The present invention involves methods, systems, and devices for analyzing a biological material, such as a cellular or other specimen. The method includes placing the specimen on a substrate having different capture regions, such as contiguous layers, wherein the different capture regions of the substrate contain different identification molecules, and transferring components of the specimen through the capture regions under conditions that allow the components to interact with different identification molecules in the different regions of the substrate. The components of the specimen can be transferred through the different layers (or other regions) of the substrate by capillary action of a solution moving through the cellular specimen or by electrophoresis. The transfer of components of the specimen through the substrate may occur while maintaining a geometric correspondence to the specimen, such as the cytoarchitecture of a cellular specimen, for example by moving the components through parallel layers having positions that correspond to positions within the specimen. When the cellular architecture of the specimen is maintained, a correlation between the different identification molecules and the components of the cellular specimens may be made. The analysis can occur with one or more different discrete (for example cellular) specimens on a surface of the substrate. Examples of cellular specimens include, but are not limited to tissue sections, particularly tumor tissue sections. The cellular specimen can also include cultured cells or a cytology sample. Cytostat tissue sections cut slightly thicker than usual, that is about 25 to about 50 μm, improves the ability to detect molecules of moderate and low level abundance.

The Human Genome Project and other gene discovery initiatives are dramatically increasing the information available regarding the number, genomic location, and sequences of human genes. Accompanying the expanding base of genetic knowledge are several new technologies geared toward high-throughput mRNA and proteomic analysis of biological samples, allowing a global view of the genes and gene products that reflect normal physiology and pathological states. Utilized together, the expanding genetic database and newly developing analysis technologies hold tremendous potential to increase the understanding of normal cellular physiology and the molecular alterations that underlie disease states. However, many biological specimens, such as whole cell tissue samples, remain uniquely difficult to analyze due to their complex cellular heterogeneity.
The first report of the application of tissue sections directly onto paper strips and subsequent electrophoresis was made by Lindner et al. (1956). Later, Saravis et al. (1979) utilized agarose gels and Bonte (1978) utilized polyacrylamide gels to achieve better separation of the analyzed proteins. As reported in a review by Neuhoff (1980), routine application of these procedures to whole cell tissues was not widespread because of technical difficulties, so methods using extraction of the proteins from the sample through cell lysis before separation predominated.
More recently, Inczedy-Marcsek et al. (1988) described the use of electrophoresis and isoelectric focusing of cryostat samples placed directly upon ultra thin polyacrylamide gels. The use of ultra thin gels allowed for extraction of the proteins from the tissue sample without lysis of the cells of the sample, and did overcome some of the technical difficulties experienced by early workers in this field. Schumacher et al. (1990) also described the use of isoelectric focusing to identify enzymes, glycoproteins, and neuropeptides present in cryostat sections. This process involved the direct placement of the sample upon ultra thin gels, followed by isoelectric focusing. The processes of both Inczedy-Marcsek et al. and Schumacher et al. produce gels in which the proteins or other molecules of interest move through the gel medium according to physical characteristics related to charge and molecular weight. However, these approaches provide information only on the total molecular content of the sample being analyzed, representing the aggregate proteins and nucleic acids present in all of the various cell types present in the specimen.
Isofocusing and electrophoresis processes have been disclosed for cryostat tissue samples, followed by immunochemical analysis. Specifically, Schumacher and Trudrung (1991) and van der Sluis et al. (1988) describe the identification of alkaline phosphatases and peptides such as vassopressin, respectively, through direct tissue isoelectric focusing followed by Western blotting. This immunochemical analysis technique involves the movement of the protein or molecules of interest, through capillary action, from the focusing gel to nitrocellulose membranes. The membrane-bound protein is then detected using immunostaining procedures. Van der Sluis et al. (1988) did attempt to generally localize the proteins within the tissue sample by applying this procedure to a series of sliced tissue sections. However, the immunodetection process was preceded by an isofocusing step, so the results only indicated presence of the protein within a particular tissue sample.
Molecular analysis of cell populations in tissue sections have been performed using immunohistochemistry (IHC) and in-situ hybridization (ISH). The ISH technique is reviewed by Jin and Lloyd (1997), and the IHC technique is reviewed by Grogan (1992). While these techniques have been valuable tools to investigate the cellular localization of a particular protein or mRNA in a complex tissue section, they both suffer from three major drawbacks. First, IHC and ISH are limited to analysis of a single molecular species per sample. Second, artifact staining based on cross-hybridization severely affects the accuracy of the test results. Finally, these methods have limited ability to visualize proteins and mRNAs expressed at moderate or low levels of abundance.
Techniques have been disclosed for separating particular subsets of cells from a whole tissue sample. For example, Emmert-Buck et al. (1996) describe the use of laser-based microdissection techniques to rapidly procure microscopic, histopathologically defined cell populations. Alternatively, tissue arrays, such as those described by Kononen et al. (1998) permit individual molecules to be studied simultaneously in hundreds of separate tissue samples. However, there remains a need in the art for an improved method of analyzing proteins or other molecules of interest present in cellular specimens where the method is capable in some embodiments of providing information concerning the location of the proteins or molecules of interest in the initial tissue sample, and/or provide a method that avoids some of the problems encountered with IHC and ISH.

Layered device with capture regions for cellular analysis

The United States of America as represented by the Secretary of the Department of Health and Human Services


A method and a system for collection of harvested tree-fruit having a collection device mounted on a hauled cart. For fruit collection, two arms are extended under the foliage of a tree to spread an apron hung between them, in a fruit receiving position. After harvesting is completed, and the apron contains the harvested fruit, the arms draw the apron away from under the tree, and swing through an arc of a circle to stop in a fruit discharge position, where fruit is discharged by gravity into the open top opening of the cart. Then, the arms are returned back from the discharge position to the fruit receiving position.

Economic pressure requires agricultural processes, alike industrial processes, to operate mechanically, thus with a minimum of manpower, and to yield superior results in the shortest possible time. Consequently, for the sake of efficient tree harvesting and fruit collection, fruit-tree grooves are planted in successive rows between which dedicated fruit harvesting and fruit collection equipment operates. Nowadays for example, mechanical harvesting is achieved by running a motorized harvester along a first row-side of a row of trees, stopping to clamp a vibrator on each successive tree-trunk, and using a deflector to guide the harvested fruit to the second row-side, for collection. In association with the deflector supported by the harvester on the first row-side, the fruit collection equipment being operated on the second row-side receives the fruit and forwards it for further transportation.
In U.S. Pat. Nos. 5,469,695 and 5,816,037, the present applicants disclose equipment for mechanical harvesting and for the collection of fruit from harvested trees, but those means are rather bulky, and expensive to acquire and maintain.
The terms "mechanical" and "mechanically" are used hereinbelow to define operations not requiring manual labor or manual intervention, besides the operation of controls by an operator or a driver.
Fruit collection equipment is required to feature simple construction, operate fast and reliably at minimal maintenance costs, and be offered to the market at low acquisition price. This contrasts with the hereinabove-mentioned fruit collection means, which are expensive to acquire and to maintain.

Mechanical collection of harvested tree-fruit


Provided are an insulation-coated oriented magnetic steel sheet having an insulating coat with excellent heat resistance; and a method for manufacturing the same. This insulation-coated oriented magnetic steel sheet has an oriented magnetic steel sheet, and an insulating coat arranged on the surface of the oriented magnetic steel sheet, the insulating coat containing Si, P, O, and Cr, and at least one element selected from the group consisting of Mg, Ca, Ba, Sr, Zn, Al, and Mn. The XPS spectrum of the outermost surface of the insulating coat has peaks observed at Cr2p1/2 and Cr2p3/2.

In general, a grain oriented electrical steel sheet (hereinafter also referred to simply as "steel sheet") is provided with a coating on its surface to impart insulation properties, workability, corrosion resistance and other properties. Such a surface coating includes an undercoating primarily composed of forsterite and forayed in final finishing annealing, and a phosphate-based top coating formed on the undercoating.
Of the coatings formed on the surface of the grain oriented electrical steel sheet, only the latter top coating is hereinafter called "insulating coating."
These coatings are formed at high temperature and further have a low coefficient of thermal expansion, and are therefore effective in imparting tension to the steel sheet owing to a difference in coefficient of thermal expansion between the steel sheet and the coatings when the temperature drops to room temperature, thus reducing iron loss of the steel sheet. Accordingly, the coatings are required to impart the highest possible tension to the steel.
In order to meet such a requirement, for example, Patent Literatures 1 and 2 disclose insulating coatings each formed using a treatment solution containing a phosphate (e.g., aluminum phosphate, magnesium phosphate), colloidal silica, and chromic anhydride.
The grain oriented electrical, steel sheet with an insulating coating may be hereinafter also simply called "grain oriented electrical steel sheet" or "steel sheet."

Insulation-coated oriented magnetic steel sheet and method for manufacturing same


A vehicle seat that accommodates at least two users includes a seating portion frame, a first backrest and a second backrest which are pivotally hinged to the seating portion frame according to a transverse axis, via a common hinge. The common hinge includes: a pivot pin comprising a first lateral portion, and a first housing arranged on the first backrest and receiving interiorly the first lateral portion by authorizing the rotation of the first backrest. The first lateral portion has a protruding rib and the first housing has a substantially keyhole shape, complementary with the radial section of the first lateral portion. The rib is oriented, according to an angle of between 30° and 60° relative to the vertical direction of the vehicle seat.

