractility and overall cardiac performance, and alteration of cardiac ion channel function can lead to sudden cardiac death. This contributed to the release of drug candidate testing guidelines from The International Conference on Harmonization (ICH).
The current preclinical drug candidate testing guidelines from the IHC (ICH S7A and S7B-Pharmacology Studies) rely on genetically modified heterologous cells and in vivo animal models. It has become increasingly recognized that these studies, such as hERG assay and QT prolongation studies, do not accurately predict cardiotoxicity and proarrhythmia risk for humans. Since 2005, cardiac safety of a drug compound has been determined almost exclusively by its effect or potential effect on the QT interval of the electrocardiogram (ECG) or the action potential duration (APD), and the potential to lead to a life-threatening arrhythmia called Torsades de Pointes (TdP). However, QT prolongation is not the ideal indicator for TdP as drugs that prolong the QT interval do not always cause TdP. It is now recognized that the QT prolongation parameter is only a surrogate marker for proarrhythmia. Data from pre-clinical and clinical trials have shown that there is no fixed relationship between the magnitude of QT prolongation and the risk for development of fatal arrhythmias such as TdP.
Therefore, the US Food and Drug Administration (FDA) and other stakeholders in drug discovery have called for an evolution in pre-clinical cardiotoxicity testing. The proposed new paradigm is called the Comprehensive In-Vitro Proarrhythmia Assay (CiPA). An integral part of the CiPA Initiative (cipaproject.org/) includes incorporation of data collected from human stem cell derived cardiomyocytes for cardiotoxicity and proarrhythmia assays. The overall goal of these new proposed guidelines is to provide a more accurate and comprehensive mechanistic based assessment of proarrhythmic potential that would more accurately assess the risk of new drugs. In review of the proposed CiPA Initiative's guidelines, the FDA has defined two advances that must be made before human cardiomyocytes can be incorporated in the new initiative. First, the growth and maturation state of human stem cell derived cardiomyocytes needs to be advanced to more closely resemble the structure and function of adult human cardiomyocytes. Second, a reliable high throughput screening platform using these cells must be developed.
There are generally three types of systems currently utilized to evaluate the electrophysiology of cardiomyocytes in vitro: 1) Patch clamping systems; 2) micro-electrode array (MEA) systems; and 3) voltage sensitive dye (VSD) visualization methods. Manual patch clamping systems are most commonly used in very early research studies to evaluate the electrophysiology of individual cells. These devices, while providing accurate and sensitive ionic current measurements, cannot be used for in vitro cell systems that more closely mimic cell-cell interaction in cardiac tissue. MEA systems include electrodes that are incorporated into cell culture wells allowing for the measurement of current across the well. While allowing for high throughput analysis and ability to measure impedance in in vitro cell systems, these systems have low spatial resolution, do not provide data on action potential shape, and hinder direct visualization of the cells and the ability to assess 3-D culture systems that more closely mimic cardiac tissue architecture. VSD systems are gaining interest as they address many of the shortcomings of the current technologies described above with features that include: 1) allowing for high throughput analysis; 2) providing high spatial resolution; 3) allowing visualization of impulse propagation across a culture dish; and 4) allowing for modification of the culture conditions including addition of extracellular matrix leading to a more natural testing environment.
The use of cardiomyocytes derived from human stem cells, such as induced pluripotent stem cells, have had limited success to date in cardiotoxicity and proarrhythmic assay screening. Cardiomyocytes derived from induced human pluripotent stem cells (hiPSC-CMs) are commercially available and can be purchased from several companies in cryopreserved vials that can be thawed and plated as monolayers. These hiPSC-CMs can be made in large scale in vitro. Also, hiPSC-CMs can be obtained from patient specific hiPSCs for a specific individual. However, there are hurdles that still need to be overcome to make the hiPSC-CMs a meaningful part of the new CiPA Initiative paradigm. 1) The maturation of hiPSC-CM structure and function must be advanced. Notably, the Kir2.1 potassium channel is absent in currently available hiPSC-CMs and sodium channel expression is low. Currently available hiPSC-CMs are very immature functionally and structurally. The vast majority of currently used hiPSC-CM-based proarrhythmia screening assays rely on immature, fetal-like cells that do not resemble the structure of function of the adult cardiomyocyte. 2) Electrical pacing of hiPSC-CM monolayers in a high throughput electrophysiological screening platform is needed. The vast majority of current hiPSC-CM-based proarrhythmia screens rely solely on field potential duration (MEA technology) or action potential duration prolongation (VSD technology) as surrogate marker for TdP induction. This is a limitation because not all drugs that prolong the action potential (QT interval) will cause fatal TdP arrhythmias. Although certain maturation states of immature hiPSC-CMs have been achieved using Matrigel™ ECM and bone-marrow cell-derived ECM in culture, use of these hiPSC-CMs in proarrhythmia screening assays did not produce consistent results in the observation of arrhythmia activation patters consistent with what is known to occur in cases of TdP in humans, especially between low risk and high risk drugs.
Thus, advanced materials and new methods are needed for the precise assessment and screening of the cardiac safety liability of drug compounds for accurate, reliable and efficient development of new drug candidates.

