The softgel drying machine comprises a casing, an air channel, a drying chamber, an air return channel, a tumbler and an air-drying system. The casing comprises an air circulation chamber and an air generation chamber. The drying chamber comprises at least one air supply opening and at least one air returning plate. The air-drying system comprises at least one air blower fan, a dehumidification module and an air return cooling module. The air blower fan comprises an air blower inlet port, an air blower outlet port, a chiller and an air supply duct. The chiller is coupled to the air blower outlet port. The air return cooling module comprises an air return duct, an air return inlet port and an air return outlet port. The air return inlet port is airtightly coupled to the air return channel through the air return duct.

When making a softgel capsule (also referred to as "softgel"), the drying process has been a big challenge. During the drying process, the softgel needs to be rotated (tumbled) so the softgel surface are evenly expose while high velocity air flow continuously circulating inside the drying chamber so that the softgel won't split and retain the desire aesthetic shape. The air temperature while drying also must be control so that the sofngel can cure and stabilize. However, the above conditions cannot easily be achieved. Sofigel manufacture(s) had invested lot of resources to build their facility to suffice these conditions to dry softgel. Currently, there are two conventional methods of drying softgel; tray drying and continuous drying.
Tray Drying—the softgel come out of the tumble air-drying systems and are placed on drying trays. The trays are then stacked on dollies and pushed into drying tunnels/rooms under a controlled environment. These controlled tunnel/rooms require a dehumidifier system to supplied control air to a large room where trays of softgel are reserved. The cost is very high to design, built and operated. In addition, tray-drying take ups lots of time because the softgels need to be cure in these control room for days to achieve the desired softgel hardness.
Continuous Drying—Continuous drying uses more and larger tumble air-drying systems, the softgels spend more time in the air-drying systems. The hardness of the softgel is achieve when unload form series of tumble units. The current continuous drying, however, still require the use of a humidifier system. Thus, this process still very costly to build and operated as well.
In addition, currently majority of the manufactures dry their softgels in a condition room. However, the condition in these room are very difficult to maintain since staff frequently have to access the room to attend the softgels. Hence, unwanted draft wind enters the room when staff enter and/or exist, causing the room condition to fluctuate quite a bit and efficiency of drying the softgel is very poor.
Therefore, a need remains for a softgel drying machine to dry the softgel that generate high velocity re-circulating inside drying chamber with capability of controlling tumbling time, temperature and relative humidity.


A ram or shutter device includes rams operable between an open position withdrawn from a bore to a closed position to contact a tubular disposed in the bore, the rams may not seal the bore. A well system in accordance to an aspect of the disclosure includes an assembly providing a bore in communication with a wellbore, a device operable to shear a tubular disposed in the bore, and a shutter device having rams operable between an open position withdrawn from the bore to a closed position contacting the tubular in the bore.

This section provides background information to facilitate a better understanding of the various aspects of the disclosure. It should be understood that the statements in this section of this document are to be read in this light, and not as admissions of prior art.
A blowout preventer is a large, specialized valve used to seal, control and monitor oil and gas wells. Blowout preventers are designed to cope with extreme erratic pressures and uncontrolled flow emanating from a well during drilling. Pressure kicks can lead to the uncontrolled release of oil and/or gas from a well resulting in a potentially subsea well event known as a blowout. Blowout preventers are critical to the safety of crew, equipment and environment, and to the monitoring and maintenance of well integrity. While blowout preventers are intended to be fail-safe devices, accidents may still occur if the blowout preventer fails to properly operate. For example, during the Apr. 20, 2010, Deepwater Horizon drilling rig explosion, it is believed that the blowout preventers may not have properly operated and/or were not activated in a timely fashion. In addition to loss of well control the wellhead equipment was damaged creating obstacles to recovering control of the well.

Ram device operable with wellbore tubulars


A stencil forming apparatus in which a stencil for a stencil printing formed from a rolled stencil sheet, includes: a guide roller; a rotatable platen roller having a central axis which is in parallel with the guide roller; a thermal head having a plurality of heat generating elements, and provided above the platen roller, wherein the stencil sheet pulled out of the rolled stencil sheet is passed through the platen roller and the thermal head through the guide roller and is subjected to thermally making fine holes thereon (the stencil of the stencil printing); and an intermediate roller provided between the platen roller and the guide roller wherein the intermediate roller is vertically movable in a predetermined range.

This invention relates to a stencil forming apparatus which make minute holes on a stencil pulled out from a rolled stencil sheet.
FIG. 7 shows a conventional stencil forming apparatus. A stencil printing sheet S for the stencil printing (hereinafter referred to merely as "a stencil sheet S") which is in the form of a roll is held by a master holder 106. A stencil sheet S pulled out of a rolled stencil sheet S is in the form of a belt. The stencil sheet S is laid over a set guide shaft 100 to change the direction of its movement, and inserted between a thermal printing head (TPH) 101 and a platen roller 102, and then laid over a winding roller 103. Furthermore the stencil sheet S is inserted between an upper load roller 104 and a lower load roller 105, thus being conveyed to an initial stop position.
In order that, when the stencil sheet S is conveyed, the part of the sheet which is held between the thermal head 101 and the platen roller 102 may not be creased, a back tension unit 107 of the master holder 106 applies tension to the stencil sheet S in the direction which is opposite to the direction of conveyance of the stencil sheet S.
When the thermal head 101 thermally makes fine holes on the stencil sheet S, the power of conveying the stencil sheet S is provided by the platen roller 102 only which holds the stencil sheet S with the thermal head 101. The stencil sheet S thus formed is moved downwardly into a holding box 108 by means of the winding roller 103. Until the thermal cutting of the stencil sheet S is accomplished by the thermal head 101, the stencil sheet S thus cut is temporarily held (stored) in the holding box 108.
After the stencil sheet S has been formed with the thermal head 101, the latter 101 is moved upwardly to release the stencil sheet S. The front end portion of the stencil sheet S thus released is conveyed to a clamp board 110 on a printing drum 109 by means of the upper and lower load rollers 104, so that the front end portion of the stencil sheet S is secured to a printing drum 109 with the clamp board 110. As the printing drum 109 turns, the upper and lower load rollers 104 and 105 are turned to convey the stencil sheet S so that the sheet S is wound on the printing drum. Thereafter, the stencil sheet S is cut off with a cutter unit 111.
The above-described stencil forming apparatus serves also as a stencil printing machine. Part of the structure of the stencil printing machine is shown in the drawings. A part of the cylindrical wall of the printing drum 109 is ink-permeable. An ink supplying means for supplying ink to the inner surface of the printing drum 109 is provided inside the drum 109. A pressing means, namely, a press roller is provided below the printing drum to press a printing sheet against the printing drum 109. The printing drum 109 is turned, while a printing sheet is fed into the space between the printing drum 109 and the pressing means, so that the printing sheet is pressed against the image region of the stencil sheet S wound on the printing drum 109. The printing ink supplied from the inner cylindrical surface of the printing drum 109 passes through the cylindrical wall of the printing drum 109, and transfers through the cuts of the stencil sheet S onto the printing sheet to form an image thereon.
The conventional stencil forming apparatus shown in FIG. 7 suffers from the following difficulties: Because the set guide shaft 100 and the platen roller 102 are not in parallel with each other, the stencil sheet S being conveyed is liable to slacken, and, when the stencil sheet S is cut, it is liable to be creased.


Methods for stabilizing an enzyme by storing the enzyme in the presence of a stabilized coenzyme are disclosed. In addition, an enzyme stabilized with a stabilized coenzyme as well as the use thereof in test elements for detecting analytes are also disclosed. Other aspects include unique compositions, methods, techniques, systems and devices involving enzyme stabilization.

