A method for covalent attachment of peptides to luminescent quantum dots or other inorganic nanoparticles. The first step in the method involves functionalizing at least a portion of a surface of the quantum dot or nanoparticle with one or more materials having at least one reactive functional group therein. Subsequently, a peptide having a reactive functional group is reacted with at least some of the quantum dot or nanoparticle reactive functional groups to covalently bond at least some of the peptide to the quantum dots or nanoparticles. Modifications of the basic method are disclosed which provide methods allowing customized fabrication of quantum dots having a variety of different functional properties and combinations of functional properties. Also disclosed are quantum dots and nanoparticles made by the methods of the present invention.

The covalent chemical attachment of an active moiety to a carrier is a fundamental process that lies at the heart of a diverse range of scientific disciplines. For example, the attachment of peptides, oligosaccharides, DNA or small bioactive organic molecules to glass slides or chips has given rise to the enormous field of diagnostic screening, with example applications such as toxicological testing of new chemical entities and genetic products. Attachment of the same type of molecules to polymeric surfaces has applications in diverse fields such as affinity purification of small molecules/proteins and smart wound dressings that elicit a physiological response to enhance the wound healing process. Alternatively, attachment of such molecules to immunostimulatory proteins has application in the field of synthetic vaccine development. Within each of these fields, successful application is dependent upon the stringent control of a number of key chemical and physiochemical parameters being achieved.
A key objective is to obtain quantitative and qualitative control of the covalent attachment chemistry since this should provide a final construct that exhibits an optimal combination of molecular display and physiochemical characteristics. Each application has many subtle variations of these key requirements to consider, given the range of chemical diversity and intrinsic characteristics present in active moieties such as peptides, oligosaccharides, DNA or small bioactive organic molecules and the different physiochemical properties of a glass slide when compared to a polymeric bead or a protein.
International patent application publication no. WO 01/71043 discloses bonding of peptides and biological molecules to semiconductor nanocrystals using chemical coupling methods. Polynucleotides along with polypeptides and other polymeric biologicals are bound to semiconductor nanocrystals and dicarboxylic acids may be used as surface ligand linker molecules. This method appears to employ a functional group in the linker molecule (e.g. the dicarboxylic acid) for reaction with the peptide to achieve bonding. The semiconductor nanocrystals are typically bonded to a substrate or microsphere.
WO 03/087824, discloses coupling reactions using H-benzotriazol-1-yloxytris (dimethylamino) phosphonium hexafluorophosphate (BOP) in Example 1B. WO 06/060664, discloses coupling reactions using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) in Examples 1-2.
U.S. Pat. No. 6,326,144 discloses a reaction for coupling proteins and peptides to water soluble quantum dots. Specifically, Example 3 in column 19 couples avidin (a protein) to water soluble quantum dots using (1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride) (EDAC) and N-hydroxysuccinimide (NHS).
U.S. patent application publication no. US 2006/0068506 A1 discloses a method for bonding a DNA biomolecule to a quantum dot in FIG. 9 and paragraph [0021]. In this method, dihydrolipoic or dihydrolipoic acid/polyethylene glycol-modified core shell quantum dots are bound to a DNA biomolecule using N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDC) and N-hydroxysulfosuccinimide (sulfo-NHS) as coupling agents.
Methods for preparing water-soluble quantum dots involve the capping of core-shell nanocrystals with ionized dihydrolipoic acid molecules and more recently the use of poly(ethylene glycol) terminated dihydrolipoic acid (DHLA-PEG) ligands with PEGs of various sizes. Electrostatic self-assembly and the metal ion affinity of histidine coordinate techniques may be used to prepare bioconjugates. Electrostatic self-assembly takes advantage of positively charged domains of proteins coupled to negatively charged carboxylate groups on the quantum dot surface (Mattoussi, H., et al., "Self-assembly of CdSe—ZnS quantum dot bioconjugates using an engineered recombinant protein," J. Am. Chem. Soc., 122, 12142-12140 (2000); Goldman, E. R., et al., "Conjugation of luminescent quantum dots with antibodies using an engineered adaptor protein to provide new reagents for fluoroimmunoassays," Anal. Chem., 74, 841-847 (2002); and Medintz, I. L., et al., "Self-assembled nanoscale biosensors based on quantum dot FRET donors," Nature Materials, 2, 630-638 (2003)). Limitations of using electrostatic self-assembly combined with DHLA-capping are that activities must be carried out in a basic environment (pH>7) and there is an inability to form direct covalently linked nanocrystal-biomolecule conjugates in aqueous environments with N-3-(dimethylamino)-propyl-N′-ethyl-carbodiimide (EDC). Employing DHLA-PEG ligands permitted expansion of the range of pH solubility while still permitting electrostatic self-assembly (Uyeda, H. T., et al., "Design of water-soluble quantum dots with novel surface ligands for biological applications," Mater. Res. Soc. Symp. Proc., 789, 111-116 (2004) and H. T. Uyeda et al., "Design of water-soluble quantum dots with novel surface ligands for biological applications," J. Am. Chem. Soc. 127, 3870-3878 (2005)).
Small organic surface ligands such as mercaptoacetic acid (MAA), aminoethane thiol (AET) and polymer encapsulation have been used to generate water-soluble quantum dot systems (Chan, W. C. W., et al., "Quantum Dot Bioconjugates for Ultrasensitive Nonisotopic Detection," Science 281, 2016-2018 (1998)). Water solubilization of quantum dots with hydrophilic dendritic structures and layer-by-layer assembly techniques have also been demonstrated with some degree of success. Such strategies, however, do not provide for pH stability and in some cases do not provide long-term water solubility. The major disadvantage of these systems is the poor temporal stability of the quantum dot-ligands due to the dynamic nature of the singly bound thiol groups, which results in aggregated solutions after a short time. Another disadvantage is the lack of the provision of compact hydrophilic quantum dots and quantum dot bioconjugates that can be easily delivered inside live cells and regions of cells and assay studies such as those based on fluorescence or Foster resonance energy transfer (FRET).
There remains a need in the art for improved coupling methods for covalent attachment of peptides and biological molecules to, for example, luminescent semiconductor nanocrystals or other nanoparticles.

Covalent attachment of peptides and biological molecules to luminescent semiconductor nanocrystals

The United States of America, as represented by the Secretary of the Navy


A gaming machine for conducting a wagering game includes a value input device for receiving a wager and a display for displaying a plurality of symbols arranged on a plurality of reels. The symbols indicate a randomly-selected outcome selected from a plurality of possible outcomes, the plurality of outcomes including at least one winning outcome. The gaming machine further includes a controller operative to receive a volatility input from a player of the gaming machine. The controller is further operative to associate an award with the at least one winning outcome wherein the associated award is either a first award amount or a second award amount based upon the volatility input. Upon the occurrence of the at least one winning outcome, the controller awards the associated award to the player.

Gaming machines, such as slot machines, video poker machines and the like, have been a cornerstone of the gaming industry for several years. Generally, the popularity of such machines with players is dependent on the likelihood (or perceived likelihood) of winning money at the machine and the intrinsic entertainment value of the machine relative to other available gaming options. Where the available gaming options include a number of competing machines and the expectation of winning at each machine is roughly the same (or believed to be the same), players are likely to be attracted to the most entertaining and exciting machines. Shrewd operators consequently strive to employ the most entertaining and exciting machines, features, and enhancements available because such machines attract frequent play and hence increase profitability to the operator. Therefore, there is a continuing need for gaming machine manufacturers to continuously develop new games and improved gaming enhancements that will attract frequent play through enhanced entertainment value to the player.
One concept that has been successfully employed to enhance the entertainment value of a game is the concept of a "secondary" or "bonus" game that may be played in conjunction with a "basic" game. The bonus game may comprise any type of game, either similar to or completely different from the basic game, which is entered upon the occurrence of a selected event or outcome in the basic game. Generally, bonus games provide a greater expectation of winning than the basic game and may also be accompanied with more attractive or unusual video displays and/or audio. Bonus games may additionally award players with "progressive jackpot" awards that are funded, at least in part, by a percentage of coin-in from the gaming machine or a plurality of participating gaming machines. Because the bonus game concept offers tremendous advantages in player appeal and excitement relative to other known games, and because such games are attractive to both players and operators, there is a continuing need to develop gaming machines with new types of bonus games to satisfy the demands of players and operators.
Traditionally gaming machines operate under control of a processor which has been programmed to execute base games and bonus games on the machine according to a predetermined mathematical model. Therefore, the volatility of the gaming machines have been fixed or preset by the manufacturer. One shortcoming of such a configuration is that different players may desire differing degrees of volatility. Volatility generally means the ratio of size versus frequency of awards. Some players enjoy playing gaming machines with lower volatility, whereby the range of awards for winning outcomes is relatively narrow and the awards occur relatively frequently. Other players enjoy games with greater volatility, whereby the range of awards for winning outcomes is relatively large and the awards occur relatively less frequently. Due to the fixed programming nature of traditional gaming machines, players are forced to select their volatility by choosing amongst the variety of gaming machines available to be played at a casino. The present invention is directed to solving these and other problems.

