A screwless quick connection system for connecting a lead connector to a generator of an active implantable medical device is shown and described. The connector head includes a housing receiving a plug of a lead connector. A mechanism for locking the plug into the housing is provided by a U-folded leaf spring. Each branch of the U is provided with a respective hole sized so that the plug passes through the holes on both branches when it is inserted into the housing. The blade is deformable between a free state, in the absence of plug, and a deformed state, with the plug inserted therein. In the free state, both holes are misaligned, while in the deformed state they are aligned. In this way, an edge of both holes exerts by reaction a radial stress force against the smooth outer surface of the plug inserted therein.

The present invention relates to an active implantable medical device as defined by the Jun. 20, 1990 directive 90/395/CEE of the European Community Council, including those devices that continuously monitor a patient's cardiac activity and, if necessary, deliver to the heart electrical pulses for stimulation, cardiac resynchronization, cardioversion and/or defibrillation, in response to a rhythm disorder detected by the device, and those devices such as neurological devices, cochlear implants, drug pumps, and implanted biological sensors.
Active implantable medical devices include a housing that is generally designated as "the generator." The generator is mechanically and electrically connected to one or more "leads" that bear on them one or more electrodes that contact those tissues to which it is desirable to deliver electrical pulses, e.g., to apply stimulation pacing pulses, and/or to collect (detect) an electrical signal. These tissues include, for example, myocardial, nerve, and muscle tissue.
The French standard NF EN 50077 and its international counterpart ISO 5841-3, Implants for Surgery—Cardiac Pacemakers—Part 3: Low-Profile Connectors (IS-1) for Implantable Pacemakers, defines a normalized connection system standard in the industry, which is identified as "IS-1". The IS-1 standard ensures interchangeability and compatibility of the leads and generators produced by different manufacturers. In this regard, it should be understood that the present invention is not limited to the particular case of a connection system according to the IS-1 standard, nor even to connection systems applicable to cardiac pacemakers.
Typically, the connection between a lead connector—hereafter more simply referred to as "plug"—and a connector of a generator is made by one or more screws that are tightened by the surgeon using an ad hoc tool (e.g., a screwdriver, possibly equipped with a torque limiter) at the time of implantation of the device and/or the lead. This known screw connection system has several drawbacks. First, in addition to requiring a specific tool for its implementation, this system requires the presence of caps provided with sealed slots through which the tool must pass to prevent the terminals from coming into contact with body fluids after implantation. This requirement for sealing the slots through which the tool passes increases the cost and requires a volume or size of the generator at the connector that is large enough to accommodate the tool.
Second, a screw connection system does not prevent from a screwing oversight, whether from an insufficient screwing or from an overtightening of the screw and damaging the device, by the surgeon.
Third, a screw connection system also introduces significant risks of damage to the silicone plug by the screwdriver with a consequent loss of insulation, of removal or stripping of the screw thread at the time of its use, of binding thereof, or of damage to the head of the screw in case of incorrect insertion of the screwdriver.
From an economic standpoint, the use of a screw system generates certain additional costs (e.g., manufacturing of the screw, threading of inserts) and requires providing with the medical device a special tool (e.g., a screwdriver with torque limiter) for tightening the screw. From an industrial standpoint, the use of a screw connector system requires an operation for inserting and adjusting the position of screws in a predetermined position during the packaging of the device, and of addition of a spot of glue to freeze this position of the screw. From a safety standpoint, the operation of screwing the screw by the physician to secure the plug requires special attention, with an implementation time large enough to make sure that the plug is maintained in the housing, precisely and durably.
Despite these acknowledged drawbacks, the screw connection system is still almost universally used. Indeed, the connectivity standards related to implantable medical devices require (i) minimum retention forces sufficient to prevent accidental disconnection at the time of implantation or during the product lifetime, and (ii) a high-quality and enduring electrical contact (i.e., a very low contact resistance) between the connector plug of the lead and the electrical terminal of the implantable device. These two mechanical and electrical requirements are particularly well satisfied by a conventional screw connection system, despite its many disadvantages.
Various other systems for securing the plug into the housing of the connector head have been proposed to overcome the many difficulties and drawbacks outlined above.
Thus, EP 0890371 A1 and its counterpart U.S. Pat. No. 6,112,120, both assigned to Sorin CRM S.A.S., previously known as ELA Medical, describe separating the electrical contact and mechanical retention functions. The electrical contact is ensured by a spring system exerting a radial pressure against the conductive surface of the plug. The mechanical retention of the plug in the housing is secured by a locking wedge inserted between the body of the plug and the housing wall at the outlet thereof.
Another solution is proposed by EP 0900577 A1 (assigned to Sorin CRM S.A.S., previously known as ELA Medical), which implements a locking system with a retractable spring-loaded eccentric, locally applied against the plug and bearing against it response to an attempted extraction.
These solutions are functionally effective, but they involve relatively complex, and therefore expensive to produce, mechanical systems (e.g., including elements such as a spring, eccentric, and slide). They also require a specific release mechanism for the removal of the plug, typically requiring the use of a special tool for removing the holding or retraction force provided by the eccentric. Finally, they require special precautions to durably ensure the efficient sealing required at the connector.
Other known efforts at alternative connection systems implement deformable elastic elements such as metal blades with one or more orifices through which the plug passes when inserting it into the slot, and exerting a radial point of contact between the edge of the orifice and the surface of the plug.
Thus, U.S. Pat. No. 5,252,090 (Giurtino et al.) proposes to block the plug with an elastically deformable metal piece, extending around the plug in a plane substantially radial to the axis of the plug. Deformable tabs formed in the part produce by stemming an anti-kickback effect, preventing any withdrawal or pulling of the plug once it is inserted in the metal part. For disassembly, the part is extended laterally by two symmetrical ears that, by pinching, deforms the piece enough to remove the tabs of the plug and release it. This device is very effective in terms of mechanical retention. However, unlocking the device requires having two entrances on each side of the part, to ensure a symmetrical pinching, and therefore requires providing two release buttons (one on each side of the head connector).
FR 2 662 310 A (Darby et al.), refers to an elastic clamp whose ends of the two arms are folded against one another and are provided with holes corresponding to the diameter of the plug. The holes are shifted when the clamp is in the free state, and they can be aligned by moving the two arms of the clamp. The plug can then be introduced through the two holes, and be retained in the clamp after release of the force exerted to bring the two arms together. This connection system is very effective in terms of mechanical retention of the plug, but it is not designed to be integrated with a generator. Rather, it is presented to serve as a dispensing connector between several leads, this connector being placed away from the generator.

Screwless quick system for connecting a lead connector to a generator of an implantable medical device


Mooring system arranged in a body of water for the mooring of multiple surface or semi-submersible vessels or platforms with a artificial seafloor grid designed as a mesh-like structure arranged in a substantially horizontal plane in the body of water. The artificial seafloor grid including means for attachment to said vessel or platform, and is mechanically coupled to the bottom of the sea using anchoring elements.

Mooring systems are known in the prior art. In WO 97/29943 a mooring system is described which includes a bridle having a star-like shape that is useful for mooring a single vessel or for mooring two or more vessels relative to one another. The mooring system describes in WO 97/29943 has a mooring bridle formed of a plurality of anchor connections spaced about a central mooring position. The system includes connecting lines attached to non-adjacent anchor buoys and attachable to the additional vessel and includes mooring lines attachable to the additional vessel holding the vessel to the mooring bridle. The mooring lines each include an anchor (of the adjacent anchor connection), an anchor line, an anchor buoy, and a vessel line. In an alternative the system described in WO 97/29943 includes interconnecting two mooring bridles to provide for close, effective mooring of two vessels relative to one another.
U.S. Pat. No. 4,342,277 illustrates a system for anchoring a large number of interconnected mooring floats in either deep or shallow bodies of water. The system includes a grid of post-tensioned cables positioned beneath the floats and a number of anchoring lines extending between the grid and attachment fixtures forming part of the floats.
U.S. Pat. No. 5,704,307 illustrates a taut leg bow mooring system which includes an anchor positioned on the floor of the sea. A riser line is secured to and extends upwardly from the anchor, and a submerged buoy secured to the end of the riser line from the anchor.
It is limitation of all the above mentioned prior art solutions that even though a vessel may be connected to the mooring system in a removable fashion, all of the mooring structures rely on elements extending up to the surface of the sea, permanently situated at or near the surface of the sea when the mooring system has been positioned.
In the mooring system of WO 97/29943 the platform forms an integral part of the mooring grid, meaning that the mooring grid will at least partly collapse and alter shape and positions of many of its structural elements if the platform is removed. Hence this mooring grid does not allow for the removal of all surface components without loosing its form. On the one hand, system elements remaining on the surface may form an undesirable obstruction. On the other hand in a system where the surface elements are also removed, the mooring system changes shape and position, thereby making it difficult to restore to its desired operation.
The anchoring system for floating moorage disclosed in U.S. Pat. No. 4,342,277 needs several floats at the surface of the sea to remain intact. If these surface floats were removed the anchoring system would fall to the bottom of the sea and be very hard to reinstall into its original shape.
There is thus a need for a more flexible mooring system which improves the predictability of the mooring of surface vessels or the like, and which provides reduced a hindrance or restriction when there are no surface vessels or the like coupled to the mooring system.
Preferably, such a mooring system should enable the mooring of a number of platforms or vessels in at all depths in such a way that the mooring is able to withstand the forces typically occurring within such systems in such waters.
In some cases a mooring system should enable the mooring in shallow to deep waters of multiple platforms or vessels in substantially fixed positions relative to each other without resulting in excessive straining forces in any part of the system.
It is thus an object of the invention to provide a mooring system which allows improved freedom of movement for surface platforms or vessels while at the same time having a possibility of secure mooring of a vessel or platform at some location at or near a mooring point while taking into account variation in ocean floor shapes and depths.