Diagnostic test elements are important components of clinically relevant analytical methods. In this connection, the focus is on the measurement of analytes, for example metabolites or substrates, which for example can be determined directly or indirectly with the aid of an enzyme that is specific for the analyte. In this case, the analytes are converted with the aid of an enzyme-coenzyme complex and subsequently quantified. This entails the analyte to be determined being brought into contact with a suitable enzyme, a coenzyme and optionally a mediator, whereby the coenzyme is physicochemically changed, for example oxidized or reduced, by the enzymatic reaction. If a mediator is additionally used, it usually transfers electrons from the reduced coenzyme released during the conversion of the analyte onto an optical indicator or the conductive components of an electrode so that the process can be detected, by way of non-limiting example, photometrically or electrochemically. A calibration provides a direct relationship between the measured value and the concentration of the analyte to be determined.
An important criterion when providing diagnostic test elements is their long-term stability. Certain test elements known from the prior art which are used in the determination of blood glucose are generally very sensitive to moisture and heat, such that upon exposure to the same the function of the coenzyme and mediator, for example, is usually impaired. Another problem of commercially available test elements is their sensitivity to ambient light where light absorption by the enzyme system can result in damage to the enzyme, coenzyme and/or mediator. In certain instances where, for example, tests are carried out by the end user himself, erroneous results can therefore occur due to an incorrect, unnoticed faulty storage of the measurement system which can be hardly detected by the user and may result in incorrect treatment of the respective disease.
A known measure that can be used to increase the stability of diagnostic test elements is the use of stable enzymes, including for example the use of enzymes from thermophilic organisms. Furthermore, it is possible to stabilize enzymes by chemical modification such as cross-linking, or by mutagenesis. In addition, enzyme stabilizers such as trehalose, polyvinyl pyrrolidone and serum albumin for example, can also be added or the enzymes can be enclosed in polymer networks by photopolymerization for example.
Attempts have also been made to improve the stability of diagnostic test elements by using stable mediators. Thus, the specificity of tests is increased and interferences during the reaction are eliminated by using mediators with a redox potential that is as low as possible. However, the redox potential of the enzyme/coenzyme complexes forms a lower limit for the redox potential of mediators. If the redox potential is lower than this limit, the reaction with the mediators is slowed down or even stopped.
Alternatively, it is also possible to use diagnostic test elements without mediators in which, for example, coenzymes such as the coenzyme NADH are detected directly. A disadvantage of such measurement systems is, however, that native coenzymes such as NAD and NADP are unstable.
NAD and NADP are base-labile molecules whose degradation pathways are described in the literature (N. J. Oppenheimer, in "The Pyridine Nucleotide Coenzyme", Academic Press New York, London 1982, Editor J. Everese, B. Anderson, K. You, chapter 3, pages 56-65). ADP-ribose is mainly formed when NAD or NADP are degraded by cleavage of the glycosyl linkages between the ribose and the pyridine unit. In contrast, the reduced forms NADH and NADPH are acid-labile: for example, epimerization is a known degradation pathway. In both cases, the instability of NAD/NADP and NADH/NADPH is due to the lability of the glycosyl linkage between the ribose unit and the pyridine unit. However, under conditions that are not drastic such as an aqueous solution for example, the coenzymes NAD and NADP are already hydrolyzed solely due to the ambient moisture. This instability may lead to inaccuracies in the measurement of analytes.
A number of NAD/NADP derivatives is described, for example, by B. M. Anderson in "The Pyridine Nucleotide Coenzymes", Academic Press New York, London 1982, editor J. Everese, B. Anderson, K. You, chapter 4. However, most of these derivatives are not well accepted by enzymes. The only derivative that has therefore been used up to now for diagnostic tests is 3-acetylpyridine adenine dinucleotide (acetyl-NAD) which was described for the first time in 1965 (N. O. Kaplan, J. Biol. Chem. (1956), 221, 823). This coenzyme also shows a poor acceptance by enzymes and a change in the redox potential.
International Patent Publication No. WO 01/94370 describes the use of further NAD derivatives with a modified pyridine group. However, modifications of the nicotinamide group generally have a direct influence on the catalytic reaction. In most cases this influence is negative.
In another stabilization concept, the ribose unit was altered in order to thus influence the stability of the glycosyl linkage. This procedure does not directly interfere with the catalytic reaction of the nicotinamide group. However, it may have an indirect influence as soon as the enzyme exhibits a strong and specific binding to the ribose unit. Kaufmann et al. disclose in this connection a number of thioribose-NAD derivatives in International Patent Publication No. WO 98/33936 and U.S. Pat. No. 5,801,006 and in International Patent Publication No. WO 01/49247. However, a relationship between the modification of the nicotinamide ribose unit and the activity of the derivatives in enzymatic reactions has not been shown to date.
carbaNAD, a derivative without a glycosyl linkage was described for the first time in 1988 (J. T. Slama, Biochemistry (1988), 27, 183, and Biochemistry (1989), 28, 7688). The ribose therein is substituted by a carbacyclic sugar unit. Although carbaNAD was described as a substrate for dehydrogenases, its activity has previously not been demonstrated clinically in biochemical detection methods.
A similar approach was described later by G. M. Blackburn (Chem. Comm. (1996), 2765) in order to prepare carbaNAD with a methylene bisphosphonate compound instead of the natural pyrophosphate. The methylene bisphosphonate shows an increased stability towards phosphatases and was used as an inhibitor for ADP-ribosyl cyclase. An increase in hydrolysis stability was not the aim (J. T. Slama, G. M. Blackburn).
International Patent Publication No. WO 2007/012494 and U.S. Pat. No. 7,553,615 finally disclose stabilized NAD/NADH and NADP/NADPH derivatives, enzyme complexes of these derivatives and their use in biochemical detection methods and reagent kits.
One non-limiting object of the present application is to provide a method for stabilizing enzymes, especially for the long-term stabilization of enzymes which at least partially eliminates the above-mentioned disadvantages.

This patent is subject to a terminal disclaimer.

Stabilization of enzymes with stable coenzymes


A word alignment apparatus includes a word extracting portion that extracts each word from an example sentence and from a translation sentence thereof, an alignment calculator that calculates at least one of a similarity degree and an association degree between a word in a first language and that in a second language to perform an alignment between words respectively included in the example sentence in the first language and those included in the translation sentence thereof in the second language on the basis of a calculated value, and an optimization portion that optimizes the alignment by performing a bipartite graph matching.

1. Technical Field
This invention generally relates to a word alignment apparatus, example sentence bilingual dictionary, word alignment method, and program product for word alignment.
2. Related Art
Machine translation is to convert from one language into another with the use of a computing machine. The research and development of the machine translation has been carried out around the glove over half a century. The machine translation system can be broadly categorized into (1) analysis-based machine translation, (2) example-based machine translation, and (3) statistics-based machine translation.
The analysis-based machine translation is a technique of analyzing a first language (morphologic analysis, syntactic and semantic analysis, and the like), converting an analysis result into a second language, and generating a translation sentence in the second language. Since the performance of analysis technique of a natural language is not good, it has limitations that to develop a good performance analysis-based machine translation system is very difficult. In addition, there are drawbacks in that learning is impossible, and thereby it is difficult to improve a translation engine.
The statistics-based machine translation is a technique of building a translation model with the use of a language model and a statistics model. In this method, realization is limited, because learning data (corpus) necessary for construction of each model is limited.
The example sentence-based machine translation imitates a mechanism how the human leans a foreign language, and translates a new document with reference to a translated example sentence that has been learned. In 1980s, Professor Nagao proposed this translation system for the first time. Since then, the research and development of the example-based machine translation have been increased.

Word alignment apparatus, method, and program product, and example sentence bilingual dictionary


A light delivery system for use in irradiating vascular tissue includes a balloon catheter with a working lumen for receiving an optical fiber therein and an inflation/flushing lumen adapted to receive a liquid at a proximal end and leading to a space defined within the balloon member attached to a distal end of the catheter. The balloon member has a pattern of holes or pores in the wall thereof through which the saline may flow when the balloon is inflated, causing any blood or other absorbing substances that may interfere with good radiant energy transmission to be flushed away from the treatment site.

1. Field of the Invention
This invention relates generally to surgical instruments for improving the outcome of percutaneous transluminal coronary angioplasty procedures, and more particularly to a light delivery system incorporating a means for irradiating a treatment site with radiant energy, e.g., U.V. or visible light, while simultaneously flushing the blood from the light path. It has been previously found that radiating the treatment site reduces the incidences of restenosis.
2. Discussion of the Prior Art
U.S. patent application Ser. No. 08/425,858, filed Apr. 20, 1995, and entitled "Method and Apparatus for Treating Vascular Tissue Following Angioplasty to Minimize Restenosis", which is assigned to applicant's assignee, provides a discussion of the prior art relating to known methods and apparatus for reducing the proliferation of smooth muscle cells at the site of a stenotic lesion that had earlier been subjected to balloon angioplasty by exposure of the treatment site to U.V. light. The system described and claimed in the above-referenced pending patent application constitutes an improvement over the prior art, especially in the manner in which the involved tissue is irradiated with U.V. light in a controlled fashion by a step-wise displacement of a radiant energy-emitting fiber. The disclosure contained in the aforereferenced application Ser. No. 08/425,858 is hereby incorporated by reference in the present application as if fully set forth herein.
In efforts to irradiate endothelial and intimal tissue with light following an angioplasty procedure, a difficulty has arisen in delivering light of low wavelength at an adequate intensity to the treatment site due to the presence of blood or other light absorbing substances between the light energy emitter and the tissue to be treated. While the apparatus disclosed in the aforereferenced pending patent application of applicant's assignee is effective in clearing the site of most blood due to the expansion of a balloon member against the wall of the vessel being treated, even the thin remaining layer of blood or blood contaminated saline trapped between the exterior of the balloon and the blood vessel drastically reduces the transmissivity of U.V. light at the desired wavelength. It has been found that even a 1% concentration of blood in saline can reduce the transmissivity of U.V. light at a wavelength of 257 nm by 70% or more. Thus, a need exists for an improved system for irradiating the interior lining of a blood vessel to impart to the system the ability to expose the blood vessel tissue to radiant energy at a sufficiently high, efficacious intensity.

Light delivery system with blood flushing capability


An intravascular dilator includes a central body acting as deflector o the blood flow to increase the value of shear stress to the artery wall. Flexible spires soldered to the deflector are radially extensible from a first diameter substantially equal to the deflector diameter to a second diameter greater than the artery diameter, the spires rest against the artery internal wall in operative position.

