The invention relates to a reactor driven in an oscillatory-rotary manner about its fixed, preferably vertical, axis, for preferably biotechnological and pharmaceutical applications. By means of its process-intensifying properties for mixing, suspension, gaseous material transport, heat transfer, irradiation and particle retention, the applicability on the industrial scale is ensured. The reactor which succeeds without a shaft seal permits particularly robust production with respect to sterile technique with avoidance of cleaning and cleaning validation required when the reactor is constructed as a single-use reactor.

In the highly regulated production of pharmaceuticals, a large expenditure in terms of time, equipment and personnel is apportioned to the provision of cleaned and sterilized bioreactors. In order to avoid cross-contamination reliably in a product change in a multipurpose plant or between two product batches, apart from the cleaning, a very complex cleaning validation is required which may need to be repeated in the event of a process adaptation. This applies not only to upstream processing, USP, that is to say the production of biological products in fermenters, but also to downstream processing, DSP, that is to say purification of the fermentation products. In USP and DSP, use is frequently made of kettles as agitator and reaction systems. Especially in the case of fermentation, an aseptic environment is essential for successful culturing. For the sterilization of batch or fed-batch fermenters, generally the SEP technique is used. In order in the case of continuous process procedure to ensure sufficient long-term sterility, the autoclave technique is also used, which however, requires laborious transport of the reactors to the autoclave and is only usable with comparatively small reactor scales. The risk of contamination during fermentation is particularly critical during sampling and at moving stirrer shafts. The latter are generally equipped with complex sealing systems (e.g.: sliding-ring seals). Technologies which succeed without such penetration of the fermentation casing are preferred because of their greater process robustness.
The downtime of the reactors necessitated by the preparation procedures can be, in particular in the case of short use periods and frequent change of product, of the order of magnitude of reactor availability. The affected steps in the USP of biotechnological production are the process steps of media production and fermentation, and in the DSP, solubilization, freezing, thawing, pH adjustment, precipitation, crystallization, buffer exchange and virus inactivation.
For carrying out the reactions in the USP and DSP, frequently a plurality of reaction conditions must be met simultaneously. For instance, fermentation, for example, in addition to oxygen supply and CO2 removal, requires gentle suspension of the cells, rapid mixing of the media and neutralizing agents for avoidance of overconcentration and also heating of the reaction liquid. Particle retention can also be required, e.g. for the use of perfusion strategies.
In the case of precipitation and crystallization, rapid addition of the precipitant, efficient temperature control and gentle holding of the particles formed in suspension are of particular importance.
Generally, in all process steps of biotechnological production, shallow temperature gradients are required in order not to damage the products. This condition, especially in freezing and thawing processes, leads to considerably increased process times with increasing reactor scale, since no mixing elements can be used in these steps. Heat transport into the reaction medium is limited by the thermal conductivity of the ice layer and also by free convection in the liquid. Long process times, however, can lead to considerable product losses in the presence of proteolytic activity.
Gentle sterilization and virus inactivation of starting materials and product solutions can be achieved by UVC irradiation at a wavelength of 254 nm. The radiation damages the DNA and RNA which lie at the absorption maximum of the viruses and microorganisms and prevents thereby their multiplication, whereas the proteins which are situated in the absorption minimum of the UVC radiation are very substantially retained. A great problem is the depth of penetration of the UVC radiation, which is frequently restricted to only a few tenths of a millimeter in biological media. This makes efficient replacement of the film in the active irradiation zone necessary in order firstly to irradiate all viruses with the required radiation dose and secondly to minimize the radiation load of the products.
The requirement of a constantly renewed boundary layer is also posed in the case of filtration, in order to counteract the development of covering layers which limit the transmembrane flow.
All process engineering steps of mass transport and heat transport, particle separation, UV irradiation and the addition or distribution of solids or additives or gases requires sufficient agitation of the reaction medium. This agitation is ensured, in the pharmaceutical industry, in the stainless steel reactors customarily used there, by means of appropriately dimensioned agitators or by sparging.