Methods for the maturation of cardiomyocytes on amniotic fluid cell-derived ECM, cellular constructs, and uses for cardiotoxicity and proarrhythmic screening of drug compounds


A system and method for automatically adjusting blade pitch in crawler dozers, motor graders, and other bladed work vehicles includes estimating a current tractive force of the work vehicle utilizing one or more controllers that establish whether the current tractive force of the work vehicle can be reduced by rotating the blade to an optimized pitch angle. A command is transmitted from the one or more controllers to a blade actuation system to rotate the blade to the optimized pitch angle. The method may be performed iteratively to repeatedly adjust the blade pitch to optimized angles as the work vehicle operates and conditions affecting the optimal blade pitch angle vary.

Crawler dozers (hereafter "dozers"), motor graders (hereafter "graders"), and other bladed work vehicles are well-suited for spreading, shearing, carrying, and otherwise moving relatively large volumes of earth. For this reason, dozers and graders are often utilized in tandem when removing or redistributing earth to impart a tract of land (hereafter an "open ground worksite") with a final grade or surface contour. Grading of an open ground worksite is commonly performed in two or more phases. During an initial rough cutting phase, dozers and possibly other work vehicles, such as tractor-scrapers, are utilized for bulk earth moving purposes. A fine grading phase may then be performed after the rough cutting phase is completed. During fine grading, graders may be utilized to create a finished grade across the upper surface of the open ground worksite, for example, corresponding to a previously-prepared topological map.
Bladed work vehicles are now commonly equipped with blade actuation systems enabling an operator to manipulate a work vehicle's blade in multiple degrees of freedom (DOFs). In the case of a crawler dozer, for example, an operator may be able to adjust the height, pitch, and rotational angle of the blade through an electro-hydraulic blade actuation system, which is integrated into a blade control assembly mounting the blade to a forward portion of the dozer. Similarly, in the case of a grader, an operator may be able to adjust blade height, blade pitch, and blade rotational angle, as well as the lateral position of the blade relative to the grader chassis within certain limits. Such multi-DOF blade movement provides a powerful and flexible tool in earthmoving operations. However, as the freedom of blade movement increases, so too does the complexity of the operator controls utilized to control blade movement. This, in turn, provides greater opportunities for sub-optimal positioning of the blade and increases the mental workload placed on an operator of the bladed work vehicle.
Advanced Grade Control Systems (GCSs) have been developed for automatically controlling the blade height and cut depth of graders and other bladed work vehicles. In contrast, such systems may not provide automatic control and optimization of blade pitch. The manner in which blade pitch is controlled during a grading operation can directly affect productivity, fuel consumption, and other measures of work vehicle efficiency. A skilled operator can improve work vehicle efficiency by maintaining the blade pitch at an optimal angle when operating a bladed work vehicle. However, the optimal blade pitch angle may vary with multiple dynamic factors including cut depth, material type, material density, moisture content, and so on. Consequently, it can be difficult for even a skilled operator to consistently maintain blade pitch within an optimal range throughout a grading operation or other task, while simultaneously controlling the various other operational parameters of the work vehicle.

Force-based work vehicle blade pitch control


An apparatus for controlling the pressure in an ink reservoir of an ink jet printer which includes at least one ink reservoir of an ink jet printer, a pressure applying device for applying a pressure in the ink reservoir, the pressure applying device communicating with the ink reservoir via a first conduit, a buffer reservoir communicating a gasteous medium with the ink reservoir via a second conduit different from the first conduit, a detection system for monitoring the actual pressure in the ink reservoir, the detection system including at least one electronic pressure sensor, and a controller for controlling the pressure applying means dependent on the actual pressure monitored by the detection system.