The present invention relates to an intravascular implant permitting radial dilatation of the arterial walls. These implants or dilatators are known as "stents" in the field of transluminal angioplasty. Transluminal angioplasty consists in treating diseased regions of the arterial system by the introduction of apparatus, particularly catheters, along natural routes. This permits localized intervention without having to have recourse to conventional surgical interventions which have, because of their seriousness, numerous drawbacks for the patients. This technique is particularly used when a constriction or stenosis of the arteries is diagnosed. There is then introduced through the femoral artery a catheter provided at its distal end with an inflatable angioplasty balloon. This catheter is then pushed and guided, with radioscopic monitoring, through the arterial system to the diseased region of the artery. Once this region is reached, the balloon is inflated to dilate the constricted region of the artery. This operation is repeated until it is determined, with the help of the radioscopic monitoring means, that the artery again has a diameter sufficient to ensure an acceptable blood flow. These interventions however have certain drawbacks. Thus, clinical observations show that in about a third of the cases treated, the artery again retracts over a period of time comprised between several days and several months. This phenomenon, which is called "restenosis", requires a new intervention in the diseased artery either by the same method, or by more serious surgical techniques.

Intravascular dilatation implant with a deflector

Ecole Polytechnique Federale de Lausanne


A uterine contractile device includes a series of perforated tubes, a sealing balloon, and an additional connecting tube to deliver a vacuum force inside the lumen of a postpartum uterus. The uterine contractile device may be used after child birth to facilitate contraction of a woman's uterus. By facilitating contraction of the uterus, a medical professional may achieve immediate and sustained hemostasis of the mother.

Postpartum hemorrhage, defined as excessive blood loss after birth, is the leading cause of maternal death in the world, claiming the lives of over 125,000 mothers every year. Inability to control postpartum bleeding can require a woman to receive multiple blood transfusions, and in severe cases, a full hysterectomy. Accordingly, it is desirable to control such postpartum bleeding, if possible, at its onset. The cause of postpartum hemorrhage, in approximately 80% of cases, is uterine atony, which is the inability of the woman's uterus to contract after delivering the child. Risk factors for uterine atony include prolonged staged of labor, preeclampsia, and multiparity.
The original technology for treating postpartum hemorrhage was oxytoxic agents, hormonal agents that induce muscle contraction. Unfortunately, studies have increasingly shown that oxytoxic agents do not significantly reduce either the incidence of postpartum hemorrhage or the amount of blood lost. Some studies have even indicated that oxytoxic agents are being over used to the point that this treatment increases the risk of uterine atony.
Other approaches have been taken, such as medical devices. U.S. Pat. No. 4,552,557 discloses a inflatable intrauterine device that inflates intrauterinely, acting a tamponade to stop blood flow. Because this device expands when inflated, this device and method do not facilitate uterine contraction. U.S. Patent Publication No. 2011/0087337 discloses a generic organ contraction device for controlling the flow of fluid in a lumen formed by a tissue wall of a patient's organ, however this device does not use suction to contract the organ. Finally, U.S. Patent Publication No. 2011/0172569 discloses a surgical vacuum device that uses a suction cup to tamponade specific surfaces of an organ. However, the suction cup is not capable of contracting a uterus.
Dr. Christopher B. Lynch has developed a technique for surgically removing the uterus, wrapping the uterus in sutures, and pulling on these sutures to contract the uterus. Although this approach has been effective at arresting postpartum hemorrhage this method is extremely invasive and potentially very harmful to the patient. What is needed is a device that can contract a postpartum uterus in a non-invasive manner.

Postpartum uterine contractile apparatus and method


A method, device, and computer-readable medium are disclosed for automatically activating a probe configured to generate test network traffic in response to evaluating a policy that accounts for aggregated information that describes traffic that was processed by a network device. The method includes storing a policy, and evaluating the policy based at least in part on an item of received aggregated information that describes a set of packets that were processed by the network device and sent or received on a network. The probe is activated at least partially in response to evaluating the policy. The probe generates test packets to emulate one or more applications, services, or devices communicating on the network.

The approaches described in this section could be pursued, but are not necessarily approaches that have been previously conceived or pursued. Therefore, unless otherwise indicated herein, the approaches described in this section are not prior art to the claims in this application and are not admitted to be prior art by inclusion in this section.
Network devices such as routers and switches may process and forward network traffic according to configurable settings. The traffic may be transmitted from device to device on a network of the devices, often on behalf of applications communicating on the network. Individual items of traffic may be transmitted as packets along a route from a source application, service, or device to a destination application, service, or device.
Network administrators may configure network devices on the network such that the devices operate together to accomplish certain objectives. The objectives may include performance goals for applications, services, or devices using the network. For example, a network of devices may be configured to give priority to certain types of traffic, deter or prevent attacks against the network, save power, minimize latency, minimize the effects of applications, services, or devices that are overusing bandwidth, or meet levels of service that are guaranteed by a service provider under service agreements. In a particular example, the network administrator may guarantee levels of service for voice over Internet Protocol ("VoIP") applications or other business-critical applications so that application users can obtain the full benefit of the applications.
Passive monitoring may provide some information about production traffic on the network. However, due to privacy and security concerns, as well as legal issues stemming from those concerns, network administrators may be limited in terms of the amount of passive monitoring that can be performed on production traffic. Also, passive monitoring may not provide enough information when there is little or no relevant production traffic.
To determine whether network devices are meeting the demands of various applications, services, or devices, the network administrator may actively monitor the network by placing physical probes between devices in the network. The physical probes generate test traffic as if the test traffic was generated by particular applications, services, or devices using the network. The privacy and security concerns may be avoided by active monitoring because the generated test traffic is synthetic.
Some network devices are equipped with logic, in hardware, software, or a combination of hardware and software such as that provided on devices running Cisco IOS® Software, which allows the network administrator to use the network devices to create logical probes without adding any physical probes to the network. In a particular example, with Cisco IOS® Software an Internet Protocol Service Level Agreement (IPSLA) is a feature that allows network administrators to actively monitor and analyze IP service levels for IP applications and services.
The probes may generate the test traffic in a predictable manner even when the applications, services, or devices using the network are generating production traffic in an unpredictable manner. As a result of sending test traffic and receiving responses to the test traffic, active network monitoring provides a more detailed understanding of how the network is performing with respect to an application, service, or device.
Network administrators use probes sparingly so that the generated test traffic does not substantially slow down the network. If an application was not actively tested during a relevant period, a network administrator may not have enough information to troubleshoot how the network is handling the application. Alternately, the network administrator may not be able to confirm that the network is handling the particular application in accordance with existing service level agreements.


Ex vivo determination of increased tumor immunogenicity of a tumor biopsy is used as a guide to identify immunotherapy of a tumor in a patient. Most preferably, the ex vivo tests will include exposure of biopsy samples to stress conditions to produce pretreated tumor cells that are then assayed with immune competent cells for increased activation or activity. Test conditions include exposure of the biopsy samples to immune stimulatory compositions, antibodies against neoepitopes, and/or modified cells, and an increase of immunogenicity is preferably determined by their exposure to T cells and/or NK cells.

The background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
Personalized medicine based on genomic or proteomic insights from a diseased tissue has become an increasingly promising tool in cancer therapy. However, and despite the significant amount of information that can be obtained from relatively small quantities of diseased tissue, treatment is typically limited to a comparatively low number of experimental or approved drugs with well-characterized targets. For example, treatment of breast cancer with antibodies that target mutant form of HER2 (trastuzumab) can improve outcome where the tumor overexpresses the HER2 protein. Likewise, where cancer growth is driven by a pathway that includes a kinase, treatment may be effective with kinase inhibitors targeting such kinases (e.g., inhibition of EGFR using afatinib, erlotinib, etc., or inhibition of Bcr-Abl with bosutinib, imatinib, etc.). However, cancers will in many cases develop resistance against specific drugs and growth often resumes.
Alternatively or additionally, cancer treatment may also include immunotherapy to help eradicate aberrant cells using one or more components of the immune system. For example, immunotherapy may involve cytokines and/or immune checkpoint inhibitors to stimulate an immune response, while in other examples cells or modified cells are employed as therapeutic agents. In yet other examples, cancer vaccines have been reported to be at least partially effective in certain diseases. Unfortunately, immune based cancer therapies are often highly unpredictable as the efficacy depends in most cases on the specific epitopes presented and/or available to the patient's immune system, and the health of the patient's immune system (which is often already compromised by prior chemotherapeutic treatments). Moreover, many tumors also exhibit strong immune evasion, and immunotherapy must account for such mechanisms, which are generally not well understood.
Some tried to solve the problem by identifying patient-specific neoepitopes and using them in the immunotherapy. For example, WO 2016/172722 discloses cancer neoepitopes and methods of using neoepitopes to generate synthetic antibodies for immunotherapy. In another example, US 2016/0326597 discloses use of neoepitopes in a patient's cancer sample where some neoepitopes have stronger binding affinities to certain MHC complexes than others. By identifying neoepitopes with stronger binding affinities, those neoepitopes can be used to identify individuals who are likely to respond to a treatment by administering immune checkpoint modulator. Others attempted to develop patient-specific tumor treatments that target individual expression patterns of tumor antigens (see e.g., WO 2014/082729) for stimulating, priming and/or expanding T cells directed against cells expressing antigens.
Still others tried to solve the problem of inconsistent immune response by determining the susceptibility of an individual patient to a cancer treatment, especially to immunotherapy. For example, WO 2011/131246 discloses ex vivo methods for determining the susceptibility of a tumor to a cancer treatment by evaluating expression of stress response markers or macroautophagic response markers.
However, none of those contemplate expression of neoepitopes and other markers on cancer cells may vary depending on stress conditions given to the cancer cells, and as such fail to recognize their variability among patients. Therefore, even though there are many treatment options for cancer known in the art, all or almost all of them suffer from several disadvantages. Consequently, there remains a need for improved systems and methods of cancer therapy.