Gaming machine having player selectable volatility


A processor includes a CPU core and an encryption processor which includes an address registration region, wherein, after power is supplied, a startup program which is stored into a memory after encryption and executed at startup registers an address range of the memory in which encrypted concealment data is stored into the address registration region, and wherein the encryption processor decrypts the startup program and the concealment data and transfers to the CPU core when an execution address of the CPU core is within the address range registered in the address registration region, and transfers the startup program and the concealment data to the CPU core without decryption when the execution address of the CPU core is not within the address range registered in the address registration region.

In an embedded system, acts such as alteration and impersonation by malware are increasing. There is a technology to acquire security of a concealment program and key information by dividing a memory region into a normal region and a secure region after startup of the system and storing the concealment program and the key information in the secure region. However, by applying this technology, both hardware and software become complicated. Besides, this technology is a security technology after startup of the system, and with regard to a countermeasure against a physical attack such as reading of data from an external ROM before power supply or a mechanism (secure boot) for safe startup or the like, another technology is applied.
There is suggested a technology in which data that includes an instruction code or the like is encrypted and stored into an external ROM, and when a processor executes a processing, the encrypted data is read from the external ROM and decrypted in the processor to execute the processing, thereby security of a system is acquired (for example, see Patent Document 1). For example, as illustrated in FIG. 18, a control program 1801, a concealment program (an encryption processing program or the like) and key information 1802 are encrypted by a common key encryption method such as an advanced encryption standard (AES) encryption method and stored into an external ROM 1813.
When a processor 1810 executes the processing of the control program or the concealment program, the processor 1810 reads encrypted data 1814 from the external ROM 1813 and performs a decryption processing in an encryption processor 1812 thereinside. Then, plaintext data 1815 being decrypted in the encryption processor 1812 is supplied to a CPU core 1811 and the processing is performed. For example, the control program calls the concealment program (an encryption processing program, a decryption processing program, or the like) (P1801), and the called concealment program accesses the key information to perform the encryption processing or the like. The control program sometimes calls an external program such as a program which is network downloaded after execution of the control program (P1802).
The system illustrated in FIG. 18, in which data (various programs and key information) to be stored into the external ROM 1813 is subjected to encryption, is effective against a physical attack such as reading of data from the external ROM. However, there is a case where the data stored into the external ROM 1813 is decrypted and plaintext data can be seen from an external program 1803 on a RAM during execution in the processor 1810, by the following reason.
There is a case where a control program copies itself in a RAM at startup and carries out execution on the RAM. Since the external ROM 1813 is accessed also when the control program is executed on the RAM, it is general that the encryption processor 1812 of the processor 1810 constantly performs a decryption processing when accessing the external ROM 1813 regardless of an address under execution. Thus, if the encrypted data (various programs and key information) stored in the external ROM 1813 is read by the program on the RAM (P1803), the data can be seen in a decrypted state (plaintext).
As a countermeasure against the above, there can be considered a method of performing authorization (safety confirmation of the program) in advance by using the concealment program or the key information, when an external program is executed. Since there are countless external programs, it is difficult to verify every one of the external programs including their behavior in advance and to confirm that malware is not included.
Patent Document 1: Japanese Laid-open Patent Publication No. 2008-210225


A method of piloting an aircraft (1) provided with at least one rotary wing (2) and a tail rotor (10) suitable for swiveling to pass reversibly from an anti-torque mode of operation to a propulsion mode of operation, said tail rotor (10) having a plurality of second blades (12) having a second variable pitch and rotating about an axis of rotation (AX), said axis of rotation presenting a first variable salient angle (θ) relative to a first plane (P1). Thus, in the anti-torque mode of operation, said second pitch is controlled using first control means (31). Furthermore, in the propulsion mode of operation, said first salient angle (θ) is controlled using first control means (31) and said second pitch is controlled using second control means (32) for controlling thrust.

(1) Field of the Invention
The present invention relates to a method of piloting a rotary wing aircraft having a tail rotor suitable for swiveling about a swivel axis, and the invention also relates to such an aircraft.
More particularly, the invention relates to aircraft provided firstly with a rotary wing for providing at least some of the lift of the aircraft, and secondly with a tail rotor suitable for opposing the torque generated by the rotary wing on the airframe of the aircraft, the tail rotor being capable of swiveling about an axis in order to contribute to propelling the aircraft.
(2) Description of Related Art
The performance of a helicopter is conventionally limited by the speed of rotation of the main rotor that constitutes the rotary wing. The speed of the blades of said main rotor relative to the surrounding air must in particular remain locally less than the speed of sound. At high speed, the lifetime of the component is reduced in particular because of the appearance of vibration.
Consequently, in order to obtain a rotary wing aircraft that is capable of moving at high speed, e.g. for ecological reasons, it is possible to use an additional source of propulsion in order to reduce or eliminate the cyclic pitch of the blades of the main rotor so as to make it possible to reduce the speed of rotation of said main rotor at high forward speed.
Document FR 1 511 006 suggests using a tail pusher propeller associated with the conventional anti-torque tail rotor of a helicopter. The pusher propeller then serves to off-load the main rotor of at least a fraction of its propulsion function.
In order to optimize the performance of a helicopter, document FR 1 017 976 suggests using an aircraft fitted with a rotary wing and a tail rotor suitable for swiveling about a swivel axis.
In a first mode of operation, the tail rotor is used to counter the torque generated by the rotary wing and to provide yaw control.
In a second mode of operation, the tail rotor swivels so as to contribute to propelling the aircraft, with yaw control being obtained by steering the tail rotor on either side of a neutral position.
Such an aircraft is sometimes referred to as a "vector-thrust helicopter".
Document U.S. Pat. No. 3,155,341 presents a convertiplane having a main rotor, a swiveling tail rotor, and a wing, the convertiplane being suitable for changing over from a helicopter mode to an airplane mode.
Document FR 1 536 412 presents a mechanism for controlling the swiveling of a tail rotor of a convertiplane. That mechanism has a single outlet for controlling pitch and two inlets for controlling yaw in helicopter mode and controlling thrust in airplane mode, with the transition from one kind of control to the other taking place progressively. Thus, in airplane mode yaw control becomes inoperative whereas in helicopter mode thrust control is inoperative.

Method and an aircraft provided with a swiveling tail rotor


A system and method for detecting a detectably labeled cell or component thereof in a sample comprising one or more cells or components thereof, at least one cell or component thereof of which is detectably labeled with at least two detectable labels. In one embodiment, the method comprises: (i) introducing the sample into one or more flow cells of a flow cytometer, (ii) irradiating the sample with one or more light sources that are absorbed by the at least two detectable labels, the absorption of which is to be detected, and (iii) detecting simultaneously the absorption of light by the at least two detectable labels on the detectably labeled cell or component thereof with an array of photomultiplier tubes, which are operably linked to two or more filters that selectively transmit detectable emissions from the at least two detectable labels.

1. Field of the Invention
The present invention relates to a method for detecting a detectably labeled cell or component thereof in a sample comprising one or more cells or components thereof, at least one cell or component thereof of which is detectably labeled with at least two detectable labels, and a system for use in such a method. Immunoassay, fluorescence, and flow cytometry are employed.
2. Description of the Related Art
Various assays for determining qualitative and/or quantitative characteristics of cells or components thereof are known in the art. Flow cytometers, for example, are used in both diagnostics and research laboratories to classify and analyze cells and components thereof. In flow cytometry, cells or components thereof are typically stained with detectable fluorescent labels and are passed in a liquid suspension through a flow cell along with a sheath fluid, such that cells or components thereof are forced by hydrodynamic focusing to flow in single file along the center axis of the flow cell. A focused light beam, such as a laser beam, then illuminates the cells or components as they flow through the examination zone of the flow cell. Optical detectors within the flow cytometer measure certain characteristics of the light as it interacts with the cells or components thereof. Commonly used flow cytometers, such as the Becton-Dickinson Immunocytometry Systems "FACSCAN" (San Jose, Calif.), for example, can measure forward light scatter (generally correlated with the refractive index and size of the particle being illuminated), side light scatter (generally correlated with the particle's size), and fluorescence at one or more wavelengths. Flow cytometers and various techniques for their use are described, generally in "Practical Flow Cytometry" by Howard M. Shapiro (Alan R. Liss, Inc., 1985) and "Flow Cytometry and Sorting, Second Edition" edited by Melamed et al. (Wiley-Liss, 1990).
While flow cytometry techniques have advanced greatly over the years, efficient single-step assay processes for simultaneously detecting multiple types of cells or components thereof, and for simultaneously identifying multiple characteristics of individual cells or components thereof, remain highly desirable in the art. It would be desirable, for example, to have adequate methods and systems for performing reliable and sensitive real-time multiple determinations, simultaneously, through a single or limited step assay process. A capability to perform simultaneous, multiple determinations in a single assay process is known as "multiplexing" and a process to implement such a capability is a "multiplexed assay."
Conventional flow cytometers, to this point, have yielded a limited capacity to perform real-time multiple determinations. This is due mainly to an inability of conventional flow cytometers to receive, compute, and/or store simultaneous detection data. Moreover, conventional detection and enumeration techniques for cells or components thereof that utilize antibody-conjugated detectable labels typically yield unsatisfactory and unreliable cell or component counts due to antibody aggregations, which yield substantial "false positives."
Thus, in view of the above, there remains a need for sensitive and reliable methods and systems for the detection and enumeration of cells or components thereof. The present invention seeks to provide such a method and system. These and other objects and advantages of the present invention, as well as additional inventive features, will become apparent to those of ordinary skill in the art upon reading the detailed description set forth herein.