The manually-operated balloon stuffing device has a minimum number of parts and is inexpensive to manufacture. The device includes a manual pump consisting of inner and outer cylindrical tubes, and a check valve in each tube that permits the passage of air in only a single direction within its respective tube. In a first embodiment, a balloon stuffing item is placed in an end of the inner tube, and the open balloon end is stretched over that tube end. The outer tube is then reciprocated along the longitudinal axis of the inner tube to pump up the balloon. The outer tube is then removed and a push rod pushes the sliding check valve, which in turn pushes the stuffing item into the inflated balloon. In an alternate embodiment, a large hollow adapter tube is placed on the end of the inner tube, and the open end of the balloon is stretched over the open end of the adapter tube. After the balloon is inflated, a push rod pushes the sliding check valve, which in turn pushes an extension rod, the latter moving the stuffing item into the balloon. In yet a third embodiment, the need for a push rod and a slidable check valve is eliminated by using a connector between the tube in which the item is placed on the upper end of the inner tube. Once the balloon is inflated as before, the inner tube is pushed through the third hollow tube, thereby pushing the item into the balloon.

This invention relates to devices for placing an item inside of an inflated balloon. More particularly, this invention relates to manually-operated balloon stuffing devices.
Several devices are known for placing an item within an inflated balloon. The balloon stuffing item may be a stuffed animal, flowers, or other novelty items. Many of the prior art balloon stuffing devices require an electrical power source to operate the air compressor used to inflate the balloon. These devices are complicated and expensive, and are limited to use in locations having a ready source of electrical power.
Other prior art devices use manually-operated pumps instead of an electrical pump to inflate the balloon. However, these devices are also expensive to manufacture since they are complicated, have numerous component parts, and require many manufacturing steps.
It is therefore desirable to provide an inexpensive, manually-operated balloon stuffing device containing a small number of parts which may be used in any location.


A first embodiment of a cell culture system has a cell death accelerator comprising one or more cell death inducing substances, including serum albumin, hemoglobin, glycine and glutamic acid. In a second embodiment a cell death inhibitor comprises one or more kinds of cell death inhibiting substances which include mercapto group containing amino acids, other mercapto group containing compounds and tryptophan. In a third embodiment a cell death inhibitor comprises an inhibitor of RNA or protein synthesis, optionally augmented with a thiol. The system can be applied to selectively induce death of cultured cells, such as neoplastic cell lines, or to inhibit death of other cells, such as neoplastic cell lines or non-neoplastic cells such as brain cells.

1. Field of the Invention
This invention relates to a cell death accelerator for inducing cell death and a cell death inhibitor for inhibiting cell death.
2. Description of the Related Art
For the purpose of culturing cells in vitro, serum is generally added to a synthetic culture medium in a concentration range of about 10-20%. The medium is a pH-balanced salt solution containing various nutrients such as vitamins, amino acids, and sugars. When serum or plasma is highly concentrated in the medium, beyond this range however, cell death is induced.
The cell death-inducing activity is seen in all the sera or plasma so far tested regardless of source (species or age), or heat treatment to inactivate complement. Two types of cell death are now generally recognized. The first is passive, resulting from lack of oxygen, mechanical crush injury, or other extreme change in the extracellular environment. The second type of cell death is called apoptosis, an active energy-requiring intracellular process that culminates in DNA fragmentation and osmotic lysis of the cell. The latter is an autonomous physiological death sometimes referred to as programmed cell death, and it occurs normally during development of the nervous system, skin, and other epithelial organs. Morphologically, apoptosis is characterized by blebbing of the plasma membrane and nuclear condensation. These visible changes are accompanied by synthesis of a specific protein(s) including nuclease followed by fragmentation of chromosomal DNA. Several apoptosis-related genes have already been identified in the nematode C. elegans and in mammalian lymphocytes.
Apoptosis is now the focus of much attention, because it appears to be crucial for normal tissue and organogenesis, neural development, and immune reactions to foreign antigens including those borne by infectious viruses.
The serum contains some components, i.e., proteins such as albumin and globulin, salts such as NaCl, KCl and CaCl.sub.2, vitamins, more than twenty amino acids, such as glycine, cystine, cysteine, alanine and tryptophan, and other components. Heretofore adequate investigation of the individual functions of each component in the serum has not been carried out. The present inventors disclosed that amino acids, such as cystine and cysteine, when added to the serum, decrease the toxic effect of the serum and accelerates growth and/or multiplication of cultured cells in Japanese Patent Application No. 270719/1990 filed on Oct. 9, 1990. At present, however, investigation of the toxic factor itself has not been carried out at all, and the characterization of components which can inhibit the toxicity has been insufficient. In the noted Japanese Application, the inventors disclosed that cysteine and cystine promoted cell growth and/or multiplication, and that tryptophan can prevent cell death.
Recently, Evan et al. (1992) reported that cultured fibroblasts died when the mitotic cycle was interrupted during c-myc expression. Serum-induced cell death may involve a similar mechanism. Cells entering the mitotic cycle in response to an excess of growth signals from serum may die after interruption of the cycle by thiol deficiency. Previously, we reported that a cell-death-inducing activity was present in a low molecular weight fraction of serum (M.W.<1,000) (Kurita and Namiki, 1993a). Subsequently, it was found that this activity was inhibited by thiols. It was water-soluble, heat-resistant, and had charcoal affinity. Approximate molecular weight of the factor was approximately 100-200 dalton upon size-sieve HPLC. In addition to low molecular weight factors, traces of macromolecules in the fraction are now thought to be necessary for cell death. The latter may act as a death signal, and c-myc may be also involved in the signal transduction. Further studies are needed to address these issues. Nevertheless, serum-induced cell death appears to be a type of apoptosis resulting from a disturbance in thiol metabolism.

Technique for acceleration of apoptotic cell death


A miniaturized in-body electronic device is provided. One or more antennas (e.g., 32) may be galvanically coupled to receive an alternating current (AC) signal through the body of a subject where the in-body electronic device is located. Power extraction circuitry (e.g., 36) is configured to extract electrical power from the AC signal received by the antenna. The extracted electrical power is used for electrically powering one or more components of the electronic device. A transmitter (e.g., 48) is coupled to receive power from the power extraction circuitry. A controller (e.g., 46) is coupled to the transmitter. The controller is configured to activate the transmitter to generate a sequence of intermittent transmission bursts for transmitting an uplink signal. A transmission burst may have a higher instantaneous power level than an instantaneous power level of the AC signal received by the antenna.

Medication compliance is the degree to which a medication is taken according to a prescribed treatment and is usually measured in terms of percent of doses taken over a given interval. It is estimated that thousands of people may die of treatable ailments because of poor adherence and a tenth of hospital admissions are associated with noncompliance at a healthcare services expense of approximately $15.2 billion annually. Medication compliance is also important in the context of clinical drug trials, geriatrics, and mental health/addiction medicine. For example, in a clinical drug trial it is desirable to know, with a high degree of certainty, the patient's compliance to a medication regimen, because without such knowledge the results from a clinical trial cannot be accurately interpreted or could even be misleading. In each case there is a clear and present need for relatively low-cost, automated technologies that can replace directly observed therapy (DOT), which is one known method of determining medication compliance. This known method tends to be costly and cumbersome since it depends on human labor.
An orally ingestible pill with an embedded passive microsystem disposed of via the gastrointestinal (GI)-tract and capable of communicating with devices external to the body can lead to an improved indirect method for monitoring a patient's adherence to a regimen. The current state of the art in passive microsystems for in-body communications does not fully address the fundamental challenges associated with severe signal attenuation inside human tissues, poor radiation properties of electrically small antennas, limited power for signaling and high path loss dependence on distance.
Known approaches utilize devices which are predominantly battery powered as at large distances the transmitted signals are severely attenuated inside the human body (i.e. the signal attenuation depends on various factors such as frequency of operation, tissue attenuation, electrical antenna size, mismatch losses, etc). Since batteries ultimately limit the potential for miniaturization (i.e. silicon devices can be orders of magnitude smaller), aspects of the present invention focus on passive microsystems. It will be appreciated, however, that the techniques described herein may also be applicable to battery powered systems.
In the context of passive devices, the operational range of biomedical devices inside the body is substantially limited (e.g., typically a few cm due to weak coupling, high tissue attenuation and/or human exposure limits to radio frequency (RF) fields). Traditional passive radio-frequency identification (RFID) transponders operating in the far-field suffer from space/frequency tradeoffs not suitable for miniaturized in-body communication. Since electrically large antennas in the far-field of operation are required to capture sufficient RF power to activate the transponder, devices with small antennas when operated at low frequencies suffer from poor radiation characteristics and when operated at high frequencies suffer from increased signal attenuation. Near-field transponders powered from low frequency magnetic fields have limited range, require multi-turn coils which are often wrapped around ferrite core materials to improve signal coupling, and suffer from power/bandwidth/size tradeoffs.

Miniaturized electronic device ingestible by a subject or implantable inside a body of the subject

University of Florida Research Foundation, Inc.


A turbine engine component has an airfoil portion with a pressure side wall and a suction side wall and a cooling system. The cooling system has at least one cooling circuit disposed longitudinally along the airfoil portion. Each cooling circuit has a plurality of staggered internal pedestals for increasing heat pick-up.