In a well-known manner, a vehicle generally comprises at least one seat intended for accommodating a driver or a passenger of the vehicle, hereinafter designated by the term "user". The seat can be intended for accommodating a single person or several persons sitting side by side, and can be disposed at the front or at the rear of the vehicle. The seat can also be part of a bench that can accommodate several persons side by side.
Thus, in terms of the invention, the term "seat" according to the invention designates a front seat of the vehicle as well as a rear seat of the vehicle. Likewise, the invention can be implemented for seats intended for any type of vehicle and in particular automobile vehicles.
A vehicle seat generally comprises a seating portion frame, provided to be connected to the floor of a vehicle.
A vehicle seat, which is provided to accommodate at least two passengers side by side, also comprises at least one first backrest, pivotally hinged according to the transverse axis of the seat to the seating portion frame, as well as one second backrest, also pivotally hinged to the seating portion frame according to said transverse axis.
In a known manner, a common hinge at the seating portion frame can be provided for the first backrest and the second backrest, at an intermediate zone of the seating portion frame, in the transversal direction of the seat, comprising a common pivot pin received simultaneously in a corresponding housing, arranged in each one of the first and of the second backrest, and so as to allow for the hinging of the first backrest and of the second backrest relative to the seating portion frame.
Such a common pivot pin is fastened to the seating portion frame, so as to remain immobile relative to the latter.
Generally, the pivot pin comprises a central portion, a first lateral portion and a second lateral portion, the two lateral portions being positioned on either side of the central portion according to the axis of the pivot pin.
Moreover, the first backrest generally comprises a first wall wherein a first housing is arranged receiving interiorly the first lateral portion of the pivot pin, by authorizing the rotation of the pivot pin relative to said housing, about the axis of the pivot pin.
In the same way, the second backrest generally comprises a second wall wherein a second housing is arranged receiving interiorly the second lateral wall of the pivot pin, by authorizing the rotation of the pivot pin relative to said housing, about the axis of the pivot pin.
A rib protruding in a radial direction can be provided on the first lateral portion of the pivot pin of the pivot pin and extending opposite the axis of the pivot pin.
Also, the first housing can have a substantially keyhole shape, complementary with the radial section of the first lateral portion of the pivot pin and of the rib, with a circular portion and a substantially rectangular portion communicating together, the substantially rectangular portion being positioned above the circular portion of the first housing, in the vertical direction of the seat, when the first backrest is in a raised position, oriented substantially in the vertical direction of the seat.
So as to prevent the sliding of the first backrest relative to the pivot pin along the axis of the pivot pin, after the mounting of the first backrest on the pivot pin, said first housing and said first lateral portion of the pivot pin can be configured in such a way that:                in a first position of the first backrest relative to the pivot pin about the axis of the pivot pin, the first lateral portion and the rib are able to slide through the first housing according to the axis of the pivot pin, and        in at least one second position of the first backrest relative to the pivot pin about the axis of the pivot pin, the sliding of the first lateral portion and the rib through the first housing, according to the axis of the pivot pin, is prevented, the rib being, at least partially, facing the first wall in the vicinity of the first housing, and facing the first backrest in the extension of the latter at the front in the longitudinal direction of the seat.
Generally, the rib is oriented, from the bottom upwards in the clockwise direction, with an angle comprised between −20° and +20° relative to the vertical direction of the seat about the axis of the pivot pin.
According to the observances of the inventor, such a positioning of the rib relative to the vertical direction of the seat has the major disadvantage that during an impact received by said seat, and in particular by the first backrest, when said first backrest is oriented substantially in the vertical direction of the seat, for example in case of projection of an element located at the rear of the seat against said first backrest, such as for example baggage located in the boot of the vehicle receiving said seat, said rib will abut against said first wall of the first backrest and damage the latter and deform the first housing. Thus, the shape of the first housing is no longer adapted to prevent the sliding of the first lateral portion and the rib through the first housing according to the axis of the pivot pin in said or in each one of said second positions. The first backrest then risks disengaging from the pivot pin, which represents a high risk for the safety of a user received on said first backrest of the seat, who is, in the normal position of use, oriented substantially in the vertical direction of the seat.


A nonvolatile memory device includes multiple first bit lines extending in a first direction, multiple word lines formed on the first bit lines and extending in a second direction different from the first direction, and multiple second bit lines, formed on the word lines and extending in the first direction. The nonvoliative memory device also includes multiple twin memory cells, each of which includes a first memory cell coupled between a first bit line and a word line and a second memory cell coupled between the word line and a second bit line. The first and second memory cells store different data.

1. Field of the Invention
The present invention relates to a nonvolatile memory device, and more particularly, to a nonvolatile memory device having twin memory cells.
2. Description of the Related Art
Nonvolatile memory devices using resistance materials include Resistive Random Access Memory (RRAM), Phase-change RAM (PRAM), and Magnetic RAM (MRAM). Dynamic RAM (DRAM) and flash memory devices store data using charges. Nonvolatile memory devices using resistance materials may store data using the resistance change of variable resistive elements (for example, RRAM), phase change of phase change materials, such as chalcogenide alloy (for example, PRAM), and resistance change of Magnetic Tunnel Junction (MTJ) thin films according to the magnetization state of a ferromagnetic substance.
More particularly, a resistance memory cell includes a variable resistive element between an upper electrode and a lower electrode, and the resistance level of the variable resistive element may be changed according to a voltage supplied to the upper and lower electrodes. The state where the variable resistive element has a high resistance is defined as high resistance data, which is reset data (1), and the state where the variable resistive element has a low resistance is defined as low resistance data, which is set data (0).

Nonvolatile memory device having twin memory cells


The invention relates to stable aqueous compositions of granulocyte colony stimulating factor that have a pH in the range of pH 5 to pH 8 and comprise a salt comprising sulfate ions, and to uses thereof.