System and method for detecting cells or components thereof

Iowa State University Research Foundation, Inc.


Methods for enhancing the efficacy, safety, and/or tolerability of a grass allergen-specific subcutaneous immunotherapy (SCIT) regimen in a subject having a grass allergy are provided. Methods comprising administering to a subject in need thereof a therapeutic composition comprising an interleukin-4 receptor (IL-4R) antagonist, such as an anti-IL-4R antibody or antigen-binding fragment thereof, are provided.

Allergies and allergic diseases are serious medical conditions with consequences ranging from non-life threatening responses that resolve over time to life threatening effects such as anaphylaxis. Allergic reactions can result from contact or exposure to a variety of products such as certain food items, insect venom, plants or plant-derived material (e.g., pollen), chemicals, drugs/medications, and animal dander.
Subcutaneous immunotherapy (SCIT) is a disease modifying treatment option for subjects with allergic rhinitis triggered by aeroallergens (such as pollen, animal dander, or dust). SCIT is recommended when pharmacological therapies are not sufficient to control symptoms. During SCIT, increasing doses of the inciting allergen are administered, followed by a maintenance dose for several years, with the goal of inducing immunological changes leading to symptom amelioration while on therapy, as well as sustained desensitization off SCIT (immune tolerance). Although SCIT can provide long-lasting protection from allergic disease, it also carries a risk of adverse reactions, has variable efficacy between subjects, and can take at least 3 years to induce immune tolerance (Durham S R, et al., N Engl J Med, 1999. 341(7): p. 468-75; Durham S R, et al., J Allergy Clin Immunol, 2012. 129(3): p. 717-725.e5; and Durham S R, et al., J Allergy Clin Immunol, 2016. 137(2): p. 339-349.e10). Typically, at the start of SCIT, patients receive injections of increasing doses of the allergen at weekly intervals over several weeks to months, under tightly monitored medical supervision. The gradual dose escalation enables tolerability to therapy and mitigates risk of severe hypersensitivity reactions related to allergen administration. However, side effects occur in 40-50% of patients ranging from mild reactions (e.g., swelling, injection site reaction, de novo allergic response, and urticaria) to life threatening reactions (e.g., asthma exacerbation and anaphylaxis) (Frew A J, Clin Exp Allergy. 2006a. 36(3): p. 251-3). Accordingly, an unmet need exists for more efficacious treatment of allergic disease and for improving the tolerability, safety, and/or efficacy of immunotherapeutic treatment strategies.

Methods for treating allergy and enhancing allergen-specific immunotherapy by administering an IL-4R antagonist


An apparatus is provided to effectively reduce the non-active detection gap between sensor elements of an optical sensor. Reducing the non-active gap can subsequently reduce the time delay between sensor elements, mitigating the image degrading effects of a composite element time delay. While applicable to use with a wide range of optical sensors, the invention may be used for detecting aspects of a variable-rate dynamic colorful object using a matrix sensor or a tri-linear color CCD sensor. In one variation, optical fibers extend from a first fiber optic faceplate to a second fiber optic faceplate. The optical fibers can be oriented toward or directly mounted to the sensor elements. A spacer may be used to separate the optical fibers for alignment with the sensor elements and the other end of the optical fibers are attached to each other.

Optical sensors are used for a wide variety of imaging purposes. An optical sensor, such as a linear sensor, may have multiple sensor elements, each of which captures a portion of the light information of an object or scene of interest. The manufacture of optical sensors may require a non-active gap between these sensor elements. The non-active gap is a portion of the optical sensor that can not detect an optical signal. In one example, linear arrays of distinct red, green and blue light capturing sensor elements are separated by a linear area, the non-active gap, where the combined sensor is not capable of capturing an optical signal.
Similarly, optical sensors with one optical sensor element may be used collectively with other such sensors to form a larger combined sensor. In such cases, non-active gaps will typically exist between the sensor elements of neighboring sensors.
For many applications that rely upon a predictable rate and distance of subject movement, such as, for example, a color imaging scanner, the size of a non-active gap does not create difficulty in the recording of subjects and subsequent accurate replay of images. However, for subjects that are dynamic or moving with unpredictable speed and/or distance relative to the sensor, this non-active gap can cause the inaccurate recording of an object or scene and result in a significant loss of image fidelity.

Method and apparatus to effectively reduce a non-active detection gap of an optical sensor


An exemplary apparatus for obtaining data for at least one portion within at least one luminal or hollow sample can be provided. For example, the apparatus can include a first optical arrangement configured to transceive at least one electromagnetic radiation to and from the portion(s). The apparatus can also include a wavelength dispersive second arrangement, which can be configured to disperse the electromagnetic radiation(s). A housing can be provided with a shape of a pill, and enclosing the first and second arrangements.

As is known in the art, introduction of endoscopy (esophagogastroduodenoscopy—"EGD") for visualization of digestive or gastrointestinal (GI) tract up to duodenum significantly has improved health care outcomes over a long period of time. This technique generally utilizes a flexible video-imaging probe, which can be advanced through a natural orifice to the luminal digestive organs. This procedure is considered to be minimally invasive. However, due to patients' discomfort, it is often performed under sedation. Sedation is one of the most important contributors to the high cost of upper endoscopy and is estimated to account for 30-50% of the total procedural cost. Because of the mortality and morbidity associated with complications related to sedation, patients likely undergo continuous cardiopulmonary monitoring and nursing support during the endoscopic procedure. Post-procedural recovery can also contribute to the expense, as it likely requires additional nursing and monitoring in a large and specialized physical space. After discharge, patients frequently need to be escorted home, and likely lose at least a day of work.
Besides cost, another limitation of upper endoscopy can be its relatively low accuracy. Studies have shown that endoscopists correctly identify the precancerous esophageal condition termed specialized intestinal metaplasia (SIM), in only approximately 40-50% of cases. Thus, for diagnostic purposes the gastroenterologist has to extract a tissue biopsy from several areas in the suspect region. The biopsy can then be processed and reviewed under a microscope by a pathologist who renders the final diagnosis. It is estimated that over 20 million such biopsies are excised and analyzed every year in the United States. Unfortunately, a biopsy represents only a fractional area of tissue, thus it can easily miss focal microscopic changes.
To address a need for a less invasive method for visualization of GI tract—capsule endoscopy (CE)—has been implemented. Since such time, a number of commercial products became available (e.g., Given PillCam and IntroMedic MiroCam) in common use at GI clinics. Capsule endoscopy generally incorporates a miniaturized version of the camera and a radio transmitter. The unsedated subject swallows the capsule endoscope, which captures images of the GI tract, and transmits them remotely as it passes through the digestive system. This technique had a high impact on examination of the small intestine—area that usually cannot be seen by other types of endoscopy, such as EGD or colonoscopy. Conventional capsule endoscopy has been also used to evaluate Barrett's esophagus. Unfortunately, such conventional capsule microscopy usually suffers from a lack of control of the capsule at the GEJ, likely resulting in few viable images obtained at the critical region of the esophagus. Relatively poor diagnostic accuracy and the fact that the capsules are not reusable (e.g., a cost of one capsule can be about $450) capsule endoscopy have limited its benefit for Barrett's screening over conventional endoscopy. Recently, string capsule endoscopy (SCE) has been described, in which the commercially available capsule can be tethered with a string to facilitate a strict control of the pill camera's location, and a repeated visualization of the GEJ. SCE capsules may also be retrieved, sterilized, and reused, thereby likely significantly decreasing the cost of the capsule endoscopy. However, SCE can be subject to the same diagnostic accuracy limitations as endoscopy.
To improve diagnostic accuracy, a further class of imaging technologies providing an "optical biopsy" in living patients without excising any tissue, has been provided.
One such technology is a confocal laser endomicroscopy ("CLE"), based on tissue illumination with a low-power laser with subsequent detection through a pinhole of the fluorescence light reflected from the tissue. This technique has an improved spatial resolution, although it likely suffers from a very narrow field of view and also requires contrast agent in order to keep high quality of data. Clinical studies have shown that CLE can be a promising approach for an early detection of cancer in the GI tract. However, this procedure can be performed either with a dedicated endoscope or a probe that can pass through the accessory channel of a standard endoscope, which usually requires patient sedation. Another technique capable of "optical biopsy" is optical coherence tomography ("OCT") and its further modified form—termed optical frequency domain imaging ("OFDI").
In both such techniques, the tissue can be illuminated with near-infrared light, which can be detected after being backscattered at the refractive index mismatch of cellular and sub-cellular components, providing images of tissue microstructure in vivo. The volumetric reconstruction of large sections of luminal organs can be achieved by the helical pullback scanning of the imaging optics. Based on clinical studies, this technique can provide structural cross-sections from entire lower esophagus, allowing for a BE diagnosis. Unfortunately, as in case of CLE, currently available OCT/OFDI catheters can be introduced during an endoscopy procedure, which usually requires sedation. Other techniques for optical biopsy can also be utilized, including confocal microscopy, spectrally-encoded confocal microscopy, and multi-photon and multi-harmonic microscopy. As with OFDI, these techniques also currently require sedated endoscopy for their implementation.
Accordingly, there may be a need to address at least some of the above-described deficiencies.
One of the areas for development in imaging of upper GI tract can include an improvement in diagnostic accuracy and decreasing cost of the procedure.
It is one of the objects of the present disclosure to provide apparatus, device and methods for obtaining microscopic image data from the GI tract that can be safe, highly tolerable to patients, and inexpensive. Such a device can be utilized, e.g., to screen a much larger population for GI tract diseases.