Power dissipation of a semiconductor integrated circuit chip is reduced when it is operated at an operating voltage of 2.5 V or below. A switching element is provided in each circuit block within the chip. Constants of the switching element are set so that leakage current in each switching element in their off-state is smaller than the subthreshold current of MOS transistors within the corresponding circuit block. Active current is supplied to active circuit blocks, while switching elements of non-active circuit blocks are turned off. Thus, dissipation currents of non-active circuit blocks are limited to leakage current value of corresponding switching elements. Thus, the sum of dissipation currents of non-active circuit blocks is made smaller than the active current in the active circuit blocks. As a result, power dissipation in the semiconductor integrated circuit chip can be reduced even in the active state.

The present invention relates to semiconductor integrated circuits suitable for high-speed and low-power operation, and particularly to a semiconductor integrated circuit formed of small-geometry MOS transistors.
The semiconductor integrated circuits have so far been developed toward the scaling down of MOS transistors. However, since the minute structure of MOS transistors reduces their breakdown voltage the more as the degree of the minuteness becomes greater, the operating voltage of the small-geometry MOS transistors must be lowered, as described in International Symposium on VLSI Technology, Systems and Applications, Proceedings of Technical Papers, pp. 188–192(May 1989). The operating voltages of the semiconductors used in the battery-operated portable electronic apparatus must be further reduced for their low power consumption.
In order to maintain their high-speed operation under reduced operating voltages, it is also necessary to decrease the threshold voltage (VT) of the MOS transistors. The reason for this is that the operating speed is governed by the effective gate voltage of the MOS transistors, or the remainder of the subtraction of VT from the operating voltage, or that it increased with the increase of this effective gate voltage. For example, in a 16-gigabit DRAM which is expected to have 0.15 μm or below in effective channel length, about 4 nm in gate oxide film thickness, 1 V in standard operating voltage within chip and about 1.75 V in boosted word line voltage, the constant current threshold voltage of transistors is calculated to be −0.04 V. The term, constant current threshold voltage of transistors is the gate-source voltage under the conditions of a ratio, 30 of effective channel width to effective channel length and a drain current of 10 nA. In this case, the substrate-source voltage is 0, the junction temperature is 25° and a typical condition is assumed. For simplicity, the threshold voltage of p-channel MOS transistors is shown with the opposite sign.
When VT is reduced, however, the drain current cannot be completely cut off due to the drain current characteristic of the subthreshold region of MOS transistors. This problem will be described with reference to FIG. 22A which shows a conventional CMOS inverter. When the input signal IN to the CMOS inverter has a low level (=Vss), the n-channel MOS transistor MN is turned off. When the input signal IN has a high level (=Vcc), the p-channel MOS transistor MP is turned off. Therefore, in either case, from the ideal point of view, no current flows from the high source voltage Vcc through the CMOS inverter to the low source voltage Vss, or ground potential.
When the threshold voltage VT of the MOS transistors is reduced, however, the subthreshold characteristic cannot be neglected. As shown in FIG. 22B, the drain current IDS in the subthreshold region is proportional to the exponential function of the gate-source voltage VGS, and expressed by the following equation (1).
                              I          DS                =                              I            0                    ·                      W                          W              0                                ·                      10                                                            V                  GS                                -                                  V                  T                                            S                                                          (        1        )            where W is the channel width of the MOS transistors, I0 and W0 are the current value and channel width used when VT is defined, and S is the subthreshold swing (the reciprocal of the gradient of the VGS-log IDS characteristic). Thus, the drain current in the subthreshold region (, or the subthreshold current) flows even under VGS=0. The subthreshold current can be expressed by the following equation (2).
                              I          L                =                              I            0                    ·                      W                          W              0                                ·                      10                          -                                                V                  T                                S                                                                        (        2        )
When the input signal to the CMOS inverter shown in FIG. 22A is not changed, or when it is not operated, the off-state transistor of the CMOS inverter is at VGS=0. Therefore, the current flowing from the high source voltage Vcc through the CMOS inverter to the low source voltage Vss, or ground potential is the current IL which flows in the off-state transistor of the CMOS inverter.
This subthreshold current, as shown in FIG. 22B, is exponentially increased from IL to IL′ when the threshold voltage is decreased from VT to VT′.
Although the increase of VT or the reduction of S reduce the subthreshold current as will be seen from the equation (2), the increase of VT, incurs the reduction of the speed due to the decrease of the effective gate voltage, while the reduction of S will be difficult for the following reason.
The subthreshold swing S can be expressed by using the capacitance COX of the gate dielectric and the capacitance CD of the depletion region under the gate as in the following equation (3).
                    S        =                                                                              k                  ·                  T                  ·                                      l                    n                                                                  10                            q                                    1                    +                                    C              D                                      C              OX                                                          (        3        )            where k is the Boltzmann constant, T is the absolute temperature and q is the elementary charge. As will be seen from the equation (3), the condition of S≧kT ln 10/q is limited for any values of COX and CD. Thus, it is difficult for S to be reduced to 60 mV or below at room temperature (about 300 k).
Thus, in the semiconductor integrated circuit including MOS transistors with a low value of VT the amount of DC current consumption of non-operating circuits is remarkably increased because of the phenomenon mentioned above when the operating voltage becomes low (for example, 2 V or 2.5 V). Particularly, upon high-temperature operation, S becomes large, making this problem further serious. In the downsizing age of future computers and so on, when reduction of power is important, the increase of the subthreshold current becomes a substantial problem.
This problem will be further considered taking a memory, which is a typical semiconductor integrated circuit, as an example. The memory generally includes, as shown in FIG. 23, a memory array MA, an X decoder (XDEC) and word driver (WD) for selecting and driving a row line (word line W) for the selection of a memory cell MC within the memory array MA, a sense amplifier (SA) for amplifying the signal on a column line (data line D), a sense amplifier driving circuit (SAD) for driving the sense amplifier, a Y decoder (YDEC) for selecting a column line, and a peripheral circuit (PR) for controlling these circuits. The main parts of these circuits are designed based on the CMOS inverter logic circuit mentioned above.
When the threshold voltage VT of transistors (hereinafter, for simplicity the absolute values of the threshold voltages of the p-channel and n-channel MOS transistors are assumed to be equal to VT) is low, a subthreshold current, that is a current flowing in the source-drain path of the MOS transistors of which the VGS, is substantially 0.
Therefore, the sum of the subthreshold currents becomes particularly great in the circuits having a large number of MOS transistors, such as decoders, drivers or the peripheral circuit section.
For example, in the decoders or drivers, a small number of particular circuits are selected from a large number of circuits of the same type by the address signal, and driven. FIG. 24 shows an example of the conventional word driver for DRAM.
If the threshold value VT of the MOS transistors of all CMOS drivers #1–#r is large enough, the subthreshold current, that is a current flowing in the source-drain paths of the MOS transistors of substantially zero VGS, is substantially zero in each of a large number of nonselected circuits. In general, the number of the decoder and driver is increased with the increase of the storage capacity of the memory. However, even though the storage capacity is increased, the total current is not increased unless the subthreshold current flows in the circuits that are not selected in the decoders or drivers.
If the threshold voltage VT is decreased as mentioned above, however, the subthreshold current increases in proportion to the number of nonselected circuits.
In the prior art, when the chip is in the standby mode (nonselected state), almost all the circuits within the chip are turned off so that the power dissipation can be reduced as much as possible. However, it is not possible any more to reduce the power current dissipation even in the standby mode because the subthreshold current flows when the MOS transistors are highly scalled down.
When VT is small, the subthreshold current that is a current flowing in the source-drain paths of the MOS transistors with VGS being substantially zero, causes a trouble not only in the standby mode but also in the operating mode. Generally the current IACT flowing when the chip is in the active mode and the current ISTB flowing when the chip is in the standby mode are respectively expressed byIACT≈IOP+IDC, andISTB≈IDC,where IOP is the charging and discharging current to and from the load capacitance of the circuits within the chip, and given byIOP=CTOT·Vcc·fin which Vcc is the operating voltage of the chip, CTOT is the total load capacitance of the circuits within the chip, and f is the operating frequency. In addition, IDC is the subthreshold current given above. The subthreshold current is exponentially increased with the decrease of VT as indicated by the equation (2).
So far, since Vcc is large and VT is also large enough, the condition ofIOP>IDCcan be satisfied. Therefore, the following equations can be given:IACT≈IOP,ISTB≈IDCIn this case, IDC is substantially zero. Thus, for IACT, only the increase of IOP has been considered to cause a problem.
However, since IDC is increased with the decrease of Vcc and VT, finally the following condition is satisfied:IOP≦IDCIn addition, it is found that if Vcc and VT are decreased, the following condition is given:IOP<IDCIn this case, the expressions ofIACT≈IDC,ISTB≈IDCcan be given. Therefore, the increase of the subthreshold current IDC also becomes a problem to the current IACT which flows when the chip is operating.
FIG. 25 shows an example of the results predicted for the current dissipation in the DRAM. This prediction is made at a junction temperature of 75° C. with typical conditions. From FIG. 25, it will be seen that the IDC of the 4-G bit DRAM exceeds IOP when its operating voltage is assumed to be 1.2 V.
If we considers the worst conditions, the subthreshold current IDC causes a problem even when the effective channel length, gate oxide film thickness and operating voltage are respectively about 0.25 μm, 6 nm and 2.5 V. Here, the values corresponding to a 256-M bit DRAM are used. In the prior art, when the operating voltage is 3.3 V, the constant current threshold voltage defined as the gate-source voltage of the transistor of which the ratio of the effective channel width to effective channel length is 30 and in which the drain current is 10 nA is one tenth of the operating voltage, or 0.33 V at a substrate-source voltage of 0 volt and a junction temperature of 25° C. with typical conditions. At this time, the extrapolated threshold voltage defined as the gate-source voltage when the drain current characteristic of a saturated region is extrapolated for zero current is about 0.2 V higher than the constant current threshold voltage, or about 0.53 V. When the operating voltage is reduced to 2.5 V, the extrapolated threshold voltage is reduced to about 0.4 V in proportion to the operating voltage in order to assure the effective gate voltage. Since the difference between the extrapolated threshold voltage and the constant current threshold voltage is substantially constant, the constant current threshold voltage is about 0.2 V. In addition, the temperature dependency of the threshold voltage must be considered. In general, when the operation of the chip at room temperature is assured, it must be guaranteed at a normal ambient temperature Ta of 0° C. through 70° C. Moreover, the junction temperature Tj within the chip can be found from the equation ofTj=Ta+θja·Pdwhere Pd is the dissipation power, and θja is the thermal conductivity of the chip, and thus a higher temperature must be considered. If the source voltage and the active current IACT are 2.5 V and 50 mA, respectively, and if Ta is 75° C. including a margin when θja is 200° C./W, the junction temperature Tj is 100° C. The constant current threshold voltage at this value of Tj is about 0.1 V when the temperature dependency of the threshold voltage is assumed to be −1.6 mV/° C. In addition, if we consider the threshold voltage variation due to the process dispersion as 0.1 V, the constant current threshold voltage with 10 nA at the worst condition is about 0.0 V. In this case, if the effective gate length is 0.25 μm, the gate width which is used when defining the constant current threshold voltage is about 7.5 μm. If the total value of gate widths of the MOS transistors within the chip which contributes to IDC is about 4 m, the subthreshold current IDC is found to be 5 mA from the equation (2) when the subthreshold swing S is 100 mV/dec. This value of 5 mA corresponds to one tenth of IACT as assumed above, and is thus too large to be neglected. Therefore, when the operating voltage is about 2.5 V or below, the subthreshold current in the CMOS logic circuit causes a problem.
We now consider the dissipation power of a CMOS LSI which is demanded for its application. The dissipation power in the LSI used in portable apparatus should be treated as the average dissipation power in the period of time in which it is energized and thus it includes both the standby current and the active current. Particularly in the battery-operated apparatus, both the currents are important because the idle time is determined by the average dissipation power. There are a number of LSIs which keep operating almost within the period of time in which they are energized, such as IC processors, memories and ASICs for high-speed operation. In these LSIs, only the active current is important, and thus the condition of IACT≈ISTB may be allowed. In either case, the reduction of IACT is an important subject in all LSIs. In the prior art, since IDC is dominant for IACT in the near future as described above, it becomes important to reduce the leakage (penetrating) current flowing through the CMOS LSI in the active mode.
Accordingly, it is an object of the invention to provide a semiconductor integrated circuit capable of reducing the dissipation power of the semiconductor integrated circuit including circuits which have enhancement type MOS transistors which operate at an operating voltage of 2.5 V or below and which cause a significant current in the source-drain path when VGS is substantially zero.