(1) Field of the Invention
The present invention relates to an improved cooling system for an airfoil portion of a turbine engine component and to a method of making same.
(2) Prior Art
Existing designs of turbine engine components, such as turbine blades, formed using refractory metal core (RMC) elements have peripheral cooling circuits placed around the airfoil portion of the turbine engine components to cool the airfoil portion metal convectively. FIG. 1 illustrates a pressure side view of one such turbine engine component, while FIG. 2 illustrates a suction side view of the turbine engine component. In some instances, the axial internal cores end in film cooling slots. The combination of film and convective cooling of peripheral microcircuits lead to significant increases in the overall cooling effectiveness. This in turn leads to extended life capability for the airfoil portion using the same amount of cooling flow as existing cooling design or less.
Existing airfoil configurations are highly three dimensional as illustrated in FIGS. 1 and 2, forming RMC elements to conform to the different airfoil shapes can be difficult, as residual stress tend to spring these core elements back to the undeformed shaped during casting. As a result, positional tolerances may be difficult to maintain during the casting preparation phases, when the wax and the core elements are assembled together. During investment casting, as the liquid metal is introduced in the casting pattern, the temperature that the cores are subject to can lead to deformation of the RMC elements, particularly if residual stress exists due to pre-form conditions.
It is desirable to minimize the consequences of pre-form operations.

Airfoil cooling with staggered refractory metal core microcircuits


A stack group merging system includes a first stack group including a first master stack device and first slave stack device(s), and a second stack group includes a second master stack device and second slave stack device(s). The first master stack device determines a first total data traffic amount transmitted by itself and the first slave stack device(s) in the first stack group. The second master stack device determines a second total data traffic amount transmitted by itself and the second slave stack device(s) in the second stack group. The first and second master stack devices exchange the first and second total data traffic amounts, and the master stack device in the stack group that transmits a higher total data traffic amount then operates as a master slave device for a merged stack group including the first and second stack group.

The present disclosure relates generally to information handling systems, and more particularly to merging stack groups provided by information handling systems.
As the value and use of information continues to increase, individuals and businesses seek additional ways to process and store information. One option available to users is information handling systems. An information handling system generally processes, compiles, stores, and/or communicates information or data for business, personal, or other purposes thereby allowing users to take advantage of the value of the information. Because technology and information handling needs and requirements vary between different users or applications, information handling systems may also vary regarding what information is handled, how the information is handled, how much information is processed, stored, or communicated, and how quickly and efficiently the information may be processed, stored, or communicated. The variations in information handling systems allow for information handling systems to be general or configured for a specific user or specific use such as financial transaction processing, airline reservations, enterprise data storage, or global communications. In addition, information handling systems may include a variety of hardware and software components that may be configured to process, store, and communicate information and may include one or more computer systems, data storage systems, and networking systems.
Information handling systems such as, for example, switch devices or other stack devices (also referred to as "stack units") known in the art, are sometimes provided in stack groups. As would be understood by one of skill in the art in possession of the present disclosure, a stack group may include a plurality of switch devices that have been configured to operate together as a single logical switch while having port capacity and other combined resources of the group of switch devices. In such stack groups, each of the stack devices may be provided a priority that allows a master stack device to be elected, with each of the remaining stack devices in that stack group operating as slave stack devices. For example, the stack device elected as the master stack device may have been provided a higher priority value than the stack device(s) that operate as slave stack device(s). However, in another example, more than one of the stack devices in the plurality of stack devices may have the same highest priority value, and the Media Access Control (MAC) address of those stack devices may be utilized to elect the master stack device (e.g., the stack device with the "highest" MAC address may be elected as the master stack device.) Following the election of the master stack device, the stack group may be configured with interface IP address(es), interface Virtual Local Area Network (VLAN) IP address(es), Layer 3 (L3) configurations, aggregation or "trunking" configurations, and/or other stack group configurations that would be apparent to one of skill in the art in possession of the present disclosure in order to allow the stack devices in the stack group to transmit data traffic between computing devices coupled to the stack group.
However, in some situations different stack groups may be combined and/or otherwise merged together into a merged stack group, and the merging of stack groups can raise issues. As discussed above, each stack group will include a master stack device that was elected for that stack group, and the merging of those stack groups will require that one of those master stack devices be elected as the master stack device of the merged stack group. Conventional stack group merging systems operate to elect the master stack device for the merged stack group in substantially the same manner as described above, with the master stack devices in the respective stack groups comparing their priorities to elect the master stack device with the higher priority as the master stack device for the merged stack group, and in the event that the master stack devices have the same priority, the master stack devices in the respective stack groups compare their MAC addresses to elect the master stack device with the "highest" MAC address as the master stack device for the merged stack group. As will be recognized by one of skill in the art in possession of the present disclosure, in most stack group deployments, the priority values assigned to the stack device do not change prior to stack group merging operations.
Thus, in situations where the master stack devices in the different stack groups have the same priority, the use of the MAC addresses of those master stack devices may result in the master stack device for the stack group that handles a relatively lower data traffic amount than the other stack group including the master stack device that is being elected as the master stack device for the merged stack group, as conventional stack group merging systems do not take into account the amount of data traffic being transmitted by the different stack groups being merged. As a result, the stack group that handled a relatively higher data traffic amount will reboot and lose its configuration, then be configured by the master stack device for the merged stack group with the configuration of the stack group that was previously handling the relatively lower data traffic amount prior to the merging of the stack groups, which can result in a loss of data traffic that was previously being handled by the stack group being reconfigured, and requires manual reconfiguration by a user or administrator of the merged stack group if it is to handle that data traffic which was being handling prior to the merging of the stack groups. As will be appreciated by one of skill in the art in possession of the present disclosure, as the number of stack devices included in the stack group being reconfigured subsequent to the merging grows, the amount of time and the number or errors associated with that reconfiguration grows as well, which delays and may even prevent the subsequent transmission of the relatively higher data traffic amount that stack group was previously handling.
Accordingly, it would be desirable to provide a stack group merging system that addresses the issues discussed above.


Small catalytic amounts of a transition metal catalyst such as Cr(O) are used in a higher order cycloaddition process in which a triene is reacted with a diene or alkene to efficiently and economically provide a cycloaddition product.

Higher-order cycloaddition processes are known in which transition metal mediated or transition metal templates are used in which the transition metal catalyst is used in stoichiometric amounts to provide cycloaddition products.
Publications are as follows:
1 Rigby and Ateeq, "Synthetic Studies on Transition-Metal-Mediated Higher Order Cycloaddition Reactions: Highly Stereoselective Construction of Substituted Bicyclo [4 4 1]undecane Systems" Journal of the American Chemical Society, 1990, 112.
2 Rigby and Henshilwood, "Transition Metal Template Controlled Cycloaddition Reactions. An Efficient Chronium(0)-Medicated [6.pi.+2.pi.] Cycloaddition", Journal of the American Chemical Society, 1991, 113.
The above publications, directed to the use of transition metal catalysts only in stoichiometric amounts, are incorporated by reference for their disclosure of triene, dienes and transition metal compounds including. chromium (0) complexes used in the transition metal mediated cycloaddition reactions.
It is desirable to provide an efficient cycloaddition process using only a small catalytic quantity of the expensive transition metal.

Catalytic metal promoted cycloaddition process


A method for preventing or treating drug dependence comprising administering to a human in need thereof a pharmaceutically effective amount of a 1,4-(diphenylalkyl)piperazine compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof, wherein R1 is lower alkoxy; R2 is lower alkoxy; A is lower alkylene and B is lower alkylene;