Apparatus, device and method for capsule microscopy


A new class of accelerometer uses a differential Eddy current sensor to sense the displacement of the proof mass. This accelerometer can provide improved performance in an open-loop configuration based on the thermal stability and improved linearity of the differential Eddy current sensor. The accelerometer may provide lower cost alternatives to commercial grade accelerometers and lower cost and higher reliability alternatives to strategic grade accelerometers.

1. Field of the Invention
This invention relates to accelerometers and more particularly to a class of accelerometers that use differential Eddy current sensing to provide improved sensitivity at lower cost and with higher reliability.
2. Description of the Related Art
The basic, open-loop accelerometer consists of a proof mass attached to a spring. The mass is constrained to move only in-line with the spring. Acceleration causes deflection of the mass. The displacement of the mass is measured. The acceleration is derived from the values of displacement, mass, and the spring constant. The system must also be damped to avoid oscillation. A closed-loop accelerometer typically achieves higher performance by using a feedback loop to cancel the deflection, thus keeping the mass nearly stationary. Whenever the mass deflects, the feedback loop causes an electric coil to apply an equally negative force on the mass, canceling the motion. Acceleration is derived from the amount of negative force applied. Because the mass barely moves, the non-linearities of the spring and damping system are greatly reduced. In addition, this accelerometer provides for increased bandwidth past the natural frequency of the sensing element. (Excerpted from Wikipedia "Inertial Navigation System" and "Accelerometer").
Conceptually, an accelerometer behaves as a damped mass on as spring. When the accelerometer experiences acceleration, the mass is displaced to the point that the spring is able to accelerate the mass at the same rate as the accelerometer body. The displacement is then measured to give the acceleration.
In commercial devices, piezoelectric, piezoresistive and capacitive components are commonly used to convert the mechanical motion into an electrical signal that is proportion to the displacement of the mass. Piezoelectric accelerometers rely on piezoceramics (e.g. lead zirconate titanate) or single crystals (e.g. quartz, tourmaline). They are unmatched in terms of their upper frequency range, low packaged weight and high temperature range. Piezoresistive accelerometers are preferred in high shock applications. Capacitive accelerometers typically use a silicon micro-machined sensing element in which the proof mass forms one side of the capacitive sense element. Their performance is superior in the low frequency range and they can be operated in servo mode to achieve high stability and linearity.
Modern accelerometers are often small micro electro-mechanical systems (MEMS), and are indeed the simplest MEMS devices possible, consisting of little more than a cantilever beam with a proof mass. Damping results from the residual gas sealed in the device. As long as the Q-factor is not too low, damping does not result in a lower sensitivity. Under the influence of external accelerations the proof mass deflects from its neutral position. This deflection is measured in an analog or digital manner. Most commonly, the capacitance between a set of fixed beams and a set of beams attached to the proof mass is measured. This method is simple, reliable, and inexpensive.
The performance of an accelerometer is primarily a combination of its bias stability and scale factor error. Bias stability is the acceleration measured by the device if the actual acceleration is zero. If the device is not accelerating due to imperfections of the device and electronics the readout will be nonzero. The scale factor error reflects the error as proportional to the actual acceleration. If for example the device is accelerating at 1 g (32 meters/sec/sec) and the device reads out 1.1 g, the scale factor error is 10%.
As shown in FIG. 1, the open-loop accelerometer with capacitive or piezoelectric sensing and the MEMs accelerometer exhibit bias stabilities typically much greater than 10 micro-g's and scale factor errors greater than 10 ppm. Although this level of performance is adequate for many commercial applications it is not sufficient for "strategic grade" military navigation systems that require bias stability less than 10 micro-g's and scale factor error less than 10 ppm. Even when provided with servo control in a closed-loop configuration the performance does not satisfy strategic grade navigation requirements. A completely different approach to precision navigation is to provide the system with a GPS receiver and the use the network of GPS satellites to measure the position of the system. This approach enables navigation position accuracy in the 1 meter class. Without the GPS enhancement, this equates to accelerometer bias stability better than 0.1 micro-g's and scale factor error of less than 0.5 ppm. However, the GPS approach is inherently dependent on outside sources of information (i.e. the GPS satellites) and thus is not considered to be an option for strategic military systems that might have to operate in GPS denied environments or under conditions in which the GPS satellite network may be degraded.
Currently, strategic grade military systems use a Pendulous Integrating Gyroscopic Accelerometer (PIGA) in which a pendulous mass is free to pivot by being mourned on a hearing (Excerpted from Wikipedia "PIGA accelerometer"). A spinning gyroscope is attached such that it would restrain the pendulum against "falling" in the direction of acceleration. The pendulous mass and its attached gyroscope are themselves mounted on a pedestal that can be rotated by an electric torque motor. The rotational axis of this pedestal is mutually orthogonal to the spin axis of the gyroscope as well as the axis that the pendulum is free to move in. The axis of rotation of this pedestal is also in the direction of the measured acceleration. The position of the pendulum is sensed by precision electrical contacts or by optical or electromagnetic means. Should acceleration displace the pendulum arm from its null position the sensing mechanism will operate the torque motor and rotate the pedestal such that the property of gyroscopic precession restores the pendulum to its null position. The rate of rotation of the pedestal gives the acceleration while the total number of rotations of the shaft gives the speed, hence the term integrating in the PIGA acronym.
PIGA class accelerometers provide strategic grade performance without requiring any outside sources of information. However, PIGA class accelerometers are expensive to build and maintain. The number of moving parts reduces reliability and requires periodic maintenance and recalibration.

Hung mass accelerometer with differential Eddy current sensing


A fuel pump trigger holder for holding the trigger of a fuel pump in an open position, where the fuel pump includes a handle against which the trigger is squeezed to allow fuel flow. The holder comprises a pair of prongs extending from an elongated base and ending at a pair of endpoints, wherein a top prong of the pair of prongs comprises a curved portion extending from the base and curving towards a bottom prong of the pair of prongs which extends at an incline relative to the base. The pair of prongs is configured for being disposed around the trigger and the handle for maintaining the trigger in a position corresponding to a fuel pump open position and releasing the trigger such that it returns to a closed position upon detecting a kicking motion from the fuel pump indicating a full fuel condition.