It is another object of the invention to reduce the subthreshold current of the MOS transistors included in the word driver, decoder, sense amplifier driving circuit and so on of a memory or a semiconductor integrated circuit in which the memory is incorporated.
In order to achieve the above objects, when some circuits of the semiconductor integrated circuit are operated to change their outputs, the subthreshold current of the MOS transistors in the other circuits which are not changed in their outputs is reduced so that the dissipation power can be decreased.
More specifically, according to this invention, there is provided a semiconductor integrated circuit chip operating at an operating voltage of 2.5 V or below, comprising:
a first terminal at which a first operating potential is applied;
a second terminal at which a second operating potential is applied;
a first circuit block coupled between the first terminal and the second terminal; and
a second circuit block coupled between the first terminal and the second terminal;
wherein the first circuit block permits an active current to flow between the first terminal and the output terminal when the first circuit block responds to an input signal to its input terminal to produce an output signal at its output terminal,
wherein the second circuit block includes a plurality of subcircuit blocks each of which includes a MOS transistor having its source connected to a first node and its gate connected to the input terminal and a load having one end connected to the drain of the MOS transistor and the other end connected to a second node,
wherein the MOS transistor of each of the plurality of subcircuit blocks causes a subthreshold current in its source-drain path when the gate-source voltage is substantially 0,
wherein the plurality of first nodes of the plurality of subcircuit blocks are coupled through a plurality of switching elements to the first terminal, and the plurality of second nodes of the plurality of subcircuit blocks are coupled to the second terminal,
wherein constants of said plurality of switching elements are set so that the leak currents of the plurality of switching elements in their off-state are smaller than the subthreshold current of the MOS transistor of the corresponding one of said plurality of subcircuit blocks, and
wherein the current dissipation in each of the plurality of subcircuit blocks of the second circuit block is limited to a leak current value of the corresponding one of the plurality of switching elements by turning off the plurality of switching elements so that the sum of the current dissipations in the plurality of subcircuit blocks is made smaller than the active current of the first circuit block.
Therefore, even when the semiconductor integrated circuit chip is active, the first circuit block operates within the chip, while the subthreshold current in the non-active second circuit block can be reduced.
In addition, according to this invention, there is provided a semiconductor integrated circuit chip operating at an operating voltage of 2.5 V or below, comprising:
a first terminal at which a first operating potential is applied;
a second terminal at which a second operating potential is applied;
a first circuit block coupled between the first terminal and the second terminal; and
a second circuit block coupled between the first terminal and the second terminal;
wherein the first circuit block permits an active current to flow between the first terminal and the output terminal when the first circuit responds to an input signal to its input terminal to produce an output signal at its output terminal,
wherein the second circuit block includes a plurality of subcircuit blocks each of which includes a MOS transistor having its source connected to a first node and its gate connected to the input terminal and a load having one end connected to the drain of the MOS transistor and the other end connected to a second node,
wherein the MOS transistor of each of the plurality of subcircuit blocks causes a subthreshold current to flow in its source-drain path when the gate-source voltage is substantially 0,
wherein the plurality of first anodes of the plurality of subcircuit blocks are coupled through a plurality of switching elements to the first terminal, and the plurality of second nodes of the plurality of subcircuit blocks are coupled to the second terminal,
wherein constants of said plurality of switching elements are set so that the leak currents of said plurality of switching elements in their off-state are smaller than the subthreshold current of the MOS transistor of the corresponding one of said plurality of subcircuit blocks, and
wherein the current dissipation in each of the plurality of subcircuit blocks of the second circuit block is limited to a leak current value of the corresponding one of the plurality of switching elements by turning off the plurality of switching elements so that the sum of the current dissipations in the plurality of subcircuit blocks is made smaller than the active current of the first circuit block,
wherein each of the plurality of subcircuit blocks of the second circuit block causes an active current to flow between the first terminal and the output terminal of each of the subcircuit blocks when each subcircuit responds to an input signal to its input terminal to produce an output signal at its output,
wherein the first circuit block includes a plurality of subcircuit blocks, each of which includes a MOS transistor having its source connected to the first anode and its gate connected to the input terminal, and a load having its one end connected to the drain of the MOS transistor and the other end connected to the second anode,
wherein the MOS transistor of each of the plurality of subcircuit blocks of the first circuit block causes the subthreshold current to flow in its source-drain path when the gate-source voltage is substantially 0,
wherein the plurality of first anodes of the plurality of subcircuit blocks of the first circuit block are coupled through the plurality of switching elements to the first terminal, and the plurality of second anodes of the plurality of subcircuit blocks of the first circuit block are coupled to the second terminal,
wherein the constants of the plurality of switching elements of the first circuit block are fixed so that the leak currents of the plurality of switching elements of the first circuit block in their off-state are smaller than the threshold current of the MOS transistor of the corresponding one of the plurality of subcircuit blocks of the first circuit block, and
wherein the plurality of subcircuit blocks of the second circuit block are made active by turning on the plurality of switching elements of the second circuit block, and the current dissipation in each of the plurality of subcircuit blocks of the first circuit block is limited to a leak current value of the corresponding one of the plurality of switching elements by turning off the plurality of switching elements of the first circuit block so that the sum of the current dissipations in the plurality of subcircuit blocks is made smaller than that of the active currents of the second circuit block.
Therefore, when the semiconductor integrated circuit chip is active, the first circuit block within the chip is operated, while the subthreshold current in the second non-active circuit block can be reduced. In addition, while the second circuit block is operated within the chip, the subthreshold current in the first non-active circuit block can be reduced.
Moreover, according to this invention, there is provided a semiconductor integrated circuit chip comprising:
a plurality of first circuit blocks;
a plurality of first switching elements;
a first operation potential power line coupled common to the plurality of first switching elements; and
a second switching element coupled between the first operation potential power line and a first operation potential point,
wherein each of a plurality of first nodes of the plurality of first circuit block is coupled to the first operation potential power line through the corresponding one of the plurality of first switching elements,
wherein a plurality of second nodes of the plurality of first circuit blocks are coupled to a second operation potential power line,
wherein each of the plurality of first circuit blocks includes a MOS transistor having its source connected to the corresponding one of the first nodes and its gate connected to an input terminal, and a load having its one end connected to an drain of the MOS transistor and the other end connected to the corresponding one of the second nodes,
wherein the MOS transistor of each of the plurality of first circuit blocks causes a subthreshold current to flow in its source-drain path when the gate-source voltage is substantially 0,
wherein constants of the plurality of first switching elements are set so that the leak current of each of the plurality of first switching elements in its off-state is smaller than the subthreshold current of the MOS transistor of the corresponding one of the plurality of first circuit blocks,
wherein the current dissipation of each of the plurality of first circuit blocks is limited to a leak current value of a corresponding one of the plurality of first switching elements by turning off the plurality of first switching elements, and
wherein a constant of the second switching element is set so that the leak current of the second switching element in its off-state is smaller than the sum of the leak currents of the plurality of first switching elements, and thus the sum of current dissipations in the plurality of first circuit blocks is limited to the leak current value of the second switching element.
Therefore, the current dissipation of each of the plurality of first circuit blocks in the standby mode is limited to the subthreshold current of the first switching elements or below. In addition, the sum of the current dissipations in the plurality of first circuit blocks coupled to the first operation potential line in the standby mode is limited to the subthreshold current of the second switching element or below.
Also, according to this invention, there is provided a semiconductor integrated circuit chip comprising:
a first terminal at which a first operating potential is applied;
a second terminal at which a second operating potential is applied;
a first circuit block coupled between the first terminal and the second terminal; and
a second circuit block coupled between the first terminal and the second terminal;
wherein the first circuit block permits an active current to flow between the first terminal and the output terminal when the first circuit block responds to an input signal to its input terminal to produce an output signal at its output terminal,
wherein the second circuit block includes a plurality of subcircuit blocks each of which includes a MOS transistor having its source connected to a first node and its gate connected to the input terminal and a load having one end connected to the drain of the MOS transistor and the other end connected to a second node,
wherein the MOS transistor of each of the plurality of subcircuit blocks causes a subthreshold current to flow in its source-drain path when the gate-source voltage is substantially 0,
wherein the plurality of first anodes of the plurality of subcircuit blocks are coupled through a plurality of switching elements to the first terminal, and the plurality of second nodes of the plurality of subcircuit blocks are coupled to the second terminal,
wherein constants of said plurality of switching elements are set so that the leak currents of said plurality of switching elements in their off-state are smaller than the subthreshold current of the MOS transistor of the corresponding one of said plurality of subcircuit blocks, and
wherein the current dissipation in each of the plurality of subcircuit blocks of the second circuit block is limited to a leak current value of the corresponding one of the plurality of switching elements by turning off the plurality of switching elements so that the sum of the current dissipations in the plurality of subcircuit blocks is made smaller than the active current of the first circuit block,
wherein each of the plurality of subcircuit blocks of the second circuit block causes an active current to flow between the first terminal and the output terminal of each of the subcircuit blocks when each of the subcircuit blocks of the second circuit block responds to an input signal to its input terminal to produce an output signal at its output,
wherein the first circuit block includes a plurality of subcircuit blocks, each of which includes a MOS transistor having its source connected to the first anode and its gate connected to the input terminal, and a load having its one end connected to the drain of the MOS transistor and the other end connected to the second anode,
wherein the MOS transistor of each of the plurality of subcircuit blocks of the first circuit block causes the subthreshold current to flow in its source-drain path when the gate-source voltage is substantially 0,
wherein the plurality of first anodes of the plurality of subcircuit blocks of the first circuit block are coupled through a plurality of switching elements to the first terminal, and the plurality of second anodes of the plurality of subcircuit blocks of the first circuit block are coupled to the second terminal,
wherein the constants of the plurality of switching elements of the first circuit block are fixed so that the leak currents of the plurality of switching elements of the first circuit block in their off-state are smaller than the threshold current of the MOS transistor of the corresponding one of the plurality of subcircuit blocks of the first circuit block, and
wherein the plurality of subcircuit blocks of the second circuit block are made active by turning on the plurality of switching elements of the second circuit block, and the current dissipation in each of the plurality of subcircuit blocks of the first circuit block is limited to a leak current value of the corresponding one of the plurality of switching elements by turning off the plurality of switching elements of the first circuit block so that the sum of the current dissipations in the plurality of subcircuit blocks is made smaller than that of the active currents of the second circuit block.
Therefore, as described above, the sum of the dissipation currents of the plurality of first circuit blocks coupled to the first operation potential line in the standby mode is limited to the subthreshold current of the second switching element or below, and the sum of the dissipation currents of the plurality of second circuit blocks coupled to the third operation potential line in the standby mode is limited to the subthreshold current of the fourth switching element or below. The total sum of the sum of the dissipation currents in the plurality of first circuit blocks and the sum of the dissipation currents in the plurality of second circuit blocks is limited to the subthreshold current of the fifth switching element or below.
The concept common to the semiconductor integrated circuit chips given in the summary of the invention is to have a plurality of circuit blocks and at least two circuit terminals through which a desired operating voltage is applied to these circuit blocks, and to have current control means provided for the subthreshold currents in the circuit blocks between each of the circuit blocks and at least one of the circuit terminals, so that the leakage current in a certain one of the circuit blocks is controlled by the current control means during a period including part of the time in which at least another one of the circuit blocks logically operates. Thus, when the semiconductor integrated circuit chip itself is in the operating state, during the period in which a certain one of the circuit blocks is operated, the leakage current in another non-operated one of the circuit blocks can be reduced. As a result, it is possible to reduce the total leakage current of the semiconductor integrated circuit chip in the active mode.
Therefore, even if the threshold voltage of the MOS transistor is decreased as it is scaled down, the leakage current flowing in the nonselected circuit can be minimized.