1. Field of the Invention
The present invention relates to drugs which contain 1,4-(diphenylalkyl)piperazine derivatives as active ingredients and are useful for the prevention or treatment of drug dependence due to drug abuse.
2. Background Art
Drug dependence is a functional adaptive condition of the central nervous system changed by interactions between living bodies and drugs. Drug dependence is classified as a psychological dependence wherein one depends on the psychological effects of drugs and has a physical dependence to avoid unpleasant bioreactions due to withdrawal (withdrawal symptoms). Symptoms always observed in drug dependence are psychological dependence on drugs which have been ingested and a strong impulse to demand the drugs (Pharmacia, 34, 900-904 (1998)).
A fear of drug dependence due to drug abuse is a serious social problem. There is not yet a direct therapy of the psychological dependence, which is the essence of drug dependence, and addiction, which is its symptom (Pharmacia, 34, 905-909 (1998)). An agonist therapy of cocaine and the like are actively being studied as a pharmacotherapy of drug dependence (Pharmacia, 34, 877-882 (1998)).
All the addicting drugs act on the central nervous system as main effects or side effects and are roughly classified as opioid analgesics, central nervous system depressants, central nervous system stimulators and psychotomimetics.
Examples of opioid analgesics are opium and morphine contained in it, heroin semisynthesized from morphine and synthetic narcotics such as pethidine and methadone having similar pharmacological actions and dependency to them, and antagonistic analgesics such as pentazocine and buprenorphine.
Examples of central nervous system depressants are hypnotics such as barbituric acid derivatives, methaqualone, benzodiazepine derivatives and chloral hydrate; antianxiety drugs such as meprobamate and benzodiazepine derivatives; organic solvents such as thinner, alcohols and the like.
Examples of central nervous system stimulators are cocaine, which is one of typical narcotics, stimulants such as amphetamines, anorexigenic agents such as phenmetrazine, stimulators such as methylphenidate and pipradrol and drugs contained in luxury goods such as nicotine and caffeine.
Examples of psychotomimetics are hallucinogens such as LSD, DOM (2-amino-1-2,5-dimethoxy-4-methyl)phenylpropane) and mescaline, PCP (phencyclidine or xe2x80x9cangel dustxe2x80x9d), cannabis and the like (xe2x80x9cNEW Pharmacologyxe2x80x9d, p. 606-611, Nankodo, 1989).
The addicting drugs are also classified according to the existence of crossing of their tolerance-dependency. Morphine type addicting drugs are exemplified by morphine, codeine, methadone, pethidine and the like. Barbiturate-alcohol type addicting drugs are exemplified by barbiturates, alcohols, weak tranquilizers and the like. Cocaine type addicting drugs are exemplified by cocaine, xe2x80x9ccrackxe2x80x9d (cocaine in ready-to-smoke form) and the like. Amphetamine type addicting drugs are exemplified by amphetamine, methamphetamine and the like. Cannabis type addicting drugs are exemplified by marijuana (THC), hashish and the like. Hallucinogen type addicting drugs are exemplified by LSD-25, mescaline, psilocibin and the like. Organic solvent type addicting drugs are exemplified by toluene, acetone, carbon tetrachloride and the like (xe2x80x9cOpioidxe2x80x9d, p. 118-120, Kagakudojin, 1991).
It was reported that 1,4-(diphenylalkyl)piperazine derivatives, which are active ingredients of the present invention, have a strong affinity for the xcexa3 receptor and are useful as therapeutic agents for cerebral nerve dysfunctions such as dementia, depression, schizophrenia and anxiety neurosis; diseases accompanied by immune disorders and cryptorrhea; digestive ulcer and the like (Japanese Laid-open Patent Publication No. 89949/1995). It was reported that such derivatives are useful as preventive or therapeutic agents for ophthalmopathy, particularly retinal diseases such as diabetic retinopathy and occlusion of retinal vessels and glaucoma, since such derivatives exhibit protective actions on retinal nerve cells (Japanese Laid-open Patent Publication No. 120569/1998).
Heretofore, a study of the drug dependence of the 1,4-(diphenylalkyl)piperazine derivatives was not done, and it is a very interesting subject.
Studying precisely in order to find new pharmacological actions of 1,4-(diphenylalkyl)piperazine derivatives, the present inventors found that the 1,4-(diphenylalkyl)piperazine derivatives exhibit inhibitory actions on drug dependence. Namely, the present inventors found that the 1,4-(diphenylalkyl)piperazine derivatives are useful as preventive or therapeutic agents for drug dependence due to drug abuse.
The present invention relates to a method for preventing or treating drug dependence comprising administering to a human in need thereof (such as a human having a drug dependency) a pharmaceutically effective amount of a compound represented by the following formula [I] or a salt thereof as active ingredients:
wherein R1 is lower alkoxy, R2 is lower alkoxy, xe2x80x9cAxe2x80x9d is lower alkylene and xe2x80x9cBxe2x80x9d is lower alkylene.
The groups defined above are described in more detail as follows. The lower alkoxy is lower alkoxy having one to six carbon atoms such as methoxy, ethoxy, propoxy or butoxy. The lower alkylene is lower alkylene having one to six carbon atoms such as methylene, ethylene, propylene or butylene.
Preferred examples of the compound are compounds wherein each group is the following in the compounds represented by the formula [I] or salts thereof:
(1a) xe2x80x9cAxe2x80x9d is lower alkylene having two to four carbon atoms; and/or
(2a) xe2x80x9cBxe2x80x9d is lower alkylene having two to four carbon atoms.
Namely,
Compounds defined by above (1a) in the compounds represented by the formula [I] or salts thereof,
Compounds defined by above (2a) in the compounds represented by the formula [I] or salts thereof, and
Compounds defined by a combination of above (1a) and above (2a) in the compounds represented by the formula [I] or salts thereof.
Particularly preferred examples of the compound are compounds wherein each group is the following in the compounds represented by the general formula [I] or salts thereof;
(1b) R1 is methoxy; and/or
(2b) R is methoxy.
Namely,
Compounds defined by above (1b) in the compounds represented by the formula [I] or salts thereof,
Compounds defined by above (2b) in the compounds represented by the general formula [I] or salts thereof, and
Compounds defined by a combination of above (1b) and above (2b) in the compounds represented by the general formula [I] or salts thereof.
Examples of particularly preferred compounds are 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl) piperazine represented by the following formula [II] or salts thereof.
The above-mentioned salts can be pharmaceutically acceptable salts, and are exemplified by hydrochlorides, sulfates, phosphates, lactates, maleates, fumarates, oxalates and the like. The above-mentioned compounds can take the form of hydrates.
The present invention can widely be applied to the drug dependence due to drug abuse and is not limited to specific drug dependence.
As a method of calibrating the existence or the intensity of the potential of drugs to induce psychological dependence, a method has been used since olden times in which selective intake behavior or self-intake behavior toward test drugs is observed. In recent years, as a relatively simple and reliable method, a method wherein effects on conditioned place preference are indexed (CPP method) is applied (xe2x80x9cOpioidxe2x80x9d, p. 118-120, Kagakudojin, 1991). The present inventors studied the existence or the intensity of the potential of addicting drugs to induce psychological dependence in the presence of the 1,4-(diphenylalkyl)piperazine derivatives by using this conditioned place preference test method (CPP method). Details are described in xe2x80x9cPharmacological Testsxe2x80x9d hereinbelow. It is found that the 1,4-(diphenylalkyl)piperazine derivatives exhibit excellent inhibitory effects on the potential of addicting drugs to induce psychological dependence and are useful for the prevention or the treatment of drug dependence due to the abuse of addicting drugs.
Examples of dosage forms of the drugs are oral preparations such as tablets, capsules and granules, injections and the like. These preparations can be prepared by general techniques. For example, in order to prepare oral preparations such as tablets, capsules and granules, the compound [I] or salts thereof can be formulated into the preparations, if necessary, by adding an extending agent such as lactose, starch, crystalline cellulose or vegetable oil, a lubricant such as magnesium stearate or talc, a binder such as hydroxypropylcellulose or polyvinyl pyrrolidone, a disintegrator such as calcium carboxymethylcellulose, a coating agent such as hydroxypropylmethylcellulose, macrogol or a silicone resin, or a gelatin film forming agent.
The dosage is appropriately adjusted depending on symptoms, age, dosage form, type of drug dependence and the like, and in the case of the oral preparations, the usual daily dosage is 1 to 1000 mg, which can be given in a single dose or several divided doses.
Pharmacological Tests are shown below as Examples.
Pharmacological Tests
Effects of 1,4-(diphenylalkyl)piperazine derivatives on the potency of induction of psychological dependence by addicting drugs were studied by using the conditioned place preference test (CPP method) according to the report of Suzuki et al. (Life Science, 57, 1277-1284 (1995)).


A method of linking alarm data from physically disassociated wireless sensors to a train in motion. The sensor secured to a wheel axle-box of a rail carriage of a train to detect an over temperature alarm to enable a driver to stop the train. If the alarm condition is confirmed as belonging to the train, a Monitor/Relay immediately notes that there is a problem and warns an operator.

In the field of rail industry safety, when any wheel bearing on a rail carriage goes into temperature alarm, it is essential that the driver of the train be notified of the problem almost immediately. This is because an unexpected and significant rise in the temperature of a wheel bearing, is typically the precursor to a catastrophic failure of that bearing.

This patent is subject to a terminal disclaimer.

Method of linking alarm data from physically disassociated wireless sensors to a train in motion


The kind of a particle is determined by pressing a hard atomic force microscope stylus having a spring constant equal to or larger than 300 N/m onto a particle to be removed and detecting bending quantity relative to a press force and a kind of a stylus used for removing the particle is changed in accordance with the kind of the particle.

The present invention relates to a method of removing a particle of a photomask by applying an atomic force microscope technology.
A micromachining technology of a nanometer order is requested for high function formation and high integration formation, and research and development of a machining technology of local anodic oxidation or microscratch machining using a scanning probe microscope (SPM) are intensely carried out. Not only a pursuit for a possibility of micromachining but also a pursuit for machining of an accurate shape or with high accuracy have been requested.
For example, recently, in an apparatus on the basis of an atomic force microscope (AFM), high accuracy correction of a micropattern surplus defect of a photomask is carried out by microscratch machining in which scanning is carried out with exerting a high press force (high load) on a stylus harder than a material to be machined and physical removal is carried accordingly for machining (Nonpatent Reference 1).
In accordance with a progress in miniaturization of lithography, a size of a particle to be removed on a silicon wafer becomes small, a and sufficient resolution cannot be obtained an optical microscope so that the particle is now observed by a scanning electron microscope or an atomic force microscope. Although removal of a particle is heretofore dependent on removal by cleaning, in the case of a small number of particles, the silicon wafer may conversely be contaminated at a cleaning step, and a method of effectively removing a small number of particles has been requested. Recently, there is also reported a method of applying an atomic force microscope technology used for observation as a method of removing a small number of fine particles on a silicon wafer (Nonpatent Reference 2).
Similar to the silicon wafer, also in the case of a photomask, with increased miniaturization of lithography, a size of a particle to be removed becomes small and a method of removing a particle which cannot be removed by cleaning is requested. When a particle is present at a photomask before being pasted with a pellicle, even when the number of particles is small, defects are produced in all of patterns to be transcribed and therefore, the particles need to be removed completely. There are various kinds of particles on a photomask such as a metal, a glass bump, a resist residue and the like and in order to ensure an optical property, there has been requested a method of removing a particle without damaging a quartz or glass substrate of a matrix as much as possible.
In order to remove a particle, it is necessary to know the kind of the particle since a method of removing a particle differs by the kind of the particle. There has been known a method of pressing a diamond stylus having a sharp tip to a particle and predicting Young's modulus of the particle from bending of a cantilever or a depth of an impression produced by the pressing and predicting a material of the particle from a value of Young's modulus as an indentation method. Recently, there has been carried out a nanoindentation method for executing an indentation method by attaching a diamond stylus having a tip diameter equal to or smaller than 100 nm to an atomic force microscope as a new application of the atomic force microscope as a method of predicting a material by calculating a hardness of a small region. The method provides a function of predicting a material of even a small object of a particle or the like.
[Nonpatent Reference 1] T. Amanao, M. Nishiguch, H. Hashimoto, Y. Morikawa, N. Hayashi, R. White, R. Bozak, and L. Terrill, Proc. of SPIE 5256 538–545 (2003)
[Nonpatent Reference 2] Junichi Muramoto, Hitoshi Kuniyasu, Tsuyoshi Hattori, Proceeding of 51st Conference of Applied Physics No. 2, 31p-B-2, p856 (2004)
It is an object of the invention to reduce damage on a quartz or glass substrate in removing a small particle on a photomask using an atomic force microscope technology.