The present invention relates to an apparatus for controlling pressure in an ink reservoir of an ink jet printer. The present invention also relates to an ink jet printer including a printhead with an ink reservoir containing liquid ink and a gas volume above the level of the ink. The present invention further relates to a method for controlling pressure in an ink reservoir of an ink jet printer.
An ink jet printer typically contains printheads having one or more nozzle arrays and an ink reservoir from which liquid ink is supplied to the nozzles of the nozzle arrays, so that ink droplets may be ejected from the nozzles by thermal or piezoelectric action, as is generally known in the art. When the level of ink in the ink reservoir is higher than the level of the nozzles, the ink reservoir should be maintained at subatmospheric pressure in order to avoid ink from leaking out through the nozzles. Since the difference between the internal pressure in the ink reservoir and the atmospheric pressure has an influence on the process of droplet generation and hence on the quality of the printed image, it is desirable to keep this pressure difference constant. However, since the internal pressure in the ink reservoir may vary in response to changes of the ink volume contained therein, thermal expansion and the like, it is necessary to control the internal pressure in the ink reservoir.
It is common to apply pressure regulating valves coupled to a pump for allowing compensation of an excessive pressure drop monitored by the detecting means in order to maintain the under pressure in the ink reservoir within a certain predetermined pressure range. Pressure regulating valves however are commonly, relatively expensive and sensitive. Thus, relatively large membranes are required to achieve a relatively high degree of precision in the regulation of the pressure within the ink reservoir. Furthermore, commonly other critical components are required, often resulting in a relatively high mutual friction and are therefore often subjected to a considerable amount of wear. Rubber parts commonly used in the known apparatus to control the pressure within the ink reservoir become fatigued relatively quickly, resulting in a decreased capacity to counteract loads during operation of the apparatus. Thus, the known device is, from a constructive point of view, relatively complex and hence, relatively expensive. Moreover, the components used in the known device are commonly subjected to a considered amount of wear during operational use.

Apparatus and method for controlling the pressure in an ink reservoir of an ink jet printer


Grating couplers and methods of fabricating a grating coupler. The grating coupler may include a plurality of grating structures arranged on a substrate and a layer arranged over the grating structures. The grating structures are composed of a first material characterized by a first refractive index with a real part. The layer is composed of a second material characterized by a second refractive index with a real part. The real part of the second refractive index is greater than the real part of the first refractive index of the first material for electromagnetic radiation with a wavelength in a range of 1 micron to 9 microns.

The present invention relates to photonics chips and, more specifically, to grating couplers and methods of fabricating grating couplers.
Photonic integrated circuits are devices on which optical and electronic components are integrated. Grating couplers are commonly used to couple light from an optical fiber into an on-chip waveguide, which is considerably smaller than the optical fiber. The grating coupler may be formed by notching the waveguide. Light that diffracts from the grating coupler will constructively interfere at a given scattering angle that is directed toward the optical fiber. The scattering angle of the grating coupler may be determined by the period of the grooves in waveguide.
Improved grating couplers and methods of fabricating grating couplers are needed.


The present disclosure relates to sharing an I/O device across multiple virtual machines. According to one embodiment, a computing system configures shared ownership of the I/O device between a first partition and one or more of the plurality of virtual machines. The computing system transfers partial ownership of the I/O device from the first partition to the one or more virtual machines and generates device configuration information for the I/O device. The virtual machines can use the generated device configuration information to access and configure the I/O device. Once the I/O device is configured for shared ownership, the computing system boots the one or more virtual machines.

The present invention relates to sharing a physical device in a computing system, and more specifically to sharing a physical device across multiple virtual machines (e.g., logical partitions [LPAR]).
In paravirtualized environments, multiple virtual machines (e.g., LPARs) may use the same physical I/O device, such as a network adapter. The hypervisor may isolate virtual machines, allowing a single virtual machine to access the physical I/O device at a time. To allow each virtual machine to use the same physical I/O device, the hypervisor may present a virtual device to each virtual machine. When a virtual machine performs I/O operations on the virtual device, the hypervisor can intercept (and queue) I/O requests by the virtual machine and pass the requested commands to the physical I/O device. Generally, the hypervisor may have full ownership of the physical I/O device, and the virtual machines may not be able to directly access the physical I/O device or perform error recovery operations on the physical I/O device.
In some virtualized environments, a physical I/O device may allow multiple virtual machines to use the device concurrently through single root I/O virtualization (SR-IOV). In SR-IOV, a physical device may have physical functions (PFs) that allow for input/output and device configuration, as well as one or more virtual functions (VFs) that allow for data input/output. For example, an n-port network adapter may expose m VFs (e.g., one or more VF for each port) that may be used by the virtual machines hosted on a computing system. A hypervisor on the host computing system may interact with the physical I/O device using the PFs, while each can directly communicate with a portion of the physical I/O device using one or more VFs.
If VMs communicate and use physical I/O devices through a hypervisor, performance may be negatively impacted due to additional processing required at the hypervisor to move data and commands from the physical I/O device to the appropriate VM. In a virtualized environment where VMs use VFs exposed by an I/O device that supports SR-IOV, VMs may not be able to use all of the features supported by the I/O device.