Semiconductor integrated circuits with power reduction mechanism


A gasoline detergent additive composition comprising a) the reaction product of a 4-alkyl-2-morpholinone and an alkylphenoxypolyoxyalkylene amine; b) the reaction product of a polyalkenyl succinic acid anhydride and a polyethylene polyamine; and c) a polyalphaolefin. A motor fuel composition is also provided.

1. Field of the Invention
This invention relates to an additive composition for use in motor fuels. More specifically, this invention relates to a motor fuel additive composition which is effective to reduce deposits on the intake valves of an internal combustion engine.
2. Description of Related Information
The combustion of a hydrocarbon motor fuel in an internal combustion engine leads to the formation and accumulation of deposits on intake valves. Intake valve deposits interfere with valve closing and eventually will lead to valve burning. Such deposits interfere with valve motion and valve seating, reduce the volumetric efficiency of the engine and reduce the maximum power obtainable. Valve deposits may be produced from, among other things, thermally and oxidatively unstable fuel or from lubricating oil oxidation products. The hard carbonaceous deposits produced collect in the tubes and runners that are part of the exhaust gas recirculation (EGR) flow. These deposits are believed to be formed from exhaust particles which are subjected to rapid cooling while mixing with the air-fuel mixture. Reduced EGR flow can result in engine knock and in nitric oxide, NO.sub.x, emission increases. It would, therefore, be desirable to provide a motor fuel composition which minimizes or overcomes the formation of intake valve deposits.
Another problem common to internal combustion engines is the formation and accumulation of deposits on various parts of the combustion chamber as well as on the fuel intake and exhaust system of the engine. The presence of deposits in the combustion chamber seriously reduces the operating efficiency of the engine. First, deposit accumulation within the combustion chamber inhibits heat transfer between the chamber and the engine cooling system. This leads to higher temperatures within the combustion chamber, resulting in increases in the end gas temperature of the incoming charge. Consequently, end gas auto-ignition occurs, causing engine knock. In addition, the accumulation of deposits within the combustion chamber reduces the volume of the combustion zone, causing a higher than design compression ratio in the engine. This, in turn, can also lead to engine knocking. A knocking engine does not effectively utilize the energy of combustion. Moreover, a prolonged period of engine knocking can cause stress fatigue and wear in pistons, connecting rods, bearings and cam rods of the engine. The phenomenon noted is characteristic of gasoline powered internal combustion engines. It may be overcome by powering the engine with a higher octane gasoline which resists knocking. This need for a higher octane gasoline as the engine accumulates operating time has become known as the engine octane requirement increase (ORI) phenomenon. It is particularly advantageous if a fuel additive's contribution to engine ORI can be substantially reduced or eliminated by preventing or modifying deposit formation in the combustion chambers of the engine.
The present invention provides a gasoline detergent additive composition which reduces the level of deposits on intake valves with no significant contribution to combustion chamber deposits.

