This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to a novel inducible gene expression system and methods of modulating gene expression in a host cell for applications such as gene therapy, large-scale production of proteins and antibodies, cell-based high throughput screetng assays, functional genomics and regulation of traits in transgenic plants and animals.

Various publications are cited herein, the disclosures of which are incorporated by reference in their entireties. However, the citation of any reference herein should not be construed as an admission that such reference is available as "Prior Art" to the instant application.
In the field of genetic engineering, precise control of gene expression is a valuable tool for studying, manipulating, and controlling development and other physiological processes. Gene expression is a complex biological process involving a number of specific protein-protein interactions. In order for gene expression to be triggered, such that it produces the RNA necessary as the first step in protein synthesis, a transcriptional activator must be brought into proximity of a promoter that controls gene transcription. Typically, the transcriptional activator itself is associated with a protein that has at least one DNA binding domain that binds to DNA binding sites present in the promoter regions of genes. Thus, for gene expression to occur, a protein comprising a DNA binding domain and a transactivation domain located at an appropriate distance from the DNA binding domain must be brought into the correct position in the promoter region of the gene.
The traditional transgenic approach utilizes a cell-type specific promoter to drive the expression of a designed transgene. A DNA construct containing the transgene is first incorporated into a host genome. When triggered by a transcriptional activator, expression of the transgene occurs in a given cell type.
Another means to regulate expression of foreign genes in cells is through inducible promoters. Examples of the use of such inducible promoters include the PR 1-a promoter, prokaryotic repressor-operator systems, immunosuppressive-immunophilin systems, and higher eukaryotic transcription activation systems such as steroid hormone receptor systems and are described below.
The PR1-a promoter from tobacco is induced during the systemic acquired resistance response following pathogen attack. The use of PR1-a may be limited because it often responds to endogenous materials and external factors such as pathogens, UV-B radiation, and pollutants. Gene regulation systems based on promoters induced by heat shock, interferon and heavy metals have been described (Wum et al., 1986, Proc. Natl. Acad. Sci. USA 83:5414–5418; Amheiter et al., 1990 Cell 62:51–61; Filmus et al., 1992 Nucleic Acids Research 20:27550–27560). However, these systems have limitations due to their effect on expression of non-target genes. These systems are also leaky.
Prokaryotic repressor-operator systems utilize bacterial repressor proteins and the unique operator DNA sequences to which they bind. Both the tetracycline ("Tet") and lactose ("Lac") repressor-operator systems from the bacterium Escherichia coli have been used in plants and animals to control gene expression. In the Tet system, tetracycline binds to the TetR repressor protein, resulting in a conformational change which releases the repressor protein from the operator which as a result allows transcription to occur. In the Lac system, a lac operon is activated in response to the presence of lactose, or synthetic analogs such as isopropyl-b-D-thiogalactoside. Unfortunately, the use of such systems is restricted by unstable chemistry of the ligands, i.e. tetracycline and lactose, their toxicity, their natural presence, or the relatively high levels required for induction or repression. For similar reasons, utility of such systems in animals is limited.
Immunosuppressive molecules such as FK506, rapamycin and cyclosporine A can bind to immunophilins FKBP12, cyclophilin, etc. Using this information, a general strategy has been devised to bring together any two proteins simply by placing FK506 on each of the two proteins or by placing FK506 on one and cyclosporine A on another one. A synthetic homodimer of FK506 (FK1012) or a compound resulted from fusion of FK506-cyclosporine (FKCsA) can then be used to induce dimerization of these molecules (Spencer et al., 1993, Science 262:1019–24; Belshaw et al., 1996 Proc Natl Acad Sci USA 93:4604–7). Gal4 DNA binding domain fused to FKBP12 and VP16 activator domain fused to cyclophilin, and FKCsA compound were used to show heterodimerization and activation of a reporter gene under the control of a promoter containing Gal4 binding sites. Unfortunately, this system includes immunosuppressants that can have unwanted side effects and therefore, limits its use for various mammalian gene switch applications.
Higher eukaryotic transcription activation systems such as steroid hormone receptor systems have also been employed. Steroid hormone receptors are members of the nuclear receptor superfamily and are found in vertebrate and invertebrate cells. Unfortunately, use of steroidal compounds that activate the receptors for the regulation of gene expression, particularly in plants and mammals, is limited due to their involvement in many other natural biological pathways in such organisms. In order to overcome such difficulties, an alternative system has been developed using insect ecdysone receptors (EcR).
Growth, molting, and development in insects are regulated by the ecdysone steroid hormone (molting hormone) and the juvenile hormones (Dhadialla, et al., 1998. Annu. Rev. Entomol. 43: 545–569). The molecular target for ecdysone in insects consists of at least ecdysone receptor (EcR) and ultraspiracle protein (USP). EcR is a member of the nuclear steroid receptor super family that is characterized by signature DNA and ligand binding domains, and an activation domain (Koelle et al. 1991, Cell, 67:59–77). EcR receptors are responsive to a number of steroidal compounds such as ponasterone A and muristerone A. Recently, non-steroidal compounds with ecdysteroid agonist activity have been described, including the commercially available insecticides tebufenozide and methoxyfenozide that are marketed world wide by Rohm and Haas Company (see International Patent Application No. PCT/EP96/00686 and U.S. Pat. No. 5,530,028). Both analogs have exceptional safety profiles to other organisms.
The insect ecdysone receptor (EcR) heterodimerizes with Ultraspiracle (USP), the insect homologue of the mammalian RXR, and binds ecdysteroids and ecdysone receptor response elements and activate transcription of ecdysone responsive genes (Riddiford et al., 2000, Vitam Horm., 60:1–73). The EcR/USP/ligand complexes play important roles during insect development and reproduction. The EcR is a member of the steroid hormone receptor superfamily and has five modular domains, A/B (transactivation), C (DNA binding, heterodimerization), D (Hinge, heterodimerization), E (ligand binding, heterodimerization and transactivation and F (transactivation) domains. Some of these domains such as A/B, C and E retain their function when they are fused to other proteins.
Tightly regulated inducible gene expression systems or "gene switches" are useful for various applications such as gene therapy, large scale production of proteins in cells, cell based high throughput screening assays, functional genomics and regulation of traits in transgenic plants and animals.
The first version of EcR-based gene switch used Drosophila melanogaster EcR (DmEcR) and Mus musculus RXR (MmRXR) and showed that these receptors in the presence of steroid, ponasteroneA, transactivate reporter genes in mammalian cell lines and transgenic mice (Christopherson et al., 1992, PNAS, 89:6314–6318; No et al., 1996, PNAS, 93:3346–3351). Later, Suhr et al. (1998, PNAS, 95:7999–8004) showed that non-steroidal ecdysone agonist, tebufenozide, induced high level of transactivation of reporter genes in mammalian cells through Bombyx mori EcR (BmEcR) in the absence of exogenous heterodimer partner.
International Patent Applications No. PCT/US97/05330 (WO 97/38117) and PCT/US99/08381 (WO99/58155) disclose methods for modulating the expression of an exogenous gene in which a DNA construct comprising the exogenous gene and an ecdysone response element is activated by a second DNA construct comprising an ecdysone receptor that, in the presence of a ligand therefor, and optionally in the presence of a receptor capable of acting as a silent partner, binds to the ecdysone response element to induce gene expression. The ecdysone receptor of choice was isolated from Drosophila melanogaster. Typically, such systems require the presence of the silent partner, preferably retinoid X receptor (RXR), in order to provide optimum activation. In mammalian cells, insect ecdysone receptor (EcR) heterodimerizes with retinoid X receptor (RXR) and regulates expression of target genes in a ligand dependent manner. International Patent Application No. PCT/US98/14215 (WO 99/02683) discloses that the ecdysone receptor isolated from the silk moth Bombyx mori is functional in mammalian systems without the need for an exogenous dimer partner.
U.S. Pat. No. 6,265,173 B 1 discloses that various members of the steroid/thyroid superfamily of receptors can combine with Drosophila melanogaster ultraspiracle receptor (USP) or fragments thereof comprising at least the dimerization domain of USP for use in a gene expression system. U.S. Pat. No. 5,880,333 discloses a Drosophila melanogaster EcR and ultraspiracle (USP) heterodimer system used in plants in which the transactivation domain and the DNA binding domain are positioned on two different hybrid proteins. Unfortunately, these USP-based systems are constitutive in animal cells and therefore, are not effective for regulating reporter gene expression, particularly, in animal cells (for comparison, see Example 1.2, below).
In each of these cases, the transactivation domain and the DNA binding domain (either as native EcR as in International Patent Application No. PCT/US98/14215 or as modified EcR as in International Patent Application No. PCT/US97/05330) were incorporated into a single molecule and the other heterodimeric partners, either USP or RXR, were used in their native state.
Drawbacks of the above described EcR-based gene regulation systems include a considerable background activity in the absence of ligands and the non-applicability of these systems for use in both plants and animals (see U.S. Pat. No. 5,880,333). Therefore, a need exists in the art for improved EcR-based systems to precisely modulate the expression of exogenous genes in both plants and animals. Such improved systems would be useful for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic animals. Improved systems that are simple, compact, and dependent on ligands that are relatively inexpensive, readily available, and of low toxicity to the host would prove useful for regulating biological systems.
For certain applications such as gene therapy, it may be desirable to have an inducible gene expression system that responds well to synthetic non-steroid ligands and at the same is insensitive to the natural steroids. Thus, improved systems that are simple, compact, and dependent on ligands that are relatively inexpensive, readily available, and of low toxicity to the host would prove useful for regulating biological systems.
Herein, Applicants describe an improved ecdysone receptor-based inducible gene expression system in which the transactivation and DNA binding domains are separated from each other by placing them on two different proteins results in greatly reduced background activity in the absence of a ligand and significantly increased activity over background in the presence of a ligand. This two-hybrid system is a significantly improved inducible gene expression modulation system compared to the two systems disclosed in applications PCT/US97/05330 and PCT/US98/14215. The two-hybrid system exploits the ability of a pair of interacting proteins to bring the transcription activation domain into a more favorable position relative to the DNA binding domain such that when the DNA binding domain binds to the DNA binding site on the gene, the transactivation domain more effectively activates the promoter (see, for example, U.S. Pat. No. 5,283,173). Since the DNA binding and transactivation domains reside on two different molecules, the background activity in the absence of ligand is greatly reduced.
A two-hybrid system also provides improved sensitivity to non-steroidal ligands for example, diacylhydrazines, when compared to steroidal ligands for example, ponasterone A ("PonA") or muristerone A ("MurA"). In addition, since transactivation based on EcR gene switches is often cell-line dependent, it is easier to tailor switching systems to obtain maximum transactivation capability for each application. Furthermore, the two-hybrid system avoids some side effects due to overexpression of RXR that often occur when unmodified RXR is used as a switching partner.
Thus Applicants' invention provides an improved ecdysone receptor-based inducible gene expression system for use in both prokaryotic and eukaryotic host cells in which ligand sensitivity and magnitude of transactivation may be selected as desired, depending upon the application.
The EcR is a member of the nuclear receptor superfamily and classified into subfamily 1, group H (referred to herein as "Group H nuclear receptors"). The members of each group share 40–60% amino acid identity in the E (ligand binding) domain (Laudet et al., A Unified Nomenclature System for the Nuclear Receptor Subfamily, 1999; Cell 97:161–163). In addition to the ecdysone receptor, other members of this nuclear receptor subfamily 1, group H include: ubiquitous receptor (UR), Orphan receptor 1 (OR-1), steroid hormone nuclear receptor 1 (NER-1), RXR interacting protein-15 (RIP-15), liver x receptor β (LXRβ), steroid hormone receptor like protein (RLD-1), liver x receptor (LXR), liver x receptor α (LXRα), farnesoid x receptor (FXR), receptor interacting protein 14 (RIP-14), and farnesol receptor (HRR-1).
Given the close relatedness of ecdysone receptor to other Group H nuclear receptors, Applicants' invention also provides a two-hybrid Group H nuclear receptor-based gene expression system comprising ligand binding domains of a Group H nuclear receptor and its respective dimerization partner. Thus, Applicants' invention also provides a two-hybrid Group H nuclear receptor-based gene expression system for use in both prokaryotic and eukaryotic host cells in which ligand sensitivity and magnitude of transactivation may be selected as desired, depending upon the application.

Ecdysone receptor-based inducible gene expression system


A multistage automatic transmission may include an input shaft, a first composite planetary gear set including first and second planetary gear sets, each of the first and second planetary gear sets including three rotary members, a first brake, a first clutch, a second brake, a second clutch selectively connecting a pair of rotary members of the first composite planetary gear set that are selectively connected to each other, and a second composite planetary gear set arranged coaxially with the input shaft and including a plurality of rotary members, wherein the plurality of rotary members include a rotary member connected to the first composite planetary gear set, a rotary member connected to the input shaft, and a further rotary member connected to an output shaft, at least two rotary members of the plurality of rotary members in the second composite planetary gear set being connected to two friction members.

1. Field of the Invention
The present invention generally relates to a multistage automatic transmission for a vehicle, and more particularly, to the configuration of a multistage transmission that can perform shifting in nine steps forward and one step rearward.
2. Description of Related Art
According to the development trend of vehicles in recent years, attempts have been made to manufacture vehicles having high efficiency and low fuel consumption in order to conform to increasingly stricter fuel consumption regulations, thus there have been efforts to develop an automatic transmission that has more steps of shifting to operate an engine more efficiently and has a simple and light configuration to improve fuel efficiency of a vehicle.
The information disclosed in this Background of the Invention section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.

Multistage automatic transmission for vehicle


A method, system, and computer program product for reducing likelihood of data loss during performance of failovers in a high-availability system comprising a primary system and a standby system are provided. The method, system, and computer program product provide for defining a halt duration, periodically determining a halt end time, halting data modifications at the primary system responsive to failure of data replication to the standby system, resuming data modifications at the primary system responsive to a last determined halt end time being reached or data replication to the standby system resuming, and responsive to the primary system failing prior to a previously determined halt end time, determining that a failover to the standby system will not result in data loss on the standby system with respect to the primary system.

In high-availability systems, data replication from primary systems to standby systems sometimes fails as a result of, for instance, failure of a connection between a primary system and a standby system. When data replication fails, if the primary system continues to process data modification requests, then the standby system will not have up-to-date data. Hence, if the primary system subsequently fails and a failover to the standby system is performed, then data loss will occur because data modifications made after data replication failure and before primary system failure will be missing from the standby system.

Reducing likelihood of data loss during failovers in high-availability systems

International Business Machines Corporation


An image processing apparatus which decorates color data contained in color image data with different decoration patterns for respective colors of the color data to output the color data includes a determination unit which determines a combination of a color of color data having a highest number of pixels among colors of color data contained in the color image data and a decoration pattern having a lowest number of pixels among the decoration patterns and a monochrome decoration output unit which decorates color data contained in the color image data in accordance with a combination of a color and a decoration pattern corresponding to the color determined by the determination unit for monochrome decoration output of the color image data.

1. Field of the Invention
The present disclosure generally relates to image processing and, more particularly, to an image processing apparatus, an image processing method and a storage medium storing a program for executing image processing in which decoration processing is performed on color text to print for monochrome output of a color document from an image processing apparatus.
2. Description of the Related Art
FIG. 1 illustrates a color document 101 including text 102 output in black, text 103 output in red, and text 104 output in blue.
Color image data acquired from the input color document 101 is gray-scale converted and is monochromatically output in black (hereinafter, called monochrome output (copy or page description language (PDL) printing)), resulting in a monochrome output material 105.
In the monochrome output material 105, the text 102 originally output in black, the text 103 originally output in red and the text 104 originally output in blue on the color document 101 are difficult to distinguish. In general, a document creator may often put color emphasis on text of an important part in a document. However, the important part with color emphasis may be output in monochrome. Possibly in this case, which part of the document is important is not noticeable for a user who has received the document from the document creator.
Against this problem, according to Japanese Patent Laid-Open No. 2008-244619, for monochrome output of color image data, a decoration having an equal color density to that of text to be originally output in a color excluding black may be given around the text to output a resulting output material 106 (hereinafter, called a monochrome decoration output material). Alternatively, a decoration may be given to text itself which should be originally output in a color excluding black to output a monochrome decoration output material 106. Thus, information describing that the subject text is important may be inherited from the color image data. For example, the text 102 output in black on a color document results in text 107 in black as it is while the text 103 output in red on the color document is converted to text 108 decorated with a black underline. The text 104 output in blue on the color document is converted to black bold text 109.
Thus, in monochrome decoration output processing, decorations having different patterns for colors may be given to inherit information that the colors have been output in different colors on a color document.
However, in the monochrome decoration output processing, a more amount of a coloring material may possibly be consumed than that in normal monochrome output processing.

Image processing apparatus, method, and storage medium for executing image processing and performing decoration processing


Methods, systems, and computer program products are provided for managing resources. A request is received for a plurality of resources from a requester. A ticket is generated for the request that indicates the resources. For each resource, a resource provider for the resource is queried to determine whether the resource can be acquired. The ticket is queued if any of the resources cannot be acquired. The ticket is granted if all of the resources can be acquired.

Storage devices are used to store data. Examples of storage devices include hard disk drives, memory devices, and optical disc drives. Data may be stored in various configurations of data storage, and may be organized in storage in various ways. For instance, data may be collected and organized in databases, which may be stored in collections of storage, such as network attached storage (NAS) arrays, storage area networks (SAN), and further arrangements of physical storage. The amount of data requiring storage continues to increase at a fast pace, and as such the need is increasing for larger capacity storage, as well as better types of storage organization.
A data warehouse is an example type of repository of historical data for an entity, such as a corporation. Data warehouses are designed to allow complex queries and analysis to be performed on the data without slowing down day-to-day operational systems. As such, data warehouses are useful for reporting and analysis. Various types of data warehouses exist, including online analytical processing (OLAP) databases.
Managing access to stored data, such as data stored in a data warehouse, is challenging because multiple users may desire to access the same data simultaneously. For instance, a first user may desire to modify particular data while a second user desires to read the data to perform operations. This may be undesirable for the second user, as the value of the particular data may change during the operations, leading to a data concurrency issue. Furthermore, a data warehouse may include numerous data sets that are managed by different providers, leading to different techniques needing to be used to interface with the different providers.

Extensible and generic framework for managing resources for data warehousing loads


The invention relates to a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of: (a) compartmentalising genetic elements into microcapsules; (b) expressing the genetic elements to produce their respective gene products within the microcapsules; (c) sorting the genetic elements which produce the gene product having a desired activity. The invention permits the in vitro evolution of nucleic acids by repeated mutagenesis and iterative applications of the method of the invention.

The present invention relates to methods for use in vitro evolution of molecular libraries. In particular, the present invention relates to methods of selecting nucleic acids encoding gene products in which the nucleic acid and the activity of the encoded gene product are linked by compartmentation.
Evolution requires the generation of genetic diversity (diversity in nucleic acid) followed by the selection of those nucleic acids which result in beneficial characteristics. Because the nucleic acid and the activity of the encoded gene product of an organism are physically linked (the nucleic acids being confined within the cells which they encode) multiple rounds of mutation and selection can result in the progressive survival of organisms with increasing fitness. Systems for rapid evolution of nucleic acids or proteins in vitro must mimic this process at the molecular level in that the nucleic acid and the activity of the encoded gene product must be linked and the activity of the gene product must be selectable.
Recent advances in molecular biology have allowed some molecules to be co-selected according to their properties along with the nucleic acids that encode them. The selected nucleic acids can subsequently be cloned for further analysis or use, or subjected to additional rounds of mutation and selection.
Common to these methods is the establishment of large libraries of nucleic acids. Molecules having the desired characteristics (activity) can be isolated through selection regimes that select for the desired activity of the encoded gene product, such as a desired biochemical or biological activity, for example binding activity.
Phage display technology has been highly successful as providing a vehicle that allows for the selection of a displayed protein by providing the essential link between nucleic acid and the activity of the encoded gene product (Smith, 1985; Bass et al. , 1990; McCafferty et al., 1990; for review see Clackson and Wells, 1994). Filamentous phage particles act as genetic display packages with proteins on the outside and the genetic elements which encode them on the inside. The tight linkage between nucleic acid and the activity of the encoded gene product is a result of the assembly of the phage within bacteria. As individual bacteria are rarely multiply infected, in most cases all the phage produced from an individual bacterium will carry the same genetic element and display the same protein.
However, phage display relies upon the creation of nucleic acid libraries in vivo in bacteria. Thus, the practical limitation on library size allowed by phage display technology is of the order of 107 to 1011, even talking advantage of xcex phage vectors with excisable filamentous phage replicons. The technique has mainly been applied to selection of molecules with binding activity. A small number of proteins with catalytic activity have also been isolated using this technique, however, in no case. was selection directly for the desired catalytic activity, but either for binding to a transition-state analogue (Widersten and Mannervik, 1995) or reaction with a suicide inhibitor (Soumillion et al., 1994; Janda et al., 1997).
Specific peptide ligands have been selected for binding to receptors by affinity selection using large libraries of peptides linked to the C terminus of the lac repressor Lacl (Cull et al., 1992). When expressed in E. coli the repressor protein physically links the ligand to the encoding plasmid by binding to a lac operator sequence on the plasmid.
An entirely in vitro polysome display system has also been reported (Martheakis et al., 1994) in which nascent peptides are physically attached via the ribosome to the RNA which encodes them.
However, the scope of the above systems is limited to the selection of proteins and furthermore does not allow direct selection for activities other than binding, for example catalytic or regulatory activity.
In vitro RNA selection and evolution (Ellington and Szostak, 1990), sometimes referred to as SELEX (systematic evolution of ligands by exponential enrichment) (Tuerk and Gold, 1990) allows for selection for both binding and chemical activity, but only for nucleic acids. When selection is for binding, a pool of nucleic acids is incubated with immobilised substrate. Non-binders are washed away, then the binders are released, amplified and the whole process is repeated in iterative steps to enrich for better binding sequences. This method can also be adapted to allow isolation of catalytic RNA and DNA (Green and Szostak, 1992; for reviews see Chapman and Szostak, 1994; Joyce, 1994; Gold et al., 1995; Moore, 1995).
However, selection for xe2x80x9ccatalyticxe2x80x9d or binding activity using SELEX is only possible because the same molecule performs the dual role of carrying the genetic information and being the catalyst or binding molecule (aptamer). When selection is for xe2x80x9cauto-catalysisxe2x80x9d the same molecule must also perform the third role of-being a substrate. Since the genetic element must play the role of both the substrate and the catalyst, selection is only possible for single turnover events. Because the xe2x80x9ccatalystxe2x80x9d is in this process itself modified, it is by definition not a true catalyst. Additionally, proteins may not be selected using the SELEX procedure. The range of catalysts, substrates and reactions which can be selected is therefore severely limited.
Those of the above methods that allow for iterative rounds of mutation and selection are mimicking in vitro mechanisms usually ascribed to the process of evolution: iterative variation, progressive selection for a desired the activity and replication. However, none of the methods so far developed have provided molecules of comparable diversity and functional efficacy to those that are found naturally. Additionally, there are no man-made xe2x80x9cevolutionxe2x80x9d systems which can evolve both nucleic acids and proteins to effect the full range of biochemical and biological activities (for example, binding, catalytic and regulatory activities) and that can combine several processes leading to a desired product or activity.
There is thus a great need for an in vitro system that overcomes the limitations discussed above.
According to a first aspect of the present invention, there is provided a method for isolating one or more genetic elements encoding a gene product having a desired activity, comprising the steps of:
(a) compartmentalising genetic elements into microcapsules;
(b) expressing the genetic elements to produce their respective gene products within the microcapsules;
(c) sorting the genetic elements which produce the gene product(s) having the desired activity.
The microcapsules according to the present invention compartmentalise genetic elements and gene products such that they remain physically linked together. Surprisingly, nucleic acid expression remains possible within the artificial microcapsules allowing for isolation of nucleic acid on the basis if the activity of the gene product which it encodes.
As used herein, a genetic element is a molecule or molecular construct comprising a nucleic acid. The genetic elements of the present invention may comprise any nucleic acid (for example, DNA, RNA or any analogue, natural or artificial, thereof). The nucleic acid component of the genetic element may moreover be linked, covalently or non-covalently, to one or more molecules or structures, including proteins, chemical entities and groups, solid-phase supports such as magnetic beads, and the like. In the method of the invention, these structures or molecules can be designed to assist in the sorting and/or isolation of the genetic element encoding a gene product with the desired activity.
Expression, as used herein, is used in its broadest meaning, to signify that a nucleic acid contained in the genetic element is converted into its gene product. Thus, where the nucleic acid is DNA, expression refers to the transcription of the DNA into RNA; where this RNA codes for protein, expression may also refer to the translation of the RNA into protein. Where the nucleic acid is RNA, expression may refer to the replication of this RNA into further RNA copies, the reverse transcription of the RNA into DNA and option. the transcription of this DNA into further RNA molecule(s), as well as optionally the translation of any of the RNA species produced into protein. Preferably, therefore, expression is performed by one or more processes selected from the group consisting of transcription, reverse transcription, replication and translation.
Expression of the genetic element may thus be directed into either DNA, RNA or protein, or a nucleic acid or protein containing unnatural bases or amino acids (the gene product) within the microcapsule of the invention, so that the gene product is confined within the same microcapsule as the genetic element.
The genetic element and the gene product thereby encoded are linked by confining each genetic element and the respective gene product encoded by the genetic element within the same microcapsule. In this way the gene product in one microcapsule cannot cause a change in any other microcapsules.
The term xe2x80x9cmicrocapsulexe2x80x9d is used herein in accordance with the meaning normally assigned thereto in the art and further described hereinbelow. In essence, however, a microcapsule is an artificial compartment whose delimiting borders restrict the exchange of the components of the molecular mechanisms described herein which allow the sorting of genetic elements according to the function of the gene products which they encode.
Preferably, the microcapsules used in the method of the present invention will be capable of being produced in very large numbers, and thereby to compartmentalise a library of genetic elements which encodes a repertoire of gene products.
According to a preferred embodiment of the first aspect of the present invention, the sorting of genetic elements may be performed in one of essentially four techniques.
(I) In a first embodiment, the microcapsules are sorted according to an activity of the gene product or derivative thereof which makes the microcapsule detectable as a whole. Accordingly, the invention provides a method according to the first aspect of the invention wherein a gene product with the desired activity induces a change in the microcapsule, or a modification of one or more molecules within the microcapsule, which enables the microcapsule containing the gene product and the genetic element encoding it to be sorted. In this embodiment, therefore, the microcapsules are physically sorted from each other according to the activity of the gene product(s) expressed from the genetic element(s) contained therein, which makes it possible selectively to enrich for microcapsules containing gene products of the desired activity.
(II) In a second embodiment, the genetic elements are sorted following pooling of the microcapsules into one or more common compartments. In this embodiment, a gene product having the desired activity modifies the genetic element which encoded it (and which resides in the same microcapsule) in such a way as to make it selectable in a subsequent step. The reactions are stopped and the microcapsules are then broken so that all the contents of the individual microcapsules are pooled. Selection for the modified genetic elements enables. enrichment of the genetic elements encoding the gene product(s) having the desired activity. Accordingly, the invention provides a method according to the first aspect of the invention, wherein in step (b) the gene product having the desired activity modifies the genetic element encoding it to enable the isolation of the genetic element. It is to be understood, of course, that modification may be direct, in that it is caused by the direct action of the gene product on the genetic element, or indirect, in which a series of reactions, one or more of which involve the gene product having the desired activity, leads to modification of the genetic element.
(III) In a third embodiment, the genetic elements are sorted following pooling of the microcapsules into one or more common compartments. In this embodiment, a gene with a desired activity induces a change in the microcapsule containing the gene product and the genetic element encoding it. This change, when detected, triggers the modification of the gene within the compartment. The reactions are stopped and the microcapsules are then broken so that all the contents of the individual microcapsules are pooled. Selection for the modified genetic elements enables enrichment of the genetic elements encoding the gene product(s) having the desired activity. Accordingly the invention provides a method according to the first aspect of the invention, where in step (b) the gene product having the desired activity induces a change in the compartment which is detected and triggers the modification of the genetic element within the compartment so as to allow its isolation. It is to be understood that the detected change in the compartment may be caused by the direct action of the gene product, or indirect action, in which a series of reactions, one or more of which involve the gene product having the desired activity leads to the detected change.
(IV) In a fourth embodiment, the genetic elements may be sorted by a multi-step procedure, which involves at least two steps, for example, in order to allow the exposure of the genetic elements to conditions which permit at least two separate reactions to occur. As will be apparent to a persons skilled in the art, the first microencapsulation step of the invention must result in conditions which permit the expression of the genetic elementsxe2x80x94be it transcription, transcription and/or translation, replication or the like. Under these conditions, it may not be possible to select for a particular gene product activity, for example because the gene product may not be active under these conditions, or because the expression system contains an interfering activity. The invention therefore provides a method according to the first aspect of the present invention, wherein step (b) comprises expressing the genetic elements to produce their respective gene products within the microcapsules, linking the gene products to the genetic elements encoding them and isolating the complexes thereby formed. This allows for the genetic elements and their associated gene products to be isolated from the capsules before sorting according to gene product activity takes place. In a preferred embodiment, the complexes are subjected to a further compartmentalisation step prior to isolating the genetic elements encoding a gene product having the desired activity. This further compartmentalisation step, which advantageously takes place in microcapsules, permits the performance of further reactions, under different conditions, in an environment where the genetic elements and their respective gene products are physically linked. Eventual sorting of genetic elements may be performed according to embodiment (I), (II) or (III) above.
The xe2x80x9csecondary encapsulationxe2x80x9d may also be performed with genetic elements linked to gene products by other means, such as by phage display, polysome display, RNA-peptide fusion or lac repressor peptide fusion.
The selected genetic element(s) may also be subjected to subsequent, possibly more stringent rounds of sorting in iteratively repeated steps, reapplying the method of the invention either in its entirety or in selected steps only. By tailoring the conditions appropriately, genetic elements encoding gene products having a better optimised activity may be isolated after each round of selection.
Additionally, the genetic elements isolated after a first round of sorting may be subjected to mutagenesis before repeating the sorting by iterative repetition of the steps of the method of the invention as set out above. After each round of mutagenesis, some genetic elements will have been modified in such a way that the activity of the gene products is enhanced.
Moreover, the selected genetic elements can be cloned into an expression vector to allow further characterisation of the genetic elements and their products.
In a second aspect, the invention provides a product when selected according to the first aspect of the invention. As used in this context, a xe2x80x9cproductxe2x80x9d may refer to a gene product, selectable according to the invention, or the genetic element (or genetic information comprised therein).
In a third aspect, the invention provides a method for preparing a gene product, comprising the steps of:
(a) preparing a genetic element encoding the gene product;
(b) compartmentalising genetic elements into microcapsules;
(c) expressing the genetic elements to produce their respective gene products within the microcapsules;
(d) sorting the genetic elements which produce the gene product(s) having the desired activity; and
(e) expressing the gene product having the desired activity.
In accordance with the third aspect, step (a) preferably comprises preparing a repertoire of genetic elements, wherein each genetic element encodes a potentially differing gene product. Repertoires may be generated by conventional techniques, such as those employed for the generation of libraries intended for selection by methods such as phage display. Gene products having the desired activity may be selected from the repertoire, according to the present invention.
In a fourth aspect, the invention provides a method for screening a compound or compounds capable of modulation the activity of a gene product, comprising the steps of:
(a) preparing a repertoire of genetic element encoding gene product;
(b) compartmentalising genetic elements into microcapsules;
(c) expressing the genetic elements to produce their respective gene products within the microcapsules;
(d) sorting the genetic elements which produce the gene product(s) having the desired activity; and
(e) contacting a gene product having the desired activity with the compound or compounds and monitoring the modulation of an activity of the gene product by the compound or compounds.
Advantageously, the method further comprises. the step of:
(f) identifying the compound or compounds capable of modulating the activity of the gene product and synthesising said compound or compounds.
This selection system can be configured to select for RNA, DNA or protein molecules with catalytic, regulatory or binding activity.


An ECU executes a program including the steps of: prohibiting startup of an engine when there is a request for execution of a deterioration diagnosis process and when the deterioration diagnosis process is in execution; and releasing prohibition of startup of the engine when the deterioration diagnosis process is completed.

There is known a hybrid vehicle including an internal combustion engine, a drive motor, and a power storage device for supplying power to the drive motor. In such a vehicle, it is necessary to diagnose, with high accuracy, whether the power storage device has deteriorated or not.
Japanese Patent Laying-Open No. 2000-131404 discloses a deterioration degree determining apparatus for diagnosing whether a power storage device has deteriorated or not, based on an amount of discharge from a fully-charged state to a prescribed discharge voltage value.

Vehicle and deterioration diagnosis method for power storage device


The present invention relates to a terminal sterilization process for biodegradable PEG-based insoluble hydrogels using irradiation. The presence of a protective solvent ensures that the hydrogel remains intact with functionally preserved three-dimensional and physicochemical properties.

1. Field of the Invention
Biodegradable PEG-based hydrogels are of interest for various medical and pharmaceutical applications such as tissue regeneration, wound closure and drug delivery. For safety reasons it is strongly preferred in some applications, like for example drug delivery, to engineer biodegradability into the PEG hydrogel. Biodegradability may be introduced into a hydrogel by ester bonds that undergo spontaneous or enzymatic hydrolysis in the aqueous in vivo environment.
It is noted that citation or identification of any document in this application is not an admission that such document is available as prior art to the present invention.
Sterility of a pharmaceutical composition or a medical device intended for implantation or topical application is mandatory to receive approval as a correspondingly marketed product. Various methods of sterilization have been proposed, such as heat, pressure, filtering, chemicals or irradiation. Unfortunately, these sterilization methods are not applicable to biodegradable PEG-hydrogels as they are not compatible with retaining the hydrogel's structure and properties, thus limiting the medical use of biodegradable PEG-hydrogels.
For instance, injectable solutions are most often sterilized in their vials by autoclaving, but biodegradable bonds will undergo drastically accelerated degradation, if subjected to high temperature. Therefore, autoclaving a biodegradable PEG hydrogel will result in a pre-degraded material which will not qualify for therapeutical applications.
Alternatively, a solution may be sterilized by filtration using filters with pore sizes of 0.2 μm to remove any microbial contaminants and subsequently filling the sterile solution into the vials under aseptic conditions. However, in case of insoluble crosslinked PEG hydrogels, the material is not soluble, but may be present in form of a suspension of microparticles or as another three-dimensional object (e.g., disc or tube), typically larger in size than 0.2 μm and therefore such suspensions or gel objects cannot be sterilized by filtration.
The international patent application WO2003/035244 describes a closed-circuit apparatus which allows the preparation of sterile microparticles. Filter-sterilized chemical components are kept sterile within the aseptic environment of the system throughout the particle formation process, thus resulting in sterile microparticles.
Such aseptic processing, which applies a sterile filtration step at the level of the starting materials and maintains aseptic conditions during the process, has certain disadvantages over sterilization after the synthesis of the hydrogel, called terminal sterilization. The earlier the sterilization step occurs in the production process, the higher is the risk of accidental contamination. Aseptic processing also requires elaborate technical equipment, thus increasing production cost. Therefore, a terminal sterilization method is preferred.
Photodegradation with UV light and gamma irradiation of polymers generate radicals and/or ions that often lead to cleavage and cross-linking. Oxidation also occurs, complicating the situation, since exposure to light is seldom in the absence of oxygen. Generally, this changes the properties of the hydrogel and the material's susceptibility to biodegradation (Encyclopedia of Polymer Science and Technology, Mark Herman (Ed) Wiley, 2004, p. 263 ff).
Treatment with ethylene oxide gas or with solutions containing hydrogen peroxide will cause similar side reactions negatively affecting the hydrogel's biodegradation properties and causing substantial deviation of the degradation kinetics of the treated hydrogel as compared to the untreated hydrogel material. In addition, care has to be taken to ensure that no significant amounts of for example ethylene oxide remain in the hydrogel, which may be toxic and cause undesired side-effects.
To circumvent the difficulties associated with terminal sterilization, the processes of crosslinking and sterilization have been combined. U.S. Pat. No. 5,634,943 details a method for generating crosslinked PEG hydrogels by gamma irradiation. In this approach, linear PEG (MW 200 kDa) was dissolved in aqueous saline, degassed and irradiated by means of a gamma source such as Co60. A dosage of between 2.5 and 25 Mrads (equivalent to between 25 and 250 kGy) was sufficient to effect crosslinking of the PEG chains by radical formation and interchain linkage, resulting in a hydrated insoluble hydrogel. Due to the fact that the irradiation dosage was also sufficiently high for sterilization, in one step a material was obtained that was suitable for implantation into the cornea of the eye.
Similarly, US patent application US20090030102 describes a method of forming a crosslinked polymer gel for use in electronic devices, based on polyalkylene oxide, polyarylene oxide, or polyglycidyl ether, which in the presence of a crosslinker and organic solvent is crosslinked through UV and/or gamma irradiation.
For other applications, such as delivery of pharmaceuticals, biodegradability of the PEG hydrogel is desirable. U.S. Pat. No. 6,537,569 details a process of generating degradable PEG hydrogels through gamma irradiation. Here, linear PEG chains connected through biodegradable ester linkages are employed (MW 10 kDa). Irradiation with 25 or 30 kGy formed interchain crosslinks and an insoluble PEG hydrogel.
It was also attempted to control drug release kinetics by varying the degree of crosslinking in UV or gamma irradiated PEG hydrogels (Minkova et al., J. Polym. Sci., Polym. Phys. 27 (1989) 621-642, Belcheva et al., Macromol. Symp. 103 (1996) 193, Rosiak and Yoshii, Nuclear Instruments and Methods in Physics research B 151 (1999) 56-64, Rosiak and Ulansky, Radiation Physics and Chemistry 55 (1999) 139-151, Dimitrov et al., Acta Pharmaceutica Turcica 46 (2004) 49-54). Nevertheless, here the presence of drug during the irradiation process is required to provide for the entrapment of drug, but the possibility of irradation-caused side reactions such as oxidation or hydrolysis or conjugations to the polymer chains render this approach impractical for most therapeutic entities.
It has also been shown, that irradiation affects other properties of PEG-based hydrogels such as swelling and roughness (Kanjickal et al, J Biomed Mater Res A. 2008 Jan. 9—Effects of sterilization on poly(ethylene glycol) hydrogels).
Various PEG-based hydrogels have been described in the literature. For example, WO2006/003014 describes polymeric hydrogel conjugates of a prodrug, in which the hydrogel consists of non-biodegradable backbone moieties interconnected by crosslinkers comprising biodegradable bonds.
The European patent application EP09167026.5 describes a PEG-based hydrogel with a characteristic late-stage burst-like degradation kinetics.
A hydrogel which only consists of PEG-moieties is described in the European patent EP1019446. Hydrolytically unstable bonds are built into the hydrogel to allow degradation. The patent also claims the use of such hydrogel as a drug delivery system.
U.S. Pat. No. 5,514,379 describes, among others, PEG-based hydrogels which may contain diagnostic labels, alone or in combination with therapeutic drugs. Similarly, U.S. Pat. No. 6,602,952 describes PEG-chitosan hydrogels, containing biologically active agents which may be injected in vivo. The PCT application WO2006/38462 describes poly(ethylene oxide)-containing hydrogels with carbamate crosslinks which are used as drug delivery devices or in other biomedical functions.
It is noted that in this disclosure and particularly in the claims and/or paragraphs, terms such as "comprises", "comprised", "comprising" and the like can have the meaning attributed to it in U.S. Patent law; e.g., they can mean "includes", "included", "including", and the like; and that terms such as "consisting essentially of" and "consists essentially of" have the meaning ascribed to them in U.S. Patent law, e.g., they allow for elements not explicitly recited, but exclude elements that are found in the prior art or that affect a basic or novel characteristic of the invention.
It is further noted that the invention does not intend to encompass within the scope of the invention any previously disclosed product, process of making the product or method of using the product, which meets the written description and enablement requirements of the USPTO (35 U.S.C. 112, first paragraph) or the EPO (Article 83 of the EPC), such that applicant(s) reserve the right to disclaim, and hereby disclose a disclaimer of any previously described product, method of making the product, or process of using the product.

This patent is subject to a terminal disclaimer.

Sterilization of biodegradable hydrogels


A secondary-side rectifier of an inductive n-phase energy transmission system with N greater than or equal to 3, the energy transmission system including in each phase a resonant oscillating circuit, each resonant oscillating circuit including at least one inductor and at least one capacitor wherein secondary-side resonant oscillating circuits are magnetically coupleable to primary-side resonant oscillating circuits, wherein the secondary-side resonant oscillating circuits are star-connected or mesh-connected and are connected to a rectifier via external conductors, wherein the rectifier includes a series connection of a plurality of diodes with identical conducting directions, wherein a smoothing capacitor is connected in parallel with the series connection and an output voltage of the rectifier is applied to connecting points of the smoothing capacitor wherein each external conductor is connected to an anode of the diodes.

Field of the Invention
This disclosure relates generally to a secondary-side rectifier for an energy transmission system.
Description of Related Art
In contactless energy transmission, usually a voltage induced in the secondary circuit of an air-gap transformer is rectified. The resulting direct-current voltage is used to supply power to consumers. For high power requirements, the multi-phase layout of the system is of advantage because power density is increased.
FIG. 1 shows a simple secondary rectifier consisting of a diode full bridge. The secondary side of the energy transmission system shown in FIG. 1 is designed as a three-phase system in which the resonant oscillating circuits that form the three phases consist of the inductors LS and the resonant capacitors CS which are star-connected. The substitute voltage sources Ui stand for the voltages Ui induced in the secondary windings. A three-phase system is the most simple multi-phase contactless energy transmission system. However, in principle, this document refers to all possible numbers of phases. Odd numbers are in most cases advantageous.
The full bridge rectifier shown in FIG. 1 generates a direct-current voltage which first and foremost depends on the coupling with the primary circuit and also from the load. Where a constant direct-current voltage is required, the rectifier voltage variable is regulated via a downstream DC/DC converter which is not shown.
FIG. 2 shows the secondary side of the energy transmission system with delta-connected phases.

Double-rectifier for a multi-phase contactless energy transmission system


An automatic beverage dispenser shut off system for a beverage dispenser includes a housing for a closed loop refrigeration system. A retaining tank feed system directs the beverage mix to a mixing cylinder having a rotatable beater bar mounted therein. The beater bar is coupled to a motor. The retaining tank cover is in actuating contact with a shut off switch in the power circuit of the beverage dispenser. Removal of the retaining tank cover automatically actuates the shut off switch and cuts off all power to the beverage dispenser.

The present invention is directed to a beverage dispenser shut off system, particularly, a shut off system which automatically shuts off power to the beverage dispenser when it is being prepared for cleaning or service, or when beverage mix is being added to the beverage dispenser.
Equipment for dispensing beverage products such as margaritas, daiquiris, frozen lemonade, and frozen or semi-frozen fruit juices are well known in the prior art. Such devices vary from simple hand crank units used to make homemade ice cream to high capacity, high output cocktail freezers used by commercial establishments. Typically, these prior art beverage dispensers include a mixing cylinder having a beater bar mounted within the mixing cylinder. The beater bar is connected to a drive motor which rotates the beater bar within the mixing cylinder. A beverage retaining tank or hopper connected to the mixing cylinder holds the beverage mix or ingredients and delivers the beverage mix to the mixing cylinder through an opening or passageway connecting the retaining tank to the mixing cylinder.
The retaining tank must be periodically filled with new beverage ingredients when the beverage level in the retaining tank reaches a predetermined lower limit. The retaining tank and mixing cylinder must also be cleaned regularly. When these function are to be performed the beverage dispenser is turned off and preferably unplugged so that no power is applied to the beverage dispenser. These safety precautions are not always followed, thereby presenting a serious risk of injury to employees re-filing or cleaning the beverage dispenser. If the power to the beverage dispenser is not shut off, accidents may occur if the dispenser is inadvertently turned on. This is particularly dangerous when personnel are cleaning or servicing the mixing cylinder and beater bar of the dispenser.
It is therefore an object of the present invention to provide a beverage dispenser shut off system which automatically shuts off power to the beverage dispenser when it is being cleaned or services.
It is another object of the present invention to provide a beverage dispenser shut off system which is actuated upon removal of the beverage dispenser cover.

Automatic shut off system for a beverage dispenser


A piece of seating furniture has a saddle-form seat surface, wherein the seat surface is arranged on a saddle support. The seat surface here is mounted between a front saddle member on a front member support and a rear saddle member on a rear member support.

The requirements which have to be met by pieces of seating furniture, in particular by office furniture, have increased constantly in the past. Of predominant importance in a large number of embodiments, in particular, are comfort-related requirements in combination with ergonomic aspects. Sitting in a manner which is kind to the back is just as important here as providing a flexible and compact piece of seating furniture which has a stable stand and provides a high level of flexibility for adjusting comfort-related parameters.
DE 1 032 492 B discloses an office stool having a mobile, three-legged base framework and a height-adjustable saddle seat.
Pieces of seating furniture have a saddle-form seat surface, wherein the seat surface is arranged on a saddle support. The seat surface is mounted between a front saddle member on a front member support and a rear saddle member on a rear member support. A saddle surface provides an anatomically comfortable way of sitting for the user. In the present embodiment of the piece of seating furniture, the surface is designed to be larger than a conventional saddle, for example of a standing seat or of a bicycle, such that support is given to the entire region of the user's bottom. This avoids the unpleasant situation where the seat leaves its impression on the user. Furthermore, it is also possible for the user's back to be positioned in the healthy S shape, since dynamic sitting, as on a sitting ball, is possible.
In one embodiment, the seat surface is formed as a minimal surface by way of a covering, which is mounted between the saddle members. This further improves the adaptation to the anatomy of the user's bottom and increases the sitting comfort. Minimal surfaces always constitute optimum uniformity of the surface progression while avoiding edge locations.
In one embodiment, the covering, by means of which the seat surface is formed, is connected to the front saddle member between a first end of the front saddle member and a second end of the front saddle member, in particular in a continuous and opening-free manner to the front saddle member along a first fastening region and also for the covering, by means of which the seat surface is formed, to be connected to the rear saddle member between a first end of the rear saddle member and a second end of the rear saddle member, in a continuous and opening-free manner to the rear saddle member along a second fastening region. This achieves optimum attachment of the seat surface or of the covering, which forms the seat surface, to the front and the rear saddle members, and it is therefore possible for the seat surface also to be made from highly flexible and/or thin materials such as woven fabrics or sheet materials, since these are retained in an opening-free manner in the region of the saddle members. It is thus, in particular, possible for the tensile stressing, which constitutes a significant factor for the load-bearing capability of thin coverings, to be transmitted uniformly to the covering and for tearing of the covering, which is more likely as a result of peaks in stressing, to be avoided. The invention provides for the covering to be clamped in at the saddle members and possibly, in addition, to be adhesively bonded and/or welded thereto or for the covering to be folded over around the front saddle member and/or around the rear saddle member and possibly, in addition, to be adhesively bonded and/or welded thereto.
A further embodiment is distinguished in that the seat surface is designed to be fixed at the saddle members and flexible between the saddle members, in particular at connecting edges 9. The connecting edges here are located in those parts of an all-round peripheral region of the seat surface where the seat surface runs between the front saddle member and the rear saddle member. This allows optimum connection to the saddle members. When the piece of seating furniture according to the invention is being used for sitting on, the user's legs usually bear against the side edges or connecting edges of the seat surface. The flexible configuration here means that there are no pressure points established.
A further embodiment of the piece of seating furniture has the seat surface mounted in a self-supporting manner between the saddle members. The avoidance of supporting structures beneath the seat surface further improves the seating comfort, since it is not possible for any pressure points to be established and the seat surface adapts itself in a fully flexible manner.
The seat surface may be defined by a woven mesh fabric which allows good ventilation and, in particular in summer, provides for a pleasant sitting experience. The covering thus has breathable properties, and therefore body heat given off by the user's body can be expelled in optimum fashion through the covering. It is also possible for a woven mesh fabric to be made to meet requirements in optimum fashion as a result of the type of weaving used and/or as a result of the properties of the weaving thread.
The first fastening region may follow a curved, convex progression of the front saddle member, wherein the first fastening region has a first length, and for the second fastening region to follow a curved, convex progression of the rear saddle member, wherein the second fastening region has a second length L6. As a result of the two convexly running saddle members, the saddle surface, which is mounted between the saddle members, is formed as a saddle surface which is curved convexly in the direction of the user's bottom, and it assumes an ergonomically advantageous shape similar to a riding saddle.
The covering may be configured with a thickness of not more than 3 mm and in particular with a thickness of not more than 2 mm. Such coverings are available cost-effectively in a wide variety of different embodiments and, in particular, can readily realize a breathable design. Such dimensioning of the covering straightforwardly ensures the necessary level of flexibility of the covering, and therefore the covering can readily follow the flexing of the front and rear saddle members.
In a further expedient embodiment, it is provided that the front saddle member on the front member support and the rear saddle member on the rear member support are designed such that they can be displaced relative to one another, in particular such that the distance between the two can be changed via a tensioning device. If the tensioning device comprises a spindle and a hand wheel, it is then possible, by virtue of the spindle being rotated by its hand wheel, to increase a distance between the two member-support portions, and thus tension the covering, or to decrease said distance, and thus reduce tensioning of the covering. The tensioning and thus the hardness of the seat surface can be adjusted as a result, and therefore said seat surface can be adapted to the individual comfort-related requirements and user-related parameters, for example body weight and sitting position.
A further-expedient configuration of the piece of seating furniture is configured with the front saddle member and the rear saddle member having, at each of their ends, a spiral turn, in which the seat surface is mounted, in particular by winding, wherein, between the saddle members, the peripheral region of the seat surface is guided in a wound manner preferably around a covering guide. Mounting the covering, which forms the seat surface, by "winding" provides a stable, tear-proof edge without it being necessary to introduce additional edge reinforcements, which reduce, for example, the flexibility. It is conceivable to fold in a flat material to provide a certain amount of guidance and dimensional stability for the wound region. At the ends of the members, the material which forms the seat surface is provided, by the spiral turn, with an advantageous guide, which is favorable for loading purposes, since edges are avoided. This makes it possible to realize a high level of material tensioning without particular reinforcements having to be carried out.
In general terms, in particular the use of point-elastic woven mesh material as the covering material creates an advantageous seat-surface embodiment which provides a high level of comfort, while advantageous stability is provided at the same time, when it is subjected, for example, to point loading by the contents of back pockets (e.g. a set of keys).
An expedient embodiment of the piece of seating furniture has the saddle support arranged on a rolling framework, wherein the rolling framework has, in particular, a front extension arm, with a front roller, and two rear extension arms, with rear rollers, and the angle α1 of, in particular, greater than 120° is formed between the front extension arm and rear extension arm. Arranging the saddle support and a seat unit, which comprises the seat surface, the saddle members and the member supports, on the rolling framework makes it possible for the piece of seating furniture to be used as a mobile workstation for project meetings and team work or to provide a high level of freedom of movement at a desk. Furthermore, the saddle support may be designed as a telescopic support which allows height adjustment of the seat unit in relation to an underlying surface. A telescopic support provided is also one, in particular, which even allows adjustment from a piece of seating furniture to a piece of sit stand furniture. The possibility of configuring the front roller and/or one or both of the rear rollers as arrestable rollers also provides for improved use as a piece of sit stand furniture.
A further expedient embodiment is configured with the seat surface defined at a front portion, by way of the front saddle member, with a height h4 and a width b4 and at a rear portion, by way of the rear saddle member, with a height h6 and a width b6, where preferably h4>h6 and b6>b4. The widths of the saddle members are measured horizontally in space and at right angles to a longitudinal axis L1 of the piece of seating furniture, said axis being defined by the front member support and being located horizontally in space. Observing the aforementioned dimensional relationships gives the seat surface a three-dimensional shape which meets the basic anatomical requirements. In principle, the highest point HP4 of the front saddle member has a difference in height H46, as measured vertically in space, in relation to the highest point HP6 of the rear saddle member, wherein the highest point HP4 of the front saddle member is located at a higher level than the highest point HP6 of the rear saddle member. The corresponding saddle geometry, which gives an advantageous seat-surface shape, promotes well-being and makes it possible for a user to sit on the piece of seating furniture for prolonged periods without feeling fatigue. The posture and body position here are made to adopt preferably a lordosis shape, with forwardly inclined curvature or an S shape, so that healthy sitting is made possible.
A further advantageous embodiment of the piece of seating furniture has the progression of the member supports corresponding, as seen in vertical projection, essentially to the progression of the extension arms. Basing the progression of the member supports on the progression of the rolling framework, and essentially on the progression of the saddle shape of the seat surface, ensures a high level of positional stability since the supports and extension arms provide support along the tilting axes of the seat surface.
Provision is also made for the front member support and the rear member support to form a carrier, a saddle here comprising the carrier, the front saddle member, the rear saddle member and the seat surface, which is formed as a covering, wherein the front saddle member is arranged at a front end of the carrier, wherein the rear saddle member is arranged at rear ends of the carrier, wherein the front saddle member and the rear saddle member are spaced apart from one another such that they are located opposite one another with no contact, wherein the covering is fastened on the oppositely located saddle members such that the covering, subjected to tensile stressing, forms the seat surface, wherein the seat surface is curved convexly in the direction of a user's bottom, wherein the covering is elastically expansible and designed, and tensioned, such that it is suitable, when subjected to elastic deformation as a seat surface, to carry the user. A piece of seating furniture designed in this way provides a high level of comfort and is flexible to use.
Finally, provision is made for the length of the first fastening region to be equal to the length of the second fastening region and for the covering, by means of which the seat surface is formed, in a state in which it rests in planar fashion on a planar surface, to be configured in the form of a rectangle, this creating a seat surface or covering which can be fastened on the two carrying members with comparable levels of pretensioning.
As an alternative, provision is made for the length of the first fastening region to be dimensioned to be greater than the length of the second fastening region, and not more than 1.5 times the length of the second fastening region, and for the seat surface, in a state in which it rests in planar fashion on a planar surface, to be configured in the form of a rectangle or of a trapezoid, this creating specific seat shapes in which the length of the fastening region of the front saddle member is longer than the length of the fastening region of the rear saddle member. As an alternative, provision is also made for the length of the second fastening region to be dimensioned to be greater than the the length of the first fastening region, and not more than 1.5 times the length of the first fastening region, and for the seat surface, in a state in which it rests in planar fashion on a planar surface, to be configured in the form of a rectangle or of a trapezoid, this creating specific seat shapes in which the length of the fastening region of the front saddle member is shorter than the length of the fastening region of the rear saddle member.
Finally, the pretensioning of the covering may be adjustable, so that the extent of elastic deformation of the covering can be adjusted to the individual requirements of a user and/or adaptation to the respective weight of a user can be effected. It is also thus possible to counteract a reduction in the tensioning as a result of material aging and/or a reduction or increase in the tensioning as a result of a change in temperature, and to establish the desired state of tensioning with minimal outlay.
The foregoing paragraphs have been provided by way of general introduction, and are not intended to limit the scope of the following claims. The various preferred embodiments, together wit further advantages, will be best understood by reference to the following detailed description taken in conjunction with the accompanying drawings.

Piece of seating furniture having a saddle-form seat surface


The reaction rate of a feed gas flowed into a plasma chamber is controlled. In one embodiment a pulsed power supply repeatedly applies a high power pulse to the plasma chamber to increase the reaction rate of plasma within the chamber, and applies a low power pulse between applications of the high power pulses.

1. Field
The present invention relates to the field of plasma sources for fabrication, pollution abatement, and cleaning processes. More specifically, the present invention relates to exciting the plasma of an inductively-coupled plasma source using pulsed power.
2. Description of the Related Art
Plasmas are typically generated in specially built chambers. Such plasma chambers can be used for gas dissociation in etching, implantation, deposition, or cleaning processes for semiconductor and micro-machining fabrication chambers. The plasma can also be used for materials processing, production of activated gases, pollutant abatement and other applications. In some applications, the plasma is generated from oxygen, argon and fluorinated gases by driving a continuous RF (Radio Frequency) current through the plasma. In such devices, the plasma is electromagnetically coupled to an excitation coil through either the air or a magnetic core. Since the excitation coil and the plasma can be modeled as the primary and secondary windings of a transformer, respectively, these inductively coupled plasma sources are sometimes also called transformer-coupled plasma sources. The plasma chamber may take different shapes, such as cylindrical, toroidal, and others. For semiconductor applications, the transformer's primary winding or coil is typically driven at RF frequencies in the range of 0.2–2 MHz, at power levels in the range of 2–10 KW.
A RF power generator is commonly used to drive the primary coil. The RF excitation for inductively coupled plasmas and other plasma sources is commonly applied in a continuous wave (CW) mode, i.e. the RF power is applied continuously to the plasma. Part of the CW mode delivered power is used to drive the reaction rate inside the plasma chamber, i.e. to dissociate and ionize the feeding gas. The reactions include dissociation, excitation and ionization. The rest of the CW mode power is dissipated from the plasma and deposited on the chamber walls in the form of heat. The dissipated power must constantly be removed to keep the walls of the chamber within the chamber's safe operational temperature range. For effective heat removal, the plasma chamber walls are typically made of thermally conductive metals, such as aluminum, and are cooled by water.
Manufacturing and industrial processes can be improved with yet higher gas flows, gas dissociation and pressures. Increasing the power supplied to the plasma increases the reaction rate within the plasma chamber, allowing the gas flow rate and pressure to be increased. However, higher power levels also increase the power dissipated to the chamber walls. As a result, in plasma sources operated in CW mode, the heat dissipation capability of the plasma chamber walls limits the amount of power that can be coupled to the plasma.

Pulsed excitation of inductively coupled plasma sources


Three-dimensional data are registered by selecting a first set of primitives from the data in a first coordinate system, wherein the first set of primitives includes at least one plane, at least one point, and a third primitive that is either a point or a plane, and selecting a second set of primitives from the data in a second coordinate system, wherein the second set of primitives includes at least one plane, at least one point, and a third primitive corresponding to the third primitive in the first set of primitives. Then, the planes are registered with each other, as are the points, to obtain registered primitives.

3D Reconstruction
Interactive and real-time 3D reconstruction of a scene is used in a number of applications, e.g., robotics, augmented reality, medical imaging, and computer vision. Real-time sparse and dense 3D reconstruction can use passive sensors such as cameras. However, passive sensors have difficulties to reconstruct textureless regions.
For reconstructing textureless regions, active 3D sensors can be used. For example, the Kinect sensor for the Microsoft Xbox uses an IR pattern for acquiring 3D data as a depth map from a viewpoint of the sensor in real time.
Other issues relate to processing time, memory requirement, and accuracy. Because of the field of view and resolution, 3D sensors usually produce a partial reconstruction of a scene. It is desired to provide an accurate and fast registration method that can combine successive partial depth maps and a model of the scene. Inertial sensors are prone to drift. Therefore, the features in an RGB (texture) image or depth map need to be relied on for accurate registration. In addition, depth maps are usually noisy without any higher-level spatial constraint. Furthermore, the point cloud requires a very large memory, and is difficult to compress.
3D-to-3D Registration
Local
Alignment or registration of 3D data is a fundamental problem in computer vision applications, which can be solved using several methods. The registration methods can be local or global. The local methods should start with a good initialization, and register two 3D point clouds using relatively small iterative moves. This is similar to a non-linear minimization method that converges to a global solution with a good initial solution. The most common local method is an iterative closest point (ICP) method, which iteratively determines corresponding 3D points and the moves using a closed-form solution.
Global
Global methods typically consider the entire 3D point cloud, identify some key geometric features (primitives), match the features across point clouds, and generate an optimal hypothesis using a minimal set of correspondences using a RANdom SAmple Consensus (RANSAC) procedure. The coarse registration obtained by global methods is usually followed by local non-linear refinement. Global methods, unlike local methods, do not require initialization. However, global methods can suffer from incorrect and insufficient correspondences. The geometric primitives typically used in global methods are either points, lines, or planes.
Several global registration methods using homogeneous and heterogenous correspondences are known. For example, it is possible to determine a closed-form solution for the registration given point-to-point, line-to-line, plane-to-plane, point-to-line, point-to-plane, or line-to-plane correspondences. One method obtains a global optimal solution from point-to-point, point-to-line, and point-to-plane correspondences using branch-and-bound. Another method uses branch-and-bound to obtain the optimal correspondences as well as transformation for the point-to-point registration problem.
SLAM Using 3D Sensors
In mobile robotics, some 3D-sensor-based methods use a simultaneous localization and mapping (SLAM) system for determining a motion of the sensor as well as reconstructing a scene structure. Those methods typically use geometric features such as point, line, or plane primitives. 3D sensors that provide a planar slice of 3D data, such as 2D laser scanners or ultrasonic sensors, can be used for determining planar, three degrees-of-freedom (DOF) motion. 3D sensors that provide full 3D point clouds, such as structured light scanners, 2D laser scanners attached on moving stages, and the Kinect sensor can be used for determining six DOF motion.
RGB-D mapping extracts keypoints from RGB images, back-projects the points in 3D using depth maps, and uses three point-to-point correspondences to determine an initial estimate of the pose using the RANSAC procedure, which is further refined using the ICP method.
Another method uses three plane-to-plane correspondences in a SLAM system with 3D sensors. That method addresses the correspondence problem using geometric constraints between planes.
Another method uses a combination of smaller field-of-view (FOV) 3D sensor and a larger FOV 2D laser scanner for the SLAM system using both planes and line segments as primitives. That method is designed for a sequential SLAM system that solves a local registration problem, and cannot solve global registration.
KinectFusion registers a current depth map with a virtual depth map generated from a global truncated signed distance function (TSDF) representation by using a coarse-to-fine ICP method. The TSDF representation integrates all previous depth maps registered into a global coordinate system, and enables higher-quality depth map generation than using a single image.
Several other variants of the ICP method are known, but the variants still suffer from local minima issues when the two 3D point clouds are distinct. Registration methods or SLAM systems that solely depend on points suffer from insufficient or incorrect correspondences in textureless regions or regions with repeated patterns. Plane-based techniques suffer from degeneracy issues in scenes containing insufficient number of non-parallel planes.
With 3D sensors such as the Kinect sensor, line correspondences are difficult to obtain because of noisy or missing depth values around depth discontinuities.

Method for registering points and planes of 3D data in multiple coordinate systems

Mitsubishi Electric Research Laboratories, Inc.


The present invention is an automated wire harness machine (40) capable of manufacturing a wire harness (42) unique in-part due to the automation process. The novel wire harness is generally a plurality of bundled, preferably un-stripped, insulated wires (46). Each un-stripped end portion (180, 182) of each wire is preferably terminated to one of a series of electrical connectors (44) of the wire harness. Each connector has at least one wafer (52) which houses a plurality of terminals (54) preferably crimped and electrically terminated to the ends of the wires. The wire harness machine preferably utilizes a pallet (56) which holds all of the wafers of one wire harness. A conveyor (58) transports the pallet and wafers through a series of stations which perform automated manufacturing steps. The first station is a terminal inserter (64) which inserts and locks the terminals within pre-assigned cavities (114) of the wafers. The next station is an automated wire loader (66) which measures, cuts and crimps the two ends of each wire into the respective terminals of the loaded wafer assembly. A third station, or ultrasonic welder (68), the galls an un-stripped non-ferrous core (270) of the crimped wire to the terminal. The pallet with the loaded wafers, crimped terminals, and terminated wires are then transported to a wire marker station (70) which marks each wire, preferably via a laser (328), for identification purposes.

Electrical wire harnesses for automotive and other applications are assembled primarily through the use of manual labor. Areas of production which contribute toward an appreciable degree of manual intervention include: measuring and cutting predetermined wire lengths, stripping of insulation jackets from each end of the cut wire, crimping a terminal to the insulation jacket near the stripped end of the wire, electrically engaging the stripped end of the wire to the terminal, and inserting the terminal into a connector housing. Each manual intervention during the manufacturing process is time consuming and can contribute toward operator error, high manufacturing costs and/or a degradation of the overall quality of the wire harness.
Known methods to electrically engage multi-stranded conductors or cores of wires to terminals requires the removal of the insulation jacket at the electrical engagement area to achieve reliable electrical conductivity. Unfortunately, and especially true for smaller gauge multi-stranded wire, the stripping process can lead to conductor/core damage thus prohibiting the use of more fragile smaller gauge wires in many electrical applications. Consequently, the cost in copper for larger gauge wire is expensive, the overall bulk of the wire harness is large and weight of the wire harness is high. Moreover, coupled with large gauge wiring and bulky harnesses, the terminals and thus electrical connector housings attached to the distal ends of the wire harness are subsequently larger than otherwise necessary.
Because wire harnesses often contain dozens, if not hundreds of wires, often having varying wire gauges and wire lengths routed to a plurality of separate connectors, various means of identifying the wires and thus preventing wrong terminations, or simply poor terminations have been utilized. One such means is assigning a specific color or color pattern of insulation jacket 178 to a specific gauge wire size. This technique can be limiting and cumbersome in the manufacturing environment of wire harnesses, because the wire must be identified prior to the termination of the wire to the terminal and insertion of the terminal into the connector housing. Moreover, the wires, terminals, and/or connector terminal cavities must still be identified to assure proper terminations and possibly assist in maintenance issues. Such identification has typically been done with ink print on the outside of the wire which has a tendency to wear off in a harsh environment.


A system/method for generating one or more new hardcopy prints from an electronic file comprising original digital image data, wherein the new hardcopy print(s) match a legacy hardcopy previously generated from the original digital image data of the electronic file, even when the legacy hardcopy was printed from an “enhanced” or “tuned” version of the original image data. The original image data and scanner data derived by scanning the legacy hardcopy are used to identify corresponding areas of constant color in the original data and the legacy hardcopy. The corresponding color areas are represented in a colorimetric color space and the original data color values are adjusted to match the legacy hardcopy color values. The adjusted data are used to print a new hardcopy. The colorimetric color space conversion is completed using a plurality of different printing device assumptions, and the printing device assumption resulting in the smallest starting color difference between the original color values and legacy hardcopy color areas is used for the color matching process.

It is not uncommon that a person possesses a legacy hardcopy that is deemed satisfactory or even ideal, and also possesses the original electronic file comprising the digital image data on which the legacy hardcopy is based, and now desires to print one or more hardcopies that match the legacy hardcopy. A problem arises when the legacy hardcopy is not merely a print-out of the raw digital image data of the electronic file but is, instead, a print of an enhanced version of the digital image data of the electronic file. For example, the legacy hardcopy can be a printed version of the original digital image data that was enhanced by a technician to make the ocean more blue, to make a sunset more orange, to make a headline font more red, etc.
One approach to the problem is to scan the legacy hardcopy to derive scanner image data from which the new hardcopies can be printed, essentially copying the hardcopy data. One drawback of this method is that the legacy hardcopy might include artifacts such as fold-lines, coffee stains or other physical marks that must be excluded from any newly generated hardcopy. Another drawback associated with the use of a scanner is that the original image data of the electronic file is, by definition, a perfect match to the legacy hardcopy, except for the above-noted image enhancement, while data derived from scanning the legacy hardcopy will include noise that will degrade the quality of any subsequent prints.
Accordingly, a need has been identified for a system that allows new hardcopies to be printed from the original image data, wherein the new hardcopies are perceived to match the legacy hardcopy.

Matching the perception of a digital image data file to a legacy hardcopy