Method of removing particle of photomask using atomic force microscope


An alignment method includes: (1) providing a substrate, applying a coating material formed from any two materials of aromatic dianhydrides, aromatic diamines or diamines containing biphenyl and hexyl in side groups; (2) sputtering a third material which is not coated in step (1) along a direction having an angle not equal to zero with the substrate for conducting a polymerization reaction with the two materials coated in step (1) to generate a reaction product; (3) thermally treating the reaction product. The diamine containing biphenyl and hexyl in side group reacts with the main group to form a side chain, and thus controls the pretilt angle while assisted with physical sputtering to sputter in a certain angle, thereby forming a pretilt direction.

In the research or application of liquid crystals, the control of the rotational direction of liquid crystal molecules is an extremely important step and is generally referred to as liquid crystal alignment. The most common liquid crystal alignment method is coating alignment materials on films formed on the surface of the substrates, and then making the molecules of the alignment films to generate directional arrangements by means of rubbing. When liquid crystal molecules attract the alignment films and form an ordered liquid crystal arrangement in virtue of intermolecular forces, the effect of liquid crystal alignment is finally achieved. The method of rubbing alignment can provide strong alignment ability for liquid crystal molecules. However, during the process of rubbing, contaminations of static electricity, scratch, particles and dust may be resulted due to the friction of rubbing cloth. These contaminations often directly cause damages in liquid crystal devices resulting in a decrease in the product yields.
Therefore, in academia and industry, non-contact alignment methods are being developed for easily controlling the alignment mode of liquid crystal molecules and for avoiding the contaminations of static electricity and particles. The most widely applied non-contact alignment method is photo alignment, such as ultraviolet light alignment.
The photo alignment utilizes linear polarized ultraviolet light to irradiate on macromolecular polymer alignment films containing photosensitizers, allowing the macromolecular polymer to have the ability of alignment. The photo alignment is able to avoid contaminations on the surface of glass substrates, to align in a small area, to make patterned alignment through photomasks, and to control the parameters of liquid crystal units such as pretilt angle and anchoring energy, etc. by the angle of incident light and irradiation time. The photo alignment material is a polymer formed by bonding many monomer molecules.
Generally alignment materials for the photo alignment may be divided into three groups: the first group is photo crosslinking reaction: After the alignment film is irradiated by the linear polarization ultraviolet light, molecules in the direction of polarization will be bonded to form long-bond molecules, allowing the alignment film to have an anisotropic distribution, and the liquid crystal molecules are consequently arranged along with the direction of the long-bond molecules. The second group is photo degradation reaction: after the alignment film is irradiated, the long-bond molecules in the direction of polarization will be degraded by the ultraviolet light, making the alignment film to form an anisotropic distribution, therefore the liquid crystal molecules will be arranged along the direction of the undegraded long-bond molecules. The third group is photo isomerization (cis-trans): generally an alignment material containing azo molecules is used, and the alignment material will form different arrangement directions before and after irradiation.
However, the process of photo alignment method is complicated and has a high cost for the necessary raw materials. Thus, this method is not suitable for large scale production.

Alignment method and liquid crystal display panel

SHANGHAI TIANMA MICRO-ELECTRONICS CO., LTD.


A covered wire connection structure is formed by the steps of: pinching a covered wire with a pair of resin chips; pressing and exciting a cover portion of the wire by ultrasonic vibration so as to conductively connect conductive portions of both the covered wires at the connection portion; and melting a pair of the resin chips so as to seal the connection portion. The resin chip comprises main melting portions for pinching the connection portion which are melted to a mating resin chip so as to seal the connection portion, and auxiliary melting portions which are formed of material compatible with the cover portion of the covered wire introduced from the main melting portions and pinch the cover portion such that they are melted to the mating resin chip. The auxiliary melting portions and cover portion of the covered wire are melted together and integrated so as to seal an introductive portion of the covered wire from the resin chips. As a result, a reliability in connecting the covered wires by ultrasonic vibration is maintained and waterproofness in the connection portion is improved.

This invention relates to a connection structure for conductively connecting covered wires (conductor) with each other or connecting a covered wire to another member.
As a conventional connection structure of this kind of covered wire, an art proposed by this applicant (see Japanese Unexamined Published Patent Application No.Hei7-320842) will be described.
When connecting two covered wires an outer periphery of which is coated with a cover portion made of resin, at their intermediate connection portions, a pair of resin chips which are of resin material, a horn for producing ultrasonic vibration, and an anvil for supporting the covered wires and the resin chips at the time of connection are utilized.
The anvil comprises a base stand and a support portion projecting from the base stand. The support portion is formed in a substantially cylindrical shape. The support portion has a bore portion which is open to a counter-side of the base stand. Two pairs of grooves are formed in the peripheral wall of the support portion so as to confront each other of the respective pairs across substantially a center of the bore portion. The four grooves are formed so as to open to the same side as the bore portion, extending along the projection direction of the support portion and intercommunicate with the confronting ones through the bore portion.
A pair of resin chips are formed in a disc shape having a slightly smaller outer diameter than the diameter of the bore portion of the anvil. Furthermore, an end portion of a head portion of the horn is formed in a disc shape having an outer diameter which is slightly smaller than that of the resin chips.
In order to connect the two covered wires to each other, both of the covered wires are overlapped with each other at connection portions thereof and the overlapped portions are pinched by a pair of resin chips from up and down. Specifically, one of the resin chips (the resin chip at the lower side) is inserted into the bore portion of the anvil such that the melting surface thereof is directed upward. Then, one covered wire is inserted into one pair of the confronting grooves from the upper side of the inserted resin chip. Then, the other covered wire is inserted into the other pair of the confronting grooves. Finally, the other (upper side) resin chip is inserted such that the melting surface is directed downward. The covered wires are arranged in the bore portion such that the respective connection portions thereof cross each other at the center of the bore portion. Through this arrangement, the connection portions of the covered wires are pinched substantially at the center of the melting surfaces of the upper and lower resin chips in the overlapping direction.
Subsequently, the cover portions at the connection portions of the covered wires are melted so as to be dispersed by ultrasonic vibration. Furthermore, the conductive wire portions (core) of the covered wires are made into conductive contact with each other at the connection portions by pressing the covered wires from the outside of the resin chips. Thereafter, the pair of the resin chips are mutually melted at the melting surfaces to seal the connection portions.
Consequently, the connection portions of the two covered wires are sealed by the pair of the resin chips such that they are conductively contacted with each other.
However, such a connection structure has a fear that the covered portions of the wires may be broken by an edge portion of the resin chip at an exit of the covered wire between the resin chips. If the covered portion is broken, there is a fear that water may penetrate through that broken portion.

Connection structure of a covered wire with resin encapsulation


In an image record organization method, camera, and system, a plurality of image records are provided and a value index is determined for each of the image records. The image records are classified into unacceptable records having respective value indexes within a predetermined threshold and acceptable records having respective value indexes beyond the threshold. The unacceptable records are demarcated from the acceptable records.

Digital imaging has vastly increased users ability to amass very large numbers of still images, video image sequences, and multimedia records combining one or more images and other content. (Still images, video sequences, and multimedia records are referred to collectively herein with the term "image records".) With very large numbers of image records, management becomes difficult.
Efforts have been made to aid users in organizing and utilizing image records by assigning metadata to individual image records that indicates a metric of expected value to the user. U.S. Patent Publication No. 2003/0128389 A1, filed by Matraszek et al., discloses another measure of image record importance, "affective information", which can take the form of a multi-valued metadata tag. The affective information can be a manual entry or can be automatically detected user reactions, including user initiated utilization of a particular image, such as how many times an image was printed or sent to others via e-mail. In either case, affective information is identified with a particular user. U.S. Pat. No. 6,671,405 to Savakis et al, discloses another approach, which computes a metric of "emphasis and appeal" of an image, without user intervention. A first metric is based upon a number of factors, which can include: image semantic content (e.g. people, faces); objective features, such as colorfulness and sharpness; and main subject features, such as size of the main subject. A second metric compares the factors relative to other images in a collection. The factors are integrated using a trained reasoning engine. U.S. Patent Publication No. 2004/0075743 is somewhat similar and discloses image sorting of images based upon user-selected parameters of semantic content or objective features in the images. These approaches place much effort into valuing of all of the images in a collection.
U.S. Pat. No. 6,535,636 is directed to a method for detecting "dud images", that is, unacceptable images, to determine images that are undesirable for placing in albums.
All of these approaches are useful, particularly in an environment, in which a user is making a deliberate effort to organize images, for example, in creating an album. Another environment, in which image management is needed is during a picture taking session with a digital still camera, cell phone camera, or the like. Some digital cameras, such as, the V-550 digital camera marketed by Eastman Kodak Company of Rochester, N.Y., include a user control labeled "Share", which can be actuated by the user to designate a respective image for preferential printing and e-mailing. It is convenient to use this user control during a picture taking session to identify images the user considers particularly good. Another environment, in which image management is an issue, is in devices having limited image handling capabilities relative to the overall requirements of a collection of images, such as an image viewer having limited storage capacity relative to received sets of images.
It would thus be desirable to provide methods and camera, in which unacceptable images can quickly and easily be managed on a camera.