1. The Field of the Invention
The present invention is directed generally to a fuel pump trigger holder, and more particularly, to a holder capable of retaining a fuel pump trigger in an open position and releasing the trigger to return to its closed position when the fuel pump detects a full fuel condition.
2. Background Art
Many fuel dispenser or pump handles are provided with a mechanism which permits the trigger to be locked in one of several levels of open positions. This allows the person filling the tank to attend to other duties such as cleaning the windows while the vehicle is being filled with fuel. In some occasions, built-in fuel pump trigger holders have been removed for safety reasons (spills, for example) due in large part to relatively few defective or improperly designed fuel pump triggers. As a result, a user is required to attend to the task of fueling during the entire period during which his or her vehicle is being fueled, as it is expected that the user would be able to respond to any malfunctions of the fuel pump trigger to prevent potential disaster. In addition to the obvious inconvenience, recent studies indicate that exposure to petroleum and petroleum fumes can cause negative health effects. Prolonged contact with gas pump surfaces can also cause transmission of bacteria and viruses.
A fuel dispenser or pump generally includes a handle that is fluidly and structurally connected to a spout, a lever or trigger operably connected to a valve for controlling fuel flow through the spout and positioned such that the palm of a hand positioned on the handle is capable of reaching and squeezing the trigger towards the handle. There is typically further a guard disposed around the trigger to protect the dispenser from accidental squeeze of the trigger or accidental dispensing of fuel. In response to the need disclosed earlier, there have been numerous devices developed in the related art which are adapted to hold the trigger in an open position so that a person pumping fuel does not have to hold the handle and continually apply manual pressure to the trigger.
Various portable devices including many types of locks, holders, latches or clamps have been devised for holding the valve of a fuel pump open. Some of these devices include "stair steps" or jagged edges configured to hold a trigger in place at various levels of trigger hold or fuel flow. There are two general types of fuel pump trigger holders. The first type includes a "C" shaped structure used to limit movement of the trigger relative to the handle. In some instances, the structure may appear as rings composed of a single or multiple segments. The second type includes an "I" shaped structure configured to be disposed between a trigger and its guard to limit movement of the trigger relative to the guard. Most of these devices are capable of attachment to a secondary item, such as a key chain, key or another attachment, such as the holder disclosed in U.S. Pat. No. 5,118,074 to Weissman (hereinafter Weissman). None of the prior art devices includes an automatic release mechanism which can automatically release the trigger upon detecting a full fuel condition.
In prior art devices, termination of fueling is made possible only by a sensing and actuating mechanism disposed inside a fuel pump nozzle. A fuel pump nozzle comprises a sensing port that is used to detect when the fuel tank is full, and hence to stop supplying fuel. This is achieved by applying a vacuum to sensing port; when fuel travels into the sensing port, fuel supply is cut off, thereby creating a kicking motion as the fuel flow is abruptly terminated. The fuel pump however is still held in an open position until the trigger is released. The capability of automatically releasing the trigger with a portable holder is a feature not available in prior art portable holders. Reference is made to U.S. Pat. No. 4,497,350 to Guertin in connection with the means by which this kicking motion is created.
Weissman discloses a device for holding a lever of a fuel pump in at least two adjusted, open positions in accordance with a desired rate of flow of fuel from a nozzle. The device includes a hook-shaped arm structured to hang over a top surface of the gas pump handle so as to be supportably engaged. A number of parallel fingers extending outwardly from an elongate portion at spaced intervals from the hook-shaped arm, each of the fingers adapted to supportably receive the lever in one of the adjusted, open positions. The device can be carried on a key ring fitted through an aperture therein. This device uses a number of fingers to provide different levels of fuel flow and not capable of continuous modulation of fuel flow. This device further lacks an automatic trigger release feature for receiving the kicking motion of a fuel pump.
U.S. Pat. No. 4,846,447 to Hanna discloses an actuator device for a trigger operable within a housing of an automatic nozzle of a gasoline pump and consists of a pair of jaws, each formed transversely onto an opposite end of a web of a predetermined length. The upper jaw fits over the housing while the lower jaw fits under the trigger when the trigger is pulled up for operation. Although a leaf spring is utilized in contacting engagement with a trigger, it is neither configured to hold the trigger at varying degrees of squeeze nor does it permit automatic disengagement of the trigger when a full fuel condition has been detected.
U.S. Pat. No. 4,176,695 to Raske discloses a device for holding the lever of a nozzle assembly in a position to open a valve, controlling the flow of fuel through a passageway in the handle of the assembly. The capability of automatically releasing the trigger of a fuel pump is also not contemplated in this device.
U.S. Pat. No. 4,683,923 to Harris discloses a clip for holding the lever of a gasoline pump dispensing handle in open gasoline dispensing position. The clip is made from a single flat plate of uniform thickness having a rear shank about 1½ inches in length with a pair of identical arms extending about 1½ inches from the opposite ends of the shank and forming between the arms an angle of approximately 40 degrees. A serrated row of similar flat-topped teeth lies along the inner edge of each arm with the flat tops of each serrated row of teeth lying in a common plane and the two planes containing the flat tops intersecting each other at an angle of approximately 40 degrees. The capability of automatically releasing a fuel pump trigger is also not contemplated in this device.
Thus, there exists a need for a holder configured to hold a fuel pump trigger corresponding to an open position and automatically release the fuel pump trigger upon detection of a full fuel condition in the tank which the fuel pump is designed to fill.

Automatic releasing fuel pump trigger holder


The invention relates to contactors suitable for use, for example, in manufacturing and chemical refinement processes. In an aspect is a hybrid indirect/direct contactor for thermal management of counter-current processes, the contactor comprising a vertical reactor column, an array of interconnected heat transfer tubes within the reactor column, and a plurality of stream path diverters, wherein the tubes and diverters are configured to block all straight-line paths from the top to bottom ends of the reactor column.

A counter-flow contactor provides efficient contact between opposing streams of material and is used to promote interaction between the two material streams. In many processes, the interaction can generate heat, causing the temperature of the materials to rise. For example, if the materials streams react chemically, then the heat of reaction can raise the temperature of the materials, sometimes causing the reaction to speed up and sometimes causing the reaction to slow down. In other process, the interaction can cause the adsorption of heat, causing the material stream temperature to decrease. For example, powdered materials can be dried by removing adsorbed water by contacting the powdered solid with hot, dry air. However, the evaporation of adsorbed water will cause the air temperature to decrease, limiting the effectiveness of the air in drying the solid. In these cases, there is a need to be able to continuously add or remove heat while these two counter flowing streams are interacting.
Relevant art: U.S. Pat. No. 4,588,024; U.S. Pat. No. 4,237,008; WO 2013094206.

Hybrid indirect/direct contactor for thermal management of counter-current processes


An apparatus for the production of hollow bodies from thermoplastic material by blow molding using a blow molding mold which includes at least first and second mold portions to enclose a generally tubular extruded preform which is expanded within the mold under the effect of an increased internal pressure within the preform. To provide for asymmetric closing and/or opening movements of the mold portions relative to the preform, the blow molding mold is displaced as an entirety parallel to the direction of the opening and/or closing movements of the mold portions, more especially during the mold closing and/or opening procedure, so that an additional motion is superimposed on the movements of the mold portions.

In a typical form of process for the production of a hollow body of thermoplastic material by means of blow molding, a preform or parison is accommodated in a blow molding mold comprising at least first and second mold portions, and expanded therein under the effect of an increased internal pressure within the preform or parison. The mold portions are moved with a reciprocating motion between an open condition in which they are at a spacing from each other and a closed condition in which they bear against each other and with their mutually facing sides define a mold cavity whose contour corresponds to the configuration of the preform when expanded by the increased pressure therein. The movement of the mold portions is produced by at least one drive system for moving them between the open and closed conditions.
In regard to the closing and opening movements of the mold portions, it is generally necessary for those movements to take place in a defined fashion relative to a reference plane of the main frame structure of the blow molding machine, and in such a way that such movements can be satisfactorily reproduced at any time. The usual procedure in that respect is that the mold portions move with a symmetrical motion towards the central plane of a preform which is disposed centrally between them, and then move, again with a symmetrical motion, away from the hollow body which is produced from the preform by expansion thereof. The preform generally hangs freely between the mold portions, before they are moved together.
Accordingly, the central plane of the preform is primarily referred to hereinafter as the above-mentioned reference plane. It should be appreciated however that other planes may constitute the reference plane, if so required.
Particularly when suing a hydraulic drive system for producing the closing and opening movements of the mold portions, by virtue of the characteristics of the drive means used in such a system, it is not possible, without taking additional precautionary steps, to achieve the desired synchronism in respect of the mold portions in the closing and opening movements thereof relative to the preform, so that there is the risk that, due to different speeds of movement the mold portions do not reach their respective open or closed condition in the proper definable positions. Such irregularities in the movements of the mold portions are generally undesirable, especially as they can occur in an uncontrollable fashion and can thus differ from one operating cycle of the machine to another.
In order to avoid such irregularities in the movements of the mold portions, as an additional precautionary arrangement in that respect the machine may have synchronisation devices which cause the mold portions to move with a defined motion relative to a reference plane of the main frame structure of the machine. The arrangement is generally such that the synchronisation assembly has at least one mechanical connecting element which is arranged non-displaceably on the main frame structure of the blow molding machine and which kinematically couples the mold portions together. The fixed arrangement of the connecting element on the main frame structure of the machine provides that the closing and opening movements of the mold portions occur in the same fashion but in opposite relationship to each other, relative to the central plane of the preform or the article produced therefrom. That design configuration ensures, while using simple means, that the mold portions open and close symmetrically and thus move into their closed condition or their open condition in properly defined positions.
In one form of such a synchronisation arrangement, the connecting element is a gear which is disposed rotatably on a shaft which is fixedly mounted on the main frame structure of the blow molding machine. The two mold portions have toothed racks which each mesh with the gear. When one of the mold portions moves, the gear is rotated by the corresponding rack, with the result that the other mold portion whose associated rack is disposed parallel to the other rack on the other side of the above-mentioned shaft carrying the gear, is moved in the opposite direction.
In another design configuration of a synchronisation arrangement, a control lever is mounted on the main frame structure pivotably about a stationary shaft. Pivotably connected to the two lever arms of the control level, which are of the same length, are rods or bars which at their other end are each movably connected to a respective mold portion. The mold portions are kinematically positively connected together and to the main frame structure of the blow molding machine, by arrangements as just described above.
Other forms of synchronisation arrangement may also be used, which are generally familiar to any person skilled in this art and which for that reason do not require more detailed description herein. Such arrangements may comprise for example an endless flexible element such as a chain, cable or the like, which is passed around two wheels, rollers or the like which are mounted rotatably but non-displaceably on the frame structure of the machine. However a common aspect of all the above-indicated constructions is that they have at least one member which is arranged stationarily even if rotatably on the main frame structure of the blow molding machine, and thus establish a reference plane, relative to which the mold portions move symmetrically in opposite relationship to each other. The reference plane in such cases is generally so selected that it coincides with the central plane of the preform, as indicated hereinbefore. The arrangement is frequently also such that disposed in the above-mentioned central plane is the blowing pipe member which co-operates with the blowing mold and the preform and through which inter alia the pressure fluid required for expansion of the preform is passed into the blow molding mold.
A possible design configuration of such a blow molding machine is to be found for example in U.S. Pat. No. 4,150,080, the disclosure of which is hereby incorporated into this application in this respect.
Particularly in the last phase of the closing movement of the mold portions, a symmetrical arrangement of the mold portions in that way is frequently desirable as, in that phase, the two mold portions embrace the preform which is hanging from an extrusion head or other suitable holding means, and squeeze off the waste material present on the preform, while at the same time the portions or regions of the preform which bear against each other are welded together to produce a closed volume for expansion of the preform by the production of an increased internal pressure therein. In the majority of cases, when the preform occupies its receiving position in which it is received by the blow molding mold, the preform will be hanging from the extrusion head of an extrusion apparatus. As however the preform can also be produced in a different fashion from extrusion, it is also possible for the preform to be held in its receiving position by another form of holding means, until it has been received by the blow molding mold.
In the course of extending the range of use of the blow molding process and in particular also for the production of hollow bodies of a highly complicated configuration, it has been found that the above-described movements of the mold portions, which occur symmetrically relative to the preform, are not always advantageous, especially as the blow molding mold is not symmetrically divided in all cases, with the result that the mold portions of the blow molding mold are of mutually different configurations. There are therefore possible uses in which it may be more appropriate or even necessary for the movements of the blow molding mold portions to be such that they occur asymmetrically relative to the preform. That may also apply in regard to the opening movements of the mold portions, relative to the manufactured article which after expansion of the preform is generally held by the blowing pipe member or another member which co-operates with the blow molding mold and which does not participate in the opening movement of the mold portions.