Gasoline detergent additive composition and motor fuel composition


The invention relates to an aerosol delivery device (10) comprising an aerosol generator (3) for generating an aerosol in the aerosol delivery device (10), a sensor (5) configured to detect a use of the aerosol delivery device (10) for aerosol treatment, and a controller (7) configured to deactivate the aerosol generator (3) if no use of the aerosol delivery device (10) for aerosol treatment is detected by the sensor (5). Further, the invention relates to a method for operating an aerosol delivery device (10), comprising the steps of operating an aerosol generator (3) for generating an aerosol in the aerosol delivery device (10), detecting a use of the aerosol delivery device (10) for aerosol treatment by means of a sensor (5), and deactivating the aerosol generator (3) by means of a controller (7) if no use of the aerosol delivery device (10) for aerosol treatment is detected by the sensor (5).

Aerosols for therapeutic purposes are generated and delivered to a desired location within a user's or patient's body with aerosol delivery devices. A fluid (i.e., medicament) to be aerosolised or nebulised is supplied to an aerosol generator of the aerosol delivery device, the fluid is aerosolised or nebulised by the aerosol generator and the resultant aerosol is supplied to a user or patient. The fluid to be aerosolised or nebulised may be, for example, stored in a fluid reservoir of the aerosol delivery device or in an ampoule that can be inserted in the device.
The requirements placed on the aerosol delivery device arise from the treatment to be performed with the aerosols, One of these requirements concerns dosage accuracy and consistency, i.e., the accuracy and consistency of the administered quantity of the medicament provided as an aerosol. Only if the dosage of a medicament administered to a user or patient is accurately and consistently established, a precise and effective treatment with highly effective medicaments can be carried out.
In order to provide a high dosage accuracy and consistency, it has to be ensured that the aerosol generated by the aerosol generator is efficiently supplied to the user or patient without the occurrence of substantial aerosol losses inside or outside the aerosol delivery device.
Two different modes of aerosol administration are commonly used in aerosol treatment or therapy, namely continuous nebulisation and breath-triggered nebulisation.
Continuous nebulisers continuously generate aerosol during the aerosol treatment or therapy. These nebulisers offer the advantage of a simple structure and the quick administration of a desired aerosol dosage. However, substantial aerosol losses occur during exhalation of the user or patient and during intentional or unintentional interruptions of the treatment or therapy.
US-A-2006/0054166 discloses an inhalation nebuliser which allows for aerosol losses occurring during exhalation of a regularly breathing user or patient to be minimised. This inhalation nebuliser comprises an aerosol generator and a mixing chamber, wherein the aerosol generator continuously produces an aerosol.
The mixing chamber has an inhalation valve that allows ambient air to flow into the mixing chamber during an inhalation phase, while preventing aerosol from escaping during an exhalation phase. Further, the mixing chamber has an exhalation valve that allows discharge of the patient's respiratory air during the exhalation phase, while preventing an inflow of ambient air during the inhalation phase.
The exhalation valve ensures that the patient's exhaled air is vented to the surroundings without significantly reaching the mixing chamber. During the exhalation phase, the continuously operating aerosol generator accumulates or concentrates the aerosol in the mixing chamber, so that during an inhalation phase not only the amount of aerosol generated due to the continuous production is available for the inhalation, but at the beginning of the inhalation phase an aerosol bolus can be inhaled, which is available because of aerosol accumulation during the exhalation phase.
Nebulisers adopting such an approach are also disclosed in EP-A-1 927 373 and US-A-2012/0037154.
The aerosol losses increase considerably and become indeterminable if a user's or patient's regular respiration through the aerosol delivery device is interrupted. Hence, in the case of such an interruption, it is impossible to accurately determine the amount of aerosol delivered to the desired location within the user's or patient's body. Therefore, such, interruptions significantly affect the accuracy and consistency of the administered aerosol dosage, thus lowering the efficiency of the aerosol treatment or therapy.
In order to minimise the aerosol losses occurring during such interruptions, some aerosol delivery devices with continuous nebulisers have been provided with a manual pause function, allowing for the nebuliser to be manually paused in the case of an interruption. However, such a manual pausing of the nebuliser is not sufficiently quick and reliable for ensuring an accurate and consistent administration of the generated aerosol.
In breath-triggered nebulisers, the aerosol generation is periodically switched on and off at the beginning and end of the inhalation phase, respectively, in order to minimise aerosol losses during exhalation periods of a user or patient. Aerosol generators of this type are disclosed, for example, in U.S. Pat. No. 7,748,377 and US-A-2008/0142002.
The aerosol generating system disclosed in U.S. Pat. No. 7,748,377 includes an aerosol generator, a controller and a breathing sensor. The controller is in communication with the aerosol generator to control the sequence of aerosolisation of a liquid for delivery to a patient. The breathing sensor is used to measure a breathing pattern of the patient, a peak flow, a breathing rate, exhalation parameters or a regularity of breathing. The measured breathing characteristics are routed to the controller and processed via a software algorithm to determine an appropriate sequence of delivery relative to the measured breathing cycle of the patient.
US-A-2008/0142002 discloses a method and a system for nebulising a liquid. The method comprises taking one or more breaths and measuring characteristics of the breath. An aerosol generator is operated based on the measured characteristics of the one or more measured breaths.
With such breath-triggered nebulisers, the aerosol losses occurring during exhalation periods of a user or patient can be considerably reduced. However, the administration of a desired aerosol dosage requires significantly more time than for the case of continuous nebulisers, thus potentially affecting patient adherence and the effectiveness of the aerosol treatment or therapy.
Hence, there remains a need for a simple aerosol delivery device and a simple aerosol delivery method, enabling the supply of an aerosol to a user or patient in a quick and efficient manner.

Aerosol delivery device and operating method for the aerosol delivery device


A fishing lure assembly and the method of making a unique fill composition that causes attractant scent compounds to be dispensed from the fishing lure assembly. The fishing lure assembly has a body that can retain a volume of fill composition. The fill composition contains an ion exchange material and attractant scent compounds that are ionically bonded together. When the fishing lure is submersed in water, the fill composition is exposed to a controlled flow of water. In an ion exchange reaction, ions contained within the water bond to the ion exchange material and thus free the previously bonded attractant scent compounds. The freed attractant scent compounds flow out of the lure assembly with the passing water.

1. Field of the Invention
In general, the present invention relates to fishing lures. More particularly, the present invention relates to fishing lures that release fish attracting compounds when submersed in water.
2. Background Art
The activity of fishing with a baited line predates recorded history. In this vast period of time, inventive fishermen have developed countless baits and lures. In the past several decades, the popularity of recreational sport fishing has grown dramatically. In light of this popularity, fishermen have been inclined to develop new instruments and techniques for finding and catching fish. It is for this reason that the prior art record of patents is replete with thousands of different fishing lure designs.
Many artificial lures are designed with unique shapes and movements that are intended to make the lures attractive to fish. However, many species of fish track their prey either partially or totally based on scent. In fact, some species of fish are so sensitive to scent that they can detect prey miles away and well out of visual range. For example, certain species of shark can detect blood in water in concentrations of only parts per billion.
Most fish species are known to have the ability to detect chemicals in the environment. It has been determined that certain compounds, such as amino acids, specific proteins, lipids, citrates, urea and other compounds, are contained within the tissues, excretions or blood of prey fish. These compounds, either individually or in combination can physiologically stimulate the olfactory and or gustatory receptors when detected by predator fish. These observed changes in certain predator fish include, increased instances of snapping, biting, and swallowing, as well as increased retention time of held bait. Some fish have been observed to swim more aggressively and across wider areas when scent compounds are detected in the water.
It is for these reasons that natural baits have long been used by fishermen in an attempt to present a natural food source to fish. It is also for these reasons that fishermen chum the waters where they are fishing in hopes of attracting predator game fish. Natural baits however, have a number of inherent drawbacks and disadvantages. These shortcomings include rapid bacteriological spoilage, high cost, unpleasant handling, and durability issues resulting in one time only use. Natural bait also smells, and fouls all surfaces it touches. This requires that fishing boats and fishing gear be cleaned repeatedly in order to be kept sanitary. Recognizing the disadvantages of natural bait, the popularity of artificial lures grew.
Although artificial lures solved many of the obvious shortcomings of natural bait, they were not as effective in catching fish. The prior art is replete with many different lure designs that incorporate scent or other perceived methods to attract predator game fish to artificial lures. In the simplest form, such prior art lures use an absorbent material that is soaked with fish oils. Such prior art lures are exemplified by U.S. Pat. No. 1,393,617 to Frame, entitled Artificial Bait; and U.S. Pat. No. 2,797,519 to Keller, entitled Artificial Bait.
A problem associated with absorbent fishing lures is that they have a tendency to release their scent quickly. Thus, after the lure has been in use in the water for a few minutes, all the oils have left the lure and the lure is saturated with only water.
In attempts to prolong the period of time that a lure releases scent, scent compounds have been incorporated within the matrix of various polymers. The reason for this is that the attractants are supposed to leech out from the lure when in the water and attract fish. This approach has several drawbacks, releasing the attractant from the lure to slowly, resulting in the decomposition of the scent, or too rapidly exhausting the attractant from the lure. These lure designs do not allow sufficient means of recharging the attractants to be of any use to the fisherman in attracting fish. These lure designs also do not allow the fisherman to introduce different attractants to the lure to quickly target specific species of fish. Thus, once the scent is exhausted, the lure cannot be refilled with scent and must be discarded. Typical of this design is that the migration of the suspended attractant agents are greatly restricted and are unable to be released in a predictable or sustained manner. Such prior art lures are exemplified by U.S. Pat. No. 4,731,247 to Wolford, entitled Artificial Fish Baits With Sustained Release Properties; and U.S. Pat. No. 4,962,609 to Walker, entitled Fish Attractant Scented Fishing Lure.
Other designs have sought a similar approach of combining scent within the matrix of the lure, but make the mistake of using water insoluble polymers or gums which do not release at a desired rate if at all. Again, these designs trap the scent attractant within their matrices where they break down and decompose, and render the lure ineffective.
It was to overcome the lack of effectiveness and expense of these described prior art devises that the present invention was developed. It can be seen that a need exists in the field of artificial fishing lures, for a lure that slowly releases scent compounds in fresh, salt or brackish water, yet can be repeatedly recharged with the scent compounds once the initial scent compounds have been exhausted. This need is met by the present invention as described and claimed below.