Sharing ownership of an input/output device using a device driver partition


A hollow porcelain insulator including an elastic insulating layer having a tensile strength of at least 150 kg/cm.sup.2 and a thickness of at least 2 mm for improving an explosion preventing property.

(1) Field of the Invention
The present invention relates to a porcelain hollow insulator for transformers, instrument transformers, switches or the like and particularly to improvement of an explosion preventing property of a porcelain hollow insulator for a gas or oil filled insulated bushing.
(2) Related Art Statement
Hitherto, there has been proposed a porcelain hollow insulator as disclosed in Japanese Patent Application Laid-open Publication No. 61-151909. Such a porcelain insulator has a resin lining layer formed on the inner wall surface by spraying a resin by means of a spray nozzle while the hollow insulator is rotated about a fixed longitudinal axis. The resin lining layer is useful to improve safety of the porcelain insulator by preventing the fragments of the insulator from scattering so as not to damage peripheral instruments and/or human bodies when the porcelain insulator is broken by an abnormal high internal pressure caused by an accidental flashover within the insulator or an external force due to an earthquake or the like.
Such conventional porcelain hollow insulators used in the bushings however have not been settled regarding numerical conditions of the adhering force, tensile strength and thickness of the resin layers. Accordingly, there is a problem that some of the porcelain hollow insulators having the resin lining layer do not have a satisfactory explosion preventing property.

Explosion preventing porcelain hollow insulator


A remotely controlled gastric band system that is practically immune to external magnetic fields, such as from a Magnetic Resonance Imaging (MRI) machine, incorporates a bi-directional pump and fluid reservoir to adjust fluid volume for hydraulic control of a gastric band. A piezoelectric driver (e.g., rotary actuator, linear actuator) selectively compresses and expands a metal bellows hermetically sealed within a biocompatible and nonferromagnetic enclosure or case such as titanium. Directly sensing a position of the metal bellows yields an accurate reading of volume contained therein, allowing for closed-loop control of the gastric band.