The invention relates to chimeric molecules comprising a virus coat sequence and a receptor sequence that can inter-act with each other to form a complex that is capable of binding a co-receptor. Such chimeric molecules therefore exhibit functional properties characteristic of a receptor-coat protein complex and are useful as agents that inhibit virus infection of cells due to occupancy of a co-receptor present on the cell. In particular aspects, the chimeric polypeptide includes an immunodeficiency virus envelope polypeptide, such as that of HIV, SIV, FIV, FeLV, FPV and herpes virus. Receptor sequences suitable for use in a chimeric polypeptide include, for example, CD4 D1D2 and CD4M9 sequences.

1. Field of the Invention
This invention relates generally to receptor ligand interactions, and more specifically to chimeric polypeptides having virus coat polypeptide and cell receptor polypeptide sequences that bind to each other and mimic the structural, functional and immunogenic properties that naturally occur when the virus protein and receptor interact in vivo.
2. Description of Related Art
Humoral immunity arising after primary infection with HIV-1 may not prevent progression to AIDS (R. A. Koup et al., Nature, 370:416 (1994); R. A. Koup et al., J. Virol. 68:4650-5 (1994)). However, it is likely that Humoral immunity can prevent infection if an individual has high-titered neutralizing antibodies prior to exposure to the virus. This concept is largely supported by passive immunization studies in which chimps were transfused with neutralizing anti-V3 monoclonal antibodies or pooled, high-titered neutralizing antisera around the time of challenge with cell-free virus (E. A. Emini et al., Nature: 355:728-30 (1992); R. Shibata et al., Nat. Med., 5:204-10 (1999)). Protection was obtained in both sets of studies, indicating that humoral immunity can be protective provided the right antibodies are present in sufficient titers at the time of challenge or shortly thereafter.
Additional studies suggest that humoral immunity can be protective against HIV-1. For example, passive immunization using the SCID-hu mouse system have shown that human monoclonal antibodies specific for the CD4 binding domain of gp120 can prevent infection (M. C. Gauduin et al., Nat. Med., 3: 1389-93 (1997); P. W. Parren et al., AIDS, 9:F1-6 (1995)). It has been further shown that passive transfer of a bivalent CD4-Ig "immunoadhesin," a chimera made between CD4 and the human IgG2 heavy chain, can protect in the HIV-1 chimp challenge system (J. W. Eichberg et al., AIDS Res. Hum. Retroviruses, 8: 1515-19 (1992); R. H. Ward et al., Nature, 352:434-6 (1991)). Additionally, neutralizing antibodies correlate strongly with protective immunity against SIV (J. L. Heeney et al., Proc. Natl. Acad. Sci. U.S.A., 95: 10803-8 (1998)). Still further, passive transfer studies in rhesus macaques showed that high-titered chimp antibodies specific for the HIV-1 DH12 isolate, provided sterilizing immunity in rhesus macaques against SHIVDH12 if a sufficient concentration of the antibodies was used (R. Shibata et al., Nat. Med., 5:204-10 (1999)). Also, passive-transfer experiments in rhesus macaques using HIVIg, 2G12, and 2F5 demonstrated 50% better protection in recipient groups compared to non-recipient controls against challenge with SHIV-89.6P (Mascola et al., J. Virol., 73:4009-18 (1999)). Thus, these studies support the idea that immunization strategies which elicit persistent, high-titered (or highly effective) neutralizing antibody responses of broad specificity may be protective. A successful strategy to reach this goal has been elusive. The subunit formulations of recombinant monomeric or oligomeric HIV envelope that have been tested elicit neutralizing responses against a narrow range of isolates (J. P. Moore et al., AIDS, 9:S117-136 (1995); Q. J. Sattentau, Curr. Opin. Immunol., 8:540-5 (1996); R. Wyatt et al., Science, 280:1884-8 (1998)).

Virus coat protein/receptor chimeras and method of use

University of Maryland Biotechnology Institute


Disclosed herein are methods, sodium-dependent glucose transporter (SGLT)1 compounds and compositions for the treatment of postprandial hypoglycemia, postprandial hypoglycemia that occurs as a consequence of gastric surgery.

Post-prandial hypoglycemia (PPH) has been observed as a side effect or complication of gastric surgery, such as gastric bypass surgery. A commonly observed side effect of gastric bypass surgery is dumping, which is consequence of the ingestion of simple sugars and rapid emptying of food into the small intestine. Early dumping occurs 10 to 30 minutes after a meal. It results from rapid movement of fluid into the intestine following a sudden addition of a large amount of food from the stomach. The small intestine expands rapidly due to the presence of hypertonic/hyperosmolar contents from the stomach, especially sweet foods. This causes symptoms due to the shift of fluid into the intestinal lumen, with plasma volume contraction and acute intestinal distention. Late dumping can occur up to a few hours after eating and results from insulin response to hyperglycemia resulting from rapid absorption of simple sugars from the proximal small intestine. Late dumping occurs 2 to 3 hours after a meal. It results from excessive movement of sugar into the intestine, which raises the body's blood glucose level and causes the pancreas to increase its release of the hormone insulin. The increased release of insulin causes a rapid drop in blood glucose levels, a condition known as alimentary hypoglycemia, or low blood sugar.
Post-prandial hypoglycemia is also a frequent complication of Nissen fundoplication, a procedure commonly performed to treat severe gastroesophageal reflux. Up to 30% of patients undergoing this procedure develop dumping syndrome. Dumping syndrome is characterized by early symptoms or "early dumping" due to the fluid shifts provoked by the osmotic load in the small bowel and "late dumping" or post-prandial hypoglycemia. See Zaloga GP, Chernow B. Postprandial hypoglycemia after Nissen fundoplication for reflux esophagitis. Gastroenterology. 1983; 84: 840-842; Bufler P, Ehringhaus C, Koletzko S. Dumping Syndrome: a common problem following Nissen fundoplication in young children. Pediatr Surg Int. 17 (5-6): 351-355, 2001; Samuk I, Afriat R, Horne T, Bistritzer T, Barr J, Vinograd I. Dumping syndrome following Nissen fundoplication, diagnosis and treatment. J Pediatr Gastroenterol Nutr. 1996; 23 (3): 235-240.
Postprandial hypoglycemia can occur in patients with gastric bypass surgery in the context of the dumping syndrome. (Singh et al., Diabetes Spectrum 2012 Nov.; 25(4): 217-221. Dumping can occur postoperatively in up to half of gastric bypass patients with ingestion of simple sugars. Id. Early dumping, a result of rapid emptying of food into the jejunum because of the surgically altered anatomy, is characterized by vasomotor symptoms (flushing, tachycardia), abdominal pain, and diarrhea. Id. Late dumping, a form of "reactive hypoglycemia," occurs 1-3 hours after meal ingestion and is a consequence of the brisk insulin response to hyperglycemia resulting from rapid absorption of simple sugars from the proximal small intestine. Id. These patients present with dizziness, fatigue, weakness, and diaphoresis, but these symptoms often resolve spontaneously and neuroglycopenic symptoms may not be prominent. Id. Most patients with dumping syndrome respond to nutrition modification, comprising frequent, small, and low-carbohydrate meals. Id. Pharmacological therapy is sometimes necessary. Id. Acarbose and somatostatin have also been empirically associated with improvement of symptoms in some patients, but the primary modality of treatment of these patients is still nutrition intervention, and pharmacotherapy is used as an add-on intervention only. Id. Indeed, the use of acarbose in patients who are not compliant with nutrition recommendations can be expected to have significant gastrointestinal side effects. Id.
An effective pharmacotherapy treatment of post-prandial hypoglycemia associated with gastric surgeries, which does not also necessarily require patient compliance with strict nutritional modifications would address a long-standing need for a convenient alternative PPH therapy. In that regard, inhibiting absorption of carbohydrates, such as glucose, at the small intestine, by blocking sodium-dependent glucose transporter (SGLT) activity subsequently can prevent an increase of blood sugar level, and, thereby, reduce or prevent the occurrence of PPH.
Subtypes of SGLT include SGLT1, which is primarily expressed in the small intestine, and SGLT2, which is expressed in the renal proximal tubule. These are responsible for absorption of glucose in the small intestine and reabsorption of glucose in the proximal tubule. U.S. Pat. No. 7,635,684, herein incorporated by reference in its entirety, describes compounds that show an inhibitory activity in human SGLT1 at the small intestine. U.S. Pat. No. 9,200,025, herein incorporated by reference in its entirety, describes potent inhibitors of SGLT1, with particular inhibitors selective inhibitors for SGLT1, and particular inhibitors having low systemic exposure, and act locally in the gut.
Mizagliflozin, 3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl-]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide, is a SGLT1 inhibitor created by Kissei Pharmaceutical Co., Ltd. No SGLT1 inhibitors have been approved to date. Mizagliflozin suppresses the uptake of glucose from the digestive tract by selectively inhibiting SGLT1. In addition, it acts primarily in the upper part of the small intestine and has a weak inhibitory effect on glucose absorption in the lower part of the small intestine since it is broken down and deactivated as it moves through the digestive tract. Gastrointestinal symptoms are not readily likely if the amount of glucose that remains without being absorbed is small.
Since an increase of SGLT1 activity in the small intestine is thought to contribute to increased carbohydrate absorption, fast development of agents, which have a potent inhibitory activity in human SGLT1, has been desired for the prevention or treatment of diabetes. See e.g., U.S. Pat. No. 8,324,176. Crystalline compounds of mizagliflozin have been described for use of prevention or treatment of a disease associated with hyperglycemia such as diabetes, impaired glucose tolerance, impaired fasting glycemia, diabetic complications or obesity, and a disease associated with the increase in blood galactose level such as galactosemia. U.S. Pat. No. 8,399,418 describes the monosebacate salt of mizagliflozin, and U.S. Pat. No. 8,354,382 describes the hemifumarate dehydrate salt of mizagliflozin. U.S. Pat. No. 9,694,027 describes the use of Mizagliflozin to treat constipation.