Fishing lure device and associated method of manufacture


A photodetector device is provided which comprises a photodiode for generating an electrical signal corresponding to an amount of incident light, and a logarithmic conversion transistor for subjecting a voltage value of the electrical signal to logarithmic conversion. The logarithmic conversion transistor comprises a first electrode which is one of a source electrode and a drain electrode, a second electrode which is the other of the source electrode and the drain electrode, and a gate electrode. The first electrode is connected to the photodiode. A first voltage is applied to the second electrode so that the logarithmic conversion transistor operates in a subthreshold region. The photodetector device further comprising a section for causing a voltage of the gate electrode to be in a floating state when the logarithmic conversion transistor subjects the voltage value of the electrical signal to logarithmic conversion.

1. Field of the Invention
The present invention relates to a photodetector device, a solid-state imaging device comprising a plurality of the photodetector devices, and a camera system comprising the solid-state imaging device.
2. Description of the Related Art
Semiconductor image sensors (e.g., CCD and MOS image sensors, etc.) have been applied to a number of image input devices. Particularly, in recent years, MOS image sensors have been reviewed and have attracted attention because their power consumption is low and they can be produced using the same CMOS technology as that which is used for their peripheral circuitry. In the field of MOS image sensors, attention has been paid to a so-called logarithm conversion image sensor. The logarithm conversion image sensor utilizes a subthreshold region of a MOS transistor, has logarithmic characteristics of the amount of irradiation and the output, and operates in a high dynamic range (see, for example, Japanese Laid-Open Publication No. 2003-158683).
FIG. 10 shows a photodetector device 900 which is provided in each unit pixel of a logarithm conversion image sensor. In the photodetector device 900, an output voltage Vout is determined so that a photocurrent Ipd generated by a photodiode 901 is balanced with a subthreshold current Ids of a logarithmic conversion MOS transistor 902.
The subthreshold current Ids of the MOS transistor 902 is represented by:Ids=Io×exp((φg−Vs)q/kT)  (1)where Io is a proportionality factor, q is the charge per electron, k is the Boltzmann constant, T is an absolute temperature, φg is a surface potential of a lower portion of the gate, and Vs is a potential of the source.
The relationship between a gate voltage Vg and the surface potential φg is represented by:Vg=mφg+a  (2)where m=dVg/dφg=1+Cd/Cox≈1.1 (Cox: oxide capacitance, Cd: capacitance of a depletion layer below the gate), and a is a constant. According to expressions (1) and (2), expression (3) is obtained:Ids=Io×exp(((Vg−a)/m−Vs)q/kT)  (3).
Assuming that Ids=Ipd and Vg=Vdd according to FIG. 10, Vout (=Vs) is represented by:Vout=(Vdd−a)/m−(kT/q)ln(Ipd/Io)  (4).
As can be seen, the output Vout and the photocurrent Ipd have logarithmic characteristics. When different amounts of light generate photocurrents Ipd1 and Ipd2 and the resulting output voltages are Vout1 and Vout2, the following expression is obtained:Vout2−Vout1=−(kT/q)ln(Ipd2/Ipd1) (5).
For example, when it is assumed that the amount of light is increased by a factor of 10 at room temperature (i.e., Ipd2=Ipd1×10), the following expression is obtained:Vout2−Vout1=−(kT/q)ln(10)≈−60 mV  (6).
This expression indicates that the amount of change in the output voltage with respect to the rate of change in the amount of light depends only on the absolute temperature, i.e., has a constant value. When the rate of change in the amount of light is assumed to be α, the amount of change in the output voltage is represented by:ΔVout=−(kT/q)ln(α)  (7).
Note that an image sensor is composed of a plurality of photodetector devices arranged in a two-dimensional manner, each photodetector device may have a structure as shown in FIG. 11 (photodetector device 910). The photodetector device 910 comprises a pixel amplifier 911 for impedance conversion and a row selection switch portion 912 in addition to the components of the photodetector device 900. A signal is generally output on a row-by-row basis. In the photodetector device 910, when a voltage is applied to a signal line SEL, the row selection switch portion 912 is switched ON, so that a signal output from the pixel amplifier 911 is output onto a column output line 913.
MOS transistor characteristics vary between each logarithmic conversion MOS transistor 902, which operates in a subthreshold region. Therefore, it is known that when an operating point of the logarithmic conversion MOS transistor 902 varies between each pixel, so-called two-dimensional fixed pattern noise occurs. To reduce the fixed pattern noise, a circuit for outputting a difference between an output signal and a reset signal in each pixel (CDS circuit) is provided (see, for example, Japanese Laid-Open Publication No. 2001-245214).
FIG. 12 shows a photodetector device 920. The photodetector device 920 comprises the components of the photodetector device 910, and in addition, a constant current power source 914, and a switch portion 915, which is connected to the constant current power source 914 and the logarithmic conversion MOS transistor 902.
FIG. 13 shows an example of driving pulse timing of the photodetector device 920. At output signal read time t1, a SEL switch is switched into conduction to output an output signal onto a column output line. In this case, the waveform of Vout has a high potential in the dark and a low potential in the light.
Next, at time t2, the switch portion 915 is switched into conduction so that the constant current power source 914 generating a constant current which is much larger than the output signal is brought into conduction with the source electrode of the logarithmic conversion MOS transistor 902. As a result, a source follower circuit whose input is Vdd is formed. This situation is equivalent to when an excessive amount of light is incident to the photodiode 901, and the potential of Vout is sufficiently lowered no matter whether it is in the dark or light.
Thereafter, at time t3, the SEL switch is switched into conduction, and when the potential of Vout is sufficiently lowered, an output signal is output as a reset signal to the column output line 913. The reset signal contains a variation in characteristics of the logarithmic conversion MOS transistor 902 (more specifically, also a variation in characteristics of the pixel amplifier 911) Therefore, a subsequent CDS circuit (not shown) is used to cancel the characteristics variation of the logarithmic conversion MOS transistor 902 in each pixel, resulting in a reduction in the fixed pattern noise. At time t4 and thereafter, the switch portion 915 is switched OFF, and an ordinary photodetection is continued until the next read operation (after one frame period).
In the above-described conventional photodetector device, when the rate of change in the amount of light is 10-fold, the amount of change in the output voltage is about 60 mV according to expression (6). An upper limit of an incident light amount range in which a photodetector device can operate is an amount of light (high luminance) which generates a large current which causes the operation of a logarithmic conversion MOS transistor to deviate from the subthreshold region. A lower limit of the incident light amount range is an amount of light (low luminance) which generates a small current in which a dark current component generated in the photodiode is not negligible. The light amount range is about 160 dB(=108). Therefore, the amount of change in the output voltage is only about 60 mV×8=480 mV. Compared to conventional linear conversion image sensor in which the amount of change in the output voltage is about 1 V, the logarithm conversion image sensor has an insufficient dynamic range of the output signal. In the case of the logarithm conversion image sensor, a gain is inevitably increased using an analog amplifier in order to A/D convert an output signal efficiently, leading to a large noise and thus a degradation in image quality. As described above, the logarithm conversion image sensor disadvantageously has a small absolute amount of change in the output voltage compared to conventional linear conversion image sensors.

Photodetector device, solid-state imaging device, and camera system