Embossing regularly textured sheets with an appropriate regular, discrete embossing pattern to improve softness can result in a combined texture that creates an interference pattern that camouflages the original texture pattern and the embossing pattern. The resulting pattern is more appealing to the eye and is more random in appearance than the initial textured sheet or the embossing pattern individually. This result is particularly advantageous for paper towels.

Two key attributes of a premium paper towel are softness and a pleasing cloth-like visual texture. Softness can be enhanced by embossing the towel basesheet with a regular pattern of relatively small, discrete embossing elements, such as a pattern of dots. However, while the softness improvement is desirable, consumers tend to associate products having such regular embossing patterns with products of lower quality. It would be desirable to be able to soften a paper towel, for example, with an embossing pattern that is less objectionable to the consumer and promotes a cloth-like appearance.

Method for embossing textured tissue sheets


To prevent any uneven solder wetting in a main surface of electrodes of a semiconductor connected with a main surface of a planar lead and any displacement of the lead vis-a-vis the electrodes due to the reflow of the solder in a semiconductor module having the semiconductor element mounted on a substrate and the planar lead electrically connected therewith, the present invention provides an improved semiconductor module characterized in that the width of at least a part of the region of the main surface of the lead facing the semiconductor element is expanded wider than or equal to the width of the electrodes formed on the semiconductor element, and preferably the other part of the main surface of the lead soldered to an electrode formed on the substrate is split in the extending direction thereof.

1. Field of the Invention
The present invention relates to the lead connection with the substrate and the semiconductor element mounted thereon in semiconductor modules such as power modules mounted on electric apparatuses for automobile.
2. Description of the Related Art
Lately electronic devices have been introduced for controlling various electric apparatuses in automobiles and other vehicles. An example of electric apparatus incorporating an electronic device is an electric power steering unit shown in FIG. 14(a). In the device, a housing containing a motor relating with the steering of the automobile has a motor drive unit on which electric devices are mounted. FIG. 14(b) is a sectional view of the motor and the motor drive unit cut along a plane crossing the rotary shaft of this motor. The above-mentioned electric device is mounted on the motor drive unit as a power module.
The power module is constituted as a so-called semiconductor module with a power element such as IGBT (Insulated Gate Bipolar Transistor) suitable for controlling electric apparatuses driven by a relatively large current such as an electric power steering device mounted thereon. This type of power module is also called "an in-vehicle module" as it is mounted on vehicles.
The control unit of the above-mentioned electric power steering unit and other power modules is required to discharge efficiently the heat generated thereby from the power module to control large current with a power element (semiconductor element) mounted thereon. In order to improve the dissipation of heat from the power module, semiconductor element represented by MOS (Metal-Oxide Semiconductor) are connected by die bonding with the power module in the form of bare chips (not sealed by resin and the like) on the substrate,
As the form of electrical connection with semiconductor element mounted on the substrate of power modules, the A1 wire bonding connection method used in other semiconductor modules has been used in the past. FIG. 1 shows an example of chip connection in the prior power modules. FIG. 1 is a sectional view showing conceptually by enlarging the part related with the chip connection of the power module, and the substrate (metal base substrate) 1 includes a metal base 1a, an insulation layer 1b covering the main surface of a side of the metal base 1a, and a wiring 1c formed by metal and other conductors on the insulation layer 1b (pad on the substrate side 1d). One side of the wiring 1c is connected by solder 2 with the lower surface of the semiconductor element 3 (one side of the main surface), and the upper surface of the semiconductor ship 3 (the other side of the main surface, opposite side of the main surface of the one side) and the other side of the wiring is electrically connected with A1 wire. Incidentally, the system of coordinates shown in FIG. 1 specifies the main surface of the substrate 1 as x-y plane and defines the positional relationship between the structure shown in FIG. 1 and the structures in other figures described below. The x axis, the y axis and the z axis in this system of coordinates need not cross each other at right angle as long as they meet the condition of crossing each other.
As the bonding wire 4 used for connecting chips by A1 wire bonding shown in FIG. 1 is slender, the resistance against current controlled by the chip necessarily grows higher. In order to avoid the rise in electric resistance in such chip connections, a plurality of wires must be connected to a MOS chip. And for mass producing power modules wherein such a chip connection method is adopted, the number of wire bonders and other similar equipment must be increased, and if the production of such power modules is to be increased, new capital investments will be required. Therefore, it is desired to realize chip connections in power modules not by wire bonding but by soldering leads producing a low resistance and suitable for the mass production of the power modules. FIG. 2 shows an example of power modules whose chips are connected with the lead. The upper surface of the semiconductor element 3 and the wiring 1c at the other end are respectively connected by solder 2 to the lead 6. And a heat spreader 5 is provided between the wiring 1c on the other end mentioned above and the lower surface of the semiconductor chip 3.
In order to realize such a lead connection of such semiconductor modules, the following technology is now under consideration. For example, Patent Document 1 teaches the method of connecting in layers a lead, semiconductor element, and a heat sink on the substrate by using a plurality of solders with different melting points, and that of connecting them in one stroke by using a Sn solder paste (containing mainly tin). This method simplifies the assembly process that will be necessarily complex by the wire bonding connection method. And Patent Document 2 examines how to improve the reliability of soldering by using a heat sink, an insulating substrate, silicon chips and a material with a linear expansion coefficient difference of 10×10−6 or less. And Non-Patent Document 1 examines how to reduce thermal stress applied by the lead to the chips and to prevent the breakdown of chip electrodes by making the ends of the lead comb-teeth shaped.
[Patent Document 2]
[Non-patent Document 1]
The patent documents each referred above or later are listed as follows.    [Patent Document 1] Japanese Patent Publication Gazette No. 3627591    [Patent Document 2] Japanese Unexamined Patent Publication No. hei 9-36186 (JP-A No. 36186-1997)    [Non-Patent Document 1] Nakajima et al.: "Lead connected type high-capacity resin-sealed power module", 11th Symposium on "Microjoining and Assembly Technology in Electronics" (Mate 2005), Vol. 11 (2005), pp. 433-436.

Power semiconductor module with MOS chip


A printer unit (100) for a 3D-printing apparatus. The printer unit comprises a printer head (105) comprising a nozzle (110) arranged to deposit printing material from the printer unit, a pressure sensor (120) configured to sense a pressure exerted on the printer head from the printing material, and a control unit (130) coupled to the pressure sensor. The control unit is configured to control the speed of the printer head based on a transfer function from the pressure sensed by the pressure sensor to a desired speed of the printer head, in order to maintain a constant deposition of the amount of printing material per length unit of deposited printing material.

Additive manufacturing, sometimes also referred to as 3D printing, refers to processes used to synthesize a three-dimensional object. 3D printing is rapidly gaining popularity because of its ability to perform rapid prototyping without the need for assembly or molding techniques to form the desired article.
By using a 3D-printing apparatus, an article or object may be built in three dimensions in a number of printing steps that often are controlled by a computer model. For example, a sliced 3D model of the object may be provided in which each slice is recreated by the 3D printing apparatus in a discrete printing step.
One of the most widely used 3D-printing processes is Fused Filament Fabrication (FFF). FFF printers often use a thermoplastic filament which in its molten state is ejected from a nozzle of the printer. The material is then placed layer by layer, to create a three-dimensional object. FFF printers are relatively fast and can be used for printing objects of various kinds, even those having relatively complex structures.
During 3D-printing, it is desirable to provide an adequate adherence of the printing material to the underlying material, and that the deposited layer of printing material has a predictable layer thickness and layer width. As a consequence, the deposited layer may be provided as a relatively smooth, homogeneous surface.
It will be appreciated that variations of the pressure of the molten material inside the printing nozzle may lead to defects and/or aesthetic deficiencies in the FDM 3D-printed products. Examples of these defects or deficiencies may be material surface roughnesses, undulations, irregularities, or the like. In the prior art, there is suggested a method to measure the nozzle pressure and trying to control the feeding rate of the printing material to try to keep a relatively constant pressure which the printing material exerts on the nozzle. However, it should be noted that an arrangement of this kind requires a relatively circumstantial control arrangement, since corrections of the feeding rate immediately influences the mentioned pressure.
Hence, alternative solutions are of interest, which are able to deposit one or more layers of printing material, resulting in a relatively smooth, homogeneous layer surface.

Printer unit for a 3D-printing apparatus and method


Techniques for implementing adaptable voice activation operations for interactive speech recognition devices and instruments. Specifically, such speech recognition devices and instruments include an input sound signal power or volume detector in communication with a central CPU for bringing the CPU out of an initial sleep state upon detection of perceived voice exceeding a predetermined threshold volume level and is continuously perceived for at least a certain period of time. If both these conditions are satisfied, the CPU is transitioned into an active mode so that the perceived voice can be analyzed against a set of registered key words to determine if a "power on" command or similar instruction has been received. If so, the CPU maintains an active state in normal speech recognition processing ensues until a "power off" command is received. However, if the perceived and analyzed voice can not be recognized, it is deemed to be background noise and the minimum threshold is selectively updated to accommodate the volume level of the perceived but unrecognized voice. Other aspects include tailoring the volume level of the synthesized voice response according to the perceived volume level as detected by the input sound signal power detector, as well as modifying audible response volume in accordance with updated volume threshold levels.

