The present invention provides a new method for preventing and controlling viral diseases in salmonid fish using Quillaja extracts, wherein said method comprises administering to salmonid fish an effective amount of a medicinal composition comprising a Quillaja saponaria extract as active ingredient.

Salmon farming industry has grown significantly worldwide in the last two decades; particularly in Chile this economic sector has become one of the most important for the country. However, different viral diseases infect fish and have a negative effect on production.
Among the viral diseases affecting fish, infectious pancreatic necrosis (IPN) is a highly contagious disease affecting farmed salmonids which causes high mortality rates in fry during their first feeding stage and in juveniles (smolts) after transfer to seawater. This disease is one of the most important diseases in Chile and is considered endemic in the country, causing great economic losses in the salmon industry (Tapia, losses D. et al. (2015). Diseases of Aquatic Organisms, 116 (3), 173-184). Its etiologic agent is the IPN virus (IPNv). Currently, the IPNv is one of the pathogens most frequently detected by diagnostic laboratories in marine and freshwater farms, and is the second leading cause of mortality in adult Atlantic salmon in fish farms in Chile (Sernapesca (2013). Informe sanitario de salmonicultura en centros marinos, 2012, Servicio Nacional de Pesca y Acuicultura. Valparaiso). However, the geographical distribution of this pathogen is not limited to Chile and it has been historically found in Norway (Diseases of Aquatic Organisms, 114 (3), 177-187 Jensen, B. et al. (2015)) and more recently in steelhead trout in South Africa (doctoral Dissertation Bragg, R R (2015). Isolation and Identification of Infectious Pancreatic Necrosis Virus from Rainbow trout (Salmo gairdneri Richardson) in South Africa), reaching a worldwide distribution. Given the negative impact on the health of fish caused by this virus, there is a constant need to seek alternatives for its control.
The virus that causes infectious pancreatic necrosis belongs to the Birnaviridae family and Aquabirnavirus genus, and it is characterized by having a non-enveloped capsid with a genome consisting of double stranded RNA. Clinical symptoms of infection include swelling of the abdomen and eyes, skin darkening, necrosis of the pancreatic tissue and spiral swim; which can cause death of fish. In the juvenile stage of freshwater, an outbreak of IPNv can cause 100% mortality. To prevent this viral agent various vaccination strategies have been provided, however, IPNv outbreak control depends on the biosafety of the farms and the level of resistance of fish (Robledo, D. et al. (2016). BMC Genomics, 17 (1), 1).
Another viral agent in the aquaculture industry is the infectious salmon anemia virus (ISA) which attacks mainly salmonids and can lead to high mortality rates in the population of affected fish, threatening the main areas of fish farming in the North Atlantic Ocean and in Chile. The ISA virus (ISAv) belongs to the Orthomyxoviridae family, Isavirus genus and has a single-stranded RNA genome with envelope (Vike, S. et al. (2014). Aquaculture, 420, 119-125). The virus inside the fish infects all organs but preferably the endothelium, causing bleeding, lethargy, abdominal distension and severe anemia in the affected fish. The mortality caused by this disease is high and few fish remain alive as carriers. In Chile, the first outbreaks occurred in mid-2007 and the solution was the elimination of all salmon infected.
To destroy cells infected with intracellular pathogens is critical that the vaccine or other non-antibiotic alternatives induce the cellular immune response. Currently, due to the nature of the virus, control using medicinal compounds is not effective or economically viable and prevention measures consist of maintaining a strong biosafety (imported egg control), use of vaccines and total elimination of sea-cages infected.
Multiple strategies to increase the resistance of fish to pathogens have been used in parallel with the development of vaccines. As an alternative, the administration of food for fish that improves health has been used. In this regard, diets rich with microalgae containing polyunsaturated fatty acids, glycans, carotenoids, among others have been used. These ingredients can promote fish welfare, improve intestinal health and increase resistance to disease (Kousoulaki, K. et al. (2015). Journal of Nutritional Science, 4, e24). Nevertheless, said compounds that do not induce a cellular mediated immune response (CIR), have a low efficacy in the control of viral diseases.
Therefore, there is a need for the development of non-antibiotic alternatives that induce both Cellular Mediated Immunity (CMI), and a Humoral Mediated Immunity (HMI) that can attack intracellular pathogens and eliminate infected cells (Munang'andu HM, Evensen Ø. (2019). Fish Shellfish Immunol 85, 132-140).
Quillaja saponaria Molina (common name Quillay) is a native tree of Chile primarily used as a soap substitute due to the presence of saponins (San Martin, R. (1999). Economic Botany, 53 (3), 302-311). Saponins can be obtained industrially as powder or liquid extracts, and may be in a purified state, partially purified or unpurified. These extracts are marketed by several companies, being one of the most important Natural Response and Desert King (San Martin, R. and Briones, R. (2000). Journal of the Science of Food and Agriculture, 80 (14), 2063-2068).
To date, the extracts rich in saponins are used as natural emulsifiers in cosmetics, food and beverages. Additionally, these are used as adjuvants for vaccine production and pharmaceutical formulations (Maier, C. et al. (2015). Journal of Agricultural and Food Chemistry, 63 (6), 1756-1762). Other uses have also been as a biocide to eliminate nematodes (US 2005/0074508 A1), mollusks (US 2007/0196517 A1) and fungi (Moya Elizondo, E. A. et al. (2010). Agro Sur, 38 (2), 87-96).
In the review of Wang, Y. et al. (2016), International Journal of Molecular Sciences, 17 (3), 325, describes the use of saponins in aquatic animals showing that these can modulate the immune system of shrimp and fish, and also promote the growth of the latter. However, the document states that most saponins are unstable in aqueous conditions and are very toxic to fish at high concentrations.
Prior art analysis regarding the application of Quillaja extracts in fish, showed patent application WO 2015/155293 A1 disclosing an oral food additive for use in the prevention and/or treatment of infections and particularly describes a composition comprising Quillaja saponaria saponins for prophylactic treatment of the ectoparasite copepod Caligus in fish. The experimental evidence provided by this document does not sustain the beneficial effect against other pathogens such as bacteria and virus that affect salmonid fish.
Zo Patent application WO 2015/179840 A1 describes combinations or compositions comprising Yucca schidigera and Quillaja saponaria, and further include antimicrobials, antibiotics and anticoccidial agents, for administration to animals to prevent diseases. As a general disclosure, it describes that can be applied to fish orally.
Patent WO 01/51083 A2 application discloses the adjuvant composition comprising a saponin and an oligonucleotide comprising at least one CpG unmethylated dinucleotide. Preferably, the composition includes saponins derived from Quillaja saponaria, and most preferably, the saponin is chemically modified or includes a substantially pure saponin (QS7, QS17, QS18 or QS21). No description is done for the use in fishes.
Chilean patent application CL 2942-2004 discloses a food additive fish formulated with purified extract of Quillaja saponaria Molina comprising 15-25% w/w of triterpene saponins obtained from the extract and 75-85% w/w of potato maltodextrin. This document discloses that the food additive improves the fish growth and feed conversion but does not mention that this food additive could be effective against pathogens such as virus and bacteria that affect salmonid fish.
The PhD thesis of Fernandes, R. N, (2014) Using Quillaia saponin (Quillaja saponaria Molina) em juvenis of pacu, Universidade Estadual Paulista, Faculty of Agricultural Sciences and Veterinary Center Aqüicultura, Brazil, describes a study wherein the effect of administering Quillaja saponins in doses from 100 to 400 mg/kg in pacu fish (Piaractus mesopotamicus). Following 15 days of feeding fish with Quillaja saponins, 325 fish were inoculated with Aeromonas hydrophila and clinical signs were observed. After seven days, the survival of pacu fish against experimental infection was higher in fish fed with Quillaja saponins in a dose of 200 mg/kg.
On the other hand, Vinay et al. (2014), Veterinary immunology and immunopathology, 158 (1), 73-85, describes an evaluation of the systemic effect of Quillaja saponins administered intraperitoneally as vaccine adjuvant in Paralichthys olivaceus. This study showed that saponins are good inducers of inflammation, but are also toxic to the fish. Saponins concentrations of 500, 160, 50, 16 and 5 μg/fish produced 95%, 65%, 20%, and 5% mortality rates, respectively, with a lethal dose (LD50) of 22.4 mg/kg. The results determined that the toxic effect of saponins depended on the level of purification and the source of the product. Finally, the authors found that a concentration of 3.4 mg/kg of fish is toxic when is administered intraperitoneally, and it is recommended to use a lower concentration in Paralichthys olivaceus.
Regarding disclosures of saponins from sources other than Quillaja saponaria, Krogdahl et al. (2015), Journal of Agricultural and Food Chemistry, 63 (15), 3887-3902 discloses that soybean saponins administered orally as feed additive in doses of 2-10 g/kg produced intestinal inflammation in Atlantic salmon (Salmo salar), and the severity is dose-dependent.
This analysis of prior art shows that, although Quillaja saponaria saponins have been described for various uses and applications, they are used mainly as adjuvants and they are not associated with treatment of viral infections in commercial fish.

Method for preventing and controlling viral infections in salmonid fish using


Vectors and methods are provided for introducing genetic material into cells of a chicken or other avian species. More particularly, vectors and methods are provided for transferring a transgene to an embryonic chicken cell, so as to create a transgenic hen wherein the transgene is expressed in the hen's oviduct and the transgene product is secreted in the hen's eggs and/or those of her offspring. In a preferred embodiment, the transgene product is secreted in the egg white.