Blow molding apparatus for the production of a hollow body of thermoplastic material


A resistor (45) of semiconductor material is formed on an insulating layer (42), then a silicon nitride film (46) is deposited on the entire surface including the resistor (45), and a silicon dioxide film (47) is sequentially deposited thereon, and thereafter electrodes (49A) and (49B)of the resistor (45) are formed, thereby preventing the fragility of the insulating layer (51) at step portions of the resistor (45), preventing the breakage of the electrodes and interconnections, and improving a withstand voltage between the resistor (45) and the interconnections crossing over it to thereby improve yield of a semiconductor device. An impurity (64) is introduced into a semiconductor film (63) to be a resistor by the ion implantation technique to thereby change the state of the film into an amorphous state, semiconductor film (63a) is heated in atmosphere including hydrogen compound gas and/or hydrogen gas, and then heated to activate it to thereby form a resistor (67), so that a resistance value of the resistor (67) at a region where the impurity is highly dosed can be decreased progressively.

It has been mainly employed, as a resistor for a semiconductor device, a diffusion resistor which uses a diffusion layer formed in a semiconductor substrate as a resistor The diffusion resistor is constituted in such a manner that boron is doped to a surface portion of, for example, an n-type epitaxial layer to form a p+ diffusion region, then electrodes (e.g., Al electrodes and so on) are formed at opposite ends of the diffusion region.
In recent years, a polycrystalline silicon resistor which uses a polycrystalline silicon film as a resistor has been employed. The polycrystalline silicon resistor is constituted in a manner as shown in FIG. 6 that a polycrystalline silicon film 3 including impurities serving as a resistor is formed on a field insulating layer (SiO.sub.2 layer) 2 formed on a major surface of a silicon substrate 1, thereafter an SiO.sub.2 layer 4 is deposited on the entire surface of the polycrystalline silicon film 3 by the chemical vapor deposition (CVD) process, then a pair of Al electrodes (interconnections) 6 are formed on opposite ends of the polycrystalline silicon film 3 through contact holes. Thus constructed polycrystalline silicon resistor 7 has the following features when compared with the above-described diffusion resistor:
(i) the diffusion resistor has such a property that a resistance value changes depending on a depletion layer, so-called back bias dependence, since a junction is separated by applying a reverse bias voltage between it and the neighboring semiconductor region, while the polycrystalline silicon resistor 7 does not have such a back bias dependence; PA1 (ii) the diffusion resistor has such a property that an expansion of a depletion layer is changed depending on a voltage applied thereto to thereby change a resistance value, so-called self bias dependence, while the polycrystalline silicon resistor 7 does not have such a self bias dependence; PA1 (iii) the diffusion resistor is changed in its resistance value depending on the orientation of a wafer and by the influence of stress applied thereto in the assembling-process (e.g., in the molding process), while the polycrystalline silicon resistor 7 is not influenced in its resistance value by the orientation of a wafer and little influenced by the stress in the assembling process; and PA1 (iv) the polycrystalline silicon resistor is more advantageous in the temperature characteristics.
Now, as one of bipolar transistors, there has been proposed a ultra-high speed bipolar transistor which is constructed in a manner that both a base leading-out electrode and an emitter leading-out electrode are formed by a polycrystalline silicon film, then a base region and an emitter region are formed in a self-alignment fashion by diffusing impurities from the polycrystalline silicon film serving as the emitter leading-out electrode. FIG. 8 illustrates an example of methods of manufacturing the ultra-high speed bipolar transistor. As shown in FIG. 8A, on a major surface of a first conductivity type, e.g., p-type silicon substrate 11, a second conductivity type, e.g., n-type collector buried region 12 and a p-type channel stopper region 13 are formed, then an n-type epitaxial layer 14 is grown thereon. Thereafter, a highly-doped n-type collector leading-out region 15 reaching to the collector buried region 12 is formed, and a field insulating film 16 is formed by the local oxidation on the regions except for the collector leading-out region 15 and a region 14A on which base and collector regions are formed in the succeeding processes. Then, a thin insulating layer, e.g., SiO.sub.2 layer 17 is formed on an entire surface thereof, and a portion thereof corresponding to the region 14A is opened to form a first polycrystalline silicon layer 18 serving as a base leading-out electrode by the CVD process, then boron acting as p-type impurities is doped to the polycrystalline silicon film 18. Thereafter, the p+ polycrystalline silicon film 18 is subjected to the patterning process by a first resist mask 19 having a pattern corresponding to the external configuration of the base leading-out electrode.
Referring to FIG. 8B, an SiO.sub.2 film 20 is deposited by the CVD process on an entire surface including the p+ polycrystalline silicon film 18 having been subjected to the patterning process, and thereafter a second resist mask 21 is formed thereon. A part of the SiO.sub.2 film 20 and the P+polycrystalline silicon film 18 corresponding to an active portion so as to form an intrinsic base region and an emitter region is selectively removed by the etching-process through the resist mask 21 to thereby form an opening 23 and also to form a base leading-out electrode 22 formed of the p+ polycrystalline silicon film 18.
Then, as shown in FIG. 8C, p-type impurity boron is implanted by the ion implantation technique through the opening 23 to form a link base region 24 on the region 14A for connecting an external base region and the intrinsic base region which are to be formed. An SiO.sub.2 film is then deposited by the CVD process and the above deposited SiO.sub.2 film by the CVD is densified by the heat treatment at about 900.degree. C. Due to the heat treatment at this time, the impurity boron from the base leading-out electrode 22 of the P.sup.+ polycrystalline silicon film is diffused to form a part of an external base region 26. Then, by the etch back-process a side wall 25 of SiO.sub.2 is formed at the inner wall of the base leading-out electrode 22 facing to the opening 23.
Thereafter, as shown in FIG. 8D, a second polycrystalline silicon film 28 finally serving as the emitter leading-out electrode is formed by the CVD process at an opening 27 defined by the side wall 25, and p-type impurity (e.g., B or BF.sub.2) is implanted by the ion implantation process into the polycrystalline silicon film 28 which is in turn annealed to form a p-type intrinsic base region 29 at the active portion, then n-type impurity (e.g., arsenic) is implanted into the film by the ion implantation process and annealed to form an n-type emitter region 30. The p-type intrinsic base region 29 and the n-type emitter region 30 may be formed instead of the above-described method in a manner that the p-type impurity and the n-type impurity are sequentially implanted into the polycrystalline silicon film 28 by the ion implantation process and simultaneously annealed. Due to the annealing-process, for forming the base and emitter electrodes, the impurity boron from the base leading-out electrode 22 of the P.sup.+ polycrystalline silicon film is diffused to finally form the external base region 26. Now, the intrinsic base region 29 is higher in the impurity density than that of the link base region 24. Thereafter, contact holes are formed, and then a base electrode 31, a collector electrode 32 and an emitter electrode 33 are formed by metal (e.g., Al), thereby constituting a ultra-high speed bipolar transistor 34.
The above-described polycrystalline silicon resistor is used in a ultra-high speed bipolar LSI, Bi-CMOS LSI etc. including the above-described ultra-high speed bipolar transistor.
However, since the above-described polycrystalline silicon resistor is formed on the field insulating layer 2, a step becomes larger, whereby interruption of the step and electromigration may occur at the Al electrode (interconnection) 6 of the upper layer due to the coverage of the CVD SiO.sub.2 film 4 at a step portion A in FIG. 6. Further, since the CVD SiO.sub.2 film 4 at the step portion A is fragile from a film quality standpoint, when the Al interconnection 8 crosses over the resistor 7 as shown in FIG. 7, a leak current may be generated between the polycrystalline silicon resistor 7 and the Al interconnection 8 at a step portion B.
The reason that the quality of the CVD SiO.sub.2 film 4 is degraded is considered as follows. Namely, when the polycrystalline silicon film 3 to be the resistor is subjected to the patterning process by, for example, the reactive ion etching (RIE) process through the resist mask, a surface of the field insulating layer 2 is damaged, and a surface of the polycrystalline silicon film 3 is polluted and damaged when the ashing of the resist mask is performed, so that the CVD SiO.sub.2 film 4 formed on the polycrystalline silicon film becomes thin in thickness and becomes fragile.
Now, in the case of the polycrystalline silicon resistor, a sheet resistance value thereof can be controlled in accordance with the kinds of impurities and an amount of dose when the thickness thereof is fixed. However, even though boron (B), arsenic (As) and phosphor (P) etc., have various characteristics, but each of these impurities has such a common tendency that when an amount of dose of the impurities is increased more than a predetermined value, a sheet resistance value is not decreased but increased due to the segregation of the impurities, etc. FIG. 4 is a graph illustrating dependence of the sheet resistance on an amount of dose of boron, wherein a curve a.sub.2 shows a conventional case. FIG. 5 is a graph illustrating dependence of the sheet resistance on an amount of dose of arsenic or phosphor, wherein a curve b.sub.2 shows a conventional case. As is clear from these drawings, it has been difficult to obtain a low resistance value by using the polycrystalline silicon resistor with a thin film (which is normally used to obtain a high resistance value).
Accordingly, in view of the above-described drawbacks of the conventional manufacturing method, an object of the present invention is to provide a method of manufacturing semiconductor devices which is capable of forming a stable insulating film with a good quality and forming a resistor with high reliability which does not cause an interruption of a step of electrodes and interconnections or a leak current between the resistor and the interconnections.
Another object of the present invention is to provide a method of manufacturing semiconductor devices which is capable of obtaining a resistor with a lower resistance value in a highly dosed region.