An artificial sphincter may be utilized in any number of applications within a patient's body where it is desirable to vary the size of an orifice or organ. Depending upon the application, artificial sphincters may take the form of a flexible, substantially non-extensible band containing an expandable section that is capable of retaining fluids. The expandable section would be capable of expanding or contracting depending upon the volume of fluid contained therein. One particular example of an artificial sphincter is an adjustable gastric banding device, such as described in U.S. Pat. Nos. 4,592,339, 5,226,429, 6,102,922, and 5,449,368, the disclosure of each being hereby incorporated by reference. Since the early 1980s, adjustable gastric bands have provided an effective alternative to gastric bypass and other irreversible surgical weight loss treatments for the morbidly obese.
The gastric band is wrapped around an upper portion of the patient's stomach just inferior to the esophago-gastric junction, forming a stoma that restricts food passing from an upper portion to a lower portion of the stomach. When the stoma is of the appropriate size, food held in the upper portion of the stomach provides a feeling of fullness that discourages overeating. However, initial maladjustment or a change in the stomach over time may lead to a stoma of an inappropriate size, warranting an adjustment of the gastric band. Otherwise, the patient may suffer vomiting attacks and discomfort when the stoma is too small to reasonably pass food. At the other extreme, the stoma may be too large and thus fail to slow food moving from the upper portion of the stomach, defeating the purpose altogether for the gastric band. Thus, different degrees of constriction are desired, and adjustment is required over time as the patient's body adapts to the constriction.
In addition to a latched position to set the outer diameter of the gastric band, adjustability of gastric bands is generally achieved with an inwardly directed inflatable balloon, similar to a blood pressure cuff, into which fluid, such as saline, is injected through a fluid injection port to achieve a desired diameter. Since adjustable gastric bands may remain in the patient for long periods of time, the fluid injection port is typically installed subcutaneously to avoid infection, for instance in front of the sternum or over the fascia covering one of the oblique muscles. Adjusting the amount of fluid in the adjustable gastric band is achieved by inserting a Huber tip needle through the skin into a silicon septum of the injection port. Once the needle is removed, the septum seals against the hole by virtue of compressive load generated by the septum. A flexible catheter communicates between the injection port and the adjustable gastric band.
While the injection port has been successfully used to adjust gastric bands, it would be desirable to make adjustments noninvasively. Insertion of the Huber tip syringe is typically done by a surgeon, which may be inconvenient, painful, or expensive for the patient. In addition, a skin infection may occur at the site of the insertion of the syringe. Consequently, it would be desirable to remotely control an adjustable gastric band.
In an afore-mentioned co-pending application entitled "PIEZO ELECTRICALLY DRIVEN BELLOWS INFUSER FOR HYDRAULICALLY CONTROLLING AN ADJUSTABLE GASTRIC BAND" to William L. Hassler, Jr., Ser. No. 10/857762, an advantageous infuser containing no ferromagnetic materials provides an accurately bi-directionally controllable volume of fluid to a closed gastric band. The infuser has a titanium bellows accumulator, which may be collapsed or extended to positively displace fluid accumulated therein, thereby serving as both a reversible pump and reservoir. Thereby a bi-directional pump that is practically immune to external magnetic fields is achieved, unlike previously known implants that contained a metal bellows for controllable dispensing of a liquid drug, such as described in U.S. Pat. No. 4,581,018. Thereby, such an implanted device may undergo Magnetic Resonance Imaging (MRI) without damage to the device or patient.
Accurate delivery of fluid from a bellows accumulator benefits from a feedback control system and as a means for determining bellows position relative to its housing. In the U.S. Pat. No. 4,581,018 patent, position feedback was provided by a rotary encoder connected to the output shaft of an electrical motor used to rotate the cylindrical metal bellows. In this instance, the rotations of the motor are determined by counting incremental marks on an optical disk of the encoder for the purpose of dispensing at a uniform rate.
However, in creating a device that may be required to pump in both directions with long intervals therebetween, it is believed that counting rotations of a rotary actuator in some instances may inaccurately reflect the volume in the bellows accumulator. For example, the current volume of the reservoir is not directly sensed, and thus integrating a rate of dispensing to calculate a change in volume still suffers if the starting point is not known or if fluid is transferred inadvertently due to leakage or other factors.
In other infuser devices, sensing fluid pressure within the bellows accumulator has been used as an indirect measurement of volume, relying upon a fixed relationship in pressure and volume since the bellows accumulator is collapsed based on a gauge pressure exerted thereon by a propellant within an infuser device housing. However, such pressure sensing assumes that the fluid pressure is not varied by pressure external to the infuser device, such as would be expected in a closed artificial sphincter system. Specifically, the amount of back pressure would vary somewhat unpredictability. Examples of such pressure-based sensing include U.S. Pat. No. 5,507,737 (pressure gauge), U.S. Pat. No. 5,974,873 (strain gauge), and U.S. Pat. No. 6,315,769 (spring and pressure sensitive resistor).
Recently, it has been recognized as desirable to sense remaining fluid volume in a drug dispensing infuser device in order to determine when refilling is necessary. To that end, U.S. Pat. No. 6,542,350 discloses forming a variable capacitance between the bellows accumulator and the infuser device housing to sense volume. Similarly, U.S. Pat. No. 6,482,177 discloses forming a variable inductance between the bellows accumulator and the infuser device housing to sense volume. In both instances, using the sensed volume for such purposes was not suggested other than relaying a value by telemetry for display to a human operator. This is understandable in that these drug dispensing applications meter small amounts of a drug without significant variations in external backpressure to the infuser. Continuous volume sensing was not addressed. Power consumption for volume sensing would create an undesirable increase in battery size. In addition, accuracy of the variable capacitors or inductors may have been insufficient for these purposes, especially as the portions of the variable capacitor or inductor move away from one another in the presence of electromagnetic interference.
Consequently, a significant need exists for sensing a position of an implanted bellows accumulator representing a fluid volume for closed loop control of an implanted artificial sphincter.

Metal bellows position feedback for hydraulic control of an adjustable gastric band