Since the development of recombinant DNA technology some twenty-five years ago, the prospect of producing proteins on a large scale, rather than extracting them from tissue where they are naturally expressed, has become a reality. In particular, over the last two decades, progress in the development of expression vectors has led to the production of thousands of recombinant proteins on a laboratory scale. Production of commercial quantities of recombinant proteins requires often difficult and expensive scaling up procedures, but has nonetheless also been successful. In addition, transgenic animals including mice, rabbits, pigs, sheep, goats and cows have been engineered to produce human pharmaceuticals in their tissues or secretions. Houdebine, L. M., J. Biotechnology 34:269-287 (1994).
Although egg white is thought to be an excellent host for recombinant protein production, preparing transgenic avians has proven to be technically difficult due in large part to problems involved in manipulating the chicken embryo. When oviposition occurs, the embryo has already reached a stage corresponding to a mammalian late blastula or early gastrula. Genetic manipulation of the embryo during earlier development requires reintroduction to the female or in vitro culture, both difficult procedures. Houdebine, L. M., J. Biotechnology 34:269-287 (1994). Despite these difficulties, transgenic chickens have been produced that are resistant to infection by avian leukosis (Crittenden and Salter, "Transgenic Livestock Models In Medicine And Agriculture" pp. 73-87 (Wiley-Liss (1990))), or have high levels of circulating growth hormone. Bosselman, R. A., et al., Science 243:533-535 (1989).
Four general methods for generating transgenic avians have been reported. One method involves excision of a developing egg from the oviduct, microinjection of DNA near the blastoderm, and in vitro culture of the manipulated embryo in solution and surrogate shells. Love, J., et al., Biotechnology 12:60-63 (1994). A second method requires the culture and transfection of primordial germ cells, with subsequent transplantation into an irradiated recipient near the same stage of development as the donor. Carsience et al., Development 117:669-675 (1993); Etches et al., Poultry Science 72:882-889 (1993). Although technically very demanding, these two approaches are attractive because large pieces of DNA can be transferred.
A third method involves blind injection of replication competent retrovirus with a needle near the blastoderm of a newly laid egg. Petropoulos, C. J., et al., J. Virol. 65:3728-3737 (1991). Although this method is the simplest, it is also limited in that the DNA to be transferred must be approximately 2 kb or less in size and, the method results in viremic hens which shed infective recombinant retrovirus. Petropoulos, C. J., et al., J. Virol. 66(6):3391-3397 (1992).
The fourth method involves a replication-defective retroviral vector system (see, e.g., U.S. Pat. Nos. 5,162,215 and 4,650,764, hereby incorporated by reference). One of these systems (Watanabe and Temin, Mol. Cell. Biol. 3(12):2241-2249 (1983)) has been derived from the reticuloendotheliosis virus type A (REV-A). Sevoian et al., Avian Dis. 8:336-347 (1964). Replication-defective retroviral vectors derived from the REV-A virus are based on the helper cell line C3 (Watanabe and Temin, Mol. Cell. Biol. 3(12):2241-2249 (1983)) which contains the components of a packaging defective helper provirus. The derivation of the C3 helping line and several replication-defective retroviral vectors have been described in detail in U.S. Pat. No. 4,650,764 and Watanabe and Temin, Mol. Cell Biol. 3(12):2241-2249 (1983). This method is more technically demanding than the replication competent technique in that the blastoderm must be exposed, and microinjection equipment must be used. Bosselman, R. A., et al., Science 243:533-535 (1989). Nonetheless, it results in transgenic hens free of replication competent retrovirus, and can transfer DNA as large as 8 kb in size.
Tissue specific expression of a foreign gene in a transgenic chicken was achieved using the replication competent retrovirus technique. Petropoulos, C. J., et al., J. Virol. 66(6):3391-3397 (1992). A replication competent retrovirus was used to deliver the reporter gene chloramphenicol acetyl transferase (CAT), driven by a muscle specific promoter, a action, to skeletal muscle. Tissue specific expression of a recombinant protein in the egg of a transgenic avian has not yet been successful.
It would thus be desirable to provide a vehicle and method for transferring a gene to an embryonic chicken cell (or other avian species) so as to create a transgenic hen wherein the gene is expressed in a tissue specific manner. It would also be desirable to provide a vehicle and method for transferring a gene to an embryonic chicken cell, wherein the gene is expressed in the hen's oviduct and secretion of the gene product is in the hen's eggs. It would also be desirable to provide a vehicle and method for transferring a gene to an embryonic chicken cell, wherein the gene is expressed in the hen's oviduct and secretion of the gene product is in the hen's eggs without compromise to the hen's health and the health of other birds in contact with her.

Retroviral vector having an ovalbumin promoter

Board of Trustees Operating Michigan State University


A method and system for acquiring and transforming existing news content for display on multiple platforms and architectures. In one embodiment, capture templates are created to harvest the news content from disparate content sources on multiple platforms. The news data is extracted from the content sources using the created capture templates and a normalized data stream is generated therefrom. The normalized data stream is provided for display on the different type of platforms and may be cached for later transmission upon request.

In the above-cited U.S. patent application Ser. No. 09/841,017, a method and system for acquiring and transforming existing content (e.g., Hyper Text Markup Language (HTML) content) for display and execution on multiple platforms and architectures were disclosed. In one embodiment, capture templates were created to harvest content from disparate content sources on multiple platforms. Data was then extracted from the disparate content sources using the created capture templates and a standardized data stream was generated from the extracted data. The standardized data stream was ultimately provided for display on one or more different type of platforms, such as a television set. These processes were enabled through the use of a syndication server more fully described in the '017 application.
For those readers not familiar with the '017 applications, syndication is a process of gathering information from a range of sources and repackaging the information for access and display at a destination. Syndication is popular with interactive television (iTV) environments, in which a viewer can interact with a broadcast or service being provided on the TV. The '017 application described in detail how to syndicate many types of content, and in particular HTML content, for such iTV applications.
HTML is not, however, the only form of content accessible to Internet users. Another popular form of content is news data, often formatted according to the so-called network news transport protocol (NNTP). In the past, NNTP data was received directly from a news-(NNTP-) based source and presented to the user directly through Java Server Pages/Servlets. Manipulation of data into a preferred display format was implemented on a page-by-page basis through hand coding.
Because multiple person teams (as opposed to just individuals) typically create software applications, this structure for obtaining NNTP data in preferred formats increases the possibility for inserting individualized (non-standard) coding techniques and duplication of code. This leads to issues with product supportability, scalability and maintainability. In addition, individualized application architectures make various processing tasks, such as error handling, much more difficult as new error handling processes would need to be implemented across each application instantiation.
Thus,                a. Prior approaches that address the gathering and provision of news content consist of custom-written programs or scripts to integrate news feeds from outside news (NNTP) sources.        b. These approaches use one program or script for each page to acquire and convert the content and assets and require programmer-level knowledge to perform the conversions.        c. These prior approaches are not designed to be a holistic system—rather, they provide a problem solution on a page-by-page basis.

This patent is subject to a terminal disclaimer.


A wire-wound inductor includes a dielectric core, terminals including wire staples that are crimped around the core, and a wire winding disposed about the perimeter of the core and connected to the terminals. A coating such as an adhesive coating is disposed over the wire winding and between the terminals. The process for manufacturing the inductors in a continuous process. Beginning with a spooled material, which may be extruded, inductors are formed on a core material sequentially. The inductors are not physically separated until the final stages of manufacturing, which is in contrast to the prior art method in which each inductor is individually constructed on an individual core that has been manufactured with tight tolerances and wound individually. By virtue of the characteristics of the inductor components, extremely tight tolerances (typically about 0.0005") can be obtained, resulting in highly controlled inductance values.

The present invention relates to wire wound inductors and, in particular, to wire wound inductors utilizing an extruded core material along with simplified terminal attachment and wire windings in order to reduce inductor manufacturing costs.
Inductors form an integral component of radio frequency (RF) circuits. As a group, inductors form about 1/3 of the basic building blocks for circuit design.
The basic form of inductors is a wire coil. The coil can be free-standing (air-core) or wrapped around a core. Other versions of inductors (such as multi-layer or printed design) are known; however, superior performance is achieved from a coil. With the advent of surface-mount technologies for high-speed manufacturing of printed circuit boards, the size of inductors has greatly decreased. Surface-mounted, wire-wound inductors are currently available in industry standard 0805 and 0603 size packages. These inductors consist of a molded core material (either a thermoset plastic or a ceramic) with wire windings and plated terminals.
The electrical measurement unit for inductance is Henries. To the first order approximation, the inductance value of a wire coil is L=(4 .pi.N.sup.2 A/W).times.10.sup.-9 Henries, where N is the number of turns in the coil, A is the cross sectional area of the coil, and W is the length of the coil. All three variables (N, A, and W) are independent such that they can be independently varied to obtain a desired inductance value L.
Inductors are currently manufactured one at a time with the wire ends of the windings being bonded while the inductor is in the winding fixture. This method is time consuming, resulting in increased manufacturing costs and can result in less than desirable tolerance deviations. In addition, conventional inductors utilize core materials that cannot be extruded in large quantities and thus cannot take advantage of a continuous process. Moreover, the conventional core materials are difficult to machine, and as a result, the cross sectional area of the coil can be difficult to determine accurately. Still further, terminals in the conventional inductors are coplanar (i.e., on the same side of the inductor), and the wire windings begin and terminate on the same side (typically the bottom) of the device. As a result, only integer multiples of windings are possible (N in the above equation for Henries). In turn, this limits the number of inductance values (L in the above equation) obtainable for a given core size. Still further, an adhesive coating (particularly a UV or heat cured plastic) is added to wire wound surface-mountable inductors in order to secure the wire windings and to provide a smooth, uniform surface for automated placement devices. Since the coating material can run over the edges of the device, an external mold may be required to provide a uniform surface.


The disclosure provides a method, device and system for teleconference information insertion. The method includes: a valid insertion content is acquired according to a stored insertion content after an conference insertion request is detected, and a real-time content of a conference is switched to the valid insertion content. Thus, a purpose of information insertion in a conference is achieved by pre-storing an insertion content before or during the conference, then acquiring a valid insertion content according to the stored insertion content after a conference insertion request is detected during the conference and finally switching the real-time content of the conference to the insertion content, thereby enhancing the effect of the conference.

With continuous and rapid construction of information communication networks in China, the communication level of China has been greatly improved to provide reliable guarantee for information exchange of every walk of life. Among numerous communication services, teleconference, especially a video conference service has shown more and more a good growth momentum. A video conference is a multimedia communication method for conferencing through a communication network by using video technology and devices. A video conference system joins conference terminals of multiple locales in a conference through a Multipoint Control Unit (MCU) so as to implement communication among a plurality of conference terminals. During the video conference, representatives at two or more different locations may hear voices from each other and see images of each other, and may also simultaneously see a scene of a conference room of each other as well as an object, a picture, a table, a file and so on presented in the conference, thus "shortening" a distance between representatives and enhancing the effect of the conference so that everybody are just like participating in the conference in the same place, and working efficiency is improved significantly.
However, information insertion may be required during the conference in practical application of a teleconference system. For example, a certain conferee wants to insert a piece of audio or video information into the conference so that the audio or video information may be presented to other conferees, or the certain conferee who cannot attend the conference pre-records a speech video or audio and it is expected that a speech content is inserted and presented to other conferees during the conference. However, a current video system still cannot satisfy such a requirement, thus the effect of the conference is influenced.

Method, device and system for teleconference information insertion


Disclosed is a diagnostic apparatus for estimating an active Heliobacter pylori infectious agent in saliva, comprising in combination an immunoassay chamber in which a first portion of said saliva is subjected to serological test for antibody to said infectious agent and a chemical reaction chamber in which a second portion of said saliva is subjected to chemical analysis for an ammonia constituent thereof.

1. Field of the Invention
The invention relates generally to methods and devices used for determination of analytes in saliva or other body fluid, and in particular, pertains to an integrated device and method to carry out chemical and immunochemical analysis simultaneously and including a sensor strip for determination of ammonia.
2. Description of the Related Art
Helicobacter pylori (formerly called Campylobacter pylori) was first isolated by Warnell and Shall in 1983 (Marshall B. J., Warren J. R., Lancet 1984:1:1311-5). H. pylori is the most widespread bacteria infection with an estimated worldwide prevalence of 50% (Marshall B. J., Epidemiology of H. pylori in Western countries. In: Hunt R. H., Tytgat G. N. J., eds. Helicobacter pylori: Basic Mechanisms to Clinical Cure. Dordrecht: Kluwer Academic Publishers. 1994:75-84; Hazell S. L., H. pylori in developing countries. In: Hunt R. H. Tytgat G. N. J., eds. Helicobacter pylori: Basic Mechanisms to Clinical Cure, Dordrecht: Kluwer Academic Publishers, 1994:85-94). H. pylori is a very important pathogen in several diseases of the stomach and duodenum. H. pylori is associated with type B gastritis, duodenal ulcer, gastric ulcer, and gastric cancer.
A variety of methods has been developed for diagnosis of H. pylori infection and evaluation of eradication of H. pylori following antibacterial treatment.
U.S. Pat. No. 5,498,528 teaches a method for detection of H. pylori strain comprising the steps of contacting a saliva sample suspected of containing H. pylori directly with a urea containing medium selective for growth of H. pylori and having a pH of about 5.5 to 7.5, and incubating the sample for a time sufficient for detection of H. pylori growth in at least 80% of true positive samples. The method is based on hydrolysis of urea contained in the growth medium by urease enzyme produced by H. pylori and detection of a hydrolysis product by release of a radioactive label from urease or by a color change resulting from action on a pH indicator. The time required to obtain a result by the method disclosed is a function of temperature, approximately 2-3 days when incubated at 23-25.degree. C. and 4-6 hours when incubated at 35-37.degree. C.
U.S. Pat. No. 5,479,935 teaches an ambulatory system for recording and analyzing gastroesophageal reflux. The system comprises a digital recorder, an analysis software package and a catheter for measurement of changes in esophageal impedance. Gastroesophageal reflux can be detected with a pH above 4. The invention allows for recording and analysis of reflux on a non-invasive basis, by using pairs of externally worn impedance sensors. Other bio-parameters, such as pH or pressure can be measured simultaneously with impedance measurement.
U.S. Pat. No. 5,477,854 teaches a system and a method for monitoring intragastrointestinal concentrations of ammonium during prolonged periods, as an indicator of the presence and activity of an intragastrointestinal H. pylori infection. The system may be used in the evaluation of treatments for H. pylori infection in the patient.
U.S. Pat. No. 5,439,801 teaches an improved test for the detection of the presence of urease associated with H. pylori in a biopsy specimen. The hydrolysis of urea by urease is detected by a combination of at least two dye indicators showing a color change. Most positive results occur in 2-10 minutes and all occur in no more than four hours.
U.S. Pat. No. 5,438,985 teaches a method and a system for ambulatory recording of the pH and the presence of various materials in compartments of the gastro-intestinal tract. The invention also reports the pH pattern in relation to the prevalence of the materials, and analysis to which degree such materials are in active or inactive states in their normal or foreign compartments. This is useful in situations, for example, when duodenal material is refluxed into the stomach and esophagus. The invention involves a gastrointestinal catheter with a pH sensor and a combined light absorption and fluorescence sensor, a signal recorder and processor, and a written report producer.
U.S. Pat. No. 5,420,016 and U.S. Pat. No. 5,314,804 teach a rapid method for determining the presence of H. pylori in a biological tissue specimen by detecting the presence of urease in the tissue. The system employs a multilayer test device for the detection of ammonia generated from urea at the presence of urease in the specimen.
U.S. Pat. No. 5,420,014 teaches a method of detecting contemporary infection by H. pylori in a mammal. The method is based on the formation of complex between a specific IgG antibody in said mucous secretion and an antigen component from H. pylori. The antigen component is immobilized onto a solid support.
U.S. Pat. No. 5,262,156 teaches an assay for detecting H. pylori. The assay involves an ELISA for urine samples, and includes a kit wherein the antigenic composition is immobilized on a solid support.
U.S. Pat. No. 4,947,861 teaches a non-invasive method for detection of C. pylori. A breath sample is collected from a patient ten minutes after the patient ingests a quantity of urea. The sample is dehydrated by passing through a solid-state body of alkaline hygrosopic material and analyzed for ammonia. The presence of ammonia indicates presence of C. pylori in the stomach.
U.S. Pat. No. 4,882,271 teaches a method for the serological detection of C. pylori. An antigen for the detection of C. pylori infections is purified from C. pylori. The antigen can be used in a variety of assays including radioimmunoassay, ELISA, latex agglutination, complement fixation, and indirect hemagglutination.
The urea breath test based on the extremely high endogenous urea activity of H. pylori is a reliable and non-invasive method with high sensitivity and specificity suitable for diagnosis and evaluation tests; however, the application of the urea breath test is restricted by high cost in isotope-labeled material, time, expensive equipment, and undesirable radioactive exposure to C.sup.14.
Against this background there remains a need for a method of diagnosing C. pylori that is rapid, non-invasive, and able to distinguish infection in an active state from dormant or non-living residues.

Estimation of active infection by heliobacter pylori

Americare International Diagnostics, Inc.


A correction curve (FIG. 19) is prepared by plotting .sup.12 CO.sub.2 concentrations and .sup.13 CO.sub.2 /.sup.12 CO.sub.2 concentration ratios which are determined on the basis of a calibration curve and .sup.13 CO.sub.2 and .sup.12 CO.sub.2 absorbances of gaseous samples having the same .sup.13 CO.sub.2 /.sup.12 CO.sub.2 concentration ratio but known different .sup.12 CO.sub.2 concentrations. A gaseous test sample containing .sup.13 CO.sub.2 and .sup.12 CO.sub.2 as component gases is introduced into a cell, and spectrometrically measured. A .sup.12 CO.sub.2 concentration of the gaseous test sample is determined by way of the spectrometric measurement. A concentration ratio correction value is obtained on the basis of the correction curve and the .sup.12 CO.sub.2 concentration of the gaseous test sample thus determined. A measured .sup.13 CO.sub.2 /.sup.12 CO.sub.2 concentration ratio is divided by the concentration ratio correction value thus obtained for correction of the .sup.13 CO.sub.2 /.sup.12 CO.sub.2 concentration ratio. Thus, the measurement accuracy of the concentration ratios of the component gases can be improved. A breath sampling bag and gas measuring system is also disclosed where each is configured such that breath inlets of the gas measuring apparatus are prevented from being respectively connected to the wrong breath introduction pipes of the breath sampling bag.