The present invention is directed toward aqueous compositions of granulocyte colony stimulating factor (G-CSF), particularly non-glycosylated G-CSF, having a pH of from about 5.0 to about 8.0, and a salt comprising sulfate ions at a concentration of from about 0.01M to about 1.0M.
The presence of the salt comprising sulfate ions unexpectedly stabilizes non-glycosylated G-CSF in an aqueous composition having a pH from about 5.0 to about 8.0.
Colony stimulating factors induce proliferation, development and maturation of specific haematopoietic cells. G-CSF, in particular, leads to enhanced levels of circulating polymorphonuclear neutrophils (PMN), which play critical roles in the destruction of infectious agents. Human granulocyte colony stimulating factor (hG-CSF), for example, is used to stimulate haematopoiesis to protect patients undergoing bone marrow-suppressive chemotherapy against opportunistic infections.
G-CSF may also be used to afford similar protection for domesticated animals such as cattle, dogs, and cats. Infectious diseases in cattle and milk-producing cows, including shipping fever and bovine mastitis respectively, are a source of significant, persistent economic losses.
Shipping fever encompasses a collection of respiratory ailments afflicting cattle that are often detected in stressed animals within a population assembled from a number of different sources into a feed lot. The initial infections, generally caused by mycoplasma, chlamydia, bacteria, viruses, or mixtures thereof, are highly contagious and, although usually not lethal, they leave the animal in a debilitated state. Subsequent infection by another, opportunistic organism, especially Pasteurella haemolytica, is often the cause of mortality under these circumstances, rather than the initial infection. Bovine mastitis refers to an infection of the udders that may be caused by either gram negative or gram positive organisms. These infections are also highly contagious and may lead to a significant reduction in milk production by the affected cow, and, if scarring occurs, this loss may be permanent. Accordingly, methods and compositions that permit successful treatment of domesticated species with G-CSF could prevent or ameliorate the effects of such infectious diseases in such commercially important animals.
Mature bovine granulocyte colony stimulating factor, bG-CSF (GenBank Accession Number AF0925333), consists of 174 amino acids, of which 82% are identical with those in the corresponding human protein (GenBank Accession Number M17706). Both the human and bovine granulocyte colony stimulating factors are hydrophobic proteins, which include an odd number (five) of cysteine residues. Consequently, at least one of the cysteine side chains will present a free thiol moiety that may lead to the formation of untoward intramolecular and intermolecular disulfide linkages, resulting in the accumulation of insoluble, biologically inactive, dimeric or polymeric structures. This hypothesis has been proposed as one possible explanation for the observation that hG-CSF, bG-CSF and other G-CSF molecules, particularly recombinant, non-glycosylated forms produced in prokaryotic hosts, are difficult to formulate as stable, pharmaceutically acceptable compositions.
Glycosylated hG-CSF has been compared with de-glycosylated hG-CSF, prepared by in vitro enzymatic digestion with neuraminidase and endo-xcex1-N-acetylgalactosaminidase, with respect to its stability as a function of pH and temperature (Oh-eda et al., 1990, J. Biol. Chem. 265 (20): 11432-35). The de-glycosylated hG-CSF, dissolved at a concentration of 1 xcexcg/mL in 20 mM phosphate buffer containing 0.2 M NaCl and 0.01% Tween 20 was rapidly inactivated within the pH range of from about pH 7 to about pH 8 after a two-day incubation at 37xc2x0 C. In contrast, glycosylated hG-CSF retained over 80% of its activity under the same conditions. Furthermore, evaluation of the thermal stability of both forms of hG-CSF, measured by biological assay and calorimetric analysis, indicated that de-glycosylated hG-CS F was less thermally stable than the native form of hG-CSF.
A number of approaches have been taken in order to provide stable, pharmaceutically acceptable G-CSF compositions. One approach to improving the composition stability of G-CSF involves the synthesis of derivatives of the protein. U.S. Pat. No. 5,665,863 to Yeh (the xe2x80x9c""863 patentxe2x80x9d) discloses the formation of recombinant chimeric proteins comprising G-CSF coupled with albumin, which have new pharmacokinetic properties. U.S. Pat. No. 5,824,784 to Kinstler et al. (the xe2x80x9c""784 patentxe2x80x9d) and U.S. Pat. No. 5,320,840 to Camble et al., (the xe2x80x9c""840 patentxe2x80x9d) disclose the chemical attachment of water-soluble polymers to proteins to improve stability and provide protection against proteolytic degradation. More specifically, the ""784 patent discloses N-terminally modified G-CSF molecules carrying chemically attached polymers, including polyethylene glycol.
An alternative approach to increasing stability of G-CSF in composition involves alteration of the amino acid sequence of the protein. U.S. Pat. No. 5,416,195 to Camble et al. (the xe2x80x9c""195 patentxe2x80x9d) discloses genetically engineered analogues of G-CSF having improved composition stability, wherein the cysteine residue normally found at position 17 of the mature polypeptide chain, the aspartic acid residue found at position 27, and at least one of the tandem proline residues found at positions 65 and 66, are all replaced with a serine residue. Furthermore, U.S. Pat. No. 5,773,581 to Camble et al. (the xe2x80x9c""581 patentxe2x80x9d) discloses the genetically engineered G-CSF analogues of the ""195 patent that have been covalently conjugated to a water soluble polymer.
Other approaches to improving the composition stability of G-CSF molecules have involved modification of the solvent in which the G-CSF is dissolved. U.S. Pat. No. 5,104,651 to Boone et al. (the xe2x80x9c""651 patentxe2x80x9d) discloses improved stability of G-CSF under conditions of low pH and minimal ionic strength. The ""651 patent discloses a stabilized pharmaceutically acceptable composition consisting essentially of a pharmaceutically acceptable amount of G-CSF and acid, where the composition has a pH of 3.0 to 3.7 and a conductivity of less than 1000 xcexcmhos/cm. In a preferred embodiment of this invention, no salt, other than a residual trace derived from the purification process, will be included in the composition.
U.S. Pat. No. 5,874,075 to Collins et al. (the xe2x80x9c""075 patentxe2x80x9d) discloses stable compositions of proteins, including G-CSF, comprising a liposome vesicle composed of negatively charged phospholipids, where only a portion of the protein is inserted into the lipid portion of the vesicle. The ""075 patent also discloses compositions comprising liposome vesicles combined with G-CSF that has been covalently linked with polyethylene glycol.
A stable G-CSF containing composition is disclosed in GB 2193621 A (the xe2x80x9c""621 application), which comprises at least one substance selected from the group consisting of a pharmaceutically acceptable surfactant, saccharide, protein and a high-molecular weight compound. Suitable high-molecular weight compounds include hydroxypropyl cellulose, hydroxymethyl cellulose, sodium carboxymethyl cellulose, polyethylene glycol, polyvinyl alcohol, and polyvinylpyrrolidone. Proteins deemed useful in the compositions of the ""621 application include human serum albumin, human serum globulin, gelatin, acid-treated gelatin, and alkali-treated gelatin.
U.S. Pat. No. 5,503,827 to Woog et al. (the xe2x80x9c""827 patentxe2x80x9d) discloses pharmaceutical preparations of G-CSF that include at least one bactericidal preservative selected from the group consisting of chlorobutanol, benzyl alcohol, benzalkonium chloride and mixtures thereof. Pharmaceutical preparations of the ""827 patent may also include auxiliary substances, examples of which are stabilizing agents and organic hydrophilic polymers. Useful stabilizers disclosed by the ""827 patent encompass oligosaccharides such as sucrose, lactose and dextrans with a molecular weight of about 10,000 to 2,000,000. Useful organic hydrophilic polymers include polyethylene glycol and polyvinylpyrrolidone.
U.S. Pat. No. 5,919,757 to Michaelis et al. (the xe2x80x9c""757 patentxe2x80x9d) discloses aqueous pharmaceutical preparations of G-CSF that are stable on storage, which comprise a buffer selected from the group consisting of citrate, maleate, a mixture of citrate and phosphate, arginine and arginine salts, and at least one surfactant, where the pH of the composition is from about pH 7 to pH 8. The ""757 patent discloses that particular pH ranges of the liquid pharmaceutical preparation, in a mixture with a particular buffer result in particularly stable compositions. Furthermore, the ""757 patent discloses that it is not advantageous to add salts, since high concentrations of salts or ions promote the formation of G-CSF aggregates. The ""757 patent also discloses that, accordingly, buffer concentrations are calculated so that the pH-stabilizing effect is achieved but the ionic strength is kept as small as possible, with buffer concentrations preferably in the range of up to 80 mM, and particularly preferably of less than 30 mM.
U.S. Pat. No. 5,919,443 to Michaelis et al. (the xe2x80x9c""443 patent xe2x80x9d) discloses lyophilized and reconstituted pharmaceutical preparations comprising G-CSF, a stabilizing agent selected from the group consisting of maltose, cellobiose, gentibiose, isomaltose and sucrose, and a surfactant that is present in an amount no greater than the amount of G-CSF present in the composition. The preparations of the ""443 patent have a pH within the range of pH 7 to pH 8, and are free of human serum albumin and polymers. The ""443 patent also discloses it may be expedient to add auxiliary substances, which are mainly non-ionized, to provide an isotonic pharmaceutical preparation. The ""443 patent further indicates that it is not advantageous to add salts to adjust the isotonicity, as high concentrations of salts or ions promote formation of G-CSF aggregates and, accordingly, salts are added in small amounts.
PCT International Publication No. WO 95/03034 (the xe2x80x9c""034 publicationxe2x80x9d) discloses stabilized aqueous compositions of G-CSF to be administered as aerosols, comprising a polar organic compound, which reduces the surface tension of water to no greater than about 65 dynes/centimeter, or a surfactant which reduces the surface tension of water to no greater than about 40 dynes/centimeter. The ""034 publication discloses preferred polar organic solvents that include polyethylene glycol and methyl pentanediol, and a preferred surfactant, Tween 80. Compositions disclosed in the ""034 publication may include a buffer or, simply, aqueous hydrochloric acid, such that the pH is adjusted to fall within the range of pH 2.5 to pH 5.5.
U.S. Pat. No. 5,554,150 to Bousseau et al. (the xe2x80x9c""150 patentxe2x80x9d) discloses compositions suitable for subcutaneous, continuous administration of G-CSF. The G-CSF compositions of the ""150 patent comprise granulocyte colony stimulating factor, serum albumin, a non-ionic surface-active agent, a saccharide, disodium phosphate, monosodium phosphate, and sodium chloride.
Solution folding of proteins is influenced by the presence of one or more salts, which may interact with both the protein and the solvent. Ionic components of salts may interact directly with the charged amino acid side chains or dipolar peptide bonds of the protein, and they may also affect the structure of the solvent, thereby influencing the interaction between the dissolved protein and the solvent. The nature of these interactions is influenced by the specific protein, its concentration, the temperature and pH of the solution, the particular salt used and the concentration of that salt. These features may be exploited for example, to allow the selective precipitation of polypeptides as part of a protein purification process. Hydrophobic proteins, which are inherently less water soluble, are particularly sensitive to aggregation and precipitation in the presence of salt, and therefore, as exemplified by the ""443, ""757, and ""651 patents, prior art G-CSF compositions have deliberately avoided the addition of salt.
The present invention is directed toward stabilized aqueous compositions of G-CSF. The invention provides unexpectedly stable aqueous compositions comprising G-CSF, particularly non-glycosylated G-CSF, having a pH of from about 5.0 to about 8.0, and a salt comprising a sulfate ion. The aqueous composition may also comprise at least one buffering agent. The concentration of G-CSF, particularly non-glycosylated G-CSF, in any of the compositions described herein is preferably at least about 0.01 mg/mL and the concentration of the salt comprising sulfate ions in the compositions is preferably from about 0.01M to about 1.0M; preferred concentrations are at least about 0.01 mg/mL non-glycosylated G-CSF and at least 0.1M of the salt comprising sulfate ions. In an embodiment of any of the compositions described herein, the granulocyte colony stimulating factor is selected from the group consisting of bovine granulocyte colony stimulating factor, canine granulocyte colony stimulating factor, feline granulocyte colony stimulating factor, and human granulocyte colony stimulating factor.
The present invention is also directed to a method of treating disease in a mammal, comprising administering to a mammal in need of such treatment, a therapeutically effective dose of granulocyte colony stimulating factor in an aqueous composition having a pH of from about 5.0 to about 8.0, which aqueous composition comprises a salt comprising sulfate ions, wherein the salt is present at a concentration of from about 0.01M to about 1.0M. In other embodiments, the aqueous composition comprises any of the above-described compositions. In an embodiment of the method, the mammal is a canine mammal. In another embodiment of the method, the mammal is a feline mammal. In another embodiment of the method, the mammal is a human. The invention is also directed to a method of treating disease or conditions alleviated by stimulation of haematopoiesis. In an embodiment, the method is used to alleviate the effects of bone-marrow suppressive therapy, as in cancer treatments. In an embodiment of the method, the disease is granulocytopenia. In another embodiment of the method, the disease is an infectious disease. In a preferred embodiment of the method, the mammal is a bovine mammal. In a more preferred embodiment of the method, the infectious disease is shipping fever or bovine mastitis, and the mammal is a bovine mammal. The invention also relates to the use of an aqueous composition as provided herein, for the preparation of a medicament for the treatment in a mammal, preferably a bovine mammal or a human, of a disease, such as granulocytopenia or an infectious disease, as described further herein.
The present invention may be understood more fully by reference to the detailed description and illustrative examples, which are intended to exemplify non-limiting embodiments of the invention.
The present invention is directed toward aqueous compositions comprising non-glycosylated G-CSF that comprise from about 0.01M to about 1.0M of a salt comprising sulfate ions, and having a pH of from about 5 to about 8. Such aqueous compositions exhibit unexpectedly improved stability.
As used herein, xe2x80x9cG-CSFxe2x80x9d refers to a protein that has the sequence of a naturally occurring mammalian granulocyte colony stimulating factor. The production of recombinant non-glycosylated bG-CSF is described in U.S. Pat. No. 5,849,883. The production of non-glycosylated human G-CSF (xe2x80x9chG-CSFxe2x80x9d) is described in U.S. Pat. No. 4,810,643 and the production of non-glycosylated canine G-CSF is described in U.S. Pat. No. 5,606,024. The G-CSF of other mammalian species can be cloned and expressed using the procedures set forth in the above noted patents concerning bovine and canine G-CSF.
As used herein, G-CSF encompasses structural analogues of this protein having one or more amino acid substitutions, additions or deletions. Also contemplated by the term G-CSF, as used herein, are portions or fragments of the mature protein which retain at least one of the biological activities of the intact molecule, whether used alone or formed as part of a chimeric protein, however constructed. Furthermore, as used herein, G-CSF also encompasses derivatives (xe2x80x9cmuteinsxe2x80x9d) of G-CSF wherein at least one residue has been replaced with another amino acid. Included are derivatives in which at least one of the following amino acid substitutions has been made (amino acid numbering is in reference to the mature protein; therefore where an N-terminal methionine is present, it is assigned position xe2x88x921 or 0): Cys17 of the native sequence replaced by a Ser17 residue, Asp27 of the native sequence replaced by a Ser27 residue, Leu15 of the native sequence replaced by a Glu15 residue, Lys23 of the native sequence replaced by an Arg23 residue, Gly28 of the native sequence replaced by an Ala28 residue, Lys40 of the native sequence replaced by an Arg40 residue, Pro∴of the native sequence replaced by an Ala44 residue, Leu49 of the native sequence replaced by a Lys49 residue, Gly55 of the native sequence replaced by an Ala55 residue, Cys60 of the native sequence replaced by a Ser60 residue, Pro111 of the native sequence replaced by a Glu111 residue, Thr115 of the native sequence replaced by a Ser115 residue, and Tyr165 of the native sequence replaced by an Arg165 residue. Such derivatives are described in U.S. Pat. No. 5,416,195, which is included herein by reference, in its entirety.
Suitable salts comprising sulfate ions, which are preferably inorganic sulfate salts, comprise sulfate ions and at least one suitable cation, which may be selected from the group consisting of alkali metal ions, alkaline earth metal ions, and ammonium ion. Preferred salts comprising sulfate ions are selected from the group consisting of ammonium sulfate, sodium sulfate, magnesium sulfate, and mixtures thereof. The most preferred salt comprising sulfate ions is ammonium sulfate. Suitable concentration ranges for the salt comprising sulfate ions in the aqueous compositions are from about 0.01 M to about 1.0M, preferably from about 0.025M to about 0.5M, more preferably from about 0.05M to about 0.25M, and most preferably greater than 0.1M but less than about 1.0M. Salts comprising sulfate ions useful in the present invention include those salts, whether anhydrous or hydrated, that are sufficiently water-soluble to provide aqueous compositions having a concentration of at least about 0.1M at 20xc2x0 C. at neutral pH.
G-CSF can be dissolved in the subject aqueous compositions to provide a therapeutically effective dose when a pharmaceutically acceptable volume is administered to the animal. The concentration of non-glycosylated G-CSF, particularly non-glycosylated G-CSF, in the present aqueous compositions is suitably from about 0.01 mg/mL to about 10 mg/mL, preferably from about 0.1 mg/mL to about 7.5 mg/mL, and more preferably from about 1 mg/mL to about 5 mg/mL.
Suitable pH values for the aqueous compositions of the present invention are from about pH 5 to about pH 8, and preferably from about pH 6 to about pH 7.5. Suitable buffering agents that are advantageously used to maintain the pH of the subject aqueous compositions include acetate, citrate, and phosphate. Alternative buffering agents include buffers containing sulfonate moieties, such as HEPES, BES, TAPS, EPPS, TES, and mixtures thereof. Generally, the buffering agent chosen has a pKa within 1 pH unit, and preferably within 0.5 pH unit, of the pH value chosen for the G-CSF aqueous composition. In some instances, buffering agents may be used at a concentration of up to about 1 M, although as used herein the buffering agents are generally used in the present compositions at a concentration within the range of from about 1 mM to about 100 mM, preferably from about 5 mM to 50 mM and, most preferably at about 10 mM.
The method of preparation of the subject aqueous compositions is not critical. For example, aqueous compositions can be prepared by dissolving G-CSF, which, for example, may be provided as a lyophilized powder, in water, followed by the addition of aliquots of concentrated stock compositions or solid reagents, pH adjustment as necessary with an acid or base, and addition of water to bring the aqueous composition to an appropriate final volume. Alternatively, the G-CSF can be dissolved in a previously prepared aqueous composition, which may comprise a suitable buffering agent and a salt comprising sulfate ions. The subject aqueous compositions may also be prepared by adding aliquots of concentrated stock solutions or solid reagents to an aqueous composition of G-CSF to provide a stabilized G-CSF composition. Other methods for preparing the aqueous compositions of the present invention include dialysis or ultrafiltration of G-CSF compositions against an aqueous composition, which may comprise one or more buffering agents and one or more salts comprising sulfate ions of the present invention.
The aqueous compositions of the present invention may also comprise other pharmaceutically acceptable solutes including additives and other therapeutic agents, as appropriate. Suitable additives are those well known in the art including, but not limited to, antioxidants, antibacterials, surfactants, chelating agents, sugars, and preservatives.
The present aqueous compositions can be lyophilized and stored as powders or lyophilisates until needed and then redissolved in an aqueous medium.
The aqueous compositions of the invention can be administered by injection, which can be intramuscular, intravenous or preferably subcutaneous. A dose of from about 0.5 xcexcg/Kg/day to about 10 xcexcg/Kg/day, preferably from about 1 xcexcg/Kg/day to 5 xcexcg/Kg/day, can be used to induce granulocytosis and reverse granulocytopenia. Generally, the dose and mode of administration of the aqueous compositions of the invention are the same as conventional bG-CSF compositions.
The following examples illustrate the compositions and methods of the present invention. It is to be understood that the present invention is not limited to the specific details of the Examples provided below.

Stabilized granulocyte colony stimulating factor


A multi-stage fluid conditioning system having a housing with a fluid inlet and outlet. A shaft extends within the housing and supports a first fan unit with a first magnet/electromagnet plate on an inlet side of said housing and a second fan unit with a second magnet/electromagnet supporting plate on an outlet side of the housing. Each of the first and second magnet/electromagnet supporting plates include at least one vane configured to direct fluid flow. The shaft rotates the plates in order to draw a fluid flow through the inlet and successively across the inlet and outlet sides for thermal conditioning resulting from creation of high frequency oscillating magnetic fields according to a succeeding conditioning operations before being outputted the conditioned fluid from the housing through the fluid outlet.

The phenomena of magnetic or electromagnetic induction heating is well known in the prior art by which heat is generated in an electrically conductive object by the generation of eddy currents, also called Joule heating. The typical induction heater includes an electronic oscillator which passes a high frequency alternating current through an electromagnet. The eddy currents flowing through the resistance of a conductive metal placed in proximity to the magnet/electromagnet in turn heat it. Put another way, the eddy currents result in a high-frequency oscillating magnetic field which causes the magnet's polarity to switch back and forth at a high-enough rate to produce heat as byproduct of friction.
One known example of a prior art heating system is taught by the electromagnetic induction air heater of Garza, US 2011/0215089. Another known device is the centrifugal magnetic heating device of Hsu 2013/0062340.

Magnetic induction furnace, cooler or magnetocaloric fluid heat pump integrated into a rotary blower and including two stage inductive heating or cooling


A Gunn diode in which the conversion efficiency can be improved without lowering the reliability, by reducing the dead zone while maintaining n.sup.+ nn.sup.+ structure. In this Gunn diode, the donor impurity concentration in the n-type active layer is graded along a direction perpendicular to a contact plane between the n-type active layer and the n.sup.+ -type layers, and an average concentration gradient of the donor impurity concentration in the n-type active layer simultaneously satisfies the following two inequalities: G>(A.sub.1 N/L)exp(-NL/S.sub.1) and G<(A.sub.2 N/L)exp(-NL/S.sub.2), where L is a thickness of the n-type active layer, N is an average concentration of the donor impurity, S.sub.1 =0.87.times.10.sup.12 cm.sup.-2 is a constant, S.sub.2 =1.32.times.10.sup.12 cm.sup.-2 is a constant, A.sub.1 =2.0 is a constant, and A.sub.2 =9.0 is a constant.

1. Field of the Invention
The present invention relates to a Gunn diode using an InP semiconductor to be used as a microwave source or a millimeter wave source.
2. Description of the Background Art
It is well known that a drift velocity of conduction electrons in an InP semiconductor has a property called negative differential resistance, i.e., it decreases for an electric field strength greater than a certain level. This is graphically shown in FIG. 1, where a vertical axis represents a drift velocity V of the conduction electron and a horizontal axis represents an electric field strength E. As shown in FIG. 1, in a region A1 the drift velocity V increases as the electric field strength E increases, so that the differential resistance which is inversely proportional to dV/dE has a positive value in this region A1. On the other hand, in a region A2 the drift velocity V decreases as the electric field strength E increases until it reaches to a saturation velocity Vs, so that the differential resistance has a negative value in this region A2, and the drift velocity is said to have a property called the negative differential resistance.
This negative differential resistance is caused by the fact characteristic to this type of a semiconductor that the effective mass of the conduction electron at a high energy level is heavier than an effective mass of the conduction electron at a low energy level.
A Gunn diode which utilizes this property of the negative differential resistance is widely used as a solid state oscillator element for generating microwaves and millimeter waves.
An example of a conventional Gunn diode is shown in FIG. 2, where the Gunn diode comprises an n-type active layer 3 sandwiched by two n.sup.+ -type layers 4 and 5, where metallic electrodes 6 and 7 are connected to the n.sup.+ -type layers 4 and 5, respectively. A distribution of a donor impurity concentration Nd in this Gunn diode of FIG. 2 is shown in FIG. 3. Here, the contacts between the n.sup.+ -type layers 4 and 5 and the metallic electrodes 6 and 7 can easily be made to be ohmic contacts, because the donor concentration of the n.sup.+ -type layers 4 and 5 is sufficiently high as shown in FIG. 3.
In this configuration, by setting a thickness and the donor impurity concentration of the active layer 3 appropriately, and applying an appropriate DC voltage between the two electrodes 6 and 7, a structure called a Gunn domain can be formed in an negative electrode side (cathode side) of the active layer 3, due to the negative differential resistance property of the semiconductor conduction electrons. In the Gunn domain, a region in which the conduction electron concentration is greater than surrounding (accumulation layer) or a portion at which a region with greater conduction electron concentration and a region with less conduction electron concentration are facing each other (dipole layer) is generated, and such a portion moves toward the positive electrode side (anode side) of the active layer 3. Such a Gunn domain disappears when it reaches to the n.sup.+ -type layer of the anode side, and then another Gunn domain is generated at the cathode side.
As this disappearance of an old Gunn domain and an appearance of a new Gunn domain is repeated, it appears that an AC current is superposed onto a DC current between the electrodes, where the frequency of this AC current is the characteristic frequency of the Gunn diode which is mainly determined from a time for the Gunn domain to move through the active layer 3 from the cathode side to the anode side. On the other hand, the velocity of the Gunn domain in the active layer 3 is approximately equal to the saturation velocity Vs of the conduction electrons, so that the characteristic frequency f of the Gunn diode is roughly given as f=Vs/L where L is a thickness of the active layer 3. Conversely, an appropriate thickness L of the active layer 3 can be given as a function of the desired characteristic frequency f in a form of L=Vs/f. Thus, it can be said that the thickness of the active layer is roughly inversely proportional to the characteristic frequency f.
Such a Gunn diode is widely used as an oscillator for high frequency waves. For example, the high frequency electromagnetic waves such as the microwaves can be obtained from the Gunn diode by appropriately arranging the Gunn diode inside a resonant cavity. Such an oscillator using the Gunn diode is called a Gunn oscillator, for which the most important quality index is a conversion efficiency indicating how much AC output can be obtained from a given DC power input, and the improvement of this conversion efficiency in the Gunn oscillator has been a major problem associated with a conventional Gunn oscillator.
Now, in such a Gunn diode having n.sup.+ nn.sup.+ structure, it is known that the Gunn domain is generated not exactly at a contact plane between the active layer and the cathode side n.sup.+ -type layer, but at a position inside the active layer which is a certain distance inward from the contact plane, as shown in FIG. 4. This FIG. 4 shows a result of a computer simulation of a Gunn domain movement, which clearly indicates an existence of a region A nearby the cathode side n.sup.+ -type layer contact plane in which no Gunn domain is present.
This phenomenon can be explained as follows. Namely, the conduction electrons entering into the active layer have not gained sufficient amount of energy from the electric field so that their energy is not sufficiently high for realizing the negative differential resistance property which is indispensable for the formation of the Gunn domain. On the other hand, as the conduction electrons passes through the active layer for a while, these conduction electrons are raised to the high energy states and start to have the negative differential resistance property, so that the formation of the Gunn domain become possible.
The region A between the cathode side n.sup.+ -type layer contact plane and the actual Gunn domain generation position where no Gunn domain is called a dead zone. The existence of this dead zone severely damages the characteristics of the Gunn diode, so that it is highly desirable to make this dead zone as small as possible, or to remove this dead zone completely. In particular, in a case of using the Gunn diode for an application using a high frequency over 40 GHz, the appropriate thickness of the active layer becomes as thin as less than 2 .mu.m as explained above, so that the thickness of the dead zone becomes unignorable compared with the thickness of the active layer, and the existence of the dead zone affects the conversion efficiency of the Gunn diode considerably.
As a method of removing the dead zone, there is known a configuration in which the cathode side n.sup.+ -type layer is removed and the metallic electrode is connected directly to the active layer on the cathode side, as shown in FIG. 5. In this configuration of FIG. 5, where the anode side metallic electrode 9 remains to contact with the anode side n.sup.+ -type layer 5, while the cathode side metallic electrode 8 is directly contacting the n-type active layer 3. In such a configuration, the contact between the active layer 3 and the cathode side metallic electrode 8 is not an ohmic contact but a Schottky contact, so that the dead zone can be removed completely by appropriately setting the characteristic of this Schottky contact, and as a result the conversion efficiency can be improved.
However, in the Gunn diode of this configuration, the appropriate setting of the Schottky contact is extremely difficult because a minute change in the Schottky contact can affect the Gunn diode characteristic considerably. In addition, compared with the ohmic contact, the Schottky contact is far more difficult technically to manufacture at a high reproducibility. Furthermore, the characteristic of the Schottky contact is quite sensitive to the environmental temperature, so that the reliability of this type of Gunn diode has been rather low.

Indium phosphide Gunn diode with dopant gradient


A noble metal and an NOx sorption member are loaded on a support which includes composite particles having a structure including a core portion in which ZrO2 is a major component and a superficial portion formed on a surface of the core portion and including an oxide, whose basicity is lower than ZrO2, more than the core portion. The composite particles exhibit a high basicity at the inside and a low basicity on the surface by Al2O3 or TiO2 which exists more in the surface. Accordingly, the sulfur-poisoning resistance is improved, and, at the same time, the post-durability NOx purifying ability is improved.

Recently, as a catalyst for purifying NOx in an exhaust gas of an oxygen-excessive lean atmosphere, an NOx sorption-and-reduction type catalyst has been utilized. This NOx sorption-and-reduction type catalyst, for example, as disclosed in Japanese Unexamined Patent Publication (KOKAI) No. 5-317,625, is one in which a noble metal, such as Pt and Rh, and an NOx sorption member, such as K and Ba, are loaded on a porous support, such as Al2O3. By using this NOx sorption-and-reduction type catalyst and controlling an air-fuel ratio from a lean side to a stoichiometric as well as rich side in a pulsating manner (rich spiking), since an exhaust gas, too, becomes from a lean atmosphere to a stoichiometric as well as rich atmosphere, NOx are sorbed in the NOx sorption member on the lean side, and they are released on the stoichiometric or rich side to react with reductive components, such as HC and CO, so that they are purified. Therefore, even when it is an exhaust gas from a lean burn engine, it is possible to purify NOx with good efficiency. Moreover, since HC and CO in the exhaust gas are oxidized by the noble metal and, at the same time, are consumed in the reduction of NOx, HC as well as CO are also purified with good efficiency.
For example, in Japanese Unexamined Patent Publication (KOKAI) No. 5-317,652, a catalyst for purifying an exhaust gas is proposed in which an alkaline-earth metal, such as Ba, and Pt are loaded on a porous oxide support, such as Al2O3. Further, in Japanese Unexamined Patent Publication (KOKAI) No. 6-31,139, a catalyst for purifying an exhaust gas is proposed in which an alkali metal, such as K, and Pt are loaded on a porous oxide support, such as Al2O3. Furthermore, in Japanese Unexamined Patent Publication (KOKAI) No. 5-168,860, a catalyst for purifying an exhaust gas is proposed in which a rare-earth element, such as La, and Pt are loaded on a porous oxide support, such as Al2O3.
However, in an exhaust gas, SO2, which is generated by burning sulfur (S) contained in a fuel, is included, and it is oxidized by a noble metal in an exhaust gas of a lean atmosphere so that it is turned into SO3. Then, it has become apparent that it is readily turned into sulfuric acid by water vapor, which is also contained in the exhaust gas, that these react with the NOx sorption member to generate sulfites and sulfates, and that the NOx sorption member is thereby poisoned to degrade. This is referred to as the sulfur poisoning of the NOx sorption member. Moreover, since the porous oxide support, such as Al2O3, has a property that it is likely to adsorb SOx, there is a problem in that the aforementioned sulfur poisoning has been facilitated. Then, when the NOx sorption member is thus turned into sulfites and sulfates so that it is poisoned to degrade, it can no longer sorb NOx, as a result, there is a drawback in that the NOx purifying performance lowers after a high-temperature durability test (hereinafter, referred to as "post-durability").
Moreover, it has been understood that another cause, by which the post-durability NOx purifying ability is lowered, lies in that a reaction occurs between cordierite, which has been used as a support substrate in general, and an alkali component, which works as the NOx sorption member, and thereby the NOx sorption ability has been lowered.
Namely, the alkali component is likely to move in a coating layer, such as Al2O3, and simultaneously exhibits a high reactivity to Si. Accordingly, it is believed that the alkali component moves in the coating layer when the temperature is high, arrives at the support substrate and reacts with Si in cordierite to form silicate, being a composite oxide. Since this silicate is a stable compound, the alkali component, which has been turned into silicate, no longer has an ability of sorbing NOx, and accordingly the NOx purifying performance has been lowered.
Moreover, it was thought of using a TiO2 support, and an experiment was carried out. As a result, since SOx flowed as they were to downstream without being adsorbed onto TiO2, and since only SO2, which contacted directly with a noble metal, was oxidized, it became apparent that the extent of sulfur poisoning was less. However, in a TiO2 support, the initial activity is low, moreover, since TiO2 reacts to an alkali component to generate titanates, it has become apparent that the post-durability NOx purifying performance is kept being low. Hence, in Japanese Unexamined Patent Publication (KOKAI) No. 8-099,034, there is proposed to use a composite support comprising TiO2—Al2O3. Moreover, it has been proposed to use a support in which rutile type TiO2 is added to Al2O3. However, even when a support made of composite oxide on made by thus adding TiO2 is used, it is difficult to suppress the reaction between an alkali component and TiO2.
While, in Japanese Unexamined Patent Publication (KOKAI) No. 8-117,602, an NOx sorption-and-reduction type catalyst is proposed in which a Ti—Zr composite oxide, an NOx sorption member and a noble metal are loaded on an Al2O3 support.
By thus making a composite support in which a Ti—Zr composite oxide is loaded on Al2O3, it is possible to highly maintain the initial NOx purifying rate due to the advantage of Al2O3. Moreover, by loading a Ti—Zr composite oxide, it is possible to raise the acidity of the support itself. Therefore, since this composite support, compared with the case where Al2O3 is used alone, is less likely to adsorb SOx, and since adsorbed SOx are likely to eliminate at a low temperature, the contacting probability between the NOx sorption member and SOx is lowered. In addition, in a support on which a Ti—Zr composite oxide is loaded, it is believed that the movement of alkali component is suppressed, and it has been understood that the reaction of the alkali component to TiO2 is suppressed. Therefore, when the aforementioned composite support is used, a high NOx purifying rate is secured even in the initial period, since the sulfur poisoning as well as the solving of the alkali metal into the support are suppressed, a post-durability NOx purifying rate is improved.
However, in a catalyst in which a Ti—Zr composite oxide is loaded on an Al2O3 support, compared with a composite support comprising TiO2—Al2O3 as disclosed in Japanese Unexamined Patent Publication (KOKAI) No. 8-099,034 or a catalyst which uses a support in which TiO2 is added to Al2O3, it is not possible to say that the suppression effect of the sulfur poisoning is sufficient, and accordingly it has been required to further suppress the sulfur poisoning and improve the NOx purifying rate.
Moreover, due to the recent improvement of engine performance, the increase of high speed driving, and the like, the temperature of exhaust gas has risen so that the improvement of NOx purifying activity in a high temperature region has become an assignment. This is because, in a high temperature region, NOx, which have been sorbed in an NOx sorption member, are likely to be released, and the NOx sorption amount is likely to be insufficient in a lean atmosphere. Hence, K, which exhibits a high basicity and is stable at a high temperature, is made into an NOx sorption member, but, in a catalyst in which K is loaded on Al2O3, and so on, there has been a problem in that the NOx sorption ability in a high temperature region is not improved so much.
Hence, it was thought of using a support which exhibits a higher basicity, and, in Japanese Unexamined Patent Publication (KOKAI) No. 5-195,755, a catalyst is disclosed in which K and a noble metal are loaded on ZrO2. In accordance with this catalyst, since the basicities of the support and NOx sorption member are high, it is likely to sorb but less likely to release NOx. Therefore, the NOx sorption ability in a high temperature region is improved, as a result, the NOx purifying performance in a high temperature region is improved.
However, in the catalyst in which K and a noble metal are loaded on ZrO2, since the basicity of the support is high, there has been a drawback in that it is likely to sorb not only NOx but also SOx so that the lowering of the activity by the sulfur poisoning is considerable. Namely, when the basicity of a support is high, although the NOx sorption ability is improved, even the sulfur poisoning is facilitated. On the contrary, when the basicity of a support is low, although the sulfur poisoning is suppressed, even the NOx sorption ability is lowered.
The present invention has been done in view of such circumstances, it is a main object to further suppress the sulfur poisoning of an NOx sorption-and-reduction type catalyst, thereby furthermore improving the high-temperature post-durability NOx purifying rate.
Moreover, the second object of the present invention is to make a catalyst which can satisfy both of the contradictory phenomena, such as the improvement of the NOx sorption ability in a high temperature region and the suppression of the sulfur poisoning, and which is good in terms of the heat resistance.
The characteristic of a catalyst for purifying an exhaust gas, of an NOx sorption-and-reduction type catalyst comprising a noble metal and an NOx sorption member loaded on a porous oxide support, which solves the aforementioned assignments and is set forth in claim 1, lies in that the porous oxide support includes composite particles having a structure comprising a core portion in which ZrO2 is a major component and a superficial portion formed on a surface of the core portion and including an oxide, whose basicity is lower than ZrO2, more than the core portion.
Moreover, the characteristic of a catalyst for purifying an exhaust gas, of an NOx sorption-and-reduction type catalyst comprising a support substrate, a coating layer formed on the support substrate and comprising a porous oxide, a noble metal loaded on the coating layer and at least one NOx sorption member loaded on the coating layer and selected from the group consisting of alkali metals, alkaline-earth metals and rare-earth elements, which solves the aforementioned assignments and is set forth in claim 9, lies in that composite particles, having a structure comprising a core portion in which ZrO2 is a major component and a superficial portion formed on a surface of the core portion and including an oxide, whose basicity is lower than ZrO2, more than the core portion, are included in the coating layer.
In the present catalyst for purifying an exhaust gas, it is preferred that the oxide, whose basicity is lower than ZrO2, can be Al2O3, and that the composite particles can be a ZrO2—Al2O3 composite oxide. In this case, a composition of the composite particles can desirably fall in a range of Al2O3/ZrO2=3/97–15/85 by molar ratio.
Further, it is preferred that the oxide, whose basicity is lower than ZrO2, can be TiO2, and that the composite particles can be a ZrO2—TiO2 composite oxide. In this case, TiO2 can desirably be included in an amount of 30% by weight or more in the superficial portion of the composite particles. Furthermore, the composite particles can desirably further include Al2O3, and Al2O3 can desirably be included in an amount of 10% by mol or more in said composite particles.
Then, in the catalyst for purifying an exhaust gas of the present invention, an average particle diameter of the composite particles can desirably be 10 μm or less.

This patent is subject to a terminal disclaimer.


A motion equation with a boundary condition regarding a future center-of-gravity horizontal trajectory of a robot is solved so that the moment around a horizontal axis at a point within a support polygon is zero when the robot is in contact with a floor or so that horizontal translational force is zero when the robot is not in contact with the floor and so that connection is made to a current horizontal position and speed of the center of gravity. In addition, a motion equation with a boundary condition regarding a future center-of-gravity vertical trajectory of the robot is solved so that vertical translational force acting upon the robot other than gravity is zero when the robot is not in contact with the floor and so that connection is made to a current vertical position and speed of the center of gravity. A motion state of a next time is determined so that, when the robot is not in contact with the floor, the moment around the center of gravity is zero, and the determined center-of-gravity position is achieved. Therefore, a stable motion pattern which allows transition between a floor contact period and a floor non-contact period is generated in real time.

A robot is a mechanical device which moves like a human being by making use of electric and magnetic actions. The term "robot" is said to be derived from the Slavic word "ROBOTA" (slavish machine). In our country, the widespread use of robots began at the end of the 1960s, many of which were industrial robots, such as manipulators and conveyance robots, used, for example, for the purpose of achieving automatic industrial operations in factories without humans in attendance.
In recent years, advances have been made in the research and development of legged mobile robots which are designed using as a model the motion and mechanism of the body of an animal, such as a human being or an ape, which moves erect using two feet. There are increasing expectations for putting such robots into practical use. Legged mobile robots which reproduce the motions and bodily mechanisms of a human being are called humanoid robots.
Bipedal motion in an erect orientation is unstable compared to, for example, crawling or motion using four or six legs. Therefore, in this case, the orientation and walking are difficult to control. However, bipedal motion in an erect orientation is advantageous in that it is a flexible motion. Therefore, robots capable of such a motion can, for example, move along a walking surface of a working path, such as a rough surface or a surface having obstacles, or move along a discontinuous surface, such as moving up and down steps or a ladder.
Many technologies for controlling the orientation of and allowing stable walking of bipedal mobile robots have already been proposed. Here, "stable walking" means "moving using the legs without falling." Controlling the orientations of robots for achieving stable orientations is very important in preventing the robots from falling. One reason is that, when robots fall, they stop performing their tasks, as a result of which considerable time and labor are required for the robots to get up and re-start their actual tasks again. Another reason is that, when robots fall, the robots themselves or objects against which the falling robots strike may be fatally damaged.
Many of the technologies for controlling the orientations of legged mobile robots or preventing them from falling while walking make use of ZMP (zero moment point) as a norm for determining the degree of walking stability. The norm for determining the degree of walking stability by ZMP is based on D'Alembert's principle in which gravitation and inertial force from a walking system to a floor surface and their moments balance floor reaction force and floor reaction moment from the floor surface to the walking system. The inference in terms of dynamics is that there is a point, that is, a ZMP where a pitch axis moment and a roll axis moment are zero on or within a side of a supporting polygon (that is, a ZMP stable area) defined by a floor surface and the points of contact of the soles with the floor. (Refer to, for example, "Legged Locomotion Robots" by Miomir Vukobratovic', and "Hoko Robot to Jinko no Ashi" by Ichiro Kato and published by The Nikkan Kogyo Shinbun Ltd.)
In summary, at any instant of walking, ZMP exists within the supporting polygon defined by the feet and floor surface and is a point allowing a robot to walk stably without falling (rotary motion of the body) as long as the robot exerts a force upon the floor surface in a pushing direction.
According to a bipedal walking pattern based on ZMP, the points where the soles contact the floor can be previously set, so that, for example, it is easy to consider kinematic constraints on the ends of the feet in accordance with the shape of the floor surface. When ZMP is used as a norm for determining the degree of stability, a trajectory instead of force is used as a target value for controlling motion. Therefore, technically speaking, the probability putting ZMP into practical use is increased.
The mode of motion of most of the related legged mobile robots is walking in which either leg is always in contact with the floor surface. For legged mobile robots for ordinary use, walking is a safe, efficient, and optimal mode of motion because excessive force is not applied to a mechanical/electrical system.
Motion having a floor non-contact period in which reaction from the floor is not received is a situation in which it is not sufficient for legged mobile robots to have only a walking function. When legged mobile robots move in contact with the floor where there is gravity, they are not continuously in a floor non-contact state for a long period of time. However, they may be in a floor non-contact state for a short period of time or discontinuously. Examples of such situations are jumping across a gap, jumping down from a higher level, running to move faster, and changing the standing position by hopping for maintaining balance.
There are still not many examples of research on controlling balance when such legged mobile robots are not in contact with a surface. Outstanding pioneering researches are disclosed in, for example, "Hanpuku Choyaku Model Biomechanism 5," 1985, published by University of Tokyo Press, Kiyotoshi Matsuoka, pp. 4501-4509; and the International Journal of Robotics Research, vol. 3, No. 2, 1984, Marc H. Raibert and two other: "Experiments in Balance with a 3D One-Legged Hopping Machine," pp. 75-92. However, these researches have not been successful in providing a practical control system of legged mobile robots for the following reasons.    {circle around (1)} Since massless legs are assumed, considerable limitations are placed on mechanical designing freedom.    {circle around (2)} Since only continuous hopping or jumping is assumed, the dynamics regarding transition to a walking state or stopped state is not satisfactorily studied.    {circle around (3)} It is difficult to impose geometrical constraints on the trajectories of the ends of the feet.
A method of calculating a motion pattern of a legged mobile robot when floor contact and floor non-contact conditions are mixed by expanding the use of the ZMP norm is disclosed in "Dorikigaku Filter ni yoru Ningengata Robot no Zenshin Undo Seisei," authored by Keiichiro Nagasaka, in Tokyo Daigaku Kogakubu Joho Kogaku Senko Hakase Ronbun, 1999. However, according to this document, since a convergence calculation is performed to solve a nonlinear equation, the calculation load is high, making it necessary to previously calculate a motion pattern offline. In other words, a motion pattern having a floor contact period and a floor contact period in, for example, walking, running, or hopping, cannot be generated in real time.
As described above, today, the method of calculating a motion pattern based on a ZMP norm is the dominant basic controlling method for controlling the motion of a legged mobile robot. The greatest merit of using the ZMP as a norm for determining the stability of the body of a robot is that it is of high practical use, such as ZMP easily providing geometrical constraints on the ends of the feet or being applicable to a wide range of mechanical models, etc. For example, there is a report about a structure of a flexible control system based on a technology of generating walking pattern a real time in order to allow a robot to walk while generating a stable motion pattern on board during its motion. (Refer to, for example, Japanese Patent Application No. 2002-288745 already assigned to the applicant.)
As mentioned above, practical controlling means for motion including a floor non-contact period, such as in walking/hopping, has not yet been proposed.
The first problem that prevents legged motion including a floor contact period and a floor non-contact period from being practically realized is that most of the controlling methods impose many limitations regarding mechanical models. In particular, since many of the methods ignore the masses of the legs because it is difficult to handle changes in inertia of a robot caused by leg motions above a surface, these methods cannot be applied to many practical legged mobile robots. (Refer to, for example, "Hanpuku Choyaku Model Biomechanism 5," 1985, published by University of Tokyo Press, Kiyotoshi Matsuoka, pp. 4501-4509; and the International Journal of Robotics Research, vol. 3, No. 2, 1984, Marc H. Raibert and two other: "Experiments in Balance with a 3D One-Legged Hopping Machine," pp. 75-92.)
Typical present-day humanoid robots have at least six degrees of freedom in one leg. Although such a legged mobile robot having many degrees of freedom in its leg requires many actuators, it is difficult to mount all of these many actuators to its main body (portion of the body near the center of gravity, such as the waist), and a considerable number of actuators are installed in the legs (probably to prevent accidental torque interference by wire conduction.) In the first place, the legs support the entire weight of a legged mobile robot, and, thus, must have mechanical strength. Therefore, the structural members have considerable weight.
Therefore, in general, the masses of the legs are increased, and, thus, cannot be ignored in a dynamic model. Consequently, it is difficult to apply related techniques to legged mobile robots having large leg masses.
The second problem is that the number of running/hopping controlling algorithms for allowing transition between walking and stopping states is small.
As already mentioned above, a legged mobile robot rarely runs or hops constantly, and, thus, is often in a stopped state or a walking state. When necessary, the robot is made to run/hop, after which it is made to walk or stop again. Depending upon the circumstances, a robot may suddenly hop from a floor contact state, or may walk gradually faster and run, and, then, smoothly slow down, walk, and stop again.
There is an earnest desire for a general controlling method which makes it possible to perform seamless motion changes even between various, irregular contact and non-contact motions while properly maintaining dynamic balance.
The third problem is that most of the running/hopping or jumping controlling methods cannot add geometrical constraints.
In particular, there are many situations in which geometrical constraints are to be imposed upon position/orientation trajectories of feet end points in an inertial coordinate system. There are many methods of manipulating a floor contact point in order to maintain balance of the body of a robot. In order to quantitatively control a legged mobile robot, it is desirable that the trajectories of the feet ends be capable of being manifestly specified. For example, it is desirable that parameters, such as walking footstep/period or the heights of the soles when hopping or jumping, be capable of being specified by a user program. When the robot is required to, for example, run up steps or jump over a plurality of successive gaps, it is not desirable to manipulate the trajectories of the feet ends for maintaining balance.
The method of controlling walking by generating a walking pattern based on a ZMP norm is very advantageous from the practical point of view in that it can impose such motion constraints. This advantage is also demanded when the use of a ZMP norm is expanded to a motion having a floor non-contact period.
The fourth problem is that there is an earnest demand for a method which can change a motion pattern in real time so as to satisfy an asynchronous outside request.
In order to allow free motion of a legged mobile robot in an actual environment, it is necessary to provide a function for immediately re-planning the motion of the whole body while maintaining dynamic balance so as to satisfy a request for a change in the motion of the upper part of the body and a request for a change in crural motion, such as footstep, step period, angle of traverse, or feet lifting height, input at various timings. Previously forming a motion pattern offline will not satisfy such requests. In addition, it is difficult to satisfy the aforementioned outside requests by a control system which only maintains balance.

Robot device, motion control device for robot device and motion control method


The invention relates to an emergency tubing set, including an oxygen mask adapted to cover a users mouth and nose, a tubing connected at a first end to said tubing set to provide oxygen to said oxygen mask, and a connect or connected to said tubing at a second end opposed to said first end, the connector being adapted to be connected to an oxygen source for supplying oxygen to said tubing. According to the invention the tubing includes an excess tubing section and a connecting tubing section wherein the excess tubing section is stored in a bottom pouch and a first part of an intermediate tubing section is arranged inside the bottom pouch and a second part of said intermediate tubing section is arranged outside said bottom pouch, wherein the intermediate tubing interconnects the excess tubing section and the connecting tubing section.

Such emergency tubing sets are used to supply oxygen to passenger or crew member of an aircraft in case of an emergency situation like a decompression situation or smoke or fire onboard of an aircraft.
Usually, an emergency oxygen system comprises an oxygen source like a chemical oxygen generator or a pressure tank comprising pressurized oxygen, a control unit for controlling the pressure of the oxygen supplied to a person using the system and a supply line directing the oxygen from the oxygen source to an oxygen mask. The oxygen mask is adapted to cover both mouth and nose of the person using the system.
Such oxygen systems must be examined in certain maintenance intervals for proper function. In the course of such maintenance, certain replacement parts having limited storage intervals must be replaced. Further, such emergency oxygen systems comprise elements which are sensitive to hygienic requirements like the oxygen mask and the tubing, and others, which are not sensitive to hygienic requirements.
A problem associated with the tubing and the oxygen mask, generally addressed as emergency tubing set in the description and the claims, is related to the need to manually connect such tubing set to an oxygen source on the one hand and hygienic requirements for protecting such tubing set against contamination with dust, bacteria or other sources which may adversely affect the hygienic requirements on the other hand.

Double tear bag for emergency oxygen system


A microstructure design for high IR sensitivity having a two level infrared bolometer microstructure, the lower level having a reflective metal film surface such as Pt, Au, or Al to reflect IR penetrating to that level, the upper level being separated from the lower level by an air gap of about 1-2 microns which allows the reflected IR to interfere with the incident IR and increase the sensitivity to a higher level.

This invention is an improvement on co-pending application Ser. No. 887,495, filed Jul. 16, 1986, entitled "Thermal Sensor", and assigned to the same assignee as the present invention. The teachings of the co-pending application are incorporated herein by reference. In the co-pending application the invention is directed to a pixel size sensor of an array of sensors, for an infrared microbridge construction of high fill factor, made possible by placing the detector microbridge on a second plane above the silicon surface carrying the integrated components and bus lines. The improvement in the present invention is directed to a structure which increases the sensitivity.

Microstructure design for high IR sensitivity


Provided is a method and apparatus for assigning a frequency in an environment where an incumbent system exists. In a frequency environment where the incumbent system exists, a frequency resource management may be smoothly performed using a plurality of frequency sets classified based on a utilization state of each sub-frequency resource. When a frequency sharing system using the same radio access technology (RAT) as a frequency sharing system to be assigned with a frequency resource exists, it is possible to reduce overhead for frequency sharing by priorly assigning a corresponding frequency resource to the frequency sharing system to be assigned with the frequency resource.

Due to the development in radio communication technologies and the introduction of new radio communication services, there has been a desire to more effectively use a finite frequency resource. To enhance a frequency utilization efficiency, a spectrum efficiency optimization scheme through a performance optimization of a radio communication system and a scheme of minimizing interference with another radio communication system, and the like have been used. The performance optimization may be, for example, a multiple access scheme, an encoding technology, a modulation efficiency, an information compression technology, and the like.
In addition to the above schemes, a frequency sharing method is proposed to enhance a frequency utilization efficiency in a currently using frequency band such as a television (TV) band.

Frequency allocation method and device for a frequency sharing system in an environment where a primary licensing system is present

Electronics and Telecommunications Research Institute


An exemplary liquid crystal display device (20) includes a rear frame (25) including a plurality of first through holes (251) and a shield (24) including a back frame (241). The back frame includes a plurality of second through holes (244) corresponding to the first through holes, respectively. The back frame further includes a plurality of fixing units (245), and the shield further includes a plurality of shielding units (240) corresponding to the fixing units respectively. Each of the shielding units is fixed to a corresponding one of the fixing units by insert directly into the fixing unit.

A typical LCD device has the advantages of portability, low power consumption, and low radiation, and has been widely used in various portable information products such as notebooks, personal digital assistants (PDAs), video cameras, and the like. The LCD device includes a frame, and the frame may be hung on the wall or supported on the top of a table.
Referring to FIG. 8, an exploded, isometric view of a typical LCD device is shown. The LCD device 10 includes a front frame 11, a display module 12, a printed circuit board (PCB) 13, a metal shield 14, and a rear frame 15 arranged in that order from left to right. The metal shield 14 is used for shielding electro magnetic interference (EMI). The display module 12, the PCB 13, and the metal shield 14 are secured between the front frame 11 and the rear frame 15. The rear frame 15 includes a plurality of first through holes 151.
Referring also to FIG. 9, an enlarged, isometric view of the metal shield 14 is shown. The metal shield 14 includes a back frame 141 and a plurality of rivets 140. The back frame 141 includes a bottom plate 142, and a plurality of side walls 143 perpendicularly extending from edges of the bottom plate 142. The bottom plate 142 and the side walls 143 cooperatively form an accommodating space to accommodate the PCB 13. The bottom plate 142 includes a plurality of second through holes 144 corresponding to the first through holes 151, respectively. The rivets 140 correspond to the second through holes 144 respectively, and are used to close up the metal shield 14 and the rear frame 15 via the first and second through holes 151, 144.
Each rivet 140 has a cylinder structure with an opening (not shown), and a thread (not shown) is disposed on an inner surface of the rivet 140 to enable the rivet 140 to function as a nut. The rivets 140 are further used for sealing the second through holes 144, so as to prevent conductive media such as iron dust from entering the PCB 13. When the LCD device 10 needs to be hung on a wall, the rivets 140 are also used to fit corresponding bolts to fix the LCD device 10 to a wall hanging device on the wall.
Referring to FIG. 10, an assembled view of the LCD device 10 is shown. When the LCD device 10 has been assembled, the PCB 13 is accommodated in the accommodating space of the metal shield 14. The front frame 11 and the rear frame 15 secure the display module 12, the PCB 13, and the metal shield 14. The openings of the rivets 140 correspond to the first through holes 151, respectively.
However, during the assembling process, the rivets 140 need to be placed in the second through holes 144 manually, and then be fixed to the bottom plate 142 by a machine. Thus the assembling process of the LCD device 10 is unduly complicated and inefficient.
What is needed, therefore, is a LCD device that can overcome the above-described deficiencies.

Liquid crystal display device having metal shield with fixing unit and shielding unit


Described herein are pharmaceutical compositions capable of blocking entry of a virus into a host cell and containing one or more compounds of the general formula I or a pharmaceutically acceptable derivative thereof and methods of treatment or prophylactic administration of these pharmaceutical compositions to treat viral infections.

Ebolavirus causes a severe infectious disease with a high mortality rate ranging 25-90% in humans. The disease progresses rapidly and can be easily transmitted through direct contact with patients and contaminated materials. The December 2013-January 2016 outbreak in West Africa resulted in more than 28,000 infected cases with about 11,300 deaths. The virus spread to the neighboring areas, and also to USA and European countries due to the global movement of people, which was difficult to control. Thus, a significant public health threat arose all around the world. However, currently there is no approved treatment therapy for Ebolavirus infection. Although several antiviral candidates have been tested in patients, none have shown clear significant benefit and emphasizes a need for development of effective antiviral therapy.

Amodiaquine analogs and methods of uses thereof


Various embodiments are described herein for systems and methods of traffic management in a road network including pathways and at least one intersection. In at least one embodiment, the method comprises receiving data signals from corresponding one or more connected vehicles and generating an intersection model for each approach of each intersection at a first time, where the intersection model comprises estimated arrival times for incoming vehicles at each approach. The method further comprises generating at the first time, for each intersection, candidate traffic timing data signals based at least on the intersection model corresponding to all approaches at the intersection, and generating, at the first time, for each intersection, an optimized traffic timing data signal, which is configured to control the operation of one or more traffic signals at the intersection, and is generated based on the candidate traffic timing data signals and a predetermined optimization variable.

Conventional systems and methods for managing traffic flow typically divert traffic away from congested pathways (e.g. roads, highways) and propose alternative routes to the vehicles to reach their destination. Typically, conventional systems and methods prioritize the preferences of each vehicle individually, without considering the overall impact on the traffic, involving many vehicles, over a larger geographical area. Consequently, the conventional systems and methods are typically inefficient and ineffective. There is a need for systems and methods to manage traffic flow in an efficient and accurate manner.

Systems and methods for managing traffic flow using connected vehicle data


An inflatable optical housing is adapted to provide a visual image and be used in connection with a separate computing device. The housing is sized by one or more bladders and at least one associated alignment member. Optical elements of the device provide an image of a display and/or an enhanced magnified image via lensing. The housing preferably is constructed of lightweight materials and is adapted for rapid inflation and deflation through a variety of mechanisms and with a variety of media. Embodiments of the invention are especially advantageous with wearable computing devices and methods.

1. Field of the Invention
This invention relates to optical assistance devices, for example those designed to be worn by a human user, and more particularly to such devices that are containable within a lightweight, compact, inflatable housing and are suitable for use in varied applications and environments.
2. Description of Related Art
Wearable computing devices of many different types are being used in a host of commercial, industrial and consumer environments and have enormous use-potential in a number of marketplaces, including the military and commercial marketplaces. Commercially, the growth of wearable/portable computing technology is being fueled by phone, pager, wireless local area network (LAN) and other options. Markets for wearable computing devices include manufacturing, police, fire, medical, elder care, transportation, distribution, retailing, and others where hands-free computing allows unimpeded hands-on work. Potential military uses include communications, sensing, imaging, maintenance, inspection, security, intelligence, and medical-related tasks. Many computers on the market presently are brick-like, however, concentrating a great deal of weight in a bulky, cumbersome box that must be strapped onto the body.
The best wearable computers are lightweight and flexible, demonstrating superior ergonomics and allowing use during all normal activities. According to one example, flexible circuitry or equivalent flexible transmission devices join physically independent computer modules, allowing comfortable distribution of the computer about the body to accommodate a wide variety of body morphologies. Standard-interconnect input/output devices allow easy user upgrades and modular replacements. Spread-spectrum wireless LANs allow interaction with other users, a host computer system, or both. Flexible wearable computing devices are comfortable, easy-to-use, convenient and powerful alternatives to the brick-like machines that until recently have been the only choice in the marketplace.
Commonly assigned U.S. Pat. Nos. 5,285,398, 5,491,651 and 5,581,492 to Janik, and commonly assigned U.S. Pat. Nos. 5,555,490 and 5,572,401 to Carroll, all of which are incorporated by reference herein, disclose a number of extremely advantageous designs that are expected to dominate over previous, brick-like wearable computers.
U.S. Pat. No. 5,523,890, granted to Reaney on Jun. 4, 1996, addresses the issue of wearable computing devices in the context of virtual reality technology. Reaney discloses a visual magnifier for use with a video display screen that can be mounted on the head. The screen is coupled to a rigid housing wherein the side surfaces are parallel to the front and the rear surfaces. U.S. Pat. No. 5,191,879, granted to Krauter on Mar. 9, 1993, discloses a rigid borescope or endoscope probe equipped with a camera or imaging device. The device allows for variable focus of the camera by means of a braid and bladder assembly capable of axial expansion. The assembly, however, is incapable of radial expansion. U.S. Pat No. 5,406,417, granted to Denvenyi on Apr. 11, 1995, discloses an optical device equipped with a pneumatic adjusting mechanism to enable the user to make changes to a focal length. The entire device is not adapted for collapsibility because the outer frame is constructed of rigid metal parts. All of the previously mentioned patents are incorporated herein by reference. None of the patents teach or disclose placing a device that is compatible with a wearable computing device within a collapsible housing.
Given the many opportunities that have arisen with the introduction of these technologies, it would be very advantageous to further develop, improve and specifically adapt these technologies to optical devices for use in wearable-computing environments, specifically wherein the device housing is adapted for collapsibility.