Method for treating post-prandial hypoglycemia


The apparatus is adapted for maintaining air/gas operated dental drills, mechanical scalers or other tools by blowing air/gas through the handpiece to purge it from excess substances in order to enhance the life of the toll and meet the requirements of health and safety regulations. The apparatus has an absorbant filter sleeve that will serve to surround the instruments to be purged and an internal filter. It uses a rigidly anchored coupling that can be replaced, as desired. It also uses pneumatic tubing and shuttle valves to direct the air/gas flow along with switches that control the power and operation of the apparatus. A pressure gauge is mounted on the housing to allow the user to observe the pounds per square inch pressure being used in the purging operation. A timer controlling the amount of time the instruments are being purged is also incorporated. A number of ports are used to allow connection air, water and fiber optic lines to the apparatus and exhaust ports are also available.

This invention pertains to dental tool purging apparatus and, in particular, to a dental handpiece lubrication purging apparatus that is designed to maintain dental handpieces while, at the same time, meeting all health and safety regulations.
There have been a number of new regulations that require proper removal of excess lubricants that are required to maintain air or gas powered high and low speed drills, mechanical scalers, mechanical condensers and other dental tools. There have been a number of attempts to deal with this problem. The United States Patent issued to J. J. Valeska, U.S. Pat. No. 3,556,669 on Jan. 19, 1971 shows a system for fluid control in dental instruments which details an adjustable air pressure controls and valving means for controlling the air pressure to a number of different handpieces. The U.S. Pat. No. 4,902,226 issued to Raymond D. Elliott on Feb. 20, 1990 shows a dental air supply system which consists of a plurality of modular sections that allows the user to accomplish a plurality of dental functions that are necessary.
What is needed is an apparatus which can be connected to any air or gas driven dental tool for the purpose of blowing air and gas through the tool's inlet ports and purging it of any excess substance within those tubes or chambers. The apparatus is designed to entrap those substances as they are blown or purged into an internal filter or an external flexible sleeve, without requiring the instrument being cleaned to be held by an individual.
It is the object of this invention to teach a dental handpiece lubrication purging apparatus which avoids the disadvantages and limitations, recited above. Another object of this invention is to provide an apparatus that is simple to operate, extremely effective and very cost effective with great ease of connection with a number of different style handpieces. It is also the object of this invention to teach an apparatus which has a multiple task capability, timing control and can be easily connected with the existing air supply found in all dental offices.

Dental handpiece lubrication purging apparatus


The substantially simultaneous tracing/monitoring of a plurality of sets of events via a single network interface. The plurality of events can be traced and/or monitored for one host or for a plurality of hosts coupled via the same network interface. The sets of events to be traced/monitored for a host are defined by the host and maintained in one or more configuration files. The configuration files may be dynamically updated.

A communications environment is provided that enables multiple hosts, such as multiple operating systems, to be connected to one or more networks via a single network interface. For example, an Enterprise Systems Architecture (ESA)/390 System, offered by International Business Machines Corporation, includes a host to network interface that facilitates connecting multiple operating systems residing in one or more partitions to one or more networks via a single network interface. While the sharing of a single network interface by multiple hosts has provided various advantages, it has also caused difficulties in, for instance, the tracing and monitoring of network data across the single network interface. For example, the tracing of one specific set of events for one host and the tracing of a different set of events for another host at the same time is not possible. Additionally, even the tracing of different sets of events for one host at the same time is not possible.
Moreover, the monitoring of data for a specific host is not provided. That is, there is no delineation of the data received via the interface for one host versus another. Further, the monitoring of different sets of events for one host at the same time is not enabled. Thus, a need exists for a capability that facilitates the analysis of network data received across a single interface. For example, a need exists for a capability that allows the tracing of one specific set of events for one host and the tracing of a different set of events for another host at substantially the same time. As a further example, a need exists for a capability that allows the tracing of a plurality of sets of events for one host at substantially the same time. As yet another example, a need exists for a capability that enables the monitoring of data for a specific host. A need also exists for a capability that enables the monitoring of a plurality of events sets for a host at substantially the same time.

Method for facilitating monitoring and simultaneously analyzing of network events of multiple hosts via a single network interface


An accessory for a waterfowl decoy, which attachment simulates the wake of a swimming fowl, thus creating the illusion of movement. The attachment is a three-part device including a hollow first member made of molded plastic. A slot is disposed in the plastic member for receiving the keel of the decoy. Two identical, elongate parts are removably connected to the plastic member. The two identical parts are also hollow and are configured in a manner to give the appearance of a wake when immersed in water and viewed from a distance.

1. Field of the Invention
The present invention generally relates to recreational accessories. More specifically, the present invention is drawn to an accessory for a waterfowl decoy.
2. Description of the Related Art
Waterfowl hunters and/or photographers are always seeking better means to attract ducks, geese and other waterfowl to a desired location. The decoy has been one of the most efficient devices in accomplishing the attraction. It is obvious that the more realistic the decoy, the better the chance of attracting large quantities of waterfowl. A decoy that simulates realistic waterfowl movement would certainly be a welcome addition to the art. Thus, a decoy having an attachment that realistically simulates the wake of a swimming waterfowl would be desired.
The related art is awash with realistic looking decoys. Pertinent examples of such related art are cited and identified in the accompanying IDS. However, none of the cited and identified related art, taken either singly or in combination, is seen to describe a decoy having a wake simulating attachment as will be subsequently disclosed and claimed in the instant invention.


A phase-locked loop employing a charge pump 7 for synthesizing RF channels permits a low supply voltage to be used by using two amplifier stages 5a, 5b, between the charge pump and a VCO4. Stage 5a may be a high impedance common emitter pair of complementary transistors allowing a wide voltage swing. Stage 5b may be an operational amplifier with resistive feedback to provide gain less than unity and a low impedance output to provide feedback around a loop filter 6 to source the current from charge pump 7 entering an inverting input of stage 5a. Alternatively, stages 5a, 5b may be reversed.

This invention relates to phase-locked loops.
The invention especially relates to phase-locked loops used for synthesizing RF channel frequencies in a transceiver, especially a transceiver used in WLAN (Wireless Local Area Network) applications. One application of the latter is in portable terminals such as lap-tops, point-of-sale terminals, which communicate with a host processor, and the transceiver may be accommodated in a standard PC expansion card such as a PCMCIA (Personal Computer Memory Card International Association)-sized card. This has a standard supply voltage of 3.0 volts .+-.10%, and the minimum supply voltage of 2.7 volts results in limitations in the implementation of the phase-locked loop.
Thus, in many conventional phase-locked loop synthesizers, a charge pump circuit is used to directly drive the voltage controlled oscillator (VCO), the loop filter components being connected from the charge pump circuit output to ground as shown in FIG. 1. The phase detector 1 provides either positive pulses from current source 2 or negative pulses from current source 3 to the voltage controlled oscillator 4, depending on whether the voltage controlled oscillator is at a higher or lower frequency than the reference oscillator. A bipolar charge pump using all NPN transistors for use with high frequency circuits has been proposed (GB-B-2 249 443), because PNP transistors are either not available or have poor performance. In this case, the charge pump circuit is followed by an operational amplifier to maintain the charge pump output at a constant voltage, and the operational amplifier output provides the VCO control voltage. When the VCO frequency range is wide, in the case of the low supply voltages referred to, it may be necessary to swing the amplifier output very close to the supply rails in order to obtain the necessary tuning range from the VCO.
A conventional operational amplifier will use a complementary output stage as shown in FIG. 2, but this will reduce the available swing at the output by at least twice the diode drop (equal to around 1.6 volts in total) which represents a considerable voltage in the case of a nominal 3 volts supply. An alternative output stage as shown in FIG. 3 uses complementary transistors in common emitter (rather than common collector as shown in FIG. 2) mode, and this reduces the voltage loss to only a few hundred millivolts if the output stage is properly designed. However, in the process, the output impedance is raised compared to FIG. 2, and this makes it difficult to restrain the charge pump output at the virtual earth input voltage of the operational amplifier.
In addition, if a charge pump circuit using all NPN transistors was employed in conjunction with an operational amplifier having the output stage shown in FIG. 3, this would be difficult to realise in practice, because the charge pump output current must be relatively high (pulses of at least .+-.1 milliamp duration 10 ns to 1 .mu.s at 1 MHz) for good noise performance, and this current would have to be sourced from the amplifier output under transient conditions if the loop settling time was not to be affected. In many high frequency processes, the size of the PNP transistor of the complementary pair shown in FIG. 3 needed to source 1 milliamp with reasonable gain would be excessive.

Phase-locked loops having two amplifiers for driving a vco


An internal vehicular transmission range switch (10) has a movable contact support (20) which slides along a straight path in a recess formed between a housing having a base member (12) and cover (14) between first and second extremities in dependence upon the movement of the manual valve (4) to which it is coupled by an arm (18) extending from the support through a slot (16) formed in the housing. An elongated slider having a lower (20e) and upper (20d) blade portions received in respective channels (12a, 14a) formed in the housing integrally attached to the movable contact support blocks ingress of contaminant particles into the recess while permitting fluid flow into and out of the recess. A second embodiment (10') has a generally U-shaped member (18') having one leg (18a') attached to the movable contact support and extending through an O-ring (24) in an end wall of the housing and a manual valve coupling arm (18c') formed at the distal end of a second leg (18b'). A third embodiment has an endless track (26) in which an elongated, flexible band (28) having opposite ends attached to the movable contact support (20) on opposite sides of manual valve coupling arm (18) blocks entry of contaminant particles through slot (16") in the housing through which arm (18) extends.