Method of manufacturing semiconductor devices


The present invention provides maintains site persistence in a hierarchical Global Server Load Balancing (GSLB) deployment. Via configuration of GSLB services locally and remotely on each of the GSLB appliances and LB appliances at a site, a site appliance identifies and associates requests from the GSLB with the site. Furthermore, the site appliance may receive a GSLB cookie with the client request and confirms the request is from the expected GSLB in the site hierarchy. When the load balancers receives a response from a server, the appliance may include the GSLB cookie with the response back to the client. The appliance may also include an LB cookie to identify the server selected by the LB. When the client sends another request, the request may include the GSLB and LB cookie.

A corporate or enterprise may deploy various services across a network to serve clients connecting to the services from many areas. A clients may request to access a service, such as a web server, provided by the enterprise. The enterprise in order to improve the access to this service may deploy multiple servers at various geographical locations in order to expedite the access and meet the demand of users. Similarly, the enterprise may provide a plurality of server farms positioned at a variety of sites and including any number of servers capable of processing the client's request. The enterprise may use a load balancer to manage network traffic across these servers and minimize the network congestion and delays. Similarly, the enterprise may also use a plurality of global server load balancer (GSLB) to manage network traffic over a plurality of such sites, each of which includes at least one load balancer managing network traffic locally over the server farm. As requests of clients are received by GSLBs and balanced across multiple sites, load balancers at each of the sites may further balance the requests among multiple servers. As the requests traverse multiple load balancers via the GSLB site hierarchy, maintaining persistence of a client or client session across the hierarchy is challenging.

This patent is subject to a terminal disclaimer.

Systems and methods for GSLB site persistence


An integrated circuit power device is disclosed having a large number of individual devices formed in an integrated circuit. Disabling devices are provided in the integrated circuit, a respective one of which is electrically connected to an associated one or more of the individual devices. Each of the disabling devices is responsive to a defect in the associated one or more individual devices, such as a short circuit, for automatically disabling the associated one or more individual devices. An operable integrated circuit power device is obtained, notwithstanding a defective one or more of the individual devices. Testing of individual devices, or customized mask generation is not necessary. In a preferred embodiment, the disabling device is a fusible link formed of a low melting point conductor. In response to the initial powering up of the device or in response to a gate pulse, all fusible links associated with short circuited individual devices will melt, thereby insulating the remainder of the devices from the short circuit.

Power devices have been widely used to carry large currents at high voltages. The problems with these devices included their large size and unreliability. However, in the early 1950's, developers of electronic power systems began to base their high power systems on semiconductor devices.
Many of these early semiconductor power devices included a single large device for handling large currents; e.g., a thyristor or rectifier. By the 1970's, devices were fabricated capable of operating at up to 3,000 volts and controlling 1,000 amperes of current. Other types of devices have also been fabricated which are adapted to carry large currents and voltages by connecting many small discrete devices, such as bipolar devices, in parallel. The bipolar devices were first developed in the early 1950's. Today it is possible to fabricate bipolar transistors with a current handling capability of several hundred amperes and a block voltage of 600 volts.
Bipolar transistors, however, have several major problems in their operation. For example, a high current is required to control the bipolar transistor, typically one-fifth to one-tenth of the collector current. Consequently, the base drive circuitry contains many intricate and expensive components. Bipolar transistors are also subject to a breakdown failure when high current and voltage are simultaneously applied to the device as required in inductive power circuits. Metal Oxide Semiconductor (MOS)-gated devices were suggested to solve these problems.
The MOS-gated power device overcomes many of the problems of bipolar devices. The control signal of a MOS-gated device is connected to a metal gate electrode that is separated from the semiconductor surface by an intervening insulator, typically silicon dioxide. Accordingly, MOS-gated devices have a high input impedance which allows for simpler gate drive circuitry and cost reduction within the power electronics. The power MOSFETs' switching speed is many orders of magnitude faster than the switching speed for bipolar transistors, thus making MOSFETs particularly suitable in high frequency circuits where switching power losses are frequent.
In many present day power devices, large numbers of parallel-connected individual bipolar, MOS or other devices, commonly referred to as "cells", are fabricated in parallel in a single semiconductor integrated circuit, using well known microelectronic manufacturing techniques. Presently, up to 100,000 or more individual low current MOS-gated cells may be fabricated in parallel to produce a power device.
A major concern in fabricating a high current power device containing a large number of parallel cells is the yield of the resulting chip. In particular, it is difficult to provide a high yield high current power device in view of the defect rate of the individual cells on the semiconductor substrate. Since these individual cells are electrically connected parallel to one another, a short circuit in one cell renders the power device unusable. Accordingly, in practice, yields of only 30% are typically obtained even for relatively small chips with size of 0.25 inch by 0.25 inch.
One attempt at overcoming this yield problem is described in the article "A Large Area MOS-GTO with Wafer-repair Technique" by Stoisiek, et al., IEDM, 1987, pages 666-669. In this approach a MOS power device is fabricated out of about 300,000 individual MOS cells on a semiconductor substrate. The individual MOS cells are grouped into cell blocks, and each cell block is individually tested for faulty operation. The substrate is covered with an insulating layer, and via hole pattern is etched into the insulating layer according to the results of the previous operational measurements, i.e. holes are etched only over the cell blocks without a fault. Consequently, the faulty cell blocks are insulated from the rest of the device. A metal layer connects all the operational cell blocks through the via holes. Thus, shorted cells are prevented from causing other cells to short circuit because they are not connected in parallel with the functional cells.
While the above described technique prevents a short circuit in one or more individual cell blocks from destroying the entire power device, this technique is not amenable to mass production of power devices. Each individual cell block must be tested for shorts, which is a time consuming process. Once shorts are identified, a custom mask must be designed for every wafer so that a via hole pattern may be etched on the insulating layer to connect only the fault-free cells or cell blocks. The cost of individual masks and the turn around time for designing the masks and then forming the individually designed via patterns makes the resultant devices prohibitively expensive. In addition, these operations increase the number of processing steps and add to overall fabrication cost for the large area device.

Integrated circuit power device with automatic removal of defective devices and method of fabricating same


A flavor source to be used as a thermally releasable flavorant for smoking articles that do not combust tobacco. The material includes tobacco particles, an aerosol precursor that forms an aerosol upon exposure to heat, and a filler material that absorbs and radiates heat to minimize the likelihood that the flavor material will ignite. The material is mixed in an extruder, extruded through a die, and cut into pellets having a substantially uniform shape. The pellets are loaded into a chamber for inclusion in a smoking article as a flavor generator.