Membrane gas introduction is used for gentle oxygen supply of cell cultures. As membranes, gas-permeable silicone tubes are wound onto a cylindrical membrane stator which receive flow from a radially-transporting anchor agitator [WO 2005/111192 A1]. A more than doubling of the exchange area and thereby a significant increase in mass transport can be achieved by paralleling the membrane stators.
Other membrane gas-introduction systems [WO 85/02195 and DE 10 2004 029 709 B4 and DE3428758], in the gas introduction, set up agitators or baskets which are covered with membrane tubes and are moved in a pendulum-like manner in the fermentation solution, or membrane stacks [U.S. Pat. No. 6,708,957 B2], which are swung in the fermentation solution. These membrane gas-introduction systems, however, are distinguished in that they can only be converted to an industrially relevant scale with limitations.
In order to meet the demand for a rapid and flexible charging of the production plant while maintaining maximum cleanliness and sterility, designs for single-use reactors are the subject of constantly growing interest on the market.
Single-use technologies for filtration have long been known. Recently, a single-use technology has also become available on the market for UVC treatment [WO02/038191 WO02/0385502, EP1464342]. Designs for single-use heat exchangers are only available for small scales [EP1464342]. All technologies are operated in continuous flow, so that in addition to a reservoir vessel, the use of pumps and lines is necessary for which cleaning and sanitation plans still need to be provided as before.
There currently exist various commercially available mixing systems which operate on the basis of a plastic bag—single-use technology. These include systems [Hyclone Laboratories, Inc. (http://www.hyclone.com)] which are equipped with blade or magnetic stirrers or circulation pump elements. The systems are available up to a volume of 200 L. [Sartorius AG (http://www.sartorius.de)] offers a single-use system which operates up to a volume of 500 L using a free-floating single-use magnetic stirrer which has no contact with the single-use plastic bag and therefore also no material wear. Single-use mixing systems up to a volume of 10 liters are available at [ATMI, Inc (http://www.atmi-lifesciences.com)]. In this system the material to be mixed is charged into a single-use bag and mixed under rotation. For larger volumes up to 200 L [ATMI, Inc.] offers a single-use bag stirring system which is distinguished in that the stirring element is invaginated into the bag. Mixing in this case is not achieved by a rotary motion around a fixed axis but by a stirring-tilting motion.
In [EP 1 462 155 A1], use is made of a single-use vessel for mixing and dispersing materials by means of a magnetic stirrer which is situated within a protective cage in order to prevent damage to the plastic bag. The product-contact region of the magnetic stirrer unit in this case likewise consists of single-use components.
[EP 1 512 458 A1] demonstrates a solution in which inflatable plastic pillows are integrated in the external or internal region of a single-use bag system. These pillows are alternately pressurized and depressurized again. This induces liquid movements which lead to intensification of mixing and suspension in the vessel.
There are a multiplicity of patents for the use of single-use technology in the fermentation technique sector. In these, in most systems mixing and oxygen supply are achieved via sparging, without further mixing systems being provided [U.S. Pat. No. 5,565,015, WO 98/13469, U.S. Pat. No. 6,432,698 B1, WO 2005/049785 A1, EP 1 602 715 A2, WO 2005/080544 A2]. If a higher oxygen demand is necessary for the culture which cannot be achieved alone via sparging, the sparging can be combined with a dispersing mixing system [WO 2005/104706 A2, WO 2005/108546 A2, WO 2005/118771 A2] or can be overlapped by pumped circulation [WO 2005/067498 A2]. The maximum process volume of a sparged unit is currently up to 1000 liters. In systems having conventional agitators, but which can also be designed as single-use systems [WO 2005/104706 A2, WO 2005/108546 A2], process volumes of up to 10 000 L are achieved.
In the case of sparging, foaming problems can make the use, and the subsequent complex removal, of antifoams necessary in the DSP. The cell stress on bubble rise, in the bursting of the gas bubbles at the surface, and in particular in the foamed destruction, is problematic in cell culture systems, since the cells can be permanently damaged by the resultant high shear forces which are introduced. This applies all the more when sparging is combined with a dispersing agitating system, that is to say an agitating system comminuting the gas bubbles. The damaged cells release proteins, the removal of which can lead to considerable product losses during workup. To maintain acceptable cell vitalities, the oxygen input into the abovementioned bioreactors and therefore also the cell density which is achievable must be restricted. The restricted cell density ultimately reduces the space-time yield of the fermenters and the capacity of the total plant. Since a precondition for reliable upscaling in most cases is not considered technically as met, in the sparged single-use reactors, the volume enlargement must be achieved by complex paralleling of the systems. If the fermenters are operated as proposed using standard agitating systems, although the volume which can be processed increases into the range of the permanently installed plants, the risk of contamination can only be managed with comparable technical expenditure, for example by the use of damped sliding-ring seals. The great technical complexity and expenditure on personnel of such installations, however, largely emphasizes the advantages of the single-use concept.
Other single-use systems provide the necessary gas-introduction rate of the culture by means of membrane or surface gas introduction. In this case the necessary exchange area for gas transport is provided either via a membrane permeable to the gases to be transferred, or via an open boundary area to a gas space. Since no direct gas introduction to the cell culture media proceeds, the particle stress in these reactors may be categorized as low.
[U.S. Pat. No. 5,057,429] describes a system in which an inner semipermeable flat bag which is filled with cell suspension is surrounded by a further bag which is filled with nutrient solution and enriched with oxygen. Nutrient transport and oxygen transport are intensified via a tilting motion of the bags. The maximum process volume of a unit is only a few liters. The oxygen input is considerably restricted by the low oxygen solubility in the charged medium and the comparatively low surface area of the membrane. Compared with standard membrane gas-introduction devices [WO 2005/111192 A1] having specific exchange areas in the order of magnitude of 30 m2/m3 in 100 L reactors, in this arrangement, only a maximum of 10% of this exchange area can be achieved. In both cases, the available exchange area, furthermore, decreases in proportion to the scale enlargement.
Other surface gas-introduction systems likewise operate with a flat bag which is clamped on a shaking apparatus. The bag is only partially filled so that a free surface having a gas space lying thereabove is formed. By means of a seesawing motion or an eccentric rotary motion, the culture medium is mixed, the nutrients which are fed are distributed, cell sedimentation is prevented and the surface is agitated [U.S. Pat. No. 6,190,913 B1, WO 00/66706, U.S. Pat. No. 6,544,788 B2]. In this technology the culture is supplied with oxygen via the free surface. The motion is continuously adapted in such a manner that the flow is gentle and the cells are not exposed to strong shear. The maximum process volume of a unit is currently 580 liters. Although this technology provides a gentle gas-introduction mechanism, it is restricted in conversion to an industrial scale. The height of the bag must be kept approximately constant so that an increase in volume at constant surface area to volume ratio can only be achieved in the two horizontal spatial directions. Upscaling can therefore only be achieved via technically complex paralleling.
The technologies available on the market make use, for freezing, of large stainless steel reactors which are supplied with cooling liquids, or small flat plastic bags which are frozen in a secondary manner via heat-conducting surfaces or by means of convective cold air. In both cases there is no possibility of agitating the product during the freezing process, which considerably lengthens the cooling and freezing processes. The metal vessels are expensive and require large storage areas in the temporary storage. Thawing is lengthy, since the liquid motion between ice block and container wall proceeds only via free convection, comparably to that in freezing. For thawing the plastic bags, these are cut open in the frozen state and subsequently charged into a stirred reactor. The procedure of cutting them open is labor-consuming and contributes to fouling of the working environment. The thawing process is time-intensive, because the ice blocks which float on the surface are hardly reached by the hydrodynamics prevailing in the reactor. Product losses in the course of the long thawing phases are therefore unavoidable.
In the employment of all of the reactors listed here, considerable losses must be accepted in performance and upscalability. In many cases, without sufficient scalability, apart from the lack of performance, an economic benefit cannot be guaranteed. Scaleup here can only be achieved at the cost of increasing complexity and decreasing the economic benefit, such as, for example, by paralleling a plurality of reactors or by the additional use of technically complex solutions (for example sliding-ring seals built into the plastic bags).
A reactor which can be scaled up to the industrial scale of 1 m3-10 m3, guarantees a very high level of sterility comparable to autoclaving by avoiding shaft seals and the problems of cleaning, permits simultaneously intense and gentle liquid motion and can be installed with low expenditure on equipment and personnel, is therefore a clear gap in the currently available range of technologies.
It was an object of the present invention to produce a reactor, in particular for pharmaceutical applications, which, even on large reactor scales, has very good reaction properties for carrying out biological, biochemical and/or chemical reactions with respect to mixing, distribution, suspension, solubilization, mass transport and heat transport, filtration and irradiation, or combinations thereof, and is preferably simple in handling, meets the high requirements of the pharmaceutical industry with respect to cleaning and sterility and contributes to increasing process robustness and to increasing the space-time yield.


A data processing method comprises maintaining a source code repository, checking out a component from the source code repository, checking in a modified version of the component to the source code repository, identifying the changes between the modified version of the component and the original component, applying one or more pattern matching techniques to the identified changes, storing the output of the pattern matching techniques, and displaying the output.

1. Technical Field
This invention relates to a data processing method and to a data processing system. The method and system handle computer source code that is stored in a source code repository.
2. Description of the Related Art
In the field of source code creation, there exist a number of tools that are arranged to carry out analysis of the changes made to a product's source code between two or more levels. These typically require third party software to analyse two or more complete levels of code retrospectively. This is then used by project management to discover areas of intense change and used to focus effort during the design and development phase of subsequent product levels.
The drawbacks of this solution are that this information is gathered retrospectively and requires specific tooling and possibly large amounts of post-processing. This tooling may be unavailable to developers and testers that are actually working on the software product. If this kind of information were gathered cumulatively and at a lower level (i.e. visible to the developers and testers making and verifying the code changes) it could be used to focus the teams involved much earlier in the release cycle than current methods, ultimately resulting in lower development costs and greater product quality.

International Business Machines Corporation


Neural responses to a repeated stimulus typically diminish, an effect known as repetition suppression. When a single visual stimulus (e.g., letter of the alphabet, word, object, face) is serially flashed in different locations of a display, several stimuli appear to be present simultaneously due to an effect known as persistence of vision. Normal human observers' estimates of how many stimuli they perceived at any instant of time are significantly lower when the same stimulus is flashed repeatedly than when a different stimulus is used for each flash. This is a result of the brain's diminishing response (repetition suppression) to the repeated stimuli. The present invention generally relates to methods for assessing the normality of neural performance, particularly as relates to the integrity of cortical inhibition, visual persistence, proliferation effect, and repetition suppression. Deficits in repetition suppression serve as early and confirmatory measures of cognitive disorders such as schizophrenia.

How the brain represents duration remains an unsolved problem (Eagleman et al., 2005). It is clear that physical time does not have a direct mapping onto perceived time—instead, subjective duration judgments are surprisingly prone to distortions (Eagleman, 2008; Kanai et al, 2006; Morrone et al., 2005; Nakajima et al., 1992; Yarrow et al., 2001), such that two stimuli of identical duration can be perceived to last different amounts of time. For example, observers watching a repeated stimulus erroneously report that the first presentation (Kanai and Watanabe, 2006; Pariyadath and Eagleman, 2007; Rose and Summers, 1995) and any 'oddball' presentation (Pariyadath and Eagleman, 2007; Tse et al., 2004; Ulrich et al., 2006) appear longer in duration than the other presentations.
Although these duration illusions were originally suggested to be caused by increases in attention (Rose and Summers, 1995; Tse et al., 2004), it has been previously shown that the emotional salience of an oddball presentation has no effect on the illusion (Pariyadath and Eagleman, 2007), suggesting that the effect has more to do with the stimulus predictability than the amount of attentional deployment.
In flicker fusion experiments, a light is rapidly turned on and off: at a low frequency, flicker is perceived, while at a high frequency, the light appears to be steady. The frequency at which perception switches from flicker to a steady light is called the critical flicker fusion threshold (CFFT). CFFT experiments always consist of a single stimulus (the light) presented repeatedly. There are subjective duration differences when viewing familiar versus novel stimuli, thus, the inventors discovered that the CFFT would change if the rapid stimulus was made novel each time it appeared.
The perceived duration of novel and repeated stimuli map on to measured neural responses to the same (Grill-Spector et al., 2006). Normal human brains show diminishing responses to stimuli that are repeated over and over. This effect is known as repetition suppression (RS). In humans, these differential responses to familiar and novel stimuli are seen using electroencephalography (Grill-Spector et al., 2006), functional magnetic resonance imaging (Henson and Rugg, 2001), positron emission tomography (Buckner et al., 1995) and magnetoencephalography (Ishai et al., 2006). In non-human primates, the same phenomenon is observed by measuring the firing rates of individual neurons in higher cortical areas (Tahy et al., 1993; Rainer and Miller, 2000).
In some disorders, such as schizophrenia, RS is impaired, as evidenced by an impaired pre-pulse inhibition of the startle response (Hong et al., 2007), impaired mismatch negativity (Light and Braff, 2005), and abnormal processing of oddball stimuli (Kiehl and Liddle, 2001). Schizophrenic patients also have a lower sensitivity for detecting flicker (Black et al., 1975; Slaghuis and Bishop, 2001), which indicates that repeatedly flashed stimuli, which diminish in perceived duration in a normal brain, seem to last longer to a schizophrenic brain (Pariyadath and Eagleman, 2007). Collectively, these findings paint a picture of reduced or absent RS in schizophrenic patients. That is, to a schizophrenic brain, certain types of repeated stimuli will continue to appear novel. Presumably this reflects a deficit in cortical inhibition, which normally functions to provide RS (Daskalakis et al., 2002a; Daskalakis et al., 2002b). Further, data indicate that damage to the brain compromises performance on simple timing tasks. Therefore, measures of time perception, which are currently missing from the clinical landscape, are well-suited to provide a rapid and inexpensive way to screen for and rapidly identify traumatic brain injury (TBI). Currently used measures to highlight subtle brain damage (such as memory or cognition batteries) take a good deal of time and expertise to administer, rendering them ineffectual on the field. By contrast, simple timing tasks have the potential to highlight damage quickly and with no human administrator.
The measure of repetition suppression and visual persistence is a powerful diagnostic tool which can be used in the study of cognitive disorders. However, despite the increased knowledge that has been gained in recent years about the factors influencing repetition suppression, the basic measuring methodology has remained essentially unchanged. There is currently no method other than that disclosed here that allows inexpensive and rapid measurement of repetition suppression. Instead, all currently available methods use the technologies referred to in the studies above, namely, electroencephalography (Grill-Spector et al., 2006), functional magnetic resonance imaging (Henson and Rugg, 2001), positron emission tomography (Buckner et al., 1995) and magnetoencephalography (Ishai et al., 2006). These methods are uniformly expensive, time intensive, cause physical discomfort, necessitate training and expertise in administering the test, and require substantial data analysis. Therefore, there would be substantial interest in computer software or a physical device that could instantly and inexpensively yield an accurate measure of visual persistence and/or repetition suppression in human observers.

Device and method for rapid measurement of repetition suppression in the brain


A manual pipette including user controllable latch and trigger mechanisms for releasably locking the plunger of the pipette in a "home" position ready for immersion of the pipette tip in a fluid to be drawn into the tip and further including a user controllable velocity governor for regulating the rate of plunger return from the "home" position to a first or upper stop position in drawing the fluid into the tip.

The present invention relates to manual pipettes and more particularly to an improved manual pipette including a velocity governor, "home" position latch and trigger release.
Certain commercially available single channel manual pipettes are illustrated and described in U.S. Pat. Nos. 3,827,305 and 4,909,991 by way of example. Each such pipette includes an elongated hand holdable pipette body housing an upwardly spring biased plunger unit. The plunger unit is supported for axial movement in the pipette body between a first or upper stop position in which an end portion of the plunger extends from an upper end of the pipette body. A pipette user grips the pipette body with his or her thumb over the exposed end portion of the plunger. Downward thumb action on the plunger moves the plunger downward from its upper stop position against the upward bias of a return spring to a second or lower stop position at which all fluid is expelled from a tip secured to the pipette. Between the upper and lower stop positions is a "home" position. The "home" position is defined by a "soft" stop.
In the commercially available pipettes described in the foregoing patents, the "soft" stop is defined by a second relatively stiff spring mechanism within the pipette body which is activated when the plunger unit reaches the "home" position. As the pipette user depresses the plunger unit by pressing downwardly with his thumb on the exposed end of the plunger, he can "feel" the activation of the second spring assembly opposing further downward movement of the plunger unit. U.S. Pat. No. 4,041,764, describes a magnetic detent which is engaged between an upper stop and a "home" position for a pipette piston and is disengaged by the pipette user exerting an increased axial force on a push button when it is desired to move the piston beyond the "home" position against the force of a return spring. German patent applications 239 539 A1 and 239 540 A1 describe pipettes with magnetic detents at lower stops which are overcome and disengaged by action of a return spring. In all such pipettes, the pipette user is required to continuously apply a steady downward force with his thumb to maintain the pipette plunger in its "home" position ready for emersion of a tip of the pipette into a fluid to be drawn into the tip by controlled upward movement of the plunger from the "home" position to the upper stop position.
Most commercially available multi-channel manual pipettes function in substantially the same manner as the single channel manual pipettes except that they contain multiple liquid ends each having a separate piston driven in unison from a common spring biased plunger unit. Other commercially available multi-channel manual pipettes such as the Costar Octapette and 12-Pette multichannel pipettes comprise a pistol grip structure for hand gripping by a user with his forefinger extending forward to engage and wrap partially around a spring biased actuator. In the Octapette, rearward movement of the spring biased actuator is translated into a vertical movement of a plunger unit common to the pistons in the liquid ends of the multi-channel pipette. In both types of multi-channel manual pipettes, the "home" position for the plunger unit is defined by a "soft" stop as in the previously described single channel manual pipettes and a steady force on the actuator is required to maintain the plunger unit at a "home" position.
With such conventional manual pipettes, in order obtain repeatability of operation, it is mandatory that the user return the plunger unit to its "home" position at start of each pipette operation and hold the pipette in "home" position while he immerses the tip in the fluid to be drawn into the pipette. He must then manually control the rate of return of the plunger unit to the first or upper stop position in a repeatable manner for each pipette operation in order that the same desired volume of fluid will be drawn into the pipette tips during each repeated operation. This places substantial physical and mental strain upon the pipette user over the course of a series of pipette operations wherein repeatability of operation is essential. In extreme cases the physical hand and wrist strain associated with extensive and prolonged manual pipette operation can contribute to or produce carpel tunnel syndrome.
While a pipette having a controlled rate of return has previously been developed for the assignee of the present invention and described in U.S. Pat. No. 4,763,535 and while a pipette having an attenuated rate of upward piston movement as it leaves a "home" position is described in German Offenlegungsschrift DE 39 03 241A1, there remains a substantial need for an improved manual pipette which is simple in design and operation and which does not present either a physical or mental strain to a pipette user to maintain the pipette in its "home" position and manually control the rate of plunger return to ensure repeatability of pipette operation. The present invention satisfies that need.

Manual pipette with plunger velocity governor, home position latch and trigger release


A lift assembly including an article to be lifted between a lowered position and a raised position, a flexible drive element coupled to the article and defining a longitudinal axis, a power mechanism coupled to the flexible drive element, a drum powered by the power mechanism and dimensioned to facilitate winding of the flexible drive element onto the drum, and a cable keeper providing a force on the flexible drive element to bias the flexible drive element toward the drum.

Performance venues such as theaters, arenas, concert halls, auditoriums, schools, clubs, convention centers, and television studios can employ battens or trusses to suspend, elevate, and/or lower lighting, scenery, draperies, and other equipment that can be moved relative to a stage or floor.
Conventional lift systems may be configured such that a pulley, or loft block, mechanism is attached directly to an overhead building support. As a result, an undesired amount of horizontal stress can be placed on the overhead building supports to which the system and associated load are attached.
Ropes or cables utilized to raise and/or lower a batten or other load may be wound about and unwound from a drum connected to a lift system motor. In conventional lift systems, the cables may rub unevenly against adjacent cables as they are being wound about and unwound from the drum. Such uneven rubbing can cause friction that may increase the rate at which the cables, drum, and other components need to be serviced and/or replaced. In addition, such friction can cause increased noise that may be undesirable in certain performance environments.
Some conventional drums can have a size and/or coil cables about the drums such that a large space is needed in which to locate the drum in or about the lift system. In "yo-yo" type drums and "pile" type drums, cables coil about the drum vertically on top of themselves. For example, in a "pile" type drum, after the cable has wound completely across the face of the drum, it is forced up to a second layer at a flange on the side of the drum. The cable then winds back across the drum in the opposite direction. In order to advance across the drum, the cable must cross over two cable "notches" of the previous coil. Such "cross-over" subjects a cable to abrasion, crushing, and pinching as it is pushed over the two cable notches across the crown of the first cable layer. Such stress can cause erratic motion of the cables as they are wound up onto the drum and/or unwound from the drum. Such vertically stacked coils of cables in conventional drums contribute to the need for increased torque to wind and unwind cables on those drums.
Conventional lift systems can include a cable management system in which electrical wires in a cable are stacked in layers back and forth on top of each other. The wires can fold back and forth periodically on themselves in a "scissoring" or "switchback" fashion, for example, every few feet. One risk of folding wires back onto themselves repeatedly is that they can be undesirably pinched, and can become worn over time.
In some conventional cable management systems, the electrical wire cable is collected in a tray positioned on top of a batten as the batten is raised. Such a tray may be referred to as a "flip flop" tray, since a portion of the electