A diffractive optical element includes a plurality of layered diffraction gratings which includes two diffraction gratings made of materials having different dispersive powers. The plurality of diffraction gratings includes a first diffraction grating having a plurality of grating portions provided on a first base surface, and a second diffraction grating having a plurality of grating portions which are provided on a second base surface. In the second diffraction grating, a height of the grating portion of the central circular zone from the second base surface is greater than a height of the grating portion of the peripheral circular zone from the second base surface.

1. Field of the Invention
The present invention relates to a diffractive optical element and an optical system having the same.
2. Description of the Related Art
Example methods are known in which a diffractive optical element having a diffractive effect is provided at a part of a lens system to reduce chromatic aberration of the lens system (see SPIE Vol. 1354, International Lens Design Conference, 1990, Japanese Patent Laid-Open No. 4-213421 corresponding to U.S. Pat. No. 5,044,706, Japanese Patent Laid-Open No. 6-324262 corresponding to U.S. Pat. No. 5,790,321, and U.S. Pat. No. 5,044,706). This method with the diffractive optical element utilizes a physical phenomenon that chromatic aberrations appear in opposite directions on a refractive surface and a diffractive surface in an optical system when a light beam with a reference wavelength is applied.
Since the diffractive optical element may provide an effect similar to an effect of an aspherical lens by properly changing a cycle of the cyclic structure of the diffractive optical element, the effect may reduce aberrations other than the chromatic aberration.
In a lens system having such a diffractive optical element, when a light beam in a usable wavelength region is concentrated to diffractive light of a certain order (also referred to as predetermined order or designed order), the intensity of diffractive light of other orders becomes low. If the intensity is 0, it means that the diffractive light does not exist. However, unnecessarily diffracted light of the orders other than the designed order actually exists. However, in fact, if the unnecessarily diffracted light has a certain intensity, the light is emitted through the optical system in a path different from that of the light beam of the designed order, resulting in flare.
Because of this, to utilize the aberration reducing effect by way of the diffractive optical element, a diffractive efficiency of the diffractive light of the designed order is required to be reliably high over the usable wavelength region. Also, it is important to carefully consider about a spectral distribution of the diffractive efficiency of the designed order, and a behavior of the unnecessarily diffracted light of the orders other than the designed order.
Various suggestions are made for diffractive optical elements to improve the diffractive efficiency and reduce the unnecessarily diffracted light (see Japanese Patent Laid-Open No. 9-127322 corresponding to U.S. Pat. No. 6,157,488, Japanese Patent Laid-Open No. 2000-98118 corresponding to U.S. Pat. No. 6,560,019, and Japanese Patent Laid-Open No. 2002-107523 corresponding to U.S. Pat. No. 6,683,718). The diffractive optical elements disclosed in these publications have a plurality of layered diffraction gratings, and the material and height of each diffraction grating are properly determined. Accordingly, a high diffractive efficiency is provided for diffractive light of a desired order over a wide wavelength region (about 98% in a wavelength region ranging from 450 to 650 nm). The diffractive efficiency is expressed by a ratio of a light intensity of diffractive light of each order, to a light intensity of the total transmitted light beam.
In such a layered diffractive optical element, if a positional shift is found between the plurality of layered diffraction gratings, a diffractive efficiency of a light beam of an order different from the designed order increases. As a result, when the diffractive optical element is applied to the optical system, the image quality of an obtained image is seriously deteriorated. Therefore, to manufacture the layered diffractive optical element, it is important to highly accurately position the plurality of diffraction gratings to be layered. Example methods for manufacturing diffractive optical elements are known in which a plurality of diffraction gratings are highly accurately positioned and layered (see Japanese Patent Laid-Open No. 2001-141918 corresponding to US Patent Application Publication No. 2001/0026399, Japanese Patent Laid-Open No. 2002-62417 corresponding to U.S. Pat. No. 6,965,476, Japanese Patent Laid-Open No. 10-274705 with no corresponding US patent publication, Japanese Patent Laid-Open No. 2000-292668 with no corresponding US patent publication, and Japanese Patent Laid-Open No. 2000-114143 corresponding to U.S. Pat. No. 6,731,431).
To increase the diffractive efficiency, a distance (air gap) between the plurality of diffraction gratings to be layered should be small.
However, if the air gap becomes small, a grating surface of one diffraction grating may come into contact with a grating surface of the other diffraction grating, causing the grating surfaces to be damaged.
In a case where a thin substrate is used for making the plurality of diffraction gratings, if an external pressure is applied to the diffraction gratings, the substrate may be deformed. Accordingly, the grating surface of the one diffraction grating may come into contact with the grating surface of the other diffraction grating, causing the grating surfaces to be damaged.
To prevent this, a positioning member may be used as a support for preventing the deformation caused by the external pressure.
However, with this method, since the positioning member is generally used only at a small area, if a large external pressure is applied, the substrate may be markedly deformed, and the grating surfaces come into contact with each other, thereby causing the grating surfaces to be damaged.

Diffractive optical element and optical system having the same


An active multi-mode overrunning clutch assembly includes concentric inner and outer members and a plurality of opposed pairs of clutch pawls operably disposed between the members. The clutch pawls are biased radially outwardly and include recessed portions and raised lands which cooperate with an axially translatable circumferential control sleeve. The control sleeve can be translated to select various combinations of active (engaged) or inactive (retracted) pawls to effect four distinct operational modes: fully engaged, i.e., locked in both directions, drive and overrunning in a first direction, drive and overrunning in the reverse direction and fully disengaged, i.e., released or inactive. The active multi-mode overrunning clutch assembly finds particular application in transfer cases of four wheel drive vehicles.

The invention relates generally to double or bi-directional overrunning clutch assemblies and more particularly to an actively controlled, bi-directional overrunning clutch assembly for use in motor vehicle driveline components such as transfer cases, transmissions, differentials and the like.
The sophistication of consumer vehicle four-wheel drive systems continues to increase. Initially, four-wheel drive systems were confined to trucks and vehicles primarily intended for off-road use. Such systems were both complex from a mechanical standpoint and complicated from an operational standpoint. Invariably, it was necessary to stop the vehicle to place the drive train into four-wheel drive and furthermore necessary to dismount the vehicle and manually activate drive hubs to couple the secondary drive wheels to the secondary axles.
Slowly the application of such systems expanded to light duty trucks, sport utility vehicles, vans and even some passenger cars as the systems became simplified, more sophisticated and easier to use. Such systems could often be activated on the fly and axle disconnects incorporated, for example, in the front differential obviated the need to dismount the vehicle to lock or unlock the manual wheel mounted locking hubs.
The current generation of four-wheel drive vehicles often includes adaptive drive systems wherein axle or wheel speed sensors provide data to a controller which selectively delivers torque or, contrariwise, applies braking, to control wheel slip, that is, front to rear speed differentials, in order to improve the driveability of such vehicles. The drivelines of such adaptive vehicle drive systems generally include a transfer case driven by the vehicle transmission which, through a modulating electromagnetic or hydraulically operated clutch, redistributes torque from the primary driveline and wheels to the secondary driveline and wheels. Typically, under conditions of no slip the primary driveline, which is coupled to and drives either the front or rear wheels of the vehicle, will carry and deliver substantially the full torque output of the transmission. When a speed differential is sensed, indicating wheel slip is present, the clutch increasingly couples the two drivelines, thereby transferring torque to the secondary driveline and wheels. When the modulating clutch is fully engaged, a fifty-fifty torque split exists between the primary and secondary drivelines.
Less complex four-wheel drive systems are also available. Typically such systems are full time rather than adaptive and include passive mechanical components such as viscous clutches or differentials having epicyclic gear trains which control torque delivery to the front and rear wheels of the vehicle. One early passive torque control configuration utilized a one-way or overrunning clutch to provide drive torque to the front wheels if the rear wheels should overspeed them, indicating that they were slipping. Such a passive, mechanical system was inexpensive but had the disadvantage of not operating in reverse gear. This disadvantage was overcome by the incorporation of double or bi-directional overrunning clutches which transfer torque to the secondary driveline in both forward and reverse gears while providing the desired torque transfer to the secondary drive wheels upon primary drive wheel overrun. However, passive mechanical double overrunning clutches do not always provide stable and predictable vehicle handling characteristics. Accordingly, improvement in the structure, operation and control of double overrunning clutch assemblies in motor vehicle drivelines is desirable.

Bi-directional overrunning clutch assembly for transfer cases and the like


Photovoltaic structures are provided with field-effect inversion/accumulation layers as emitter layers induced by work-function differences between gate conductor layers and substrates thereof. Localized contact regions are in electrical communication with the gate conductors of such structures for repelling minority carriers. Such localized contact regions may include doped crystalline or polycrystalline silicon regions between the gate conductor and silicon absorption layers. Fabrication of the structures can be conducted without alignment between metal contacts and the localized contact regions or high temperature processing.

Diffused-junction solar cells have been developed having homogeneous as well as double-diffused (selective) emitter structures. Homogeneous emitter structures have the same doping level under passivated and metal (e.g. finger contact) regions. In contrast, double-diffused emitter structures have relatively high doping levels under and aligned with the metal regions (also known as the metal grid) and lower doping levels between these regions. The highly doped regions repel minority carriers (holes) from the metal contacts. This arrangement provides good contact performance and low recombination losses. High efficiency solar cells have been achieved using double-diffused emitter structures.
FIG. 1 is a schematic illustration of a photovoltaic structure 20 including a double-diffused emitter structure. The emitter layer includes n+ regions 22 between n++ regions 24. The highly doped n++ regions are directly below metal fingers 26. The structure 20 further includes a dielectric anti-reflective coating (ARC) layer 28 adjoining one side of the emitter layer and a p-type silicon substrate 30 adjoining the opposite side thereof. The silicon substrate functions as an absorber layer. The fabrication process for forming photovoltaic structures including double-diffused emitters is relatively expensive because of the process complexity and high temperatures required for the process.

Field-effect localized emitter photovoltaic device

INTERNATIONAL BUSINESS MACHINES CORPORATION


A switch assembly has a base, a cover and multiple conductive slices. The base has an extending board and multiple inserting recesses. The inserting recesses are formed in the extending board and each have two mounting posts and an inserting hole. The mounting posts are formed on and protrude up from the recess. The inserting hole is formed through the extending board. The cover is mounted over the base. The conductive slices are attached to the inserting recesses and each has an elastic tab and a mounting tab. The mounting tab is contacted with the elastic tab, is attached to the inserting recess and has two mounting holes, an opening and two clamping slices. The mounting holes are formed through the mounting tab and correspond to the mounting posts. The opening is formed through the mounting tab and corresponds to the inserting hole. The clamping slices are attached to the mounting tab.

1. Field of the Invention
The present invention relates to a switch assembly, and more particularly to a switch assembly that can connect with electric wires without a soldering process.
2. Description of Related Art
A conventional switch assembly is used as a bridge between a power source and an electric equipment and usually has a case, a conductive device, a button device and multiple conductive slices. The case has a cover and a base. The cover is securely mounted around the base and formed an inner chamber between the cover and the base. The conductive device is mounted in the inner chamber. The button device is attached to the cover and is contacted to the button device. The conductive slices are respectively attached to and protrude out from the base and are contacted to the conductive device.
When the switch assembly is assembled between the power source and the electric equipment, electric wires of the power source must be connected to the conductive slices of the switch assembly by a soldering process.
Even though the conventional switch assembly can be used as a bridge between the power source and the electric equipment, the conventional switch assembly also has the following shortcomings.
1. To assemble the switch assembly between the power source and the electric equipment, a soldering machine and the soldering material are necessary, and this will increase cost and time for assembling the switch assembly to the power source and the electric equipment.
2. With the soldering material for connecting the wires to the conductive slices, the switch assembly is not detachable to the wires so that to repair or change a damaged switch assembly is trouble and difficult.


An electric double-layer capacitor has an electrolyte solution and an element constructed of a positive electrode and a negative electrode which are each composed of a current collecting substrate and an active material composition, and a separator situated between the positive and negative electrodes. When the element is in place within the capacitor, the portion of the separator sandwiched between the active material compositions of the respective electrodes has a pore volume which is at least 0.4 times the total pore volume of the positive and negative electrodes. This construction enables the separator to hold the electrolyte solution required by the electrodes for charging and discharging, thus endowing the capacitor with a high capacitance and a long cycle life.

1. Field of the Invention
The present invention relates to electric double-layer capacitors, and particularly electric double-layer capacitors suitable for use as automotive power supplies and power supplies for electrical storage systems.
2. Prior Art
An electric double-layer capacitor is an electrochemical device composed of a positive electrode, a negative electrode and a solution containing positive and negative ions (electrolyte solution). It uses a very thin dielectric layer, or electric double layer, that forms at the interfaces between the electrodes and the electrolyte solution as a dielectric, and is capable of storing and discharging electricity by the adsorption and release of negative ions at the positive electrode and positive ions at the negative electrode.
In such an electric double-layer capacitor, a separator is generally provided between the positive electrode and the negative electrode for the dielectric separation of the positive and negative electrodes and to hold the electrolyte solution.
Examples of separators used in electric double-layer capacitors include separators made of cellulose fibers (see JP-A 1998-256088), polyolefin nonwoven fabrics (see JP-A 2001-68380, JP-A 2001-110678, and JP-A 2002-266281), and porous polymer films.
However, electric double-layer capacitors which use a cellulose separator do not have a long enough life on account of the low chemical stability of cellulose itself. Polyolefin nonwoven fabric and porous polymer film generally have a lower melting point than cellulose and thus lack thermal stability. In addition, these latter separators can be manufactured to a porosity of at best 40 to 60 vol %, which is low compared to the 60 to 70 vol % porosity of cellulose separators. Accordingly, the amount of electrolyte solution such separators can hold is small and they also have a poor ability to absorb electrolyte solution.
Separators composed of glass fibers are described in JP-A 1997-289140 and JP-A 1997-260214. These glass fiber separators have an excellent chemical stability, thermal stability and electrolyte absorption. In addition, because they can be manufactured to a porosity of about 80 vol %, they also have an excellent ability to hold electrolyte solution.
However, such glass fiber separators have a lower mechanical strength during drying and during electrolyte absorption than do the other types of separators mentioned above. Therefore, in elements which in fact contain a glass fiber separator, when the separator is subjected to pressure during capacitor production, the thickness decreases, making it difficult to maintain the shape of the separator. As a result, the porosity within the separator decreases.


A track-module apparatus comprising: (a) idler-arm axle structure for a vehicle and having leading and trailing idler-arm axles; (b) a leading idler arm rotatably attached to the leading idler-arm axle and extending forwardly to a leading-arm distal end at which a leading ground-engaging idler wheel is rotatably attached and rearwardly to a rearward suspension end; (c) a trailing idler arm rotatably attached to the trailing idler-arm axle and extending rearwardly to a trailing-arm distal end at which a trailing ground-engaging idler wheel is rotatably attached and forwardly to a forward suspension end; (d) bogie-axle structure (i) affixed to one of the idler arms, (ii) having at least one bogie-arm axle, and (iii) positioning the at least one bogie-arm axle adjacent to and below the idler-arm axle of the idler arm to which it is affixed; (e) leading-arm and trailing-arm suspension elements rotatably attached to and extending downwardly from the rearward and forward suspension ends, respectively, and each having a lower end; (f) front and rear bogie connecting arms rotatably attached to the front and rear axles, respectively, and extending forwardly and rearwardly to rotatable attachments at the leading-arm and trailing-arm suspension-element lower ends, respectively; (g) front and rear ground-engaging bogie-wheel sets rotatably attached to distal ends of the front and rear bogie connecting arms, respectively; and (h) an endless track extending around the wheels.

A wide variety of both powered and unpowered load-carrying vehicles are used in agriculture, oil fields, construction and the like in which it is desirable to minimize the load per square foot on the ground on which the vehicle is moving. Typically, such vehicles are supported on the ground by large wheels with tires. However, track-module systems (or "track modules" or "track-module apparatus") may be used in place of wheels with tires to provide a much larger ground-surface engagement area supporting the weight of the vehicle and to prevent difficulties while moving over mud or other soft ground surfaces.
It is highly-desirable to distribute the load supported by the track module among all of the ground-engaging wheels of the module as evenly as possible. The loads encountered by the module are both static and dynamic and may vary considerably during operation. Loads change as the module runs over uneven ground, as the vehicle turns and as the slope of the ground being traversed changes. Ideally, all such wheels remain in contact with the ground through the endless belt and share a portion of the load at all times.
One track-module unit which is intended to distribute load relatively evenly is disclosed in U.S. Pat. No. 9,415,818 by ATI, Inc. of Mt. Vernon, IL, the owner of the present invention. Another track-module unit which is intended to distribute load relatively evenly is disclosed in U.S. Pat. No. 7,628,235 (Satzler et al.) owned by CLAAS Industrietechnik GmbH of Paderhorn, Germany. A third vehicle track-module unit is disclosed in United States Published Patent Application No. 2013/0154345 (Schultz et al.) owned by CLAAS Selbstfahrende Erntemaschinen GmbH of Harsewinkel, Germany. CLAAS also has its Lexion Terra Trac product line which includes configurations which are intended to address some of these challenges.
Each of the four track modules disclosed in these documents, although at least in part addressing some of the common challenges encountered by track modules and addressed by the present invention, none of the four prior art systems disclosed in these documents includes the particular structure of the present invention. In particular, not only is the even distribution of loading on the ground-engaging wheels a desirable characteristic of a track module, it is also desirable to minimize the the fore-and-aft movement of the bogie wheels and to provided commonality of bogie-wheel fore-and-aft movement. It is also desirable to reduce the coupling between the vertical movement of the idler wheels and the fore-and-aft movement of the bogie wheels. In addition, the shorter length of the arm which guides a bogie-wheel set provides more enhanced directional stability for the bogie-wheel sets in a track module.
All three of these desirable characteristics of bogie wheels in a track module are features of the present invention, provided by the unique structure of the kinematic linkage in the inventive track-module apparatus disclosed herein.