It is conventional to provide a switch assembly to receive mechanical gear selection inputs from the driver of a vehicle through various linkages and output electrical signals to the transmission electronic control unit indicative of the gear selection. Such switch assemblies are coupled to the detent lever and the manual valve of the transmission and generally comprise either a rotary movable contact mechanism such as those shown in U.S. Pat. Nos. 5,527,768 and 5,440,087, assigned to the assignee of the present of the invention, or a straight linear movable contact mechanism such as that shown in U.S. Pat. No. 5,231,254, also assigned to the assignee of the present invention. The present invention relates to the latter type in which an actuator carrying a set of movable contacts is caused to slide back and forth in a straight line in dependence upon the longitudinal movement of the manual valve. The movable contacts are spring biased into engagement with a stationary contact board having contact segments arranged in a selected pattern so that on/off output signals are obtained based on the longitudinal position of the manual valve. The housing of the switch mechanism is open to the passage of transmission fluid including contaminants into and out of the switching chamber.

Internal transmission range switch system


A semiconductor device such as a flash memory includes a semiconductor substrate, two gate insulating films formed on the substrate so as to have a first film thickness and a second film thickness smaller than the first film thickness respectively, and a polycrystalline silicon film formed on the gate insulating films so that parts of the polycrystalline silicon film on the respective gate insulating films are on a level with each other and serving as a gate electrode. The substrate is formed with a recess defined by a bottom and sidewalls substantially perpendicular to the bottom, the recess corresponding to the part of the gate insulating film with the first film thickness.

1. Field of the Invention
The present invention relates to a method of fabricating a semiconductor device including a plurality of gate insulating films with different film thicknesses.
2. Description of the Related Art
Semiconductor devices of the above-noted type include non-volatile semiconductor devices such as a flash memory. The flash memory comprises a memory cell region and a peripheral circuit region both necessitating different gate breakdown voltages. Accordingly, gate insulating films having different film thicknesses corresponding to the different gate breakdown voltages respectively. In one of methods of fabricating semiconductor devices, a film structure of gate electrodes is formed first and subsequently, a structure of gate electrodes is formed together with formation of an element isolation region. When the gate insulating films have different film thicknesses in the aforesaid fabrication method, the following defect occurs: when a trench serving as shallow trench isolation (STI) is first formed and subsequently, an insulating film buried in the trench is planarized by a chemical mechanical polishing (CMP) process, the difference in the film thicknesses of gate insulating films results in differences in the level of a silicon nitride film serving as a stopper film in the CMP process. Accordingly, when polishing reaches part of the silicon nitride film at a lower side in the CMP process, part of the silicon nitride film is cut away to an abnormal extent corresponding to the level difference. As a result, an amount of process margin becomes smaller as the level difference in the silicon nitride film is increased. Furthermore, the level difference easily tends to result in discrepancies such as dishing in the CMP process.
To overcome the aforesaid discrepancies, U.S. Pat. No. 6,642,105B2 discloses a semiconductor device in which a thick oxide film is formed by a method of selective oxidation such as local oxidation of silicon (LOCOS) on a part where a gate oxide film with a larger film thickness is formed. The thick oxide film is etched so that a necessary film thickness is obtained, whereupon the difference due to the film thickness difference is reduced.
Thus, in the above-noted U.S. Patent, in order that the difference in the film thickness of the gate oxide films may be resolved, a thick oxide film is formed by the selective oxidation on a part of the silicon substrate on which a thick gate oxide film is to be formed in a region where a thick gate oxide film is to be formed. The thick oxide film is etched so that a suitable film thickness is obtained, whereby a gate oxide film with a desired film thickness is formed. However, the method disclosed in the above-noted U.S. patent has the following disadvantage: an oxide film formed by the selective oxidation, namely, LOCOS, results in formation of a distorted region called "bird beak" formed in a peripheral edge of the oxide film. The distorted region cannot be used as contributing to the characteristic of the device. Consequently, the distorted region needs to be taken into consideration in the design of the semiconductor device, resulting in constraints to reduction I an area of the semiconductor device.

Semiconductor device and method for fabricating the same


The method for bonding a semiconductor element comprises the step of applying to solder bumps 10 of a semiconductor chip 12 a soldering flux 16 which contains a thermosetting resin, a polyhydric alcohol and an organic acid and in which the thermosetting resin remains uncured after reflow-bonding, the step of reflow-bonding the solder bumps 10 to the electrodes 18 of the circuit board 20 with the soldering flux 16 while melting the solder bumps 10, and the step of filling an underfill material 22 between the semiconductor chip 12 and the circuit board 20 with the soldering flux 16 being left, the underfill material 22 containing a thermosetting resin of the same group as the thermosetting resin contained in the soldering flux 16 and at least one of a curing agent and a cure catalyst for curing the thermosetting resins.

The present invention relates to a soldering flux and a method for bonding a semiconductor element with the soldering flux, more specifically, a soldering flux and the method for bonding a semiconductor element with the soldering flux which can increase the reliability.
Recently, as electronic devices are increasingly downsized and lightened, the flip-chip method, which mounts a semiconductor chip facedown on a circuit board, is prevalently used as a mounting method for semiconductor chips such as LSI chips, etc.
The conventional flip-chip bonding will be explained with reference to FIGS. 5A-5D and 6A-6C. FIGS. 5A-5D and 6A-6C are sectional views illustrating the conventional flip-chip bonding.
A semiconductor chip 102 with solder bump electrodes, i.e., solder bumps 100 formed on is prepared.
Then, the solder bumps 100 of the semiconductor chip 102 are brought into contact with a flux 106 printed in advance on a flat plate 104 with a squeegee to transfer the flux 106 to the solder bumps 100 (FIG. 5A). The flux 106 is made of, e.g., rosin or others.
Next, a circuit board 110 with electrodes 108 formed on is prepared. Solder bumps 112 are formed on the electrodes 108 of the circuit board 110.
Next, the solder bumps 100 of the semiconductor chip 102 and the electrodes 108 of the circuit board 110 are aligned with each other (FIG. 5B).
Then, the solder bumps 100 of the semiconductor chip 102 and the solder bumps 112 of the circuit board 110 are melted with each other by heating to reflow-bond the solder bumps 100 of the semiconductor chip 102 to the electrodes 108 of the circuit board 110 (FIG. 5C).
Next, the flux 106 remaining between the semiconductor chip and the circuit board is washed off with a solvent 114 (FIG. 5D). The flux 106 is washed off so as to ensure filling and the adhesion strength of an underfill material to be filled between the semiconductor chip 102 and the circuit board 110.
Next, the underfill material 116 of a thermosetting resin is filed between the semiconductor chip 102 and the circuit board 110 (FIGS. 6A and 6B).
Next, the underfill material 116 between the semiconductor chip 102 and the circuit board 110 is cured by heating (FIG. 6C). The underfill material 116 reduces the thermal expansion strain between the semiconductor chip 102 and the circuit board 110 and prohibits the intrusion of water to thereby prevent the corrosion of the solder bumps 100, the electrodes 108, etc.
As semiconductor chips are more integrated, the number of the pins of the semiconductor chips tends to increase. The size of the solder bumps tends to be smaller, and the pitch of the solder bumps tends to be smaller. Recently, it is becoming accordingly difficult to wash off the flux after the solder bonding. The flux residue which has not been washed off and remains between the semiconductor chip and the circuit board causes defects of the filling and decreases of the adhesion strength of the underfill material, which much decrease the reliability of the bonded parts. To perfectly wash off the flux, a long period of time of the washing step and the use of a special washing apparatus are necessary, which causes cost increase.
As a countermeasure to this, as a flux to be used in the flip-chip bonding, a nonwash-type flux, which can be used without washing for removing the flux, is required. The use of a flux of a thermosetting resin instead of rosin is being studied. The nonwash-type flux of a thermosetting resin contains, e.g., epoxy resin as the thermosetting resin, a curing agent for the epoxy resin, an activator having the property of removing oxide film, etc. to activate the bonding surface and cause the solder to exert the bonding strength, and an accelerator for accelerating the cure of the epoxy resin. The nonwash-type flux of the thermosetting resin is being generally used in the surface mount, and is designed to be perfectly cured after the solder bonding so that the flux which has been cured is not melted in reliability tests, etc.
Such nonwash-type flux is used in bonding the solder bumps of the semiconductor chip and the electrodes of the circuit board, whereby the underfill material can be filled without washing the flux.
However, in the flip-chip bonding of a below 100 μm including 100 μm gap between the semiconductor chip and the circuit board, it is difficult to use the nonwash-type flux of a thermosetting resin. The reason is as follows.
The flux which has been cured after the solder bonding form an interface with the underfill material to be filled later. Accordingly, the underfill material has the adhesion strength decreased, and the reliability of the bonded parts is decreased.
The flux which has been cured after the solder bonding further narrows the gap between the semiconductor chip and the circuit board to thereby block the flow of the underfill material, which causes defective filling of the underfill material and voids. Such defective filling and voids decrease the reliability of the bonded parts.
The related arts are disclosed in, e.g., Japanese published unexamined patent application No. 2001-7158, Japanese published unexamined patent application No. 2004-1030 and Japanese published unexamined patent application No. Hei 10-195487 (1998).

Soldering flux and method for bonding semiconductor element