This invention relates to a thermally releasable flavor source for use in smoking articles which produce substantially no smoke. More particularly, this invention relates to a tobacco-containing thermally releasable flavor source that provides the sensations associated with the smoking of tobacco without the burning of tobacco.
A substantial number of previous attempts have been made to produce a smoking article which produces an aerosol or vapor for inhalation, rather than smoke. For example, Siegel U.S. Pat. No. 2,907,686 shows a smoking article consisting of a charcoal rod and a separate carrier impregnated with flavorants and a synthetic "smoke" forming agent which is heated and volatized by the burning charcoal rod. The charcoal rod is coated with a concentrated sugar solution so as to form an impervious layer during burning. It was thought that this layer would contain the gases formed during smoking and concentrate the heat thus formed, thereby thermally releasing the flavorants.
Another smoking article, shown in Ellis et al. U.S. Pat. No. 3,258,015, employs burning tobacco in the form of a conventional cigarette to heat a metallic cylinder containing a source of nicotine, such as reconstituted tobacco or tobacco extract. During smoking, the vapors released from the material inside the metal tube mix with air inhaled through an open end of the tube which runs to the burning end of the smoking article. Ellis et al. U.S. Pat. No. 3,356,094 shows a similar smoking article in which the tube becomes frangible upon heating, so that it will break off and not protrude as the surrounding tobacco burns away.
European patent application 0 177 355 by Hearn et al. shows a smoking article which produces a nicotine-containing aerosol by heating, but not burning, a flavor generator. The flavor generator could be fabricated from a substrate material such as almumina, natural clays and the like, or tobacco filler. The flavor generator is impregnated with thermally releasable flavorants, including nicotine, glycerol, menthol and the like. Heating of the flavor generator is provided by hot gases formed as a result of the combustion of a fuel rod of pyrolized tobacco or other carbonaceous material.
Banerjee et al. U.S. Pat. No. 4,714,082 shows a variation of the Hearn et al. device which employs a short fuel element. The performance of the device is improved by maximizing heat transfer between the fuel element and the aerosol generator. This is effected by preventing heat loss by insulation, and by enhancing heat transfer between the burning fuel and the flavor generator by a metallic conductor. A spun glass fiber insulator surrounds the fuel element and aerosol generator assembly.
European Application No. 0 212 234 shows a smoking article having an aerosol generating means abutting a fuel element. The aerosol generating means is said to include a thermally stable, porous particulate substrate material, for example, carbon, tobacco, or mixtures of carbon and tobacco formed into densified spherical particles in a one step process (e.g., as described in U.S. Pat. No. Re 27,214) in a "Marumerizer" type machine. The substrate materials carry one or more aerosol forming materials and may include one or more volatile flavoring agents. The smoking article may include optionally a plug of tobacco at the mouth end of the fuel element whereby hot gases passing through the tobacco may vaporize volatile components in the tobacco without combustion.
European Application 0 254 848 shows a substrate material having a decreased retentive capacity for use as a carrier for aerosol materials, e.g., alumina or modified carbon.
The prior art devices that rely on thermally releasable flavorants have not heretofore adequately provided a flavor source for smoking articles that will provide the smoker with the taste and satisfaction that has become expected of a conventional tobacco-burning smoking article. Accordingly, there is a continuing need for a flavor source that can be heated to provide an acceptable taste comparable to a conventional smoking article without being burned. Further, there is a continuing need to provide such a flavor source containing tobacco.

Thermally releasable flavor source for smoking articles


Provided is an electronic apparatus including a storage configured to store video contents shot by a user; a reproducer configured to reproduce the stored video contents; a controller configured to analyze each of the video contents to extract lower meta-information items, to analyze the extracted lower meta-information items to derive an upper meta-information item, and to calculate, based on an upper meta-information item of a first video content being reproduced and upper meta-information items of second video contents other than the first video content among the video contents, a score for each of the second video contents; and an output unit configured to output, according to the calculated score, a recommendation information item for recommending at least one of the second video contents after the reproduction of the first video content is stopped.

1. Field of the Invention
The present invention relates to an electronic apparatus capable of recommending, among video contents shot by a user, a video content that a user might want to view, so as to reproduce the video content, and to a content recommendation method and a program in the electronic apparatus.
2. Description of the Related Art
In the related art, a technique of recommending a video content (hereinafter, abbreviated as video) that a viewer of a certain video supposedly wants to view next has been used in "YouTube" (URL: http://www.youtube.com), for example.
In the recommendation technique, information items of "tag information", "evaluation of viewer", and "action of viewer" indicating a title, a tag, and a description which are associated with a video have been used. The "tag information" includes information items that are considered by a creator of a video to be associated with the video, and those information items need to be input by the creator. The degree of freedom of the tag information as information is high, but the tag information depends on subjective view of the creator. Specifically, one thinks that videos are similar to each other, the other may not think so. The "evaluation of viewer" includes evaluation information items of videos by viewers. For example, the evaluation includes good, middle, and bad evaluations. Those information items need to be input by the viewers. The "action of viewer" includes information items regarding the fact that an image has been reproduced to the end, the fact that a video has been shifted to another video in the middle, and which video is viewed before another video is viewed, and those information items need to be input by viewers.
The recommendation technique is mainly divided into a "rule-based" system, a "content-based" system, and a "collaborative filtering" system.
The "rule-based" system means a technique in which a recommendation rule is predetermined, for example, "in a case of A, B is recommended". This technique uses the "tag information". Therefore, as information items to be used are increased, the maintenance and inputs for rule setting become troublesome. Further, in a case where no tag information can be obtained, it does not work well.
The "content-based" system means a technique of measuring similarity between videos, and recommending a similar video. In this technique, the "tag information" is used. Therefore, if tag information items between videos are not different from each other contents similar to each other may be recommended. Further, in a case where no tag information item can be obtained, it does not work well.
The "collaborative filtering" system means a technique of calculating similarity of preferences between users based on information items of "evaluation of viewer", "action history of viewer", and the like irrespective of the contents of the videos, and recommending a video, which the user has not viewed yet, taking a user having a high similarity in preference with respect to a target user for reference. Further, other than the user-based system of calculating the similarity of preferences between users, there has also been a content-based system of calculating the similarity between videos based on "evaluation of viewer" or "action history of viewer". Both methods as described above perform a recommendation based on part not associated with the contents of videos, and hence there is a possibility that surprising contents are recommended. In addition, in the above-mentioned methods, it is difficult to obtain a sufficient result if histories of users are not sufficiently accumulated.

Electronic apparatus, content recommendation method, and program therefor


A syringe (1) for mixing and ejecting an active pharmaceutical ingredient is disclosed. The syringe (1) comprises a syringe body (2) defining a first lumen (8), a first plunger (4) arranged movably in said first lumen (8), said first plunger (4) being hollow, thereby defining a second lumen (9) being separated from the first lumen (8), and a second plunger (5) arranged movably in said second lumen (9). A liquid diluent is contained in one of the first lumen (8) and the second lumen (9), and an active pharmaceutical ingredient is contained in the other of the first lumen (8) and the second lumen (9). The second plunger (5) is movable in such a manner that the active pharmaceutical ingredient and the liquid diluent are brought together, e.g. in the first lumen (8) or in the second lumen (9), thereby causing the active pharmaceutical ingredient to be diluted by the diluent, and the first plunger (4) and/or the second plunger (5) is/are movable in such a manner that diluted active pharmaceutical ingredient can be ejected from the syringe (1). The syringe (1) provides a single device for mixing and ejecting the active pharmaceutical ingredient. This reduces the risk of contamination, and the syringe (1) can be easily operated by an untrained user.

Previously, active pharmaceutical ingredient and diluent had to be provided in separate containers, and the contents of the separate containers needed to be brought together, e.g. in a vial or a syringe, in order to mix the contents prior to delivering the mixed drug. Thus, in prior art systems, the diluent, the active pharmaceutical ingredient and the mixing volume need to be kept under sterile conditions. Furthermore there is a risk that the active pharmaceutical ingredient and the diluent are not properly mixed.

Syringe for mixing and ejecting an active pharmaceutical ingredient


In a semiconductor memory device comprising a plurality of memory cells, a test request detection circuit responds to a voltage, on an input terminal, higher than a range of voltages supplied under ordinary operation condition for producing a test signal. Responsive to the test signal, data which has been supplied to the semiconductor memory device are simultaneously written into a plurality of memory cells, and data are simultaneously read from a plurality of memory cells, and judgement is made as to whether or not the data from the memory cells coincide with the data originally supplied to the semiconductor memory device.

The present invention relates to a semiconductor memory device incorporating a field effect transistor, and particularly to improvements in such a semiconductor memory for shortening the test time.
The storage capacity of semiconductor memory devices is making rapid progress: the capacity is quadrupled every 3 years or so. The time required for testing the operation of the memory device is increased with the increasing storage capacity.
A dynamic RAM of a 1 M words .times.1 bit configuration in which the addresses are duplexed and which has been placed on the market is shown in 1985 IEEE ISSCC, p. 238, "An 85 ns 1 Mb in a plastic DIP", Yasukazu Inoue, et al., and 1985 IEEE ISSCC, p. 240, "A 90 ns 1 Mb DRAM with Multi-Bit Test Mode", Masaki Kumanoya, et al. If, in this dynamic RAM, "0" data is written into all the memory cells and "0" data is read out of all the memory cells, and "1" data is written into all the memory cells and "1" data is read out of all the memory cells, and if the cycle time (the maximum pulse width of the RAS (row address strobe)signal) is 10 microsec., the test time T1 is given by the following equation (1): ##EQU1## With an ordinary dynamic RAM, the above-described test must be repeated for the maximum (5.5 V) and the minimum (4.5 V) voltages of the operating power source voltage range, and for the highest (70.degree. C.) and the lowest (0.degree. C.) temperatures of the operating temperature range. The total test time T2 will therefore be as follows: EQU T2=40 sec. .times.4=160 sec. . . . (2)
The test time given by the equation (2) is relatively long as a test time of an IC, and reduces the productivity.