A superabsorbent polymer composite including superabsorbent polymers and cellulosic nanofibrils having a diameter equal to or less than 100 nm. The composite may be in the form of particles or a foam. Methods for producing the composite and absorbent articles including the superabsorbent polymer composite are also provided.

Advances in absorbent article technology have stimulated the search for absorbent (often superabsorbent) materials with desirable properties such as high absorption, high storage capacity and high gel and mechanical strength.
The absorbent materials may include two or more layers such as liquid acquisition layers, storage layers and distribution layers.
In order to obtain good liquid acquisition capacity it is important that the absorbent material has a high momentaneous liquid acquisition capacity. Open, bulky structures with large capillaries have a high momentaneous liquid acquisition capacity and examples of such materials are cellulosic fluff pulp of thermomechanic or chemithermomechanic (CTMP) type, chemically stiffened cellulosic fibres fibers, waddings of synthetic fibers and porous foam materials.
In order to obtain a good liquid storage capacity it is common that the absorbent structure contains superabsorbent materials. Superabsorbent materials are crosslinked polymers with the capacity to absorb liquid many times their own weight. Organic materials suitable for use as a superabsorbent material can include natural materials such as polysaccharides (particularly modified polysaccharides such as CMC: carboxymethylcellulose), polypeptides and the like, as well as synthetic materials such as synthetic hydrogel polymers. Such hydrogel polymers include, for example, polyacrylates (particularly alkali metal salts of polyacrylic acids), polyacrylamides, polyvinyl alcohol, polyacrylamides, polyvinyl pyridines, and the like. Other suitable polymers include polyvinylamine, hydrolyzed acrylonitrile grafted starch, acrylic acid grafted starch, and isobutylene maleic anhydride copolymers and mixtures thereof. The absorption mechanism of such superabsorbents is thought to be based on the fact that the polymer chain contains a plurality of charged groups, which make it possible for the polymer network to absorb aqueous liquids by means of osmotic forces.
The superabsorbent material in an absorbent structure, i.e. a diaper core, is often in the form of small particles, which are arranged and contained in a fibrous matrix. The fibrous matrix usually includes cellulosic fluff pulp of thermomechanic, chemical or chemithermomechanical type, but a certain amount of synthetic fibers are also common.
One problem with absorbent structures containing superabsorbent material is that it is difficult to distribute and maintain the superabsorbent material in the desired location in the absorbent structure, both during storage and during use of the article. Another problem with absorbent structures containing superabsorbent material is so-called gel blocking. This problem occurs by the fact that the liquid-containing superabsorbent particles swell and form a gel. The gel blocks the liquid transport and gives rise to an accumulation of liquid in certain portions of the absorbent structure while other portions of the structure become more-or-less non-utilized.
In order to obtain a superabsorbent material with high mechanical strength, the degree of crosslinking of the polymer is crucial. The more crosslinking in a polymeric structure, the more the mechanical strength increases. However, a high degree of crosslinking within a structure restricts the swelling capacity of the material, and highly-crosslinked superabsorbent materials are brittle and break easily. The performance of superabsorbent materials in different applications is highly dependent on the elastic modulus, the resistance to fracture and the water absorbance capacity among other properties. These properties are strongly affected by the degree of crosslinking. It has been shown that for polyacrylic acid (PAA) the equilibrium degree of swelling decreases and the elastic modulus increases with an increasing degree of crosslinking, as expected from theory.
Absorbent web composites including a superabsorbent polymer component and fibrous material, such as cellulose fibers and processes for their production are known.
An example of this type of material is described in US 2003/0111163, which describes a process for making an absorbent fibrous web composite including a stable and controllable dispersion of superabsorbent polymer. Two polymer precursors, for example, acrylic acid or methacrylic acid, are added in separate stages to form a superabsorbing polymer on or in a pre-formed fibrous web, which includes a plurality of hydrophilic fibers, e.g. microfibrillar cellulose or microcrystalline cellulose.
Similarly, US 2003/0111774 describes a process for making an absorbent fibrous composite nonwoven web including e.g. superabsorbent polymers and plurality of hydrophilic fibers. The polymerization of the superabsorbent polymer is integrated into the process of forming the absorbent composite nonwoven web.
EP 1 207 914 further discloses an absorbent structure including an open-cell foam structure wherein the pore walls of the structure include a liquid-storing material, e.g. polyacrylate. The absorbent structure is characterized in that the pores of the foam structure contain hydrophilic fibers, e.g. cellulose fibers, at which at least the main part of the hydrophilic fibers are firmly anchored in the pore walls of the foam structure, and that the fiber amount is at least 10% by weight of the total weight of the open-cell foam in dry condition.
Foam materials made of traditional superabsorbent polymers (e.g. polyacrylic acid/polyacrylate polymers) are usually hard and stiff when dry, and inelastic when wet—they tend to fall apart under pressure. For these reasons, superabsorbent materials are usually included in absorbent articles in granular form.
It would therefore be advantageous to design a new absorbent material including superabsorbent polymers and cellulosic fibers with improved mechanical and gel properties in a swollen condition, and at the same time retain absorbent, spreading and storage properties. In particular, it would be useful to provide an absorbent material which has improved strength, yet which—at the same time—does not suffer from lack of flexibility and brittleness.

Superabsorbent polymer composite comprising a superabsorbent polymer and cellulosic nanofibrils


The present invention provides compositions and methods for producing a heterologous protein of interest by inserting a copy of a gene encoding the heterologous protein of interest into the chromosome of a host cell, such as E. coli. A chromosomal transfer DNA (a circular, non-self-replicating DNA) is used to integrate the gene encoding the heterologous protein of interest into the host cell chromosome. The chromosomal transfer DNA comprises at least one selectable marker and may optionally include repeated DNA sequences flanking the selectable marker, facilitating chromosomal amplification of the integrated DNA. The gene encoding the protein of interest may be expressed after integration into the chromosome of the host cell; selection for chromosomal amplification may be performed prior to expression of the gene.

Genetic engineering has made it possible to produce large amounts of heterologous proteins or polypeptides in bacterial cells by means of recombinant expression systems, especially by expression in such prokaryotes as Escherichia coli (E. coli).
The expressed heterologous proteins may be of mammalian, other eukaryotic, viral, bacterial, cyanobacterial, archaebacterial, or synthetic origin.
Unlike native bacterial proteins, which can often be efficiently accumulated within a bacterial cell even when encoded by a single chromosomal gene copy, there are no published reports to date of heterologous proteins being successfully accumulated within bacterial cells to levels exceeding 0.1% of total cell protein when expressed from a single chromosomal gene location.
0.1% of total cell protein (150 micrograms protein per trillion bacterial cells) is chosen as a practical measure of successful accumulation of protein because it approximately defines the lower limits of (a) economically significant accumulation of a desired protein by contemporary recombinant bacterial production standards, and (b) visual detection of a protein band by Coomassie-stained polyacrylamide gel analysis of whole bacterial cell extracts.
The relatively poor performance of non-bacterial genes when expressed in bacterial cells, even when placed under the control of the strongest known bacterial promoters, has been generally attributed to poor translation of the non-bacterial mRNAs and rapid degradation of newly synthesized non-bacterial proteins. It has almost universally been assumed that, in order to achieve successful accumulation of non-bacterial or heterologous proteins in bacterial cells, the genes encoding the heterologous proteins must be located on multicopy plasmid vectors.
A gene carried on one of the multicopy plasmids commonly used for cloning and expressing genes encoding heterologous proteins in E. coli usually has a copy number of more than 20 copies/cell. Even low copy number plasmids (e.g., pACYC177 and pLG339) generally exist at 6-10 copies per cell. One disadvantage imposed by plasmid gene dosages is that the expression of even minute amounts of some foreign proteins can kill host cells (see Meth. Enzymol. 185:63-65, ed. D. Goeddel, 1990). For this reason, it would be advantageous to reliably limit the copy number of genes encoding such toxic gene products, such as by integrating the gene into the bacterial chromosome at one or a small number of copies per cell. For example, such a system would allow one to make more representative cDNA expression libraries in bacterial hosts if the high-copy expression of one or more of the cDNAs in the library could kill the bacterial host or cause it to grow poorly.
Chromosomal integration of genes encoding heterologous polypeptides would also be advantageous as an alternative means for expression of heterologous proteins in bacterial host cells. Multicopy vectors are often unstable and require the use of antibiotics in the growth medium for maintenance. Present methods of integrating foreign genes into the bacterial chromosome suffer from inefficiency, the inability to control the site of integration of the foreign gene, and/or the inability to control the copy number of the integrated gene. Most importantly, all efforts to date to create recombinant DNA constructs on the bacterial chromosome, wherein a bacterial promoter is fused to a heterologous gene, have involved the creation of viral or plasmid intermediates carrying the construct. Because such intermediates replicate at high copy number, they may be difficult or even impossible to recover in cases where the foreign gene product is toxic to the bacterial cell. Expression of the encoded gene, even at low levels, may be toxic to the host cells, due to the high copy number of these intermediates, which effectively multiplies the level of expression.
Previous methods for achieving the integration of heterologous genes into the chromosome of a bacterial host include the use of phage lambda vectors. The phage DNA in circular form is inserted linearly into the bacterial chromosome by a single site specific recombination between a phage attachment site (attP), 240 bases long, and a bacterial attachment site (attB), only 25 bases long. The two sites have 15 bases in common. This site-specific recombination is catalyzed by a special integrase, specified by the phage gene INT (VIROLOGY pp. 56-57 (Lippincott, 2nd ed., R. Dulbecco and H. Ginsberg, eds., Philadelphia, Pa, 1985).
Phage vectors which are INT.sup.- can be integrated into the chromosome in a normal fashion as long as integrase is supplied in trans, e.g., by an INT+ helper phage (see, e.g., Borck et al. (1976) Molec. Gen. Genet. 146:199-207).
Phage vectors which are both att- and INT- can likewise be integrated into the bacterial chromosome as double lysogens by using att+INT+ helper phage. Double lysogens are formed by linkage of the prophages at the bacterial attachment site and are integrated into the chromosome by general bacterial recombination between homologous sequences on the defective phage and on the helper phage (see e.g., Struhl et al. (1976) Proc. Natl. Acad. Sci. USA 73:1471-1475). Similarly, it is also possible to integrate non-replicating colE1 replicons into the genome of polA strains of E. coli by means of recombination between the host chromosome and homologous sequences carried by the plasmid vector (Greener and Hill (1980) J. Bacteriol. 144:312-321).
More recently, systems have been specifically designed for the integration of foreign genes into a bacterial host chromosome. For example, U.S. Pat. No. 5,395,763 (Weinberg et al.) discloses a chromosomal expression vector for the expression of heterologous genes. This vector was created utilizing a multicopy number plasmid intermediate, into which the gene of interest is cloned, placing the gene in operable linkage with the bacteriophage middle promoter, Pm. This plasmid intermediate, which comprises a defective Mu genome (lacking the genes necessary for the formation of phage particles) is introduced into a packaging strain to produce infectious Mu particles, which are then used to introduce the vector into host cells and integrate the vector into the host cell genome. This vector system is amplifiable once integrated into the host cell genome, but the mechanism of amplification (replicative transposition) is normally toxic to the host cell, due to integration of the replicating prophage into essential host cell genes (Neidhardt et al., ESCHERICHIA COLI AND Society for Microbiology, Neidhardt et al. eds., Washington, D.C., 1987). Because the amplification of this integrated prophage is normally toxic, it is very difficult to obtain and propagate a host cell strain carrying the amplified integrated DNA. This then requires that the gene be amplified each instance that protein production is desired.
Diederich et al. ((1992) "New plasmid vectors for integration into the 1 attachment site attB of the Escherichia coli chromosome", Plasmid 28:14-24) also disclose a system for introducing a gene onto the chromosome of a bacterial host cell. This system utilizes a set of multicopy plasmid vectors which can be integrated into a bacterial chromosome via a phage lambda attachment site. A DNA sequence encoding a promoter operably linked to a gene of interest is cloned into one of the described multicopy number plasmid vectors, the plasmid's origin of replication is removed by restriction enzymes, and the resulting DNA is recircularized and transferred to a host cell, where it integrates into the chromosome.
These new gene transfer systems suffer from the same defect as earlier systems. Both USP 5,395,763 (Weinberg et al.) and Diederich et al. require that the gene of interest be cloned into a multicopy number plasmid while in an operable configuration during the construction of the transfer DNA. The configuration of this multicopy number plasmid makes expression of toxic foreign genes difficult, if not impossible, because the (toxic) gene of interest will be expressed as the multicopy number plasmid is propagated.
Accordingly, there is a need for a method of producing heterologous proteins which can produce large amounts of protein and which minimizes any toxic effect of the heterologous protein to host cells during construction of the producing strain. Applicants have shown surprisingly high protein accumulation (approximately 20% of total cell protein) from expression of low (approximately two) copies of the gene encoding the heterologous protein as shown in Example 2.

Chromosomal expression of heterologous genes in bacterial cells


A grounding switch is comprised of a structural frame, at least one first contact, at least one second contact, at least one spacer, and a geared drive assembly. The opening and closing of the grounding switch is controlled by the geared drive assembly. The geared drive assembly is operable to rotate the at least one second contact around the axis of a connecting rod to move the at least one second contact into and out of contact with the at least one first contact. The closing of the grounding switch first and second contacts serve to connect a transformer or other electrical device to ground potential.

Grounding switches are used in dry-type transformer applications to connect the transformer to ground potential. The primary terminals of the transformer are normally grounded during installation, maintenance and other events through the use of the grounding switch. Typical dry-type grounding switches have a fairly large footprint whether they are located inside or external to a transformer enclosure. The large footprint is due to the size of a drive assembly integrated within the grounding switch. The drive assembly often comprises long connecting rods that are used to open and close the contacts of the grounding switch. When the grounding switch is located inside the transformer enclosure, the size of the transformer enclosure must be increased to accommodate the grounding switch having such a drive assembly. If the grounding switch is externally located, the overall external footprint of the transformer with the grounding switch is relatively large. Therefore, there is room for improvement in grounding switches and more particularly, drive assemblies utilized in grounding switches. The present application is directed to an improved grounding switch with a smaller footprint and providing ease of operation.


A microcontroller system is determining to exit a power saving mode and, in response, enable a reference current source to begin providing a reference current for a memory module. The microcontroller system determines that the reference current has reached a substantial fraction of a target reference current, and, in response to determining that the reference current has reached a substantial fraction of the target reference current, enables the memory module to begin performing one or more memory operations.

Low power consumption is an increasingly important parameter for microcontroller systems. The wakeup time from a power saving mode is also an important parameter. Various components of the system can add to the time for the system to exit a power saving mode. For example, a memory module can increase the wakeup time from a power saving mode by waiting on a reference current source to reach a target reference current, which can vary depending on temperature or other environmental conditions or both.
Conventional systems rely on a system clock to determine how long it takes a reference current source to reach a target reference current. The length of time to wait for the reference current source is fixed based on a maximum estimated time for reaching the target reference current.

Current monitoring circuit for memory wakeup time


An ultrasonic catheter having at least two ultrasonic arrays is provided which has good near and far field resolution and provides an outline of the heart chamber which assists in understanding and interpreting the images obtained by the catheter. Also the ultrasonic catheter allows three dimensional images to be constructed of the region examined by the catheter in a precise but facile manner.

Catheter-mounted ultrasonic transducers have in the past taken several forms, including (1) single-element transducer crystals that are pointed radially outward and rotated about the axis of the catheter, (2) radial phased array transducers and, (3) linear array transducers. For example, Bom U.S. Pat. No. 3,958,502 discloses a catheter with a radial phased ultrasonic array arranged circumferentially around the axis of the catheter. Proudian U.S. Pat. No. 4,917,097 describes a similar catheter with a radial phased ultrasonic array (and alludes to other geometries). Other catheters with radial phased ultrasonic arrays are described in Griffith et al. U.S. Pat. No. 4,841,977; O'Donnell et al. U.S. Pat. No. 5,186,177; and Barlow et al. U.S. Pat. No. 5,456,259. Seward et al. (Seward, J. B., D. L. Packer, R. C. Chan, M. G. Curley, A. J. Tajik (1996)), "Ultrasound Cardioscopy: Embarking on a New Journey," Mayo Clinic Proceedings, 71(7)) describe a catheter having a linear phased ultrasonic array for insertion into the heart. Eberle et al. U.S. Pat. No. 5,368,037 describes a catheter that has an ultrasound transducer array according to several embodiments. In one embodiment the array is configured as a cylinder about a cylindrical core (see FIG. 1 of the '037 patent), in another embodiment the transducer array is a side fire, side-looking linear array (see FIGS. 7A and 7B of the '037 patent) and in another embodiment the transducer array is an end fire, forward-looking array (see FIGS. 8A-C of the '037 patent).
Thus, with respect to known catheters, which incorporate ultrasonic transducer technology, only one type of transducer array is incorporated in the catheter, whether it be a radial phased array, a linear array or single crystal design.
While radial phased transducers provide good near field resolution, i.e. about 1-5 cm, a disadvantage of catheters that utilize a radial phased array is that the radial phased image format generated by the array does not have the diagnostic image resolution or penetration that a linear phased array can produce. In addition, radial phased imaging devices cannot image across the heart to opposite chambers or image larger cardiac structures or image far beyond the vessel it is placed in.
Conversely, while catheters having linear phased arrays have good resolution in the near and far fields, i.e., up to about 12 cm, and are able to image across the heart to opposite chambers, or across vessels to other organs, the location of an image plane is sometimes difficult to interpret.
Thus, it is desirable to provide a catheter incorporating ultrasonic transducer technology that allows good near and far field resolution while accurately depicting the location in the heart or vessel.
In addition, catheters that utilize a single type of ultrasonic transducer array only provide two dimensional information of the region examined by the catheter. Attempts have been made to construct three dimensional images using a catheter with a linear ultrasonic array by collecting multiple two dimensional image data frames using the array mounted on the catheter along with relative positional information among the image data frames so that these image frames may be subsequently assembled into a three dimensional volume to form the desired three dimensional reconstruction. The relative positional information is acquired by externally rotating the catheter while trying to maintain angular control. Such manual techniques are slow and cumbersome and therefore have many drawbacks.
One approach is described in the article by Gussenhoven et al., entitled "Displacement Sensing Device Enabling Accurate Documentation of Catheter Tip Position," Intravascular Ultrasound, pg. 157-166 (1993), involves incrementally inserting a catheter having a radial scanning array into a region of interest to acquire multiple spaced two dimensional radial scans while monitoring the incremental increase in depth of penetration by passing the catheter between rollers which are attached to rotary encoders. The inclusion of mechanical sensing devices, however, compromises reliability of the measurements. In addition, the rollers may slip against the surface of the catheter thereby introducing error in the measurements.
Thus it is also desirable to provide a catheter that incorporates ultrasonic transducer technology that allows three dimensional images to be constructed of the region examined by the catheter in a precise but facile manner.

Ultrasonic catheter, system and method for two dimensional imaging or three-dimensional reconstruction


The present invention provides compositions and methods for the use of antigenic peptides derived from the Fc portion of the epsilon heavy chain of IgE molecules from two unrelated species as vaccines for the treatment and prevention of IgE-mediated allergic disorders. In particular, the invention provides compositions for the treatment and prevention of IgE-mediated allergic disorders comprising an immunogenic amount of one or more antigenic peptides.

Immune-mediated allergic (hypersensitivity) reactions are classified into four types (I-IV) according to the underlying mechanisms leading to the expression of the allergic symptoms. Type I allergic reactions are characterized by IgE-mediated release of vasoactive substances such as histamine from mast cells and basophils. The release of these substances and the subsequent manifestation of allergic symptoms are initiated by the cross-linking of allergen-bound IgE to its receptor on the surface of mast cells and basophils.
An IgE antibody is a complex molecule consisting of two identical heavy chains and two identical light chains held together by disulfide bonds in a "Y" shape-configuration. Each light chain consists of a variable (VL) domain linked to a constant domain (CL), and each heavy chain consists of a variable domain (VH) and four constant domains (CH1, CH2, CH3, and CH4, also known as Cε1, Cε2, Cε3, and Cε4; respectively). The two arms of an IgE antibody contain the site at which an IgE antibody binds to its specific antigen (allergen) and each arm is referred to as a Fab (fragment-antigen-binding) fragment. The tail of an IgE antibody is termed Fc (fragment-crystalline) as it can form crystals when separated from the Fab fragments of the antibody under appropriate experimental conditions. The Fc fragment of an IgE antibody consists of the CH2, CH3, and CH4 domains and contains the biologically active structures of the IgE antibody (e.g., receptor binding sites).
The production of IgE antibodies requires interactions and collaborations among three cells; antigen presenting cells (APC), T lymphocytes (T helper cells; Th) and antibody producing cells (B lymphocytes; B cells). When a foreign substance, an allergen, is introduced for the first time into the body of subjects (e.g., by inhalation of environmental allergen, ingestion of certain foods, or via the skin), the allergen is taken up by APC's (e.g., macrophages) which then digest or process the allergen into smaller fragments (epitopes). These fragments are displayed on the surface of APC's in association with specific molecules known as major histocompatibility complex proteins. The allergen fragment/MHC complex displayed on the surface of APC's is recognized and bound by receptors on the surface of specific T lymphocytes. This recognition and binding event leads to the activation of T lymphocytes and the subsequent expression and secretion of cytokines such as interleukin-4 (IL-4). These cytokines induce the multiplication, clonal expansion and differentiation of B cells specific for the allergen in question (i.e., B cell which express on their surface immunoglobulin receptors capable of binding to the allergen) and ultimately lead to the production of IgE antibodies from these B cells. A portion of the activated T lymphocytes and IgE producing B cells eventually become committed to a pool of cells called T and B memory cells, which are capable of faster recognition of allergen upon subsequent exposure to the allergen.
In individuals suffering from type I allergic reactions, exposure to an allergen for a second time leads to the production of high levels of IgE antibodies specific for the allergen as a result of the involvement of memory B and T cells in the 3-cell interaction required for IgE production. The high levels of IgE antibodies produced cause an increase in the cross-linking of IgE receptors on mast cells and basophils by allergen-bound IgE, which in turn leads to the activation of these cells and the release of the pharmacological mediators that are responsible for the clinical manifestations of type I allergic diseases.
Two receptors with differing affinities for IgE have been identified and characterized. The high affinity receptor (FcεRI) is expressed on the surface of mast cells and basophils. The low affinity receptor (FcεRII/CD23) is expressed on many cell types including B cells, T cells, macrophages, eosinophils and Langerhan cells. The high affinity IgE receptor consists of three subunits (alpha, beta and gamma chains). Several studies demonstrate that only the alpha chain is involved in the binding of IgE, whereas the beta and gamma chains (which are either transmembrane or cytoplasmic proteins) are required for signal transduction events. The identification of IgE structures required for IgE to bind to the FcεRI on mast cells and basophils is of utmost importance in devising strategies for treatment or prevention of IgE-mediated allergies. For example, the elucidation of the IgE receptor-binding site could lead to the identification of peptides or small molecules that block the binding of IgE to receptor-bearing cells in vivo.
Over the last 15 years, a variety of approaches have been utilized to determine the FcεRI binding site on IgE. These approaches can be classified into five different categories. In one approach, small peptides corresponding to portions of the Fc part of an IgE molecule were produced and analyzed for their ability to inhibit IgE from its receptors. See, for example, Nakamura et al., EP0263655 published Apr. 13, 1988, Burt et al., 1987, European Journal of Immunol., 17:437-440; Helm et al., 1988, Nature 331:180-183; Helm et al., 1989, PNAS 86:9465-9469; Vercelli et al., 1989, Nature 338:649-651; Nio et al., 1990, Peptide Chemistry, 2: 203-208; Nio et al., 1993, FEBS Lett. 319:225-228; and Nio et al., 1992, FEBS Lett. 314:229-231. Although many of the peptides described in these studies were shown to inhibit the binding of IgE to its receptors, different studies reported different sequences as being responsible for IgE binding.
Helm et al. (1988, Nature 331:180-183) identified a 75 amino acid peptide that spans the junction between CH2 and CH3 domains of IgE and showed that this peptide binds to the IgE receptor with an affinity close to that of the native IgE molecule. On the other hand, Basu et al. (1993, Journal of Biological Chemistry 268: 13118-13127) expressed various fragments from IgE molecules and found that only those fragments containing both the CH3 and CH4 domains were able to bind IgE and that CH2 domain is not necessary for binding. Vangelista et al. (1999, Journal of Clinical Investigation 103:1571-1578) expressed only the CH3 domain of IgE and showed that this domain alone could bind to IgE receptor and prevent binding of IgE to its receptor. The results of Basu et al. and Vangelista et al. are inconsistent and conflict with those of Helm et al. cited above.
In a second approach to identify the FcεRI binding site on IgE, polyclonal antibodies against peptides corresponding to parts of the CH2 domain, CH3 domain or CH4 domain were produced and used to probe for receptor binding site on IgE (Robertson et al., 1988, Molecular Immunol. 25:103-118). Robertson et al. concluded that the amino acid residues defined by a peptide derived from the CH4 domain were not likely to be involved in receptor binding, whereas amino acid residues defined by a peptide derived from the CH3 domain of IgE were most likely proximal to the IgE receptor-binding site (amino acids 387-401). However, the anti-CH3 peptide antibodies induced in response to the CH3 peptide released histamine from IgE-loaded mast cells indicating that the amino acids defined by the CH3 peptide did not define the bona fide IgE receptor-binding site and that anti-CH3 peptide antibodies could cause anaphylaxis.
In a third approach to identify the FcεRI binding site on IgE, several investigators produced IgE mutants in an attempt to identify the amino acid residues involved in receptor binding (see, e.g., Schwarzbaum et al., 1989, European Journal of Immunology 19:1015-1023; Weetall et al., 1990, Journal of Immunology 145:3849-3854; and Presta et al., 1994, Journal of Biological Chemistry 269:26368-26373). Schwartzbaum et al. demonstrated that an IgE antibody with the point mutation proline to histidine at amino acid residue 442 in the CH4 domain has a two fold reduced affinity for the IgE receptor. Schwartzbaum et al. concluded that the CH4 domain of an IgE antibody is involved in IgE binding to its receptor. However, Schwartzbaum's conclusion contradict Weetall et al.'s conclusion that the binding of IgE to its high affinity receptor involves portions of the CH2 and CH3 domains of the IgE antibody, but not the CH4 domain. Further, Schwartzbaum et al.'s conclusions contradict Presta et al.'s conclusion that the amino acid residues of the IgE antibody important for binding to the FcεRI are located in the CH3 domain.
In a fourth approach to identify the FcεRI binding site on IgE, chimeric IgE molecules were constructed and analyzed for their ability to bind to the FcεRI. Weetall et al., supra constructed a series of chimeric murine IgE-human IgG molecules and tested their binding to the IgE receptor. Weetall et al., supra concluded that the CH4 domain does not participate in receptor binding and that the CH2 and CH3 domains are both required for binding to the high affinity receptor on mast cells. In another study, Nissim et al. (1993, Journal of Immunol 150:1365-1374) tested the ability of a series of human IgE-murine IgE chimera to bind to the FcεRI and concluded that only the CH3 domain is needed for binding to the FcεRI. The conclusion by Nissim et al. corroborates the conclusion by Vangelista et al. that the CH3 domain of IgE alone binds to the FcεRI. However, the conclusions by Nissim et al. and Vangelista et al. contradict the conclusions of Weetall et al. and Robertson et al.
Presta et al., supra produced chimeric human IgG in which the CγH2 was replaced with CH3 from human IgE. When tested for receptor binding, this chimera bound to the FcεRI albeit with a four-fold reduced affinity compared with native IgE. The results of Presta et al. appear to corroborate with the results of Nissim et al., but conflict with those of Weetall et al., Helm et al., and Basu et. al., cited above. In a further attempt to define the exact amino acid residues responsible for the binding of IgE to its receptor, Presta et al. inserted specific amino acid residues corresponding to CH2-CH3 hinge region and three loops from the CH3 domain of human IgE into their analogous locations within human IgG and called these mutants IgGEL. Unfortunately, when these IgGEL variants were tested for receptor binding, they exhibited minimal binding compared to the native IgE or the IgG in which the full length IgE CH3 domain replaced the full length CγH2 domain. In a fifth approach to identify the FcεRI binding site on IgE, monoclonal antibodies have been developed and analyzed for their ability to block IgE binding to the FcεRI. See, for example, Del Prado et al., 1991, Molecular Immunology 28:839-844; Keegan et al., 1991, Molecular Immunology 28:1149-1154; Hook et al., 1991, Molecular Immunology 28:631-639; Takemoto et al., 1994, Microbiology and Immunology 38:63-71; and Baniyash et al., 1988, Molecular Immunology 25:705-711. Although many monoclonal antibodies have been developed, they have provided little information on the bona fide IgE receptor-binding site because in many cases the amino acid sequence recognized by these monoclonal antibodies have not or could not be identified. Further, the monoclonal antibodies developed may block IgE from binding to its receptor by steric hindrance or induction of severe conformational changes in the IgE molecule, rather than by the binding and masking of IgE residues directly involved in receptor binding.
It is apparent from the above discussion that approaches that have been devised to identify the receptor binding site on IgE have produced conflicting results. The difficulty in the identification of the amino acid residues of IgE responsible for receptor binding could be further complicated by the possibility that the site on IgE used for binding to the receptor may not be a linear sequence of amino acids, which could be mimicked by a synthetic peptide. Rather, the binding site may be a conformational determinant formed by multiple amino acids that are far apart in the IgE protein sequence which are brought into close proximity only in the native three-dimensional structure of IgE. Studies with IgE variants, IgE chimera, and monoclonal anti-IgE antibodies strongly suggest that the binding site is a conformational determinant.
Currently, IgE-mediated allergic reactions are treated with drugs such as antihistamines and corticosteroids which attempt to alleviate the symptoms associated with allergic reactions by counteracting the effects of the vasoactive substances released from mast cells and basophils. High doses of antihistamines and corticosteroids have deleterious side effects such as renal and gastrointestinal toicities. Thus, other methods for treating type I allergic reactions are needed.
One approach to the treatment of type I allergic disorders has been the production of monoclonal antibodies which react with soluble (free) IgE in serum, block IgE from binding to its receptor on mast cells and basophils, and do not bind to receptor-bound IgE (i.e., they are non-anaphylactogenic). Two such monoclonal antibodies (rhuMab E25 and CGP56901) are in advanced stages of clinical development for treatment of IgE-mediated allergic reactions (see, e.g., Chang, T. W., 2000, Nature Biotechnology 18:157-62). The identity of the amino acid residues of the IgE molecule recognized by these monoclonal antibodies are not known and it is presumed that these monoclonal antibodies recognize conformational determinants on IgE.
Although early results from clinical trials with therapeutic anti-IgE monoclonal antibodies suggest that these therapies arc effective in the treatment of atopic allergies, the use of monoclonal antibodies for long-term treatment of allergies has some significant shortcomings. First, since these monoclonal antibodies were originally produced in mice, they had to be reengineered so as to replace mouse sequences with consensus human IgG sequences (Presta et al., 1993, The Journal of Immunology 151:2623-2632). Although this "humanization" process has led to production of monoclonal antibodies that contain 95% human sequences, there remain some sequences of mouse origin. Since therapy with these anti-IgE antibodies requires frequent administration of the antibodies over a long period of time, some treated allergic patients could produce an antibody response against the mouse sequences that still remain within these therapeutic antibodies. The induction of antibodies against the therapeutic anti-IgE would negate the therapeutic impact of these anti-IgE antibodies at least in some patients. Second, the cost of treatment with these antibodies will be very high since high doses of these monoclonal antibodies are required to induce a therapeutic effect. Moreover, the frequency and administration routes with which these antibodies have to be administered are inconvenient. A more attractive strategy for the treatment of IgE-mediated disorders is the administration of peptides which induce the production of anti-IgE antibodies.
One of the most promising treatments for IgE-mediated allergic reactions is the active immunization against appropriate non-anaphylactogenic epitopes on endogenous IgE. Stanworth et al. (U.S. Pat. No. 5,601,821) described a strategy involving the use of a peptide derived from the CH4 domain of the human IgE coupled to a heterologous carrier protein as an allergy vaccine. However, this peptide has been shown not to induce the production of antibodies that react with native soluble IgE. Further, Hellman (U.S. Pat. No. 5,653,980) proposed anti-IgE vaccine compositions based on fusion of full length CH2-CH3 domains (approximately 220 amino acid long) to a foreign carrier protein. However, the antibodies induced by the anti-IgE vaccine compositions proposed in Hellman will most likely result in anaphylaxis since antibodies against some portions of the CH2 and CH3 domains of the IgE molecule have been shown to cross-link the IgE receptor on the surface of mast cell and basophils and lead to production of mediators of anaphylaxis (see, e.g., Stadler et al., 1993, Int. Arch. Allergy and Immunology 102:121-126). Therefore, a need remains for vaccines for the treatment of IgE-mediated allergic reactions which do not induce anaphylactic antibodies.
The significant concern over induction of anaphylaxis has resulted in the development of another approach to the treatment of type I allergic disorders consisting of mimotopes that could induce the production of anti-IgE polyclonal antibodies when administered to animals (see, e.g., Rudolf, et al., 1998, Journal of Immunology 160:3315-3321). Kricek et al. (International Publication No. WO 97/31948) screened phage-displayed peptide libraries with the monoclonal antibody BSW17 to identify peptide mimotopes that could mimic the conformation of the IgE receptor binding. These mimotopes could presumably be used to induce polyclonal antibodies that react with free native IgE, but not with receptor-bound IgE as well as block IgE from binding to its receptor. Kricek et al. disclosed peptide mimotopes that are not homologous to any part of the IgE molecule and are thus different from peptides disclosed in the present invention.
A major obstacle facing the development of an anti-IgE vaccine is the lack of information regarding the precise amino acids representing non-anaphylactogenic IgE determinants that could be safely used to immunize allergic subjects and induce non-anaphylactogenic polyclonal antibodies (i.e., polyclonal anti-IgE antibodies that do not bind to receptor-bound IgE). The peptide compositions of the present invention are selected to be non-anaphylactogenic; i.e., the peptide compositions do not result in production of anti-IgE antibodies that could bind or cause cross-linking of IgE bound to mast cells or basophils. Thus peptides of the present invention have superior safety profile and are differentiated by sequence composition from disclosed vaccines based on full-length C2H-CH3 domains.

Non-anaphylactogenic IgE fusion proteins


A method for manufacturing an armature including securing a core to the shaft having a plurality of slots extending in the axial direction formed on the outer circumferential surface thereof, forming a coil composed of a plurality of coil portions by simultaneously winding wires a plurality of turns around a pair of slots separated by a predetermined number of slots and offsetting each of the coil portions one slot at a time in the circumferential direction of the core, securing a commutator to the shaft having a plurality of segments, adjacent coil portions having a slot along one side thereof, and electrically connecting segments which should have the same electric potential by means of equalizing connectors so that each pairs of the segments that should have the same electric potential has a substantially equal electrical potential.

1. Field of the Invention
The present invention relates to an armature for a dynamo-electric machine in which side portions of adjacent coil portions, etc., share a slot.
2. Description of the Related Art
FIG. 11 is a side elevation of an armature 1 for a conventional motor. The armature 1 is disposed so as to be freely rotatable within a stator (not shown) having four poles. The armature 1 comprises: a motor shaft 2; a core 3 secured to the motor shaft 2 having slots 4 extending in the axial direction; a coil 6 composed of wires 5 coated with enamel wound around the core 3; and a commutator 8 secured to the motor shaft 2 at one end of the core 3.
The commutator 8 has twenty-one segments 11; insulating segments 10 electrically insulating the segments 11 from each other; and hooks 12 disposed so as to protrude from each of the segments 11 which are electrically connected to the wires 5.
FIG. 12 is a front elevation of the core 3. Twenty-one slots 4 are formed in the core 3 spaced equidistantly in the circumferential direction and teeth 9 are disposed between the slots 4. The coil 6 is composed of wires 5 wound onto the core by so-called "lap winding".
FIGS. 13 to 15 are diagrams explaining the winding of the wires 5 onto the core 3 by the lap winding method.
FIG. 13 is a diagram showing the wires 5 being simultaneously supplied from the nozzles of a winding device (not shown) which winds the wires 5 onto the core 3, simultaneously forming a first coil portion A 30, a first coil portion B 31, and a first coil portion C 32, respectively. The first coil portion A 30 is formed by winding a wire 5 supplied from a first nozzle, for example, ten or so turns around tooth No. 2 of the teeth 9 and tooth No. 6 of the teeth 9 which are separated by four slots 4. The first coil portion B 31 is formed by winding a wire 5 supplied from a second nozzle, for example, ten or so turns around tooth No. 9 of the teeth 9 and tooth No. 13 of the teeth 9 which are separated by four slots 4. The first coil portion C 32 is formed by winding a wire 5 supplied from a third nozzle, for example, ten or so turns around tooth No. 16 of the teeth 9 and tooth No. 20 of the teeth 9 which are separated by four slots 4.
FIG. 14 is a diagram showing wires 5 continuing to be supplied from the nozzles of the winding device (not shown) after engaging the hooks 12, additionally forming a second coil portion A 36, a second coil portion B 37, and a second coil portion C 38, respectively.
FIG. 15 is a diagram showing the completed winding of the wires 5 between the teeth 9 of the core 3. A third coil portion A 42, a fourth coil portion A 45, a fifth coil portion A 48, a sixth coil portion A 51, and a seventh coil portion A 54 are additionally and continuously formed by the wire 5 supplied from the first nozzle. A third coil portion B 43, a fourth coil portion B 46, a fifth coil portion B 49, a sixth coil portion B 52, and a seventh coil portion B 55 are additionally and continuously formed by the wire 5 supplied from the second nozzle.
In the above motor, the armature 1 is rotated about the motor shaft 2 by electromagnetic action by supplying an electric current to the coil 6 from outside by means of brushes (not shown) which contact the segments 11. The segments 11 contacted by the brushes are switched in succession, switching the direction of the current supplied to the coil 6, so that whatever rotational position the armature 1 is in, the rotating force on the armature 1 is in a specific direction.
In the conventional (but not prior art) armature 1 described above, there are twenty-one slots 4 in total and three nozzles, the total number of slots 4 being evenly divisible by the number of nozzles, and the wires 5 are wound uniformly in each of the coil portions, making the impedance substantially the same in adjacent coils portions.
However, if, for example, the number of slots is increased from twenty-one to twenty-two in order to increase torque, and four nozzles are used to wind the wires onto such a core, as shown in FIG. 17, adjacent coil portions must share a slot along one side.
FIG. 17 is a diagram showing wires being simultaneously supplied to the core from four nozzles of a winding device (not shown) having two rotational angles, 98.2 degrees and 81.8 degrees, as shown in FIG. 16, simultaneously forming a first coil portion A 108, a first coil portion B 109, a first coil portion C 110, and a first coil portion D 111, respectively.
The first coil portion A 108 in FIG. 17 is formed by winding a wire supplied from a first nozzle, for example, ten or so turns around tooth No. 4 of the teeth 107 and tooth No. 22 of the teeth 107 which are separated by four slots 102. The first coil portion B 109 is formed by winding a wire supplied from a second nozzle, for example, ten or so turns around tooth No. 5 of the teeth 107 and tooth No. 9 of the teeth 107 which are separated by four slots 102. The first coil portion C 110 is formed by winding a wire supplied from a third nozzle, for example, ten or so turns around tooth No. 11 of the teeth 107 and tooth No. 15 of the teeth 107 which are separated by four slots 102. The first coil portion D 111 is formed by winding a wire supplied from a fourth nozzle, for example, ten or so turns around tooth No. 16 of the teeth 107 and tooth No. 20 of the teeth 107 which are separated by four slots 102.
In this case, the slot 102 between tooth No. 4 of the teeth 107 and tooth No. 5 of the teeth 107 is shared by a side portion of the first coil portion A 108 and a side portion of the first coil portion B 109, and the slot 102 between tooth No. 15 of the teeth 107 and tooth No. 16 of the-teeth 107 is shared by a side portion of the first coil portion C 110 and a side portion of the first coil portion D 111.
For that reason, differences in impedance arise between the coil portions 108 to 111 in the slots 102 shared by the coil portions 108 to 111 because the wires are wound under conditions in which the coil portions 108 to 111 interfere with each other, leading to the following problems:
Differences in induced voltage arise in the coil portions 108 to 111 and unbalanced currents flow through the brushes, and as a result, the rectifying action of the brushes deteriorates, the temperature in the brushes and the commutator increases together with the increase in sparks generated by the brushes, the life of the brushes and the commutator is reduced, torque ripples increase, and the operating noise of the motor increases markedly due to the combined effects of the above.

Method for manufacturing an armature for a dynamo-electric machine having offsetting and overlapping coils


The present invention comprises a ratchet wrench which has a pawl and spring arrangement such that the pawl's rotational movement is limited when out of engagement with the ratchet wheel so as to assure that the spring does not become disengaged from the pawl to render the wrench inoperative. The spring is provided with a pivotal action which eliminates loading on the end of the spring and provides more desirable spring action.

1. Field of the Invention
This invention relates in general to a ratchet wrench and in particular to an improved ratchet wrench which has an improved pawl and spring.
2. Description of Related Art
Prior art ratchet wrenches utilize a pivoted pawl which engages a ratchet wheel to stop its motion in one direction and which allows it to turn in the opposite direction. A spring engages the pawl to bias it. Under certain conditions, the pawl can rotate beyond its intended position such that the spring disengages the pawl and can fall out of the wrench. When this occurs, the ratchet wrench is rendered inoperative.
See also U.S. Pat. Nos. 5,010,792, 3,742,788, 5,157,994, 2,500,835, 1,903,514, 1,459,591, 1,455,147 and 2,507,455.


A thruster pig for sending through a pipe from an entrance facility to a receiving location, for servicing or monitoring, by pumping a thrusting fluid into the pipe to force the pig forward is disclosed. The thruster pig includes a body having a front end and a back end, where the back end includes a reaction surface to which said the thrusting fluid applies a motive force. The body is slightly smaller in diameter than the inner diameter of the pipe. The pig also includes a seal circumferentially arranged on the pig to seal between said body and said pipe. A desired differential pressure is maintained over the pig to urge said pig forward through the pipe by pumping a fluid into the annulus between the pipe and the return flow line while returning fluid through said return flow line utilizing connected servicing or monitoring equipment. A connector releasably connects a return flow line to the pig. The connector includes a shifting mandrel that may be activated to open the connector by a ball pumped through the return flow line, where the ball is retained in the return flow line after releasing the connector. A blanking device is then provided to blank the bore within the pig that is left after the return flow line is disconnected.

Pigs are currently available in many designs for many operations for diverse industries. Pigs can be passively flowing with the flow in a pipeline, without external connection, or the pig can be connected to, for example a line, a pipe or coiled tubing. Such a connection is usually used for withdrawing the pig. A description of pig technology can be found in U.S. Pat. No. 6,651,744 B1 entitled "Bi-Directional Thruster Pig Apparatus and Method of Utilizing Same" which is considered the closest prior art to the present invention. Relevant background art is also described in U.S. Pat. No. 6,315,498 B1 entitled "Thruster Pig Apparatus For Injecting Tubing Down Pipelines"; U.S. Pat. No. 6,122,791 entitled "Retrievable Pig"; U.S. Pat. No. 6,343,657 B1 entitled "Method of Injecting Tubing Down Pipelines"; and U.S. Pat. No. 6,260,617 B1 entitled "Skate Apparatus for Injecting Tubing Down Pipelines". The above-identified patents are incorporated herein by reference.
A thruster pig is urged into a pipe by pumping a fluid into the pipe at a location behind the pig such that the pig is pushed further into the pipe by said pressurized fluid. If the pipe bore is completely blocked with, for example, hydrates, only a thruster pig system with a return flow line or flow way is useful, since fluid ahead of the pig must be taken out to avoid pressure buildup against the blockage. Thruster pigs having a separate flow line connected have so far been designed with connections and flow line both for fluid flow delivery or return, as well as for withdrawing both the coiled tubing and the connected pig. The separate flow line often consists of coiled tubing.
The insertion and withdrawal of pigs connected to coiled tubing become more difficult as the injection length of the pig and coiled tubing increases, the number of bends increases, and the extent of horizontal or upwards sloping sections in the pipe increases. Such difficulties limit the usability of thruster pigs.
Particularly in the oil and gas industry the demand for pigging operations is significant. Severe problems often occur in long subsea pipelines at large depths and in cold waters. Such problems may include hydrate formation blocking the pipelines, in addition to various deposits such as ice, wax and debris. The initially warm well fluid is cooled down by cold seawater, thereby inducing condensation, precipitation and hydrate formation. Hydrates can be melted with thermodynamic inhibitors such as MEG (glycol coolant) or methanol shifting the melting point of the hydrates to below the ambient temperature. In case of a shutdown or failure in the inhibitor injection system, severe blocking by hydrates is likely.


Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are amide compounds which can be prepared from certain heteroaryl carboxylic acids and certain diazabicycloalkanes. The compounds exhibit selectivity for, and bind with high affinity to, neuronal nicotinic receptors of the α4β2 subtype in the central nervous system (CNS). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, particularly CNS disorders. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects, and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g. side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastrointestinal tract, and significant effects upon skeletal muscle).

The therapeutic potential of compounds that target neuronal nicotinic receptors (NNRs), also known as nicotinic acetylcholine receptors (nAChRs), has been the subject of several recent reviews (see Breining et al., Ann. Rep. Med. Chem. 40: 3 (2005), Hogg and Bertrand, Curr. Drug Targets: CNS Neurol. Disord. 3: 123 (2004), Suto and Zacharias, Expert Opin. Ther. Targets 8: 61 (2004), Dani et al., Bioorg. Med. Chem. Lett. 14: 1837 (2004), Bencherif and Schmitt, Curr. Drug Targets: CNS Neurol. Disord. 1: 349 (2002)). Among the kinds of indications for which NNR ligands have been proposed as therapies are cognitive disorders, including Alzheimer's disease, attention deficit disorder and schizophrenia (Newhouse et al., Curr. Opin. Pharmacol. 4: 36 (2004), Levin and Rezvani, Curr. Drug Targets: CNS Neurol. Disord. 1: 423 (2002), Graham et al., Curr. Drug Targets: CNS Neurol. Disord. 1: 387 (2002), Ripoll et al., Curr. Med. Res. Opin. 20(7): 1057 (2004), and McEvoy and Allen, Curr. Drug Targets: CNS Neurol. Disord. 1: 433 (2002)); pain and inflammation (Decker et al., Curr. Top. Med. Chem. 4(3): 369 (2004), Vincler, Expert Opin. Invest. Drugs 14(10): 1191 (2005), Jain, Curr. Opin. Inv. Drugs 5: 76 (2004), Miao et al., Neuroscience 123: 777 (2004)); depression and anxiety (Shytle et al., Mol. Psychiatry 7: 525 (2002), Damaj et al., Mol. Pharmacol. 66: 675 (2004), Shytle et al., Depress. Anxiety 16: 89 (2002)); neurodegeneration (O'Neill et al., Curr. Drug Targets: CNS Neurol. Disord. 1: 399 (2002), Takata et al., J. Pharmacol. Exp. Ther. 306: 772 (2003), Marrero et al., J. Pharmacol. Exp. Ther. 309: 16 (2004)); Parkinson's disease (Jonnala and Buccafusco, J. Neurosci. Res. 66: 565 (2001)); addiction (Dwoskin and Crooks, Biochem. Pharmacol. 63: 89 (2002), Coe et al., Bioorg. Med. Chem. Lett. 15(22): 4889 (2005)); obesity (Li et al., Curr. Top. Med. Chem. 3: 899 (2003)); and Tourette's syndrome (Sacco et al., J. Psychopharmacol. 18(4): 457 (2004), Young et al., Clin. Ther. 23(4): 532 (2001)).
A limitation of some nicotinic compounds is that they are associated with various undesirable side effects, for example, by stimulating muscle and ganglionic receptors. It would be desirable to have compounds, compositions and methods for preventing and/or treating various conditions or disorders (e.g., CNS disorders), including alleviating the symptoms of these disorders, where the compounds exhibit nicotinic pharmacology with a beneficial effect (e.g., upon the functioning of the CNS), but without significant associated side effects. It would further be highly desirable to provide compounds, compositions and methods that affect CNS function without significantly affecting those receptor subtypes which have the potential to induce undesirable side effects (e.g., appreciable activity at cardiovascular and skeletal muscle sites). The present invention provides such compounds, compositions and methods.

Nicotinic acetylcholine receptor sub-type selective amides of diazabicycloalkanes


A standard-SIP (session initiation protocol) protocol control module and an expanded sip protocol control module are provided so as to correspond to respective Sip protocol corresponding terminals, such as wireless LAN terminals compliant with the SIP. A signal (a request) from each Sip protocol corresponding terminal is converted into a signal according to a protocol of an IP-PBX and is sent to a PBX basic-connection-processing providing module. A signal (a response for the request or a request to the Sip protocol corresponding terminal) from the PBX basic-connection-processing providing module is converted into an Sip protocol signal and is sent to the Sip protocol corresponding terminal. A location-information management module collects a basic service set identifier (BSSID) from each wireless LAN network and stores the BSSID information into a database.

1. Field of the Invention
The present invention relates to networks, private branch exchanges (PBXs), wireless local-area-network (LAN) terminals, and multiprotocol communication-terminal control methods therefor, and, more particularly, to a terminal connected to a network including an internet-protocol (IP) private branch exchange.
2. Description of the Related Art
This type of network has heretofore been constituted by connection of a private branch exchange to a fixed phone terminal, a radio terminal such as a personal handy-phone system (PHS), a voice over Internet protocol (VoIP) terminal or the like via a local area network (LAN).
As the VoIP terminal, in addition to an IP phone terminal and an Internet phone terminal, there is a session initiation protocol terminal. The SIP is a communication protocol for use in starting or ending multimedia communication such as sound communication (fixed phone, cellular phone, etc.), video communication such as television phone, chat (conversation by characters) and the like in an environment of an IP network using data having a form referred to as an IP packet.
In the IP network, in general, connection-less type communication is performed without confirming connection to a target as in electronic mails. On the other hand, in the fixed phone, in general, connection type communication is performed while confirming the connection with the target. The SIP realizes the connection type communication in the IP network.
The SIP basically comprises methods (operations) such as INVITE (session between users is established), ACK (acknowledgment), CANCEL (INVITE is ended during the establishment of the session), and BYE (the end of the session). The respective methods are exchanged as requests and responses to the requests between clients and servers to thereby establish or end the session.
Moreover, the SIP has characteristics that applications can be comparatively easily prepared. For example, when a new service is added to H.323 of ITU-T for use in the IP phone, an H.450.x protocol which defines the H.323 additional service is added, and all H.323 end points on the network and software of a gate keeper need to be updated. However, in the SIP, an SIP application server which provides the new service is added, and the corresponding application is added. Then, the new service is usable.
Japanese Unexamined Patent Publication (JP-A) H11-341532A and an article entitled "SIP: Session Initiation Protocol" (RFC (Request for Comments) 3261, June 2002, pp. 8-34) disclose the earlier techniques described above.
In the known network described above, wireless terminals, such as PHS terminals, can connect to a private branch exchange via an access point included in a wireless LAN, but has a problem. Specifically, even when an SIP-compliant wireless terminal is covered by services of the private branch network, only limited services (e.g., a transfer service, three-way calling service, and call waiting service) defined by IETF (Internet Engineering Task Force) can be offered for communication between the wireless terminal and the SIP terminal.
That is, even when the wireless terminal and the SIP terminal are connected to the network, there is a problem in that a wide range of services (e.g., a call-back service, extension-call interruption service, third-party control service) are not available for communication between the wireless terminal and the SIP terminal.
Further, since the wireless terminal is connected to the private branch exchange via an access point, the wireless terminal can connect to the private branch exchange anytime and anywhere as long as an access point exists at a location to which the user of the terminal wireless moves. This makes it difficult to keep a track of the current location of the user.

Network, private branch exchange, wireless LAN terminal, and multiprotocol communication terminal control method therefor


Machines, systems and methods for efficient data communication are provided. The method comprises receiving a data packet to be transmitted to a destination node in a overlay-based communications network, wherein the destination information is included in a virtual header that includes a virtual address of the destination node; determining a physical address of the destination node based on the virtual address of the destination node; replacing the virtual header for the received data packet with a physical header that includes the physical address; and transmitting the data packet over the communications network to a destination host based on the physical address included in the physical header.

In modern, large-scale, virtualized, multi-tenant environments (e.g., enterprise data centers, private and public clouds, etc.), requirements towards the interconnect technology are different and more demanding than in traditional data centers. These requirements (i.e. multi-tenant isolation, management scalability, operational flexibility, etc.) call for virtualizing the networking infrastructure, where the compute and the storage resources are virtualized.
While there are multiple approaches to network virtualization, network virtualization solutions by many vendors involve overlays to achieve isolation and separation from the physical infrastructure and centralized control to achieve flexible and scalable controllability with the logically centralized controller commanding forwarding devices. A typical drawback associated with using overlays is the encapsulation overhead.
The overhead is manifested in (1) higher processing overheads in adding and removing encapsulation headers by forwarding devices, (2) increase in the packet size, and (3) additional fragmentation and disabling the hardware off-load engines. While smart encapsulation formats and offload techniques may be used to avoid fragmentation and benefit from hardware acceleration, such methods do not address the added overhead associated with the processing and large packet.

Reducing encapsulation overhead in overlay-based networks

International Business Machines Corporation