1. Field of the Invention
The invention generally relates to interactive speech recognition instruments which recognize speech and produce an audible response or specified action based on developed recognition results, and is particularly concerned with voice-based activation of such instruments.
2. Description of the Related Art
Speech recognition devices can be generally classified into two types. The first type is the specific-speaker speech recognition device that can only recognize the speech of a specific speaker, and the second general type is the non-specific speaker speech recognition device that can recognize the speech of non-specific speakers.
In the case of a specific speaker speech recognition device a specific speaker first registers his or her speech signal patterns as reference templates by entering recognizable words one at a time according to an interactive specified interactive procedure. After registration, when the speaker issues one of the registered words. speech recognition is performed by comparing the feature pattern of the entered word to the registered speech templates. One example of this kind of interactive speech recognition device is a speech recognition toy. The child who uses the toy pre-registers, for example, about 10 phrases such as "Good morning," "Good night" and "Good day,", as multiple speech instructions. In practice, when the speaker says "Good morning," his speech signal is compared to the speech signal of the registered "Good morning." If there is a match between the two speech signals, a electrical signal corresponding to the speech instruction is generated, which then makes the toy perform a specified action.
As the name implies, of course, this type of specific speaker speech recognition devices can recognize only the speech of a specific speaker or speech possessing a similar pattern. Furthermore, since the phrases to be recognized must be registered one at a time as part of device initialization, using such a device is quite cumbersome and complex.
By contrast, a non-specific speaker speech recognition device creates standard speech feature patterns of the recognition target phrases described above, using "canned" speech examplars spoken by a large number (e.g., around 200) of speakers. Phrases spoken by a non-specific speaker/user and then compared to these pre-registered recognizable phrases for recognition.
However, such speech recognition devices usually become ready to perform recognition operations and responses only when an external switch is turned on or external power is delivered to the device is turned on, regardless of whether the device uses specific or non-specific speaker recognition. But, in some types of speech recognition devices, it would be more convenient if the device were in a standby state waiting for speech input at all times, and performed recognition operations by sensing speech input, without the need for the user to turn on the switch every time.
Take a stuffed toy utilizing speech recognition, for example. If the toy can be kept in a speech input standby state, i,e., a so-called sleep mode, and can instantly respond when the child calls out its name, it can respond quickly without the need for plugging the device in or pressing, a button, thereby greatly enhancing its appeal as a user-friendly device especially for younger children where applying external power may raise safety concerns. In addition to toys, the same can be said of all electronic instruments that utilize speech recognition.
Some issues must be resolved when keeping the device in a sleep mode and having it perform recognition operations by sensing speech input, as explained above. These include, for example, power consumption and the ability of the device to differentiate between phrases to be recognized and noise, and to act only in response to phrases to be recognized. In particular, since most toys run on batteries, minimizing battery drain is a major issue. Additionally, product prices must also be kept low to maintain commercial appeal for such devices , so using expensive, conventional activation circuitry is undesirable. So, heretofore, there have been a large number of technical restrictions on commercializing interactive speech devices which also feature voice activation.

Voice-activated interactive speech recognition device and method


An agitating retort (100) includes an outer shell (102) within which the drum structure (112) is disposed for rotation within the shell while supporting a number of baskets (114) for holding products to be processed within the retort. Processing fluid is applied to the interior of the shell (102) through a rotary coupling (115) disposed within the shell. The coupling routes processing fluid to a distribution system (116) to outlet holes or nozzles (118) positioned within the drum structure (112).

Agitating retorts are widely used for in-container preservation of foodstuffs, either for pasteurization or sterilization processes. FIGS. 1-3 illustrate constructions of known agitating retorts. Referring initially to FIGS. 1 and 2, the illustrated agitating retort 18 consists of an outer retort shell 20, which in essence is a generally cylindrically shaped pressure vessel that houses a drum 22 for rotation within the shell. The drum is adapted to receive baskets 24 within which are stacked containers of foodstuffs or other products to be processed. The containers may be in the form of cans, glass jars, or of other types. Alternatively, the foodstuff containers may be arranged on trays carried by pallets, not shown. The baskets of foodstuff containers are held in place within the drum to restrain the baskets and containers during the retorting process.
The drum 22 may be of various constructions, including that shown in FIGS. 1 and 2, wherein the drum is shown as being of an open design. Drum 22 is constructed from a number of spaced-apart vertical discs 30 that are joined together by a series of longitudinal tube structures 32 spaced about the perimeter portion of the discs to provide structural strength of the drum. Reinforcing braces 34 may be welded or otherwise affixed between the tubes in a crisscross pattern for further structural strength and/or rigidity. A door 36 is used to close the open end of the shell 20 into which baskets holding the containers are loaded and unloaded from the drum 22.
In some retort processes the drum 22 is rotated about its longitudinal axis. Rollers 38 located in the lower portion of retort shell 22 support the drum for such rotation of movement. A powered shaft 40 may be coupled to the end of the drum opposite door 36 for rotation of the drum. As shown in FIG. 2, generally square- or rectangular-shaped openings 42 are formed in the discs for receiving the baskets 24. Various types of clamping systems, not shown, may be used to hold the containers and baskets in place when the drum is rotated
The retorting process may be of various types, including water spray, combined water and steam spray, and water immersion. In the water spray and combined water and steam spray process, the processing fluid is typically supplied to an inlet 48 at the top portion of the retort, and then through lines or pipes 50 running the full length of a retort shell in the space between the inside diameter of the shell and the outside diameter of the drum. Injection holes or nozzles 52 are disposed along the length of the pipes 50 for directing the processing fluid toward the containers disposed within the rotating drum. As will be appreciated, a certain portion of the processing fluid from the nozzles 52 strikes the tube structures 32 and reinforcing braces 34, and thus, may never reach the interior of the drum. Moreover, when the fluid droplets from the overhead pipes 50 actually reach the interior of the drum and contact either the drum interior, the basket or containers, such droplets are during rotation of the drum subjected to a centrifugal force that counteracts the downward gravitational forces acting on the droplets, thereby reducing the capacity of the droplets to reach the center portion of the baskets. With increasing rotational speed of the drum this results in increasingly less uniform distribution of the processing water inside the baskets. Eventually the processing fluid collects at the bottom of the retort shell and is routed out of the shell through an outlet 54 to a recirculation pump that re-injects the processing fluid through openings in the top and sides of the retort to the lines or pipes 50.
FIG. 3 illustrates another embodiment of an existing retort which is constructed similarly to the retort shown in FIGS. 1 and 2, and thus like parts are given the same numbers, but with prime (′) designation. The retort 18′ shown in FIG. 3 is designed for use with a water immersion process. The level of processing fluid in the retort may vary, or the retort may be completely filled with the processing fluid. The processing fluid may be introduced into the retort shell by multiple inlets 48′ shown at the top of the shell 20′ over the length of the retort. Typically, one inlet 48′ is present per basket. As a consequence, the processing fluid does not flow evenly through the baskets 24, especially when the drum is held stationary. This leads to uneven heating and cooling of the containers disposed within the baskets, and thus, a variation in the sterilization value of the products in the containers. As a consequence, often it is necessary to rotate the retort drum 22′ to provide adequate mixing and distribution of the processing fluid within the retort 18′. The present invention seeks to address the limitations and drawbacks of existing retorts, including agitating retorts.

Process fluid distribution system for agitating retorts


A dental floss tool has a short flat handle in a first plane, with a floss winding post extending from the upper surface thereof. Extending downwardly from the lower surface are a pair of spaced legs attached to the handle at one end and spaced apart from one another at the opposite end thereof. Guide grooves are placed on the legs for guiding dental floss from the winding post to the end of the first or outermost leg, back to the second leg, and then upwardly through a hole in the handle located between the winding post and the second leg, back to the winding post. The floss, which extends from the lower end of the second leg through the hole, then may be engaged by the thumb of the user to adjust the tension of the floss extending between the ends of the two legs.

Dentists recommend using dental floss after each meal, or at least daily, to clean between teeth to fight placque buildup and to stimulate the growth of strong and healthy gums. Placque is a leading cause of tooth decay, gum disease and bad breath. Food particles frequently become lodged between the teeth, and placque builds up between the teeth in regions where a toothbrush cannot reach. This buildup between the teeth increases the danger of infection of the gums and tooth decay.
Typically, dental floss is wrapped around a finger on each hand, with the person then sticking his or her fingers in the mouth to effect the flossing. Many persons, however, dislike flossing their teeth in this manner.
To overcome the disadvantages of wrapping floss around the fingers to accomplish flossing of teeth, various flossing tools have been developed. One such tool is a disposable handle with a pair of spaced legs on one end forming a U-shaped extension. In this tool, a short strip of floss is molded into the ends of the two legs across the space forming the U-shaped end. The floss in this tool is not removable; so that if it should become caught between the teeth, it is necessary to break it in order to remove the floss and tool. This can be a significant disadvantage, since the floss cannot simply be pulled through the space between the teeth if it should become caught. In addition, even if the floss is under tension when it is molded between the legs of the tool, it tends to stretch and deform in use, and quickly loses tension. Since the floss itself is molded into the ends of the legs of the U-shaped end, there is no way to re-tension the floss extending across the gap between the legs.
Other flossing tools have been developed, which also employ a pair of legs in a U-shaped or wishbone-shaped configuration across which dental floss is stretched. In these tools, floss is not embedded in the plastic legs; but a provision is made for winding a length of floss around an anchor pin or holder, and then extending it through grooves across the opening between the legs and back around the holder. The initial tension can be adjusted by the person applying the floss to the holder. If the floss should become stuck between the teeth, it can be released from the anchor pin and pulled through the teeth; so that such tools are not subject to the disadvantages noted above for tools where the ends of the floss are permanently molded into the legs across the space between the two legs. This tool, however, also is subject to the same disadvantage of the previous tool inasmuch as when the floss is placed under stress, it tends to stretch and become loose and baggy. The floss then must be unwound from the anchor post, pulled tight and re-positioned for further use. This is inconvenient. Frequently, users of such tools find that it is easier simply to wrap the floss around the fingers of two different hands in the conventional manner and floss without the tool.
It is desirable to provide a dental floss tool which is inexpensive, easy to use and which overcomes the disadvantages of the prior art noted above.


The present invention provides a method of producing functional protein domains, which are fragments of primary translational products consisting of one or more distinct protein domains encoded by specific subsets of exonic sequences. The method is based on the integration, by a single homologous recombination event, of a regulatory unit into the eukaryotic gene coding for the primary translational product at the level of the intronic genomic region immediately adjacent to the exonic sequences which code for the functional protein domain.

The functionality of a protein is tightly connected with its structural properties, which are organized into different levels: the primary structure (corresponding to the amino acid sequence encoded by the gene), the secondary structure (preferred relative backbone locations of sequentially consecutive residues), tertiary structure (the relative position of all atoms of a polypeptide chain), and quaternary structure (the arrangement of different protein subunits, each corresponding to a distinct polypeptide chain, into a complex).
In addition to these levels of organization, a polypeptide of interest may correspond to a protein domain, which can be defined in two ways. From a structural perspective, a domain is a region of compactly folded polypeptide comprising one or more secondary and/or tertiary structures. Small proteins (<100 amino acids) are often composed of a single structural protein domain, while larger proteins usually consist of multiple structural protein domains. In the three-dimensional structure of a protein, a structural protein domain is seen as a unit of independently folded polypeptide that is well distinct from other parts of the protein. Associated with this structural definition, a second view of a protein domain is that it is the smallest piece of a protein that retains a function, resulting from its interaction with one or more proteins, nucleic acids, sugars, lipids, or any other organic or inorganic compound. A functional domain is generally composed of 50-350 amino acids and therefore may consist of one or more structural domains.
In nature, proteins can contain one or more functional protein domains, sequentially linked to each other and arranged tridimensionally. While the assignment of a particular amino acid sequence to a class of structural domains is possible by NMR or X-ray crystallography, the demonstration that a protein sequence is associated to a function is mostly obtained by identifying sequence homologies to known functional protein domains and/or by generating altered forms of the original protein to be tested in a relevant biochemical or biological assay in the so-called structure-activity or structure-function studies.
Many proteins share highly homologous functional and/or structural protein domains, probably as a consequence of a process called "exon shuffling". According to this evolutionary theory, a certain number of genes have been created through a series of duplications, intronic recombinations, combinatorial assembly and mutations of existing exons coding for protein "modules" (Patthy L, Gene (1999), 238(1):103-114).
The idea that protein evolution in eukaryotes is also mediated by sexual intronic homologous recombination of parental genomes, creating new genes from the combination of exons associated to specific protein domains, is now widely accepted also because a series of studies demonstrate a relationship between the phase and the position of introns to the structural boundaries between protein domains (de Souza S J et al., Proc Natl Acad Sci USA. (1996), 93(25): 14632-6). In a significant number of situations it is evident that protein modules are associated to one or more exons limited by introns having phase zero (the intron does not interrupt a codon) or having always the same phase. In this way the exons coding for such "mobile" domains can be more easily combined into novel proteins composed by mosaic of such protein modules, without any problem of frame (de Souza S J et al., Proc Natl Acad Sci U S A. (1998), 95(9): 5094-9; Kolkman J A and Stemmer W P, Nat Biotechnol. (2001), 19(5): 423-8).
However, it has been also shown that a functional protein domain can exert biological activities clearly distinct from the one exerted in the context of the complete protein when it is physically separated from the rest of the primary translational product, that is, the protein obtained by directly translating the mRNA transcribed from a gene. Such functional protein domains are obtained in vivo following a proteolytic cleavage, which can be executed by an endopeptidase produced either by the cell encoding the primary translational product itself or by other cells, for example, when the primary translational product is secreted or exposed onto the cellular membrane. Such events are becoming more and more frequently characterized and it is evident that the functional protein domains so produced may have important physiological activities (Kiessling L L and Gordon E J, Chem. Biol. (1998), 5(3): R49-R62; Halim N S, The Scientist (2000), 1 (16): 20; Blobel C P, Curr. Opin. Cell Biol. (2000), 12(5): 606-612).
A number of commercially valuable Eukaryotic proteins correspond to these functional protein domains which, in a certain number of cases, are encoded by a subset of the coding exons making up the full gene.
An example is endostatin, an endogenous inhibitor of angiogenesis and tumor growth, which corresponds to the C-terminal proteolytic fragment of Collagen XVIII 1alpha, a collagenous protein of the extracellular matrix. Endostatin is encoded essentially by the 3 exons at the 3′ end of the Collagen XVIII 1alpha (COL18A1) gene but it is fully functional only after being released by proteolysis from Collagen XVIII.alpha-1, the primary translational product (O'Reilly M S et al., Cell (1997), 88(2): 277-285).
Another example is Tumor Necrosis Factor (TNF)-related activation-induced cytokine (also called TRANCE, RANKL, OPGL, or ODF), a type II transmembrane protein that is involved in the signaling pathway activating the rapid induction of genes that trigger osteoclast development. TRANCE is made as a membrane-anchored primary translational product, which is cleaved by the metalloprotease-disintegrin TNF-alpha convertase (TACE), generating a soluble TRANCE, a fully functional protein having potent dendritic cell survival and osteoclastogenic activity. The sequence of this soluble protein corresponds to the one encoded by the last 3 exons of the TRANCE gene (Lum L et al., J. Biol. Chem. (1999), 274(19): 13613-8).
For the commercial-scale production of a functional protein domain, there are two main alternatives, each having its drawbacks.
One could attempt to emulate nature, and produce in the first instance the primary translational product, which is subsequently proteolytically processed to obtain the desired protein.
To conduct this whole process by recombinant DNA technology is technically demanding. Not only the primary translational product has to be expressed, but also the proteolytic enzyme specific for the desired functional protein domain has to be identified, expressed and allowed to interact with the primary translational product, either in a cellular model or in an in vitro system, to ensure appropriate cleavage before further processing.
As a second approach, an expression construct, containing only the DNA coding sequence for the functional protein domain isolated from the original mRNA or gene, can be prepared. Even this commonly used technology requires a series of operations which may sensibly delay the development of a recombinant product (Makrides S C, Protein Expr. Purif (1999), 17(2): 183-202; Kaufman R J, Mol. Biotechnol. (2001), 16(2): 151-60). It is necessary to isolate the coding sequence of interest from the full cDNA sequence, which has to be modified so that it can be further subcloned into an expression vector containing all the transcription and translation control elements necessary for the correct expression in the host cell. The construct is then used to transform the host cell and, finally, a screening procedure is applied to the transformants to isolate clones expressing the exogenous protein, correctly and at high level.
The isolation of relevant clones can be time-consuming since ordinary expression vectors, in addition to the requirements listed previously, need to recombine with the genomic sequence of the host cell. Expression constructs maintained extrachromosomally are unstable and allow only a transient expression of the protein, usually insufficient to allow production on a commercial scale.
Therefore, a recombination event involving coding and non-coding exogenous DNA and host cell genomic DNA is necessary to transmit the expression construct to all cells generated by the subsequent cycles of DNA replication and mitotic division of the originally transformed cell. This process is also completely random and error-prone, since no specific features of the expression vector can drive the complete incorporation of the exogenous sequence into the host cell genome. Thus, any part of it, having even a very low homology with any endogenous sequence, can be used by the cell for non-homologous recombination events, which are known to be orders of magnitude more frequent than homologous recombination, often resulting in the incomplete integration of the necessary exogenous sequences.
These problems lead to the development of genetic enrichment and selection procedures whose purpose is to eliminate transformants where the expression construct has been integrated in an incomplete form. Since some essential parts of the exogenous sequence may have been lost or altered during the recombination process, the coding sequence of interest may be mutated, truncated, or not expressed at all. In any case, a vast majority of transformants, whatever technique is used to introduce the DNA and select the cells, fail to produce the expected protein.
Finally, it is well established in the literature that the correct expression of recombinant proteins in eukaryotic cells depends on many factors related to the specific host cell. Features like the toxicity of the recombinant protein, mRNA processing and stability, and other post-translational events are strictly related to the product itself, to both coding and non-coding sequence in the expression vector, and to the interaction of exogenous sequences with the genomic background of the host cells. In fact, the random insertion of a complete recombinant gene, which may contain many Kilobases of DNA, may severely perturb the genome of the host cell, compromising its stability and viability. Therefore, even if the exogenous sequences have been entirely integrated, some clones cannot be used to produce the protein whenever such sequences disrupt genomic sequences important for cell metabolism and/or replication. Such clones may be lost due to selective pressure in the cell culture, or they replicate so slowly that it is difficult to obtain enough cells stably expressing the desired protein with a satisfying efficiency.
Alternative strategies have been developed in order to minimize the drawbacks of essentially uncontrolled exogenous gene integration. They are mostly based on homologous recombination, a unique technology allowing insertion of a specific exogenous sequence into a predetermined genomic sequence of a mammalian cell. This technique has been mostly used for the characterization of genes or regulatory sequence in animal and cell models by modifying them, as recently reviewed (Muller U, Mech. Dev. (1999), 82(1-2): 3-21; Sedivy J M and Dutriaux A, Trends Genet. (1999), 15(3): 88-90), generating disrupted, non-functional or chimeric genes. Various vectors and selectable marker genes have been introduced, for example, in the genome of mouse Embryonic Stem (ES) cells, in order to study the effects of genetic alterations on various phenotypic features, like hormonal regulation, fertility, immunological response, organ development.
The feasibility of homologous recombination-based techniques for the production of recombinant proteins has been demonstrated at the level of entire primary translational products (WO 91/09955, WO 95/31560), which have been obtained by putting a complete endogenous gene under the control of exogenous transcriptional regulatory sequences. Alternatively, truncated proteins may be obtained by antisense oligonucleotides that, once transfected into a cell, can pair to the endogenous mRNA blocking the ribosome to go through the entire coding sequence (WO 97/23244). However, none of the documents in the literature suggests the use of homologous recombination for expressing selectively one or more exons of an endogenous target gene encoding a functional protein domain comprised in a primary translational product by integrating exogenous regulatory sequences.

Method of producing functional protein domains


In one embodiment, the outboard motor lock comprises an outboard motor lock bracket and an outboard motor lock securing mechanism. The bracket comprises a back plate, side plates and a lip, and may be attached to a boat hull or other surface through bracket attachment holes. The securing mechanism comprises a base and one or more securing rods. The securing mechanism can be inserted into the bracket by inserting the one or more securing rods through corresponding bracket securing holes. One or more aligned bracket locking holes and securing mechanism locking holes allow for a locking device to be passed through and lock the securing mechanism to the bracket. When the securing mechanism is inserted into the bracket after an outboard motor attaching mechanism has engaged the bracket, the securing mechanism prevents the attaching mechanism from being removed from the bracket.

This system relates to an outboard motor lock. More particularly, the lock assists in securing an outboard motor to the hull of a boat.
The design of most outboard motors facilitates easy attachment and removal from the hull of a boat. In addition to providing convenience for the boat owner, it also means that outboard motors can be easily targeted for theft while the boat is not in use. While likely no method of securing an outboard motor to a boat could fully prevent theft, an easy way to secure the motor and deter theft, while also providing beneficial protection to the boat hull itself, is desirable.


A surge protector is provided that has a gas tube and at least one MOV that is coordinated with the gas tube such that the MOV interacts with the gas tube to lower the impulse breakdown voltage of a gas tube of a type that has a wide range of DC breakdown voltages across a population of the gas tubes. The gas tube is a generally cylindrical three element gas tube and the MOVs are disposed at opposite ends of the gas with fusible elements maintained in position by a clip. A population of the gas tubes has a range of breakdown voltages and the clamping voltage of the MOVs is set within this range such that the MOV will interact with any gas tube with a breakdown voltage in the population range to divert a surge to ground.

Gas tube arresters are commonly used to protect telecommunication lines from electrical surges. Since gas tube arresters need to be hermetically sealed to perform the protection function, there is the possibility that the gas will vent from the arrester resulting in a much higher breakdown voltage than originally intended and rendering the gas tube unable to protect. To provide for continued protection should venting occur, arresters are provided with back up protection in the form of an air gap or with a solid state device, for example, a metal oxide varistor (MOV).
U.S. Pat. No. 5,388,023 discloses a gas tube protector with one or two MOVs used as a back up. A gas tube protector with a back up device is sometimes referred to as "vent safe." In such protectors, the gas tube is sometimes termed the "primary protector." Gas tubes are widely used as primary protectors because of their ability to repeatedly divert large surge currents to ground and remain functional to protect.
Because it is desired that the gas tube and not the back up divert surges to ground, the operate voltage of the MOVs are set higher than the operate voltage of the gas tube. The '023 patent discloses "5 to 10% or else between 10 and 40% above the response voltage of the overvoltage arrestor." With the response voltage of the MOVs set in such a range, the MOVs are intended to only divert surges if the gas tube has vented. In normal operation, the gas tube alone is intended to divert surges to ground. The '023 patent defines the response voltage of the MOV as the voltage at which the varistor conducts a current of 1 mA.
U.S. Pat. No. 5,500,782 also discloses the use of a MOV with a gas tube with the clamping voltage of the MOV above the breakdown voltage of the gas tube. While the '782 patent uses the term "hybrid" to describe the disclosed protector arrangement, the MOVs are used as a back up protection device in the event that the gas tube should vent. The '782 patent teaches that the 1 mA clamping voltage of the MOV is selected to be just above the upper tolerance of the DC breakdown voltage of the gas tube so that the gas tube acts as the primary surge protector and the MOV provides back up protection in case the gas discharge tube fails to operate properly.
MOVs are preferred over traditional air gaps because they have a more repeatable clamping voltage than air gaps in response to fast rising voltage transients and they are not susceptible to contamination and moisture like the air gap.
One drawback of gas tubes as protectors is their ionization time which contributes to a higher peak surge voltage, or impulse breakdown voltage. The DC breakdown voltage of a gas tube is the voltage at which a gas tube will ionize when the voltage is increased slowly, for example, 100 volts per second. By raising the voltage slow enough such that the ionization time of the gas tube is taken into account, the DC breakdown voltage of the gas tube can be determined. If the voltage is a surge voltage, for example, 100 volts per microsecond, the gas tube will breakdown at a voltage predominantly higher than its DC breakdown voltage because of the ionization time of the gas tube. This higher voltage is termed "surge breakdown voltage" or "impulse breakdown voltage." It is possible that the impulse breakdown voltages of the gas tubes are sufficiently high that there could still be a shock to a person that is in contact with the circuit at the time of the surge Therefore, it is possible to have personnel injury and/or equipment damage from a gas tube protected circuit.
Therefore a need exists for a telecommunications protector with a robust gas tube protector as the primary protector but that is "assisted" by a secondary protector against fast surges to lower the impulse voltage. A further need exists for a protector where the secondary protector is capable of acting as a back up should the gas tube vent.
Another drawback of gas tubes is that there are wide variances of the DC breakdown voltages among gas tubes of the same type and made by the same manufacturing process. This variance is much wider than the variances for other components such as MOVs and fusible elements. Thus a need exists for a gas tube protector with a secondary protector that lowers the impulse voltage that takes into account the wide range of DC breakdown voltages across a population of gas tubes of the same type.
While both the '023 and '782 patents disclose incorporation of "fail safe" arrangements in the protector to short to ground any surges that overheat the protector, one drawback of the '782 patent arrangement is its bulkiness. The MOVs are spaced from the gas tube and arranged in a manner that takes up more space than the arrangement in the '023 patent which compactly locates two MOVs on opposite ends of the gas tube while still incorporating a thermal overload short to ground arrangement. Either one of the MOVs alone or the gas tube alone if overheated will melt the thermal element in the '023 arrangement to short to ground. Also, the MOVs in the '782 patent are not of sufficient size to impact the surge voltage under normal operating conditions.

Gas tube surge protector with interacting varistors


Sensor apparatus and methods for operating the same for measuring acceleration are disclosed. In some embodiments, circuitry inside a sensor digitizes a measured acceleration signal from an accelerometer into a digitized acceleration signal, which is processed by a digital equalization filter within the sensor to provide an equalized acceleration signal. The equalized acceleration signal may have a frequency response that is substantially flat over a frequency range that extends beyond the resonant frequency of a MEMs sensor within the accelerometer of the sensor.

Sensors operate by detecting a change in a sensed condition, and output electrical signals representing the sensed condition. The sensed condition may include acceleration, velocity, pressure, or other mechanical or environmental conditions. The output electrical signal is a time-domain signal that reflects how the sensed condition changes versus time. The output electrical signal can also be represented in the frequency domain in terms of magnitude and frequency. The magnitude of the output electrical signal can be influenced by characteristics of the processing circuitry that receives the sensor output. It is desirable, in many applications, to use the processing circuitry to enhance the frequency response of the sensor element. The enhancement is in the form of magnitude adjustment, so that the bandwidth of the sensor is widened.

Method and apparatus for improving MEMs accelerometer frequency response


A quick release connector for a power tool accessory having a center aperture. The connector comprises a body having a first end adapted to be attached to a shaft of a power tool and a second end that includes a connector head that is adapted to be moved axially into and to fit within the center aperture of the accessory for transferring motion from the power tool to the accessory. In one embodiment, the connector includes an indicator for providing a positive indication to a user that the connector head is properly secured to the accessory and, in another embodiment, the connector includes an ejector for pushing the accessory off of said connector head.

The present invention is directed to a quick release connector for an accessory adapted for use with a power tool and, more particularly, to a quick release connector for an accessory such as a buffing pad adapted for use with a power buffer. The quick release connector allows, in one embodiment, for a two-sided buffing pad to be quickly released from a power buffer, reversed, and reattached to the power buffer.
Buffing pads for use in high speed polishing of automobiles and the like may be one-sided or two-sided. A one-sided buffing pad is typically circular and comprises a buffing medium (e.g., foam, wool, etc.) attached to one face of a rigid backing plate which is attached by a central hub to the drive shaft or spindle of a motor for a power buffer. The buffing medium may be permanently attached to the backing plate or releasably attached thereto in order to allow for replacement without disposing of the backing plate. A two-sided buffing pad includes buffing medium attached to each face of a rigid backing plate. The plate includes a hub for releasably attaching the buffing pad to the drive shaft or spindle of the buffing motor. The pad may be attached to the drive shaft or spindle of the motor from either side of the buffing pad, thereby allowing the pad to be reversed after one side has been used.
U.S. Pat. No. 4,607,412 to Ashworth discloses a reversible buffing pad that includes a hub that can be releasably attached to a drive shaft from either side of the hub. A center disk is attached to the hub and a pair of buffing pads is provided.
U.S. Pat. No. 5,461,750 to Kaiser discloses a backing plate for a rotary buffing pad assembly that provides cushioned support for a pair of curved edge buffing pads mounted back-to-back.
U.S. Pat. No. 6,640,377 to Krause et al. discloses a quick release buffing pad assembly. A buffing pad assembly having a right pad, a left pad, a disk securing the two pads together, and an elongated member for releasably attaching the buffing pad to the drive shaft of a buffing motor is disclosed. Each pad has a central aperture. The disk has a connector located in the center thereof with an opening therethrough. The right and left pads are secured to first and second faces, respectively, of the disk so that the apertures and opening are aligned when the buffing pad is assembled. The elongated member has a body, a head, and an indented area separating the head and the body. The head fits through either of the apertures and through the opening of the connector. The elongated member also has an open end which may be secured to the spindle of a buffing motor. Contained within the indented area is an O-ring which releasably secures the elongated member within the opening yet allows for the pad to be easily snapped off of the elongated member so that either side of the buffing pad may be used.
In another iteration of the quick release buffing pad assembly just described, the O-ring was replaced with spring biased balls that cooperate with complementary recesses in an opening in the disk so that the buffing pad can be easily and quickly attached to and removed from the drive shaft or spindle of a buffing motor to which the connector is secured.


Benzoate inducible promoters and promoter systems are disclosed, and uses thereof. Polynucleotides disclosing Benzoate Response Elements are also disclosed.

The application of genetic engineering techniques to plants promises to revolutionize plant agriculture. One result of this revolution would be the ability to control gene expression in plants. For example, pests and diseases have been controlled by applying pesticides or biocides to crop plants; however, application of chemicals to plants affects more than the plant pests or diseases whose control is desired, and poses a general risk to the environment, often with deleterious consequences. In an effort to ameliorate these risks, transgenic plants have been recently developed to constitutively express insect resistance genes or disease resistance genes. However, constitutive expression means that these resistance genes are always expressed, not just when and where and to what level they are needed; such general expression can represent a metabolic drain on a plant, with consequent decreased productivity, or it can be too low to be effective. Moreover, constitutive expression of a protein may not be desirable, particularly if this protein interferes with the early stages of plant development. In other instances, high protein levels cause toxicity to the plant.
Thus, in the last few years, there has been increasing interest among plant scientists on means to precisely control the location, timing and level of expression of transgenes in plants, as well as of endogenous genes. Controlling the location of gene expression, or a more precise control of transgene expression in a specific plant tissue, has been accomplished by means of using one of several different tissue-specific promoters. Controlling the timing and level of gene expression, or temporal and quantitative control of expression, could be accomplished by inducing gene expression upon the application of a specific stimulus. Such inducible gene expression would have numerous practical applications; for example, turning on engineered plant defense genes only upon attack of a pathogen or insect predator could save millions of dollars in pesticide application, as well as decrease unwanted adverse environmental effects. Inducing gene expression would also be a powerful research tool, where it could be used in studies ranging from examining phenotypes associated with specific gene expression to investigations of gene interactions in plants.
One type of inducible promoter is a chemically inducible promoters. These are synthetic promoter systems often constructed by combining known regulator elements whose activity is modulated by the presence of chemical effectors.
A chemically inducible promoter preferably satisfies several criteria to be useful in an agricultural application. Such criteria include sufficient stability and relative non-toxicity of chemical inducers. Chemically-induced gene promoters have been isolated, but none of these are suitable for practical application because of the nature of the chemical inducers. The chemicals are either too volatile (such as ethanol) or toxic to the environment or the plants to which it is applied (such as copper ions, antibiotics, or steroids).
Thus, what is needed are inducible promoters that are activated by chemicals which are sufficiently stable and non-toxic to the environment, including the plants to which they are applied. Preferably such chemical inducers can also be easily applied to large acreages of crop plants; even more preferably, such chemical inducers are inexpensive.


The present invention is a spin bike pedal load changing means, and foot rest means for use in stationary training, that collectively greatly improves the capabilities of spin bikes over what is currently available in the art. The pedal load changing means allows the calibration of a range of pedal working loads, tailored to the individual rider""s capabilities and at the same time can be used as an emergency brake. The foot rest allows for the safe parking of the rider""s free leg during one-legged cycling training. The foot rest feature and pedal load change features both effectively increase the performance and safety of the spin bike in use, which is a much-desired feature for health clubs and gyms. The spin bike further allows the instructor to carry out a group class exercise routine, where each rider can set the pedal load changing means on each spin bike to fit their individual strength and stamina capabilities and also allows the rapid changing of pedal load settings to predetermined levels.

1. Field of the Invention
The invention relates to exercise bicycles and in particular to pedal load changing devices for use on stationary exercise bicycles, generally called spin bikes that are used in health clubs, cycle clubs, home environments and the like.
2. Description of Prior Art
Presently there are millions of stationary exercise bikes or spin bikes used in health clubs and exercise clubs around the US and abroad. These bikes were initially developed for use by cyclists who wished to maintain a training schedule even during times when outside weather conditions and/or access to suitable outdoors cycling amenities was not available. For instance, a cyclist who is in training for a race is not always able to ride outdoors, especially at night and so spin bikes were developed to allow training to take place, during these times. These stationary spin bikes are now used both by cyclists and non-cyclists alike, for training and exercise purposes.
These bikes are however, of very basic design and limit the rider in his range of exercise options. The spin bikes supply minimal component adjustments to meet the physical needs of the rider. The spin bikes also use simple adjustment knobs connected to a friction load-generating device mounted on the front wheel, to raise and lower the loads on the pedals. These knobs are turned to change the pedal load and when a number of riders use the bike, each rider has difficulty resetting the pedal load to their own requirements, as there are generally no setting marks on the knob or on the adjacent bike surfaces. Typically many turns of the knob are needed to make a change to the pedal loads, which makes any adjustment difficult during the exercise period.
For this reason, instructors at the clubs with spin bikes have a difficult time coordinating a class of club members on spin bikes as the knobs on these bikes do not allow quick or easy changes of pedal load settings. Because of these limitations in their design, spin bikes do not allow the rider or the instructor to mimic the riding conditions of an outdoors bike or track bike.
As an example, the most popular brand of spin bike has not changed the design of its essential pedal load changing components for many years. Other competitive spin bikes have similar designs and all lack good pedal load changing features which, if present, could greatly improve the spin bike""s performance and so meet the needs of a wider variety of users and health club instructors.
In the current art of spin-bikes, pedal loads are varied by turning a control knob, which changes the force on a friction pad or pads on top of, or on the sides of the front wheel, which creates changes in the pedal loads.
In the most common design of spin bike pedal load changing feature, the knob is turned and rotates a threaded rod inside a stationary threaded nut, causing the rod to move up or down. The rod is attached by a cable, or through a set of rotating arms, to two brake pads on either side of the rim of the flywheel. The length of the rod and the flex in the cable attaching it to the attendant pads, combined with the fine thread pitch on the threaded nut, requires the rider to turn the knob a large number of turns, to produce the desired change to the load on the bike pedals. This is an annoyance and does not give the rider the ability to quickly change his pedal loads during a workout.
In some of the more recent models of spin bikes the pedal load changing feature consists of a friction pad mounted on the top of the front wheel rim. Turning the control knob directly raises or lowers a threaded rod, which changes the force on the friction pad. The force is generated by turning the knob inside a square threaded nut, mounted on the spin bike frame. The threaded nut is loosely constrained from turning but can slide up or down within a limited envelope, defined by a square tube mounted on the frame of the spin bike. This sliding feature is used to integrate the emergency brake with the pedal load changing means as follows: When the rider pushes down on the top of the control knob, the entire pedal load changing means slides down and increases the force on the top of the friction pad and so the bike wheel comes to a quick stop.
Also in spin bike training there is a need by many cyclists to do one legged training exercises. This is done to improve their pedal strokes, since cycling on one leg quickly shows up the parts of the pedal stroke that are deficient as it is not masked by the other leg""s contribution. A problem arises in finding a suitable and safe place to park the free leg. If held out to the side the rider runs the risk of striking it against the free rotating pedal, and if he elects to park it on part of the frame it pulls his body out of the correct cycling position. There is nothing available in the art, which addresses this problem.
There are a number of spin bike models currently being sold and used but in all cases they are limited in design and operation as described above. Basically the construction and essential features of the pedal load changing features and one legged cycling requirements on spin bikes currently in use, do not meet the physical or training needs of the riders.
There is no known prior art in the field of spin bike design that addresses the problems discussed above. The present invention overcomes these problems and in so doing, also adds new features, which improve the capabilities of a spin bike.
Thus addition of the present invention to a stationary exercise spin bike creates a bike with a good pedal load-changing feature and leg parking capability, which immediately enhances indoor spin bike exercise and training possibilities.
The present invention is an advanced design of pedal load changing means and foot parking means not presently available on spin bikes currently in use. These features produce a spin bike that can more closely mimic the operational features of a road bike and also allow for advanced cycling training, using one leg.
The design of the friction device incorporated on the present invention, used to load up the pedals, can be activated about 5 times faster than on standard spin bikes, thus allowing the rider to more rapidly change pedal loads.
The invention includes an up to 10-step, simple pedal load changing means which is based on the following: There is a scale of difficulty known as the Borg Scale, well recognized by the health and fitness training business, which is a scale of perceived exertion for riding a bicycle. The top of the scale is 10 and this represents a load that is almost imporsible for the rider to turn the pedals against. The bottom of the scale is 1, which represents a very light pedal load. The pedal load changing means of the present invention mimics the Borg Scale used in general fitness evaluation and adds a very useful exercise feature to a spin bike.
To establish the Borg Scale, using the pedal load changing means on the spin bike incorporating the present invention, the rider gets on the spin bike and starts pedaling. He gradually turns a pressure-adjusting knob, which forces a friction pad downward onto the front wheel rim. This increases the load on the pedals, until he is at the highest load setting that he can handle. This is his number #10 setting. By then simply moving a load change lever down from this #10 setting, the rider can back off from his highest pedal load by increments, all the way down to a very light pedal load, which represents his #1 setting. Note that the scale has now been set up for this individual and his particular abilities, which could of course, be very different for another individual with higher or lower strength and cycling power.
The pedal load change lever has a spring-loaded ball bearing on each side, which fit into a series of holes in the two side plates adjacent to the lever. The rider can then mimic the effect of gear changes on a road bike by pushing the load change lever up or down and feel it slide into the next hole with a sudden resistance, accompanied by an audible xe2x80x98clickxe2x80x99. Thus these clicks can be used to control pedal load settings while the rider is exercising, without distraction.
This pedal load changing system is an essential feature of the present invention, as it allows the individual to set a spin bike""s pedal load range to match his or her capabilities. Thus a novice or older person with little body strength, or persons with lighter or heavier body weights, can establish their individual maximum setting for pedal loads as described above. They can then establish up to 10 increments of lower loads by use of the pedal load change lever, and thus stay well within their capabilities. Thus by simply setting the load to the different settings using the pedal load change lever, the person can vary the loads on the pedal and so simulate the variable conditions which are desirable to get a full aerobic workout, yet stay within their own body strength and stamina range.
Another advantage of this pedal load setting invention is that a group of spin bike riders can make adjustments to their individual spin bike pedal loads, to match their individual abilities. Then the instructor can now lead the class through a series of pedal load settings that give the whole class a full workout. No longer does the individual have to fiddle with the turn knob to try and change pedal loads from high to low, while he is pedaling. He can merely reach down and push or pull the load change lever through the desired number of clicks called out by the instructor, which changes pedal resistance and therefore level of workload.
In an exercise class using current state-of-the-art spin bikes, the instructor is severely limited when he tries to get each individual to change the pedal loads in any consistent manner, due to the large number of knob turns required and the absence of an indicator to show knob position. With spin bikes incorporating the present invention, the instructor can now tell the class to xe2x80x9cgo up 3 clicksxe2x80x9dor xe2x80x9cgo down 6 clicksxe2x80x9d and they can all do this very easily and quickly, without much effort or distraction, by activating the pedal load change lever.
Riders with widely different levels of ability can now exercise together and each can get a workout adjusted and tailored to their individual capabilities. This can be done on a group of spin bikes each incorporating the present invention. The pedal load settings can be automatically re-adjusted at the beginning of the workout as the rider""s level of ability changes. Or the pedal load change can be made even in the middle of the workout by turning the pedal load change knob up or down which will automatically reset the entire 10-step range, controlled by the lever.
The present invention also incorporates an emergency brake integral with the pedal load change feature, that is activated by a push down thrust of the rider""s arm that is a much easier motion for the rider to make, in an emergency situation, when his body is also moving forward after he has lost contact with the pedals. Thus the embodiment described above includes the pedal load changing means and an emergency brake means, both contained in the same assembly and illustrated in FIG. 2a.
In the preferred embodiment of the invention, the load change lever can also be used as an emergency brake as follows: When the settings for the load change lever have been established as described above by the rider, the top setting of the lever is the one where the rider can barely turn the pedals and represents a high pedal load and therefore a high friction load on the front wheel. This top setting generates enough load on the front wheel, that in the case of an emergency, when the rider wants to stop the spin bike""s rotation, the rider can push the lever forward, which clicks it into higher and higher load settings until the bike""s wheel quickly comes to a stop. Thus the pedal load change device can serve both functions, the first to control pedal loads and the second to act as an emergency brake. This preferred embodiment greatly simplifies the design of the embodiment described earlier and allows the same device to function as both pedal load changer and emergency brake as illustrated in FIG. 2e.
The spin bike incorporating the present invention also includes a foot rest mounted on the frame of the bike. This foot rest is not available on commercially available spin bikes and so presently when a rider is doing one-leg training he has to hold the other leg out to the side or rear of the bike in an unsupported manner. If he is not careful, he runs the risk of striking his leg against the free rotating pedal of the bike, causing injury. This one-leg pedaling is also used by riders, as part of a training method or to isolate each leg in turn to measure leg strength or when riding on one leg to smooth out the riders pedal stroke.
The foot rest is best located towards the rear of the bike frame, since this is the best position to park a free leg during isolated leg cycling as it does not disrupt the rider""s normal pedal stroke or throw the riders body out of balance. A foot rest positioned towards the front of the bike structure upsets the body""s position and alignment when used to park a free leg, which is not conducive to good cycling training routines.
As can be seen from the above description, the spin bike incorporating the present invention includes a number of useful features, which together increase the performance, and versatility of spin bikes for use in indoor exercise and training.

Device for changing pedal loads on a spin bike


A process for the manufacture of particles comprises mechanically working a mixture of a drug and a hydrophobic and/or hydrophilic fusible carrier in a high speed mixture so as to form agglomerates, breaking the agglomerates to give controlled release particles and optionally continuing the mechanical working with the optional addition of a low percentage of the carrier or diluent.

The present invention relates generally to a method of manufacturing pharmaceutical dosage forms, for human or veterinary use, preferably sustained release particles, such particles having diameters ranging from 0.1 to 3.0 mm. Such particles may contain analgesics, such as morphine, or other active ingredients. The present invention also relates to dosage forms obtained by processing of the aforesaid particles, such as tablets, suppositories or pessaries.
Patent Application PCT/SE93/00225 published under No. WO 93/18753 describes a process for the preparation of sustained release pellets which comprises pelletizing a mixture containing the drug in finely divided form and a binder; the process is characterized in that:
(a) the binder is in particle form consisting of one or more water-insoluble or water-soluble, wax-like binder substance(s) with a melting point above 40.degree. C. and PA1 (b) the pelletization step is performed by mechanically working the mixture, in a so-called high-shear mixer, under the input of a sufficient amount of energy for the binder to melt and pelletization to take place. Patent Application PCT/SE92/06679 describes a similar process. PA1 (a) mechanically working in a high-speed mixer, a mixture of a particulate drug and a particulate, hydrophobic and/or hydrophilic fusible carrier or diluent having a melting point from 35.degree. to 150.degree. C. and optionally a release control component comprising a water soluble fusible material or a particulate, soluble or insoluble organic or inorganic material, at a speed and energy input which allows the carrier or diluent to melt or soften, whereby it forms agglomerates; PA1 (b) breaking down the larger agglomerates to give controlled release particles; optionally PA1 (c) continuing mechanically working optionally with a further addition of low percentage of the carrier or diluent; and PA1 (d) optionally repeating step (c) and possibly (b) one or more, e.g. up to five, times.
Processes of this kind are sometimes referred to as "melt-pelletization" processes. We have found that operating according to these processes using commercial manufacturing equipment with a standard stainless steel interior, which is also the method described in Schaefer et al. (Drug Development and Industrial Pharmacy, 16(8), 1249-1277 (1990) and Taggart et al. (International Journal of Pharmaceutics 19 (1984) 139-148), results in yields of pellets in the preferred size range of only about 30 to 60% compared with the theoretical. Use of a wider particle size range to improve the yield results in an erratic in vitro release rate and irreproducible performance.
There is, therefore, a need for a commercial process for producing satisfactory controlled release particles which has a much higher yield. One object of the invention is, therefore, to provide a process which has an improved yield and preferably produces a product with reproducible controlled release characteristics.
The present invention thus includes in one aspect a process for the manufacture of particles, preferably sustained release particles, which comprises
This process is capable of giving a high yield (over 80%) of particles in a desired size range, with a desired in vitro release rate and, uniformity of release rate.
The resulting particles may be sieved to eliminate any oversized or undersized material then formed into the desired dosage units by for example, encapsulation into hard gelatin capsules containing the required dose of the active substance or by tabletting, filling into sachets or molding into suppositories, pessaries or forming into other suitable dosage forms.
The drug may be water soluble or water insoluble. Water soluble drugs will usually be used in amounts giving for example a loading of up to about 90% w/w in the resulting particles; water insoluble drugs may be used in higher amounts eg. up to 99% w/w of the resulting particles. Examples of water soluble drugs which can be used in the method of the invention are morphine, hydromorphone, diltiazem, diamorphine and tramadol and pharmaceutically acceptable salts thereof; examples of water insoluble drugs which can be used in the process of the invention are naproxen, ibuprofen, indomethacin and nifedipine.
Among the active ingredients which can be used in the process of the invention are the following;
ANALGESICS
Dihydrocodeine, Hydromorphone, Morphine, Diamorphine, Fentanyl, Alfentanil, Sufentanyl, Pentazocine, Buprenorphine, Nefopam, Dextropropoxyphene, Flupirtine, Tramadol, Oxycodone, Metamizol, Propyphenazone, Phenazone, Nifenazone, Paracetamol, Phenylbutazone, Oxyphenbutazone, Mofebutazone, Acetyl salicylic acid, Diflunisal, Flurbiprofen, Ibuprofen, Diclofenac, Ketoprofen, Indomethacin, Naproxen, Meptazinol, Methadone, Pethidine, Hydrocodone, Meloxicam, Fenbufen, Mefenamic acid, Piroxicam, Tenoxicam, Azapropazone, Codeine.
ANTIALLERGICS
Pheniramine, Dimethindene, Terfenadine, Astemizole, Tritoqualine, Loratadine, Doxylamine, Mequitazine, Dexchlorpheniramine, Triprolidine, Oxatomide.
ANTIHYPERTENSIVE
Clonidine, Moxonidine, Methyldopa, Doxazosin, Prazosin, Urapidil, Terazosin, Minoxidil, Dihydralazin, Deserpidine, Acebutalol, Alprenolol, Atenolol, Metoprolol, Bupranolol, Penbutolol, Propranolol, Esmolol, Bisoprolol, Ciliprolol, Sotalol, Metipranolol, Nadolol, Oxprenolol, Nifedipine, Nicardipine, Verapamil, Diltiazem, Felodipine, Nimodipine, Flunarizine, Quinapril, Lisinopril, Captopril, Ramipril, Fosinopril, Cilazapril, Enalapril.
ANTIBIOTICS
Democlocycline, Doxycycline, Lymecycline, Minocycline, Oxytetracycline, Tetracycline, Sulfametopyrazine, Ofloxacin, Ciproflaxacin, Aerosoxacin, Amoxycillin, Ampicillin, Becampicillin, Piperacillin, Pivampicillin, Cloxacillin, Penicillin V, Flucloxacillin, Erythromycin, Metronidazole, Clindamycin, Trimethoprim, Neomycin, Cefaclor, Cefadroxil, Cefixime, Cefpodoxime, Cefuroxine, Cephalexin, Cefradine.
BRONCHODILATOR/ANTI-ASTHMATIC
Pirbuterol, Orciprenaline, Terbutaline, Fenoterol, Clenbuterol, Salbutamol, Procaterol, Theophylline, Cholintheophyllinate, Theophylline-ethylenediamine, Ketofen.
ANTIARRHYTHMICS
Viquidil, Procainamide, Mexiletine, Tocainide, Propafenone, Ipratropium.
CENTRALLY ACTING SUBSTANCES
Amantadine, Levodopa, Biperiden, Benzotropine, Bromocriptine, Procyclidine, Moclobemide, Tranylcypromine, Tranylcypromide, Clomipramine, Maprotiline, Doxepin, Opipramol, Amitriptyline, Desipramine, Imipramine, Fluroxamin, Fluoxetin, Paroxetine, Trazodone, Viloxazine, Fluphenazine, Perphenazine, Promethazine, Thioridazine, Triflupromazine, Prothipendyl, Thiothixene, Chlorprothixene, Haloperidol, Pipamperone, Pimozide, Sulpiride, Fenethylline, Methylphenildate, Trifluoperazine, Thioridazine, Oxazepam, Lorazepam, Bromoazepam, Alprazolam, Diazepam, Clobazam, Clonazepam, Buspirone, Piracetam.
CYTOSTATICS AND METASTASIS INHIBITORS
Melfalan, Cyclophosphamide, Trofosfamide, Chlorambucil, Lomustine, Busulfan, Prednimustine, Fluorouracil, Methotrexate, Mercaptopurine, Thioguanin, Hydroxycarbamide, Altretamine, Procarbazine.
ANTI-MIGRAINE
Lisuride, Methysergide, Dihydroergotamine, Ergotamine, Pizotifen.
GASTROINTESTINAL
Cimetidine, Famotidine, Ranitidine, Roxatidine, Pirenzipine, Omeprazole, Misoprostol, Proglumide, Cisapride, Bromopride, Metoclopramide.
ORAL ANTIDIABETICS
Tolbutamide, Glibenclamide, Glipizide, Gliquidone, Gliboruride, Tolazamide, Acarbose and the pharmaceutically active salts or esters of the above and combinations of two or more of the above or salts or esters thereof.
The hydrolysis of drugs constitutes the most frequent, and perhaps therefore the most important, route of drug decomposition. Analysis of a collection of stability data in Connors KA, Amidon GL, Stella VJ, Chemical stability of pharmaceuticals: A handbook for pharmacists, 2nd ed. New York: John Wiley & Sons, 1986, a standard text, shows that over 70% of the drugs studied undergo hydrolytic degradation reactions. Of these, 61.4% can be classed as reactions of carboxylic acid derivatives (esters, amides, thiol esters, lactams, imides), 20% of carbonyl derivatives (imines, oximes) 14.3% of nucleophilic displacements, and 4.3% of phosphoric acid derivatives. Cephalosporins, penicillins and barbituates are particularly susceptible drug classes.
The process of the invention may advantageously be used for preparing dosage forms containing active substances as mentioned above which are unstable in the presence of water, e.g. diamorphine. Thus stable formulations of such drugs having normal or controlled release characteristics can be obtained in accordance with the invention.
In a preferred method according to the invention morphine sulphate, or other water soluble drug, e.g. tramadol, is used in an amount which results in particles containing e.g. between <1% and 90%, especially between about 45% and about 75% w/w active ingredient for a high dose product and e.g. <1 and 45% for a low dose product.
In the method of the invention preferably all the drug is added in step (a) together with a major portion of the hydrophobic or hydrophilic fusible carrier or diluent used. Preferably the amount of fusible carrier or diluent added in step (a) is between e.g. 10% and <99% w/w of the total amount of ingredients added in the entire manufacturing operation.
The fusible carrier or diluent may be added stepwise during mechanical working, in step a) or step c).
In step (c) the amount of additional fusible carrier or diluent added is preferably between 5% and 75% w/w of the total amount of ingredients added.
Stage (a) of the process may be carried out in conventional high speed mixers with a standard stainless steel interior, e.g. a Collette Vactron 75 or equivalent mixer. The mixture is processed until a bed temperature above 40.degree. C. is achieved and the resulting mixture acquires a cohesive granular texture, with particle sizes ranging from about 1-3 mm to fine powder in the case of non-aggregated original material. Such material, in the case of the embodiments described below, has the appearance of agglomerates which upon cooling below 40.degree. C. have structural integrity and resistance to crushing between the fingers. At this stage the agglomerates are of an irregular size, shape and appearance.
The agglomerates are preferably allowed to cool. The temperature to which it cools is not critical and a temperature in the range room temperature to 41.degree. C. may be conveniently used.
The agglomerates are broken down by any suitable means, which will comminute oversize agglomerates and produce a mixture of powder and small particles preferably with a diameter under 2 mm. It is currently preferred to carry out the classification using a Jackson Crockatt granulator using a suitable sized mesh, or a Comil with an appropriate sized screen. We have found that if too small a mesh size is used in the aforementioned apparatus the agglomerates melting under the action of the beater or impeller will clog the mesh and prevent further throughput of mixture, thus reducing yield.
The classified material is preferably returned to the high speed mixer and processing continued. It is believed that this leads to cementation of the finer particles into particles of uniform size range.
In one preferred form of the process of the invention processing of the classified materials is continued, until the hydrophobic and/or hydrophilic fusible carrier or diluent materials used begin to soften/melt and additional hydrophobic and/or hydrophilic fusible carrier or diluent material is then added; most preferably the additional hydrophobic and/or hydrophilic fusible carrier or diluent material is added after any fines generated in stage (b) have been taken up by the larger sized particles. Mixing is continued until the mixture has been transformed into particles of the desired predetermined size range.
In order to ensure uniform energy input into the ingredients in the high speed mixer it is preferred to supply at least part of the energy by means of microwave energy.
Energy may also be delivered through other means such as by a heating jacket or via the mixer impeller and chopper blades.
After the particles have been formed they are sieved to remove any oversized or undersized material and then cooled or allowed to cool.
The resulting particles may be used to prepare dosage units, e.g., tablets or capsules in manners known per se.
In this process of the invention the temperature of the mixing bowl throughout the mechanical working is chosen so as to avoid excessive adhesion, suitably to minimize adhesion of the material to the walls of the bowl. To minimize adhesion we have generally found that the temperature should be neither too high nor too low with respect to the melting temperature of the material and it can be readily optimized to avoid the problems mentioned above. For example in the processes described below in the Examples a bowl temperature of approximately 50.degree.-60.degree. C. has been found to be satisfactory and avoids adhesion to the bowl. It is not possible to generalize as to the appropriate temperature for any particular mixture to be processed. However, in practice, it is a matter of simple experimentation and observation to establish a suitable temperature and processing time for a particular mixture under consideration.
The process of the invention described above is capable, in a preferred form, of providing particles which function as sustained release dosage forms. In particular, as described in co-pending European Patent Application No. 94303128.6 filed on 29th Apr. 1994, an orally administrable sustained release dosage unit form containing morphine, or a pharmaceutically acceptable salt thereof, as active ingredient which formulation has a peak plasma level of morphine from 1 to 6 hours after administration.
We have found that by suitable selection of the materials used in forming the particles and in the tabletting and the proportions in which they are used, enables a significant degree of control in the ultimate dissolution and release rates of the active ingredients from the compressed tablets.
Suitable substances for use as hydrophobic carrier or diluent materials are natural or synthetic waxes or oils, for example hydrogenated vegetable oil, hydrogenated castor oil, Beeswax, Carnauba wax, microcrystalline wax and glycerol monostearate, and suitably have melting points of from 35.degree. to 150.degree. C., preferably 45.degree. to 90.degree. C.
Suitable substances for use as hydrophilic carrier or diluent materials are natural or synthetic waxes or oils, for example polyethylene glycols (PEGs) having molecular weights of 1000 to 20,000 e.g. 1,000 to 6,000 or 10,000 suitably having melting points of from 35.degree. to 150.degree. C., preferably 45.degree. to 90.degree. C.
The optionally added release control component when a water soluble, fusible material may be a PEG of appropriate molecular weight; suitable particulate inorganic and organic materials are, for example dicalcium phosphate, calcium sulphate, talc, colloidal anhydrous silica, and lactose, poloxamers, microcrystalline cellulose, starch, hydroxypropylcellulose, and hydroxypropylmethylcellulose.
We have also found that particles produced by the melt pelletization processes described in application PCT/SE93/00225 and the process described herein are particularly useful for processing into the form of tablets.
To produce tablets in accordance with the invention, particles produced as described above may be mixed or blended with the desired excipient(s), if any, using conventional procedures e.g. using a Y-Cone or bin-blender and the resulting mixture compressed according to conventional tabletting procedure using a suitably sized tabletting tooling. Tablets can be produced using conventional tabletting machines, and in the embodiments described below were produced on standards single punch F3 Manesty machine or Kilian RLE15 rotary tablet machine.
Generally speaking we find that even with highly water soluble active agents such as morphine or tramadol tablets formed by compression according to standard methods give very low in-vitro release rates of the active ingredient e.g. corresponding to release over a period of greater than 24 hours, say more than 36. We have found that the in vitro release profile can be adjusted in a number of ways. For instance in the case of water soluble drugs a higher loading of the drug will be associated with increased release rates; the use of larger proportions of the water soluble fusible material in the particles or surface active agent in the tabletting formulation will also be associated with a higher release rate of the active ingredient: Thus, by controlling the relative amounts of these ingredients it is possible to adjust the release profile of the active ingredient, whether this be water soluble or water insoluble.
In Drug Development and Industrial Pharmacy, 20(7), 1179-1197 (1994) by L J Thomsen et al, which was published after the priority date of this application, a process similar to that described in PCT/SE93/00225 is discussed in detail. In the results and discussion on page 1186 it is states that glyceryl monostearate was the only substance which showed pronounced potential as a meltable binder, and then only with mixers lined with polytetrafluoroethylene. By contrast the process of the present invention has been found to work satisfactorily with other binders and using conventional mixers with stainless steel linings.
In Pharmaceutical Technology Europe October 1994 pp 19-24 L J Thomsen describes the same process as mentioned in the above article. In the passage bridging pages 20 and 21 it is stated higher drug loads with larger drug crystals did not pelletize and that his results suggest manufacturers using melt pelletization should avoid starting materials containing amounts of crystals larger than 60 .mu.m and that electrostatic charging of mass and adhesion to the walls of the mixer bowl made it impossible to make acceptable quality pellets with a binder of pure microcrystalline wax so that substantial amounts of glycerol monostearate was essential. In the process of the invention described herein drug crystal size has not been found to be a critical parameter; in the Examples described below the morphine sulphate typically has a particles size distribution with 50% of particles larger than 24 to 50 .mu.m and 10% larger than 100-140 .mu.m.
In order that the invention may be well understood the following examples are given by way of illustration only.


A cluster system according to the present invention includes an active server and a standby server which have a failover function, and a shared disk. The active server includes a control device configured to operate free of influence from an OS, and a disk input/output device configured to input and output data into and from the shared disk. The control device of the active server includes a communication module configured to communicate with the standby server, and an initialization module configured to, when a failure occurs in the active server, initialize the disk input/output device and notify to the standby server via the communication module.

A failover cluster system is known, which is equipped with both an active server and a standby server and a shared disk to prevent the stoppage of processing due to occurrence of a computer failure, for example, as shown in Patent Document 1. In such a failover cluster system, data of a business application running in each of the servers are stored in the shared disk that can be accessed from both the active server and the standby server. When a failure occurs in the active server, cluster software starts the business application in the standby server by executing switchover (referred to as "failover" hereinafter) of the business application. The business application started in the standby server uses the data stored in the shared disk to restart business processing from a time point of stoppage of the business application in the active server.
Since a failover cluster system equipped with a shared disk stores data in the shared disk as mentioned above, there is a fear that the data is destroyed if both the active server and the standby server write into the shared disk simultaneously. Therefore, such a system executes exclusive control so as to cause only the active server to write usually.
(1: Exclusive Control at the Time of Failover)
For executing failover from an active server to a standby server, it is required to start a business application in the standby server after certainly stopping the active server from accessing a shared disk.
(2: Exclusive Control in the Split-Brain State)
There is a structure (a split-brain solution method) that, when a cluster goes into a split-brain state in which the cluster cannot recognize the statues of servers due to a failure of a network between the servers, a server to which the cluster should switch a business application is decided based on the presence of access to a shared disk. This split-brain solution method possibly invites a situation that, when a server with a fault network device accesses the shared disk, the cluster falsely recognizes the fault server is normally operating. Thus, it is required to securely prevent the fault server from accessing the shared disk.
As stated above, when executing failover in a cluster system, it is required to properly execute exclusive control to certainly stop a fault server from accessing a shared disk.
[Patent Document 1] Japanese Unexamined Patent Application Publication No. JP-A 2012-173752
As a method for stopping access to a shared disk in a cluster system, unmounting a disk, making the port of a FC (Fibre Channel) switch inactive, causing an OS (Operating System) panic, or the like, is used. However, each of the abovementioned methods has a problem as described below.
Unmounting a disk has a problem that it takes time to execute and, when a process being written in exists, unmounting the disk fails. Making the port of a FC switch inactive has a problem that it takes time to connect because a server connects to a module outside the server and the server cannot connect to the FC switch depending on the type of a failure. Causing an OS panic has a problem that an input/output remaining in the cache of a HBA (Host Bus Adapter) card may be written in.
Further, in the case of executing I/O fencing that prevents writing into a shared disk in a HW (Hardware) layer, supply of power to the card is shut off, for example. Executing I/O fencing in the HW layer realizes secure I/O fencing, but there is no means for notifying the completion of I/O fencing to a standby server. Therefore, for example, the standby server needs to wait for heart beat communication timeout to start failover, and there is a problem that it is impossible to rapidly execute failover.
Thus, there has been a problem that it is impossible to speedily execute failover while protecting shard data in a failover cluster system.


Generalized non-limiting embodiments include employing a dipole antenna and/or a half slot antenna. Each of the antennas constitutes three mutually perpendicular radiating elements to achieve good isolation and low antenna signal correlation between the three ports. In one generalized non-limiting embodiment the antennas are fabricated on FR-4 epoxy boards. Experimental results show that the antennas resonate a reasonable frequency and have a desired mutual coupling. In addition experimental results for the diversity performance and the MIMO channel capacity are also provided for these antennas and these results show that the herein described antennas offer good diversity gain and the channel capacity can be increased by as much as three times by using these antennas over conventional antennas.

Multiple-input multiple-output (MIMO) technology is a technique that exploits multiple antennas to increase channel capacity without requiring additional spectrum or transmit power. With multiple antennas at the transmitter and receiver, capacity gains can be achieved by utilizing spatial and polarization diversity. In practical applications, due to the constraint of the spacing of the antenna elements, polarization diversity is preferred since the antennas can be co-located. At least one study has concluded that, with three orthogonal components of the electric field and three of the magnetic field, it is possible to obtain 6 independent channels at a single point. However there are few published MIMO antenna designs, and even fewer exploiting tri-polarization.
A MIMO wireless communication system is one that includes typically a plurality of antennas at a transmitter and one or more antennas at a receiver. The antennas are employed in a multi-path rich environment such that due to the presence of various scattering objects (buildings, cars, hills, etc.) in the environment, each signal experiences multipath propagation. User data is transmitted from the transmit antennas using a space-time coding (STC) transmission method as is known in the art. The receive antennas capture the transmitted signals and a signal processing technique is then applied as is known in the art, to separate the transmitted signals and recover the user data.
MIMO wireless communication systems are advantageous in that they enable the capacity of the wireless link between the transmitter and receiver to be improved compared with previous systems because higher data rates can be obtained with MIMO. The multipath rich environment enables multiple orthogonal channels to be generated between the transmitter and receiver. Data for a single user can then be transmitted over the air in parallel over those channels, simultaneously and using the same bandwidth. Consequently, higher spectral efficiencies are achieved than with non-MIMO systems.
One problem with existing MIMO systems concerns the large size of the transmit and receive antenna arrays. Typically, MIMO transmit and receive antenna arrays have used spatially diverse antenna arrays. That is, the spacing between the individual antenna elements is arranged to be large enough such that decorrelated spatial fading is obtained. This is desired in order to reduce a need for the number of orthogonal channels from being reduced. That is, if the fading characteristics between antenna elements are similar (correlated) then the number of orthogonal channels that can be realized is reduced. For example, for rooftop installations, or antennas on towers, separations of up to 20 wavelengths can be required to achieve decorrelated fading due to the low angle spread of the multipath propagation.
It is desirable to both provide more axes such as exploiting tri-polarization with a three axis antenna and smaller size such as can be provided with a compact 3-port orthogonally polarized MIMO antenna.

Compact 3-port orthogonally polarized MIMO antennas