Isotopic analyses are useful for diagnosis of a disease in a medical application, in which metabolic functions of a living body can be determined by measuring a change in the concentration or concentration ratio of an isotope after administration of a drug containing the isotope. In the other fields, the isotopic analyses are used for studies of the photosynthesis and metabolism of plants, and for ecological tracing in a geochemical application.
It is generally known that gastric ulcer and gastritis are caused by bacteria called helicobacter pylori (HP) as well as by a stress. If the HP is present in the stomach of a patient, an antibiotic or the like should be administered to the patient for bacteria removal treatment. Therefore, it is indispensable to check if the patient has the HP. The HP has a strong urease activity for decomposing urea into carbon dioxide and ammonia.
Carbon has isotopes having mass numbers of 12, 13 and 14, among which .sup.13 C having a mass number of 13 is easy to handle because of its non-radioactivity and stability.
If the concentration of .sup.13 CO.sub.2 (a final metabolic product) or the concentration ratio of .sup.13 CO.sub.2 to .sup.12 CO.sub.2 in breath of a patient is successfully measured after urea labeled with the isotope .sup.13 C is administered to the patient, the presence of the HP can be confirmed.
However, the concentration ratio of .sup.13 CO.sub.2 to .sup.12 CO.sub.2 in naturally occurring carbon dioxide is 1:100. Therefore, it is difficult to determine the concentration ratio in the breath of the patient with high accuracy.
There have been known methods for determining the concentration ratio of .sup.13 CO.sub.2 to .sup.12 CO.sub.2 by means of infrared spectroscopy (see JPB 61(1986)-42219 and JPB 61(1986)-42220).
In the method disclosed in JPB 61(1986)-42220, two cells respectively having a long path and a short path are provided, the path lengths of which are adjusted such that the light absorption by .sup.13 CO.sub.2 in one cell is equal to the light absorption by .sup.12 CO.sub.2 in the other cell. Light beams transmitted through the two cells are lead to spectrometric means, in which the light intensities are measured at wavelengths each providing the maximum sensitivity. In accordance with this method, the light absorption ratio can be adjusted to "1" for the concentration ratio of .sup.13 CO.sub.2 to .sup.12 CO.sub.2 in naturally occurring carbon dioxide. If the concentration ratio is changed, the light absorption ratio also changes by the amount of a change in the concentration ratio. Thus, the change in the concentration ratio can be determined by measuring a change in the light absorption ratio.
(A) However, the method for determining the concentration ratio according to the aforesaid document suffers from the following drawbacks.
Calibration curves for determining the concentrations of .sup.12 CO.sub.2 should be prepared by using gaseous samples each having a known .sup.12 CO.sub.2 concentration.
To prepare the calibration curve for the .sup.12 CO.sub.2 concentration, the .sup.12 CO.sub.2 absorbances are measured for different .sup.12 CO.sub.2 concentrations. The .sup.12 CO.sub.2 concentrations and the .sup.12 CO.sub.2 absorbances are plotted as abscissa and ordinate, respectively, and the calibration curve is determined by the method of least squares.
The calibration curve for the .sup.13 CO.sub.2 concentration is prepared in the same manner as described above.
For determination of the concentrations by means of infrared spectroscopy, the preparation of the calibration curves is based on an assumption that the relation between the concentration and the absorbance conforms to the Lambert-Beer Law. However, the Lambert-Beer Law itself is an approximate expression. The actual relation between the concentration and the absorbance does not always conform to the Lambert-Beer Law. Therefore, all the plotted data do not perfectly fit to the calibration curve.
FIG. 1 is a graphical representation in which concentration ratios of .sup.13 CO.sub.2 to .sup.12 CO.sub.2 are plotted with respect to .sup.12 CO.sub.2 concentrations, the .sup.12 CO.sub.2 concentrations and the .sup.13 CO.sub.2 concentrations having been determined by using calibration curves prepared on the basis of measurements of the absorbances of gaseous samples having the same concentration ratio (.sup.13 CO.sub.2 concentration/.sup.12 CO.sub.2 concentration=1.077%) but different .sup.12 CO.sub.2 concentrations.
As shown in FIG. 1, the concentration ratios determined for different .sup.12 CO.sub.2 concentrations deviate from the actual concentration ratio (1.077%), and form an undulatory curve when plotted.
Although the cause of the deviation has not been elucidated yet, the deviation supposedly results from changes in the spectroscopic characteristics such as reflectance, refractive index and stray light in dependence on the .sup.12 CO.sub.2 concentration and from the error characteristics of the least square method employed for the preparation of the calibration curves.
If the concentration of a component gas is determined without correction of the characteristics associated with the deviation, a critical error may result.
(B) A variety of experiments have revealed that, where the infrared spectrometry is employed to measure the concentration of .sup.13 CO.sub.2 or the concentration ratio of .sup.13 CO.sub.2 to .sup.12 CO.sub.2 (hereinafter referred to as ".sup.13 CO.sub.2 concentration ratio"), measurement results differ from the actual .sup.13 CO.sub.2 concentration or .sup.13 CO.sub.2 concentration ratio depending on the concentration of oxygen contained in a gaseous sample.
FIG. 2 is a graphical representation in which .sup.13 CO.sub.2 concentration ratios are plotted with respect to oxygen contents, the .sup.13 CO.sub.2 concentration ratios having been determined by measuring gaseous samples containing .sup.13 CO.sub.2 diluted with oxygen and nitrogen and having the same .sup.13 CO.sub.2 concentration but different oxygen concentrations. The determined .sup.13 CO.sub.2 concentration ratios are normalized on the basis of a .sup.13 CO.sub.2 concentration ratio for an oxygen content of 0%.
As shown in FIG. 2, the .sup.13 CO.sub.2 concentration ratio is not constant but varies depending on the oxygen concentration.
If the .sup.13 CO.sub.2 concentration or the .sup.13 CO.sub.2 concentration ratio of a gaseous sample containing oxygen is measured in ignorance of this fact, it is obvious that a measurement differs from an actual value.
FIG. 3 is a graphical representation illustrating the result of measurement in which gaseous samples having different .sup.13 CO.sub.2 concentration ratios and containing no oxygen were measured. In FIG. 3, the actual .sup.13 CO.sub.2 concentration ratios and the measured .sup.13 CO.sub.2 concentration ratios are plotted as abscissa and ordinate, respectively. The .sup.13 CO.sub.2 concentration ratios are normalized on the basis of the minimum .sup.13 CO.sub.2 concentration ratio.
FIG. 4 is a graphical representation illustrating the result of measurement in which gaseous samples having different .sup.13 CO.sub.2 concentration ratios and containing various concentration of oxygen (up to 90%) were measured. In FIG. 4, the actual .sup.13 CO.sub.2 concentration ratios and the measured .sup.13 CO.sub.2 concentration ratios are plotted as abscissa and ordinate, respectively. The .sup.13 CO.sub.2 concentration ratios are normalized on the basis of the minimum .sup.13 CO.sub.2 concentration ratio.
A comparison between the results shown in FIGS. 3 and 4 indicates that the relationship between the actual .sup.13 CO.sub.2 concentration ratio and the measured .sup.13 CO.sub.2 concentration ratio in FIG. 3 is about 1:1 (or the scope of the fitting curve in FIG. 3 is about 1) while the relationship between the actual .sup.13 CO.sub.2 concentration ratio and the measured .sup.13 CO.sub.2 concentration ratio in FIG. 4 is about 1:0.3 (or the scope of the linear fitting curve in FIG. 4 is about 0.3).
Thus, the measurement of the .sup.13 CO.sub.2 concentration or the .sup.13 CO.sub.2 concentration ratio is influenced by the concentration of oxygen contained in a gaseous sample, the cause of which has not been elucidated yet.
If the concentration or concentration ratio of a component gas is determined without performing a correction in consideration of the oxygen concentration, it is predicted that a critical error may result.
(C) Since the concentration of CO.sub.2, particularly, the concentration of .sup.13 CO.sub.2 is extremely low, highly sensitive measurement is required. When the sensitivity of measurement is increased, a measured light intensity is responsive to changes in parameters of the measurement system, e.g., the light intensity of a light source, the temperature of a sample gas, the temperature of a cell to which the gas is introduced, the sensitivity of a photodetector and the like. Thus, the measured value may have an error caused by factors not related to the sample gas.
To solve this problem, the measurement is started after the measurement system is stabilized in a time-consuming manner. This reduces the operation efficiency and makes it impossible to meet a user demand to measure a large amount of samples in a short time.
For measurement of one breath sample, the .sup.12 CO.sub.2 absorbance is measured and the .sup.12 CO.sub.2 concentration is determined on the basis of a calibration curve for .sup.12 CO.sub.2. The .sup.13 CO.sub.2 absorbance is measured and the .sup.13 CO.sub.2 concentration is calculated on the basis of a calibration curve for .sup.13 CO.sub.2, as well. The measurement of another breath sample is carried out in the same manner.
If the CO.sub.2 concentrations of the aforesaid two breath samples are at substantially the same level, the ranges of the calibration curves for .sup.12 CO.sub.2 and .sup.13 CO.sub.2 to be used for the concentration determination can be limited. Thus, the measurement accuracy can be increased by using limited ranges of the calibration curves.
(D) In a conventional infrared spectrometric method as described above, a bag containing a gaseous sample is connected to a predetermined pipe of a spectrometric apparatus, and the gaseous sample is introduced into a cell through the pipe by manually compressing the bag.
However, even small turbulence may drastically reduce the measurement accuracy because the absorbance of .sup.13 CO.sub.2 present in a trace amount is measured in the isotopic gas analysis. The gaseous sample cannot be passed through the cell at a constant flow rate by the manual compression of the bag. This generates a nonuniform flow of the gaseous sample in the cell and causes the gaseous sample to have a local temperature change and an incidental concentration change, thereby fluctuating a light detection signal.
The flow rate of the gaseous sample may be controlled to be constant by using a pump and a flow meter in combination. However, the accuracy of the flow control cannot be ensured, because the volume of the bag containing the gaseous sample is small and the flow rate is low. Alternatively, an apparatus called mass flow meter for electronic flow control may be employed as flow control means. This improves the accuracy of the flow rate control, but results in a complicated apparatus and an increased cost.
(E) In the method disclosed in JPB 61(1986)-42220, the length of the cell is reduced and, therefore, a cell-absent space is filled with air. The air space hinders highly accurate measurement. If the lengths of paths between the light source and the cell and between the cell and the photoreceptor are increased, highly accurate measurement may be hindered.
More specifically, since the absorbance of .sup.13 CO.sub.2 present in a trace amount is measured in the isotopic gas measurement, even a small external disturbance reduces the measurement accuracy. A few percentage of .sup.12 CO.sub.2 and a trace amount of .sup.13 CO.sub.2 are present in the aforesaid air space and spaces between the light source and the cell and between the cell and the photoreceptor. A .sup.13 CO.sub.2 spectrum partially overlaps a .sup.12 CO.sub.2 spectrum and, if a filter is used, the band-pass width thereof influences the measurement. Therefore, the presence of .sup.12 CO.sub.2 indirectly influences the measurement of the .sup.13 CO.sub.2 absorbance, and the trace amount of .sup.13 CO.sub.2 directly influences the measurement of the .sup.13 CO.sub.2 absorbance.
To eliminate the influence of CO.sub.2 present in a light path, an apparatus (see JPB 3(1991)-31218) has been proposed in which a light source, a sample cell, a reference cell, a interference filter, a detection element and like elements are accommodated in a sealed case which is connected to a column filled with a CO.sub.2 absorbent through a tube and a circulation pump for circulating air within the sealed case and the column to remove CO.sub.2 from the air in the sealed case.
The apparatus disclosed in this document can remove CO.sub.2 which may adversely affect the measurement, but requires the column filled with the CO.sub.2 absorbent, the tube and a large sealed case for accommodating the respective elements, resulting in a large-scale construction. In addition, the fabrication of the apparatus requires a laborious process such as for sealing the large case.
Further, a nonuniform flow of the air within the sealed case causes a local temperature change and an incidental concentration change, thereby causing a light detection signal to be fluctuated.
(F) In the infrared spectroscopic measurement, breath is sampled in breath sampling bags before and after a diagnostic drug is administered to a living body, and the breath samples in the breath sampling bags are respectively measured for determination of the .sup.13 CO.sub.2 concentration or the .sup.13 CO.sub.2 concentration ratio.
The measurement of such breath samples is typically performed in a professional manner in a measurement organization, which manipulates a large amount of samples in a short time. Therefore, breath samples obtained before and after the drug administration are often mistakenly manipulated.
More specifically, breath samples obtained from one patient before and after the drug administration are mistaken for those obtained from another patient, or a breath sample obtained before the drug administration is mistaken for that obtained after the drug administration.
Such mistakes lead to erroneous measurement results and, therefore, should be assuredly prevented.
Further, if a breath sample includes a gas remaining in the oral cavity of a patient, the measurement accuracy is reduced. To reduce a measurement error, breath from the lung of the patient should be sampled.
Still further, since moisture in a breath sample adversely affects the optical measurement, the moisture should be removed from the breath sample. Furthermore, a consideration should be given to the breath sampling bag to prevent the breath sample from escaping from the bag.
It is an object of the present invention to provide a method for spectrometrically measuring an isotopic gas, which is employed to precisely determine the concentration or concentration ratio of a component gas in a gaseous test sample containing a plurality of component gases by way of spectrometry when the gaseous test sample is introduced into a cell.
It is another object of the present invention to provide a method for spectrometrically measuring an isotopic gas, which is employed to precisely determine the concentration of a component gas in a gaseous test sample containing a plurality of component gases by way of spectrometry by using a limited range of a calibration curve when the gaseous test sample is introduced into a cell.
It is further another object of the present invention to provide a method for spectrometrically measuring an isotopic gas, which is employed to precisely determine the concentration or concentration ratio of .sup.13 CO.sub.2 contained in a gaseous test sample by way of spectrometry in consideration of the concentration of oxygen when the gaseous test sample into a cell.
It is still another object of the present invention to provide a method for spectrometrically measuring an isotopic gas, which is employed to precisely determine the concentration or concentration ratio of a component gas in a gaseous test sample containing a plurality of component gases by way of spectrometry in such a manner that time-related influences on a measurement system can be minimized when the gaseous test sample is introduced into a cell.
It is yet another object of the present invention to provide an apparatus for spectrometrically measuring an isotopic gas, which has a simple construction and is capable of introducing a gaseous test sample containing a plurality of component gases at a constant flow rate for spectrometry.
It is still another object of the present invention to provide a breath sampling bag, which is given a consideration to assuredly prevent a breath sample from being mistakenly manipulated.
It is yet another object of the present invention to provide a breath sampling bag, which prevents the sampling of air present in the oral cavity of a patient but allows the sampling of breath from the lung of the patient.
It is still another object of the present invention to provide a breath sampling bag, which is capable of removing moisture from breath blown therein.
It is yet another object of the present invention to provide a breath sampling bag, which has a construction to prevent a breath sample from being escaped therefrom.

Apparatus and breathing bag for spectrometrically measuring isotopic gas


A hand held musical instrument is capable of emitting sound through the combination of three elements: a hollow tube, a striking member, and a hinge to secure the striking member to the tube. The hollow tube is constructed of an ergonomic shape that allows easy and fatigue-free grasping. For low notes, the slots on the resonating end of the hollow tube are multi-sized to eliminate buzzing. The clapper is attached to the hollow tube through a combination of a stainless steel axle, polymer bearings and adjustable tensioning screws. This combination improves the durability of the instrument yet still allows the musician to adjust the strike feel. The invention also provides improvements in the clapper heads for both low note and middle and high note handchimes. For low notes, the clapper head is constructed of multiple layers that optimize sound quality. For middle or high notes, the rubber clapper head provides multiple settings which allows the musician to easily and precisely adjust the timbre setting.

The prior art discloses many inventions that cause sound to be emitted by striking a hammer, knocker, clapper, or similar means against a tube, triangle or other object. These devices can be differentiated by, but are not limited to, the sounds that they emit, the striking means itself, the object being struck, the method of attaching the striking means to the device, or the method of playing the device.
Handchimes vibrate in an infinite number of ways, or modes, when struck by a clapper. Only a few of these modes cause the surrounding air to vibrate at a frequency strong enough to be audible to the human ear. The lowest frequency vibration, or the lowest pitch, is called the fundamental. The clapper of a handchime drives the generated frequencies.
Like handbells, handchimes are typically sold in octave or multi-octave sets. A handchime, like a handbell, is individually tuned to emit a particular note. Handbells are tuned by removing metal from their inner diameter. Handchimes are tuned by adjusting the length and/or width of their slots.
The handchimes within an octave set vary in cross sectional area depending upon the note the chime will emit. Larger cross-sectional areas are used for lower octave or lower note handchimes. For example, a three octave or 37 note set of handchimes may utilize three different cross-sectional areas. Therefore, in a typical three octave set, 13 notes, which include C4, C.music-sharp.4/D.music-flat.4, D4, D.music-sharp.4/E.music-flat.4, E4, F4, F.music-sharp.4/G.music-flat.4, G4, G.music-sharp.4/A.music-flat.4, A4, A.music-sharp.4/B.music-flat.4, B4, and C5, are considered lower note or larger cross-section handchimes. The balance of the typical three octave set or the remaining 24 notes, C.music-sharp.5/D.music-flat.5, D5, D.music-sharp.5/E.music-flat.5, E5, F5, F.music-sharp.5/G.music-flat.5, G5, G.music-sharp.5/A.music-flat.5, A5, A.music-sharp.5/B.music-flat.5, B5, C6, C.music-sharp.6/D.music-flat.6, D6, D.music-sharp.6/E.music-flat.6, E6, F6, F.music-sharp.6/G.music-flat.6, G6, G.music-sharp.6/A.music-flat.6, A6, A.music-sharp.6/B.music-flat.6, B6 and C7 are considered smaller cross-section handchimes and emit middle or higher pitched notes. The cross sectional areas of the handchimes will change with respect to each other as a three octave set is expanded to 4, 5 or 6 octaves.
Few of the devices disclosed in the prior art allow control over the musical tones that are produced. Ease of playing or the economical manufacture of the device is at the sacrifice of the overall musical quality of the instrument. Lastly, in the devices disclosed that contain moving parts for the striking means, the moving parts are seldom durable over the life of the product.
One objective of the present invention is to produce a handchime of an ergonomic shape that allows ease of holding and long-term fatigue-free use.
It is an additional objective of the invention to fabricate the support shaft for the striking member of a sufficient weight such that it requires no additional weight to obtain the proper impact force.
It is a further objective of the invention to attach the striking member to the main body of the instrument in a manner that allows the musician to set the strike "feel" to their preference yet still allow long life, durability, and ease of operation.
For middle and higher pitched notes or smaller cross-section handchimes, it is another objective of the invention to design the cross-section of the support shaft to correspond to the various timbre settings of the clapper head for flexible voicing yet still allow for quick and easy adjustments without the benefit of elaborate tools.
For lower note or larger diameter handchimes, it is an objective of the invention to allow proper sound generation without any discordant overtones such as "slapping" or "pinging."
Lastly, for lower note or larger cross-section handchimes, it is a further objective of the invention to eliminate the discordant overtone known as "buzzing" by controlling the width and length of the slot.


A crib liner or runner made of a soft blanket that is secured in place over a crib mattress's fitted sheet via an easily applied fastener. Design intent is to provide parents of infant and toddler children a practical way in which to “change” their child's bedding in the event it is soiled with formula, drool or other bodily wastes, without requiring them to change the fitted sheet in order to do so. Modified versions of the crib & mattress runner could also be made available for use with children and adult bedding.

1. Field of the Invention
The present invention relates generally to the field of runner and liner devices and more specifically relates to a crib and mattress runner system.
2. Description of the Related Art
A child's nursery is perhaps the most precious and vital room in a family's home. Filled with cuddly stuffed animals, stacks of fresh diapers, baby lotions and sweet smelling powders, an infant's nursery provides the new addition with a space all their own. Perhaps the most important element of any nursery is the furnishings. A large dresser filled with tiny clothing and accessories, a comfortable rocking chair where parents can sit for hours gently holding their child and a changing table loaded with supplies, are but a few of the furniture items that make a nursery complete. While all of these items are important for a functioning nursery, by far, the most necessary of all furnishings is a crib. Comprised of an elevated mattress surrounded by four, railed walls, an infant crib is a comfortable bed which protects the child from falling or rolling off their mattress during rest. Most parents apply bedding to their child's crib that is similar to that which is used on beds geared for adults. As such, fitted crib sheets are a necessary item that provide a soft and barrier between the infant and the actual mattress.
Unfortunately, because crib mattresses are typically surrounded by four, raised railings, applying fitted sheets can be a time consuming and challenging endeavor. Lifting the mattress up off the crib frame while wedging the fitted sheet between the mattress and the railing can be a difficult task. Because of this, as long as the fitted sheet is clean, most parents feel comfortable leaving it in place atop the mattress for several days between changing. Not surprisingly however, most conscientious parents recognize that soiled sheets are unsanitary for the infant and thus if the child spills their bottle during the night, drools on the sheet or experiences a leaky diaper, there is no other choice but to change the bedding. As can be imagined, dealing with the hassle of changing a soiled fitted sheet at three o'clock in the morning, while trying to simultaneously comfort a crying infant can be a difficult endeavor at best, rendering both the parent and child frazzled and exhausted. This is not desirable.
Various attempts have been made to solve problems found in liner and runner device art. Among these are found in: U.S. Pat. No. 4,199,830 to Yoshie Ogata; U.S. Pub. No. 2005/0028278 to Jo-Ann Landry; and U.S. Pat. No. 2,450,923 to Edward H. Spiro, Jr. This prior art is representative of liner and runner devices. None of the above inventions and patents, taken either singly or in combination, is seen to describe the invention as claimed.
Ideally, a crib and mattress runner system should be user-friendly and safe in-use and, yet may operate reliably and be manufactured at a modest expense. Thus, a need exists for crib and mattress runner system which is structured and arranged to be removably-coupled to a top sheet covering a mattress inside of a crib and is removable when the crib and mattress runner becomes soiled with formula, fluids and waste matter during a course of an infant sleeping and to avoid the above mentioned problems.


A method and apparatus to ensure that protocol data units received out of order do not have to be buffered by a reassembly buffer in the performance path is presented. When an application or device requests to transfer data with another application or device, a framing protocol sends one or more complete protocol data units preceded by a framing header that is aligned with the transport header. The framing header contains information that allows the receiving application or device to determine where the protocol data unit should be placed so that successive protocol data units can be recovered when a previous protocol data unit has been received out of order.

Computer networking allows applications residing on separate computers or devices to communicate with each other by passing data across the network connecting the computers. The amount of data segments being sent across networks is rapidly increasing. The increase is due to several factors. These factors include the growth in the number of networked computers and the explosion in growth of digitally based multimedia, which is the combination of video and audio in a digital format for viewing on a computer or other digital device.
Data is typically sent in segments or packets. One of the problems that has occurred as a result of the increased data flow is segment delay, segment loss and reordering of segments (e.g., segments arriving out of order). The segment delay, segment loss, and reordering of segments causes problems for many applications that rely on the data being received timely and in the order it was sent. For example, applications such as digitally based multimedia that receive data sent in segments must receive the data in the order the segments were sent and without any delay for proper playback.
Many data transmission protocols account for segment delay, loss, and reordering by placing the data in an intermediate reassembly buffer to restore the sending order which may have been lost as a result of segment delay, loss, or reordering. If data comes in order, the data is put directly in a destination buffer. If data does not come in order, the data is put into an intermediate reassembly buffer. The bandwidth required to move data in and out of the buffer memory of the intermediate reassembly buffer is more than twice the bandwidth of the incoming data. The size of the buffer memory required is:K*(window_size)*(# connections)where K is a constant. Window_size is generally assumed to be the bandwidth delay product, which is the round trip time (RTT) of data sent between the sending computer and the receiving computer multiplied by the bandwidth of the data. As the speed of networks increases, the required speed and size of the buffer also increases. For example, on a local area network running at one gigabit/sec with a one millisecond RTT having 100 simultaneous connections, the memory required is 12.5 MB. For wide area networks running at ten gigabits/sec and having 100 millisecond RTT and 100 simultaneous connections, the total buffer memory required is 12.5 GB.
The required buffer memory is a problem when the Transmission Control Protocol (TCP) is offloaded from the host to a network interface card (NIC). When the TCP is running on a NIC, the intermediate reassembly buffer is typically placed on the NIC connection (i.e., on the network interface card). Today, network interface cards having megabytes or gigabytes of memory are not cost competitive due to the memory size and high speed requirements.
One approach that the computer industry has taken to reduce the amount of memory needed is the development of upper layer protocols (ULPs), such as those which perform bulk data transfer, that permit the final location (i.e., a client's buffer) to be known when the data is received. An upper layer protocol is a protocol that resides above the data transmission protocol layer in the computer or other digital device. The ULPs that perform bulk data transfer include specific application ULPs such as iSCSI and generic hardware acceleration ULPs such as a remote direct memory access (RDMA) protocol. When an upper layer protocol that permits the final location to be known is used, the data can be directly placed at the final location by a direct placement network interface that has knowledge of the final location.
The information required to find the final location is contained in the upper layer protocol protocol data unit (ULP PDU) header. A ULP PDU is an upper layer protocol data packet or message. However, the ULP PDU is not always identical to the size of the transport segment used by the transport protocol to send the data over the network. When this occurs, the ULP PDU is split and placed into several transport segments. This results in the ULP PDU header not being located in every transport segment and located at any place in a transport segment. The transport segments that do not contain the ULP PDU header are called non self-describing transport segments because they do not have sufficient information to directly place the data into its final location. The ULP PDU header must be located for direct placement to work.
One solution to finding the ULP PDU header in the transport segment (i.e., transport data packet) is to put a marker in each transport segment at a predefined period that provides a pointer to ULP PDU header of the next PDU. If the period is high relative to packet loss rate (e.g., once per segment), the location of the next PDU can be found with a very high likelihood when a previous PDU header has been lost. The problem with this solution is that data must still be buffered. The minimum size of the buffer required is:k*(the size of the ULP PDU)*(the number of connections)where k is a constant. If the size of the ULP PDU is limited to the transport segment size, the minimum buffer size required is:(maximum transport segment size)*(the number of connections)In cases where many transport segments having ULP PDU headers are lost, the buffer size required for direct placement approaches the intermediate reassembly buffer sizes of multiple gigabytes as indicated above.

Apparatus and method for scaling TCP off load buffer requirements by segment size


A computer system has a cache located between input/output devices and a main system memory. All system memory accesses by the input/output devices are made through the cache. Memory accesses through the cache are limited to those addresses which are accessible to a central processor and input/output devices. All access to such addresses by the central processor are made through the cache.

1. Technical Field
The present invention is related generally to computer systems, and more specifically to computer systems containing cache memories.
2. Background Art
Computer systems generally have several different storage layers defining a memory hierarchy. These layers typically include registers in a central processing unit, main system memory, and mass storage, such as disks. The performance of these different levels is quite different. The processor registers are much faster than system memory, which in turn is significantly faster than access to mass storage.
In order to improve system performance, a cache consisting of a small, fast memory, is often used between the central processor and system memory. The cache takes advantage of the locality of reference phenomenon within computer programs to store data which is likely to be reused into the fast memory.
The use of a cache memory between the central processor and system memory allows the system memory to be designed for high speed access. Transfer of data between the cache memory and the system memory is performed as block transfers which have a length dependent upon the cache memory design. The system memory design can be optimized for block data transfers to take advantage of this. For example, interleaved memory accessing can be used for the main system memory.
In many systems, input/output devices also have access to the main system memory. In systems of this type, the main memory cannot be designed to only support block transfers, because the input/output devices are generally not capable of block data transfers. In fact, many input/output devices, such as keyboards and input/output ports, are single character oriented devices.
Many cache designs for use between the central processor and system memory do not allow use by the input/output devices and overall system performance is adversely affected. Input/output devices must access system memory at their lower performance levels. Although the central processor can operate on data in its cache at any time, a cache miss causes the central processor to wait whenever an input/output device is performing a read to, or write from, system memory.
It would be desirable to provide a computer system which allows efficient access of a system memory by input/output devices. It would also be desirable for a computer system to provide that the performance central processor access to system memory is not greatly degraded during system memory access by input/output devices.

International Business Machines Corporation


A fixation device serves in facilitating reduction and repair of a fractured humerus. The fixation device includes a bone plate adapted to overlie and contact portions of a proximal humerus and a humeral shaft. The bone plate includes at least a body portion overlying the humeral shaft, and an end portion overlying a portion of the proximal humerus. The end portion can facilitate attachment of the bone plate to the lesser tuberosity of the proximal humerus.

1. Field of the Invention
The present invention generally relates to a fixation device used to facilitate reduction and repair of a fractured bone. More particularly, the present invention relates to a bone plate for creating a mechanically stronger connection between the bone plate and portions of a fractured humerus including the proximal humerus and the humeral shaft. More specifically, the present invention relates to a bone plate configured to provide optimal angles for bone screws received therethrough to decrease the incidence of penetration of the bone screws through the articular surface of the humeral head.
2. Description of the Prior Art
Current state of the art in surgical fracture fixation of the proximal humerus requires the application of a bone plate to the greater tuberosity of the proximal humerus. To attach the bone plate to the proximal humerus, bone screws (threadably or non-threadably engaging the bone plate) are inserted through the bone plate into the proximal humerus. In attaching the bone plate to the proximal humerus, the bone screws are ultimately received under the surface of the humeral head.
The bone screws used to attach the bone plate to the proximal humerus will likely be disposed at a significantly perpendicular angle with respect to the articular surface of the humeral head. This attachment orientation provides insufficient mechanical strength to maintain rigid attachment of the bone plate to the proximal humerus when subjected to joint reaction forces. As such, there remains a significant incidence of loss of fracture reduction and fracture fixation. In order to maximize stability of the connection, it is necessary to utilize long bone screws, so as to maximize the purchase thereof. However, given the significantly perpendicular angle of the bone screws relative to the articular surface, if there is any collapse or subsidence of the humeral head relative to the bone plate, the tips of the bone screws will penetrate the articular surface. Accordingly, there also remains a significant incidence of joint penetration.
Therefore, there is a need for a fixation device and method of use associated therewith that provides more optimal screw angles with respect to the articular surface of the humeral head and a mechanically stronger connection between the bone plate and the humerus. Such a fixation device can insure that bone screws are disposed at varying angles that are more tangential to the articular surface to prevent loss of fracture fixation and fracture reduction, and/or prevent penetration of the bone screws through the articular surface of the humeral head.

Anterior lesser tuberosity fixed angle fixation device and method of use associated therewith


Disclosed in an electrolyte for a rechargeable lithium battery, including a mixture of organic solvents including a cyclic solvent and a nitrile-based solvent represented by formula 1 and a lithium salt.

Recently, the rapid development of smaller, lighter, and higher performance electronic and communication equipment has required the development of high performance and large capacity batteries to power such equipment. The demands for large capacity batteries have led to investigations into rechargeable lithium batteries. Positive active materials for rechargeable lithium batteries generally use lithium-transition metal oxides, and negative active materials generally use crystalline or amorphous carbonaceous materials or carbon composites. The active materials are coated on a current collector with a predetermined thickness and length, or they are formed as a film to produce electrodes. The electrodes together with a separator are wound to produce an electrode element, and the electrode element is inserted into a battery case such as a can followed by insertion of an electrolyte to fabricate a battery.
The electrolyte includes lithium salts and organic solvents. The organic solvents may be mixed solvents of between two and five components of cyclic carbonates such as ethylene carbonate or propylene carbonate, or linear carbonates such as dimethyl carbonate, ethylmethyl carbonate, or diethyl carbonate. However, these solvents are known to severely expand at high temperatures, causing a swelling phenomenon. The swelling phenomenon is partly manifested in a battery by gas generated due to decomposition of the electrolyte at high temperatures in the battery.
Such a swelling phenomenon can be reduced in lithium polymer batteries compared to lithium ion batteries. However, the use of a polymer electrolyte with a nickel-based positive active material (e.g. LiNiMO2, where M is selected from Co, Mn, Al, P, Fe or Mg) has generally been ineffective.
Several attempts to use solvents with a high boiling point and a high dielectric constant, such as γ-butyrolactone, have been promising. Conventionally, the high dielectric constant solvent is generally used together with ethylene carbonate, which results in an extremely high viscosity with poor wettability of the separator. In another attempt, solvents with low boiling points and low dielectric constants have been used. However, these attempts still have problems associated with high swelling (Japanese Patent Laid-Open No. 2000-235868, U.S. Pat. Nos. 5,079,109, 5,272,022, 5,552,243, 5,521,027, 6,117,596, and 5,851,693, and "New thin lithium-ion batteries using a liquid electrolyte with thermal stability" Journal of power sources, 97-98, 677-680(2001), Notio Takami et al.)
Other attempts to inhibit the swelling phenomenon are in U.S. Pat. No. 4,830,939 disclosing a liquid electrolyte containing a polyethylenically unsaturated monomeric material or a prepolymeric material, and U.S. Pat. No. 4,866,716 disclosing a cross-linked polyether which is a product of a vinyl-ether. In addition, U.S. Pat. No. 4,970,012 discloses that a polymeric solid electrolyte includes crosslinked molecules of a radiation-cured substance of a cinnamate ester and polyethene oxide, and U.S. Pat. No. 4,908,283 discloses that a polymeric electrolyte includes a cured product of an acryloyl-denaturated polyalkylene oxide.
Such a swelling phenomenon is especially severe in batteries with a mixture of a lithium cobalt-based compound and a lithium nickel-based compound which exhibits higher capacity than other compounds.

Electrolyte for rechargeable lithium battery and rechargeable lithium battery comprising same


The liquid-phase epoxidation reaction of an olefin with hydrogen and oxygen in the presence of a catalyst mixture containing a titanium zeolite and a supported catalyst surprisingly produces less ring-opened products such as glycols when performed in the presence of a buffer. This is particularly surprising because a typical palladium on titanium zeolite catalyst is little effected by the presence of a buffer. Surprisingly, the use of a buffer also typically improves the activity of the process.

This invention relates to a liquid-phase epoxidation process using a mixed catalyst system to produce epoxides from hydrogen, oxygen, and olefins wherein the liquid-phase system contains a buffer. The mixed catalyst system contains a titanium zeolite and noble metal catalyst. Surprisingly, the use of a buffer in the process results in decreased ring-opening to unwanted glycols and glycol ethers in olefin epoxidation and also typically improves the activity of the process.
Many different methods for the preparation of epoxides have been developed. Generally, epoxides are formed by the reaction of an olefin with an oxidizing agent in the presence of a catalyst. The production of propylene oxide from propylene and an organic hydroperoxide oxidizing agent, such as ethyl benzene hydroperoxide or tert-butyl hydroperoxide, is commercially practiced technology. This process is performed in the presence of a solubilized molybdenum catalyst, see U.S. Pat. No. 3,351,635, or a heterogeneous titania on silica catalyst, see U.S. Pat. No. 4,367,342. Hydrogen peroxide is another oxidizing agent useful for the preparation of epoxides. Olefin epoxidation using hydrogen peroxide and a titanium silicate zeolite is demonstrated in U.S. Pat. No. 4,833,260. One disadvantage of both of these processes is the need to pre-form the oxidizing agent prior to reaction with olefin.
Another commercially practiced technology is the direct epoxidation of ethylene to ethylene oxide by reaction with oxygen over a silver catalyst. Unfortunately, the silver catalyst has not proved very useful in epoxidation of higher olefins. Therefore, much current research has focused on the direct epoxidation of higher olefins with oxygen and hydrogen in the presence of a catalyst. In this process, it is believed that oxygen and hydrogen react in situ to form an oxidizing agent. Thus, development of an efficient process (and catalyst) promises less expensive technology compared to the commercial technologies that employ pre-formed oxidizing agents.
Many different catalysts have been proposed for use in the direct epoxidation of higher olefins. For liquid-phase reactions, the catalysts typically contain palladium on a titanium zeolite support. For example, JP 4-352771 discloses the epoxidation of propylene oxide from the reaction of propylene, oxygen, and hydrogen using a catalyst containing a Group VIII metal such as palladium on a crystalline titanosilicate. The vapor-phase oxidation of olefins has been shown to produce epoxides over gold supported on titanium oxide (Au/TiO2 or Au/TiO2xe2x80x94SiO2), see for example U.S. Pat. No. 5,623,090, and gold supported on titanosilicates, see for example PCT Intl. Appl. WO 98/00413.
Mixed catalyst systems for olefin epoxidation with hydrogen and oxygen have also been disclosed. For example, JP 4-352771 at Example 13 describes the use of a mixture of titanosilicate and Pd/C for propylene epoxidation. U.S. Pat. No. 6,008,388 also describes a catalyst in which palladium is typically added to a titanium zeolite to form a catalyst system, but additionally teaches that the palladium can be incorporated into a support before mixing with the zeolite. However, the only supports that are disclosed include silica, alumina, and activated carbon. In addition, copending Application Ser. No. 09/624,942 discloses a mixed catalyst system that is useful in olefin epoxidation comprising a titanium zeolite and a gold-containing supported catalyst.
One disadvantage of liquid-phase epoxidation reactions using these catalysts is that they are prone to ring-open under standard reaction conditions to form less desirable ring-opened products such as glycols or glycol ethers. The formation of these undesired by-products is especially likely to happen when water is used as the solvent.
In sum, new processes for the direct epoxidation of olefins are eeded. Particularly valuable processes would have good productivity nd selectivity to epoxides, while reducing the likelihood of ring-opening epoxides to glycols or glycol ethers.
The invention is an olefin epoxidation process that comprises reacting an olefin, oxygen, and hydrogen in a solvent in the presence of a catalyst mixture, wherein the solvent contains a buffer. The catalyst mixture comprises a titanium zeolite and a noble metal catalyst. The process is surprisingly found to produce much lower amounts of undesired glycol by-products compared to the process without use of the buffer. Surprisingly, the use of a buffer also typically improves the activity of the process.
The process of the invention employs a catalyst mixture that comprises a titanium zeolite and a noble metal-containing supported catalyst. Suitable titanium zeolites are those crystalline materials having a porous molecular sieve structure with titanium atoms substituted in the framework. The choice of titanium zeolite employed will depend upon a number of factors, including the size and shape of the olefin to be epoxidized. For example, it is preferred to use a relatively small pore titanium zeolite such as a titanium silicalite if the olefin is a lower aliphatic olefin such as ethylene, propylene, or 1-butene. Where the olefin is propylene, the use of a TS-1 titanium silicalite is especially advantageous. For a bulky olefin such as cyclohexene, a larger pore titanium zeolite such as a titanium zeolite having a structure isomorphous with zeolite beta may be preferred.
Titanium zeolites comprise the class of zeolitic substances wherein titanium atoms are substituted for a portion of the silicon atoms in the lattice framework of a molecular sieve. Such substances are well known in the art.
Particularly preferred titanium zeolites include the class of molecular sieves commonly referred to as titanium silicalites, particularly xe2x80x9cTS-1xe2x80x9d (having an MFI topology analogous to that of the ZSM-5 aluminosilicate zeolites), xe2x80x9cTS-2xe2x80x9d (having an MEL topology analogous to that of the ZSM-11 aluminosilicate zeolites), and xe2x80x9cTS-3xe2x80x9d (as described in Belgian Pat. No. 1,001,038). Titanium-containing molecular sieves having framework structures isomorphous to zeolite beta, mordenite, ZSM48, ZSM-12, and MCM-41 are also suitable for use. The titanium zeolites preferably contain no elements other than titanium, silicon, and oxygen in the lattice framework, although minor amounts of boron, iron, aluminum, sodium, potassium, copper and the like may be present.
Preferred titanium zeolites will generally have a composition corresponding to the following empirical formula xTiO2 (1xe2x88x92x)SiO2 where x is between 0.0001 and 0.5000. More preferably, the value of x is from 0.01 to 0.125. The molar ratio of Si:Ti in the lattice framework of the zeolite is advantageously from 9.5:1 to 99:1 (most preferably from 9.5:1 to 60:1). The use of relatively titanium-rich zeolites may also be desirable.
The catalyst mixture employed in the process of the invention also contains a noble metal catalyst. While any noble metal catalyst can be utilized (i.e., gold, silver, platinum, palladium, iridium, ruthenium, osmium metal catalysts), either alone or in combination, palladium and gold are particularly desirable. Suitable noble metal catalysts include high surface area noble metals, noble metal alloys, and supported noble metal catalysts. Examples of suitable noble metal catalysts include high surface area palladium and palladium alloys. However, particularly preferred noble metal catalysts are supported noble metal catalysts comprising a noble metal and a support.
For supported noble metal catalysts, the support is preferably a porous material. Supports are well-known in the art. There are no particular restrictions on the type of support that are used. For instance, the support can be inorganic oxides, inorganic chlorides, carbon, and organic polymer resins. Preferred inorganic oxides include oxides of Group 2, 3, 4, 5, 6, 13, or 14 elements. Particularly preferred inorganic oxide supports include silica, alumina, titania, zirconia, niobium oxides, tantalum oxides, molybdenum oxides, tungsten oxides, amorphous titania-silica, amorphous zirconia-silica, amorphous niobia-silica, and the like. Preferred organic polymer resins include polystyrene, styrene-divinylbenzene copolymers, crosslinked polyethyleneimines, and polybenzimidizole. Suitable supports also include organic polymer resins grafted onto inorganic oxide supports, such as polyethylenimine-silica. Preferred supports also include carbon. Particularly preferred supports include carbon, silica, silica-aluminas, titania, zirconia, and niobia.
Preferably, the support has a surface area in the range of about 10 to about 700 m2/g, more preferably from about 50 to about 500 m2/g, and most preferably from about 100 to about 400 m2/g. Preferably, the pore volume of the support is in the range of about 0.1 to about 4.0 mL/g, more preferably from about 0.5 to about 3.5 mL/g, and most preferably from about 0.8 to about 3.0 mL/g. Preferably, the average particle size of the support is in the range of about 0.1 to about 500 xcexcm, more preferably from about 1 to about 200 xcexcm, and most preferably from about 10 to about 100 xcexcm. The average pore diameter is typically in the range of about 10 to about 1000 xc3x85, preferably about 20 to about 500 xc3x85, and most preferably about 50 to about 350 xc3x85.
The supported noble metal catalyst also contains a noble metal. While any of the noble metals can be utilized (i.e., gold, silver, platinum, palladium, iridium, ruthenium, osmium), either alone or in combination, palladium and gold are particularly desirable. Typically, the amount of noble metal present in the supported catalyst will be in the range of from 0.01 to 20 weight percent, preferably 0.1 to 5 weight percent. The manner in which the noble metal is incorporated into the supported catalyst is not considered to be particularly critical. For example, the noble metal (for example, Pd tetraamine bromide) may be supported on the support by impregnation, adsorption, ion-exchange, precipitation, or the like.
There are no particular restrictions regarding the choice of noble metal compound or complex used as the source of the noble metal in the supported catalyst. For example, suitable compounds include the nitrates, sulfates, halides (e.g., chlorides, bromides), carboxylates (e.g. acetate), and amine complexes of noble metals.
Similarly, the oxidation state of the noble metal is not considered critical. In the case of palladium for instance, the palladium may be in an oxidation state anywhere from 0 to +4 or any combination of such oxidation states. To achieve the desired oxidation state or combination of oxidation states, the noble metal compound after being introduced into the supported catalyst may be fully or partially pre-reduced. Satisfactory catalytic performance can, however, be attained without any pre-reduction.
After supported catalyst formation, the supported catalyst may be optionally thermally treated in a gas such as nitrogen, helium, vacuum, hydrogen, oxygen, air, or the like. The thermal treatment temperature is typically from about 50 to about 550xc2x0 C.
The titanium zeolite and the noble metal catalyst may be used in the epoxidation process as a mixture of powders or as a mixture of pellets. In addition, the titanium zeolite and noble metal catalyst may also be pelletized or extruded together prior to use in epoxidation. If 25 pelletized or extruded together, the catalyst mixture may additionally comprise a binder or the like and may be molded, spray dried, shaped or extruded into any desired form prior to use in epoxidation. The weight ratio of titanium zeolite:noble metal catalyst is not particularly critical. However, a titanium zeolite:noble metal catalyst ratio of 0.01-100 (grams of titanium zeolite per gram of noble metal catalyst) is preferred.
The process of the invention comprises contacting an olefin, oxygen, and hydrogen in a solvent in the presence of the catalyst mixture. Suitable olefins include any olefin having at least one carbon-carbon double bond, and generally from 2 to 60 carbon atoms. Preferably the olefin is an acyclic alkene of from 2 to 30 carbon atoms; the process of the invention is particularly suitable for epoxidizing C2-C6 olefins. More than one double bond may be present, as in a diene or triene for example. The olefin may be a hydrocarbon (i.e., contain only carbon and hydrogen atoms) or may contain functional groups such as halide, carboxyl, hydroxyl, ether, carbonyl, cyano, or nitro groups, or the like. The process of the invention is especially useful for converting propylene to propylene oxide.
The process of the invention also requires the use of a solvent. Suitable solvents include any chemical that is a liquid under reaction conditions, including, but not limited to, oxygen-containing hydrocarbons such as alcohols, aromatic and aliphatic solvents such as toluene and hexane, chlorinated aromatic and aliphatic solvents such as methylene chloride and chlorobenzene, and water. Suitable oxygenated solvents include water and oxygen-containing hydrocarbons such as alcohols, ethers, esters, ketones, and the like. Preferred oxygenated solvents include lower aliphatic C1-C4 alcohols such as methanol, ethanol, isopropanol, and tert-butanol, or mixtures thereof, and water. Fluorinated alcohols can be used. A preferred solvent is water. It is also possible to use mixtures of the cited alcohols with water.
The process of the invention also requires the use of a buffer. The buffer will typically be added to the solvent to form a buffer solution. The buffer solution is employed in the reaction to inhibit the formation of glycols during epoxidation. Buffers are well known in the art.
Buffers useful in this invention include any suitable salts of oxyacids, the nature and proportions of which in the mixture, are such that the pH of their solutions may range from 3 to 10, preferably from 4 to 9 and more preferably from 5 to 8. Suitable salts of oxyacids contain an anion and cation. The anion portion of the salt may include anions such as phosphate, carbonate, acetate, citrate, borate, phthalate, silicate, aluminosilicate, or the like. The cation portion of the salt may include cations such as ammonium, alkylammoniums (e.g., tetraalkylammoniums), alkali metals, alkaline earth metals, or the like. Cation examples include NH4, NBu4, Li, Na, K, Cs, Mg, and Ca cations. More preferred buffers include alkali metal phosphate buffers. Buffers may preferably contain a combination of more than one suitable salt. Typically, the concentration of buffer in the solvent is from about 0.0001 M to about 1 M, preferably from about 0.001 M to about 0.1 M, and most preferably from about 0.005 M to about 0.05 M.
Oxygen and hydrogen are also required for the process of the invention. Although any sources of oxygen and hydrogen are suitable, molecular oxygen and molecular hydrogen are preferred. The molar ratio of hydrogen to oxygen can usually be varied in the range of H2:O2=1:100 to 5:1 and is especially favorable at 1:5 to 2:1. The molar ratio of oxygen to olefin is usually 1:1 to 1:20, and preferably 1:1.5 to 1:10. Relatively high oxygen to olefin molar ratios (e.g., 1:1 to 1:3) may be advantageous for certain olefins.
In addition to olefin, oxygen and hydrogen, an inert gas carrier may be preferably used in the process. As the carrier gas, any desired inert gas can be used. Suitable inert gas carriers include noble gases such as helium, neon, and argon in addition to nitrogen and carbon dioxide. Saturated hydrocarbons with 1-8, especially 1-6, and preferably with 1-4 carbon atoms, e.g., methane, ethane, propane, and n-butane, are also suitable. Nitrogen and saturated C1-C4 hydrocarbons are the preferred inert carrier gases. Mixtures of the listed inert carrier gases can also be used. The molar ratio of olefin to carrier gas is usually in the range of 100:1 to 1:10 and especially 20:1 to 1:10.
Specifically in the epoxidation of propylene according to the invention, propane can be supplied in such a way that, in the presence of an appropriate excess of carrier gas, the explosive limits of mixtures of propylene, propane, hydrogen, and oxygen are safely avoided and thus no explosive mixture can form in the reactor or in the feed and discharge lines.
The amount of catalyst used may be determined on the basis of the molar ratio of the titanium contained in the titanium zeolite to the olefin that is supplied per unit time. Typically, sufficient catalyst is present to provide a titanium/olefin per hour molar feed ratio of from 0.0001 to 0.1.
For the liquid-phase process of the invention, the catalyst is preferably in the form of a suspension or fixed-bed. The process may be performed using a continuous flow, semi-batch or batch mode of operation. It is advantageous to work at a pressure of 1-100 bars. Epoxidation according to the invention is carried out at a temperature effective to achieve the desired olefin epoxidation, preferably at temperatures in the range of 0-250xc2x0 C., more preferably, 20-200xc2x0 C.

Direct epoxidation process using a mixed catalyst system


Three printed boards are stored in a case, and a relay connector for connecting the three printed boards is mounted on the second printed board at the middle position. The relay connector is provided with a first terminal storing part, which is long in a vertical direction, and a short second terminal storing part. The relay connector connects a terminal pin of the first printed board at an upper position with a terminal pin of the third printed board at a lower position, via a long first relay terminal stored in the first terminal storing part, while connecting a terminal pin of the first printed board and/or the terminal pin of the third printed board with a conductor of the second printed board, via a short second relay terminal stored in the second terminal storing part.

Conventionally, a casing of an electric junction box mounted on a car body accommodates a laminate composed of bus bars formed by punching a conductive metal plate into a predetermined configuration and insulating plates layered on the bus bars alternately and circuit components consisting of an insulating substrate on which an electric conductor of a copper foil or the like is printed in a required pattern to form a printed-circuit board. When one casing accommodates a plurality of circuit components layered one upon another, electric conductors of the circuit components are connected with one another through a relay connector.
An electric junction box 1 of this kind accommodating the relay connector is provided, as disclosed in Japanese Patent Application Laid-Open No. 2001-15952 (patent document 1). As shown in FIG. 9, the electric junction box 1 has the laminate 2 of bus bars and the printed-circuit board 3. The housing (relay connector) 4 accommodating the relay terminal (not shown) is projected from the insulating plate of the bus bar laminate 2. The bus bars of the bus bar laminate 2 are connected with the relay terminal from below, and one end 5a of the connection terminal 5 is connected with the relay terminal from above. The other end 5b of the connection terminal 5 is soldered to the electric conductor of the printed-circuit board 3. Thereby the bus bars of the bus bar laminate 2 and the electric conductor of the printed-circuit board 3 are connected with each other.
But the number of circuits has increased owing to a rapid increase of electric and electronic parts in recent years. Thus in forming a required circuit from two circuit components, the circuit is necessarily horizontally large. The relay connector connecting the circuit components with each other is also necessarily large. Thereby the electric junction box is horizontally large.
In a construction in which three circuit components 6, 7, and 8 are accommodated in the casing of the electric junction box, with the circuit components 6, 7, and 8 vertically spaced at certain intervals, and the circuit components 6, 7, and 8 are connected with one another, it is possible to make the circuit components compact. But as shown in FIG. 10, it is necessary to form a housing 4 on the circuit component 7 located at an intermediate position and the circuit component 8 located at a lower position. Thus when the housing is formed on the circuit components 7 and 8, the interval between the circuit components is necessarily large. Therefore the electric junction box is very large in a vertical direction.
Patent document 1: Japanese Patent Application Laid-Open No.2001-15952


A timepiece assembly including a combined resonator with at least two degrees of freedom which includes a first linear or rotary oscillator with reduced amplitude in a first direction relative to which oscillates a second linear or rotary oscillator with reduced amplitude in a second direction substantially orthogonal to the first direction. The rotary oscillator includes a second weight carrying a sliding-block. A wheel set is arranged for application of a torque to the resonator, the wheel set including a groove in which the sliding-block slides with minimal play. The sliding-block is arranged at least either to follow curvature of the groove when present, or to rub with friction in the groove, or to repel the inner lateral surfaces of the groove by magnetically or electrically charged surfaces in the sliding-block.

There is a known combined resonator comprising two resonators with flexible bearings placed in series with each other, and wherein a weight of one resonator carries a pin that cooperates with a groove of a wheel set subjected to a torque.
However, there remains in this pin-groove connection friction which is not constant or controlled.

Combined resonator with improved isochronism

The Swatch Group Research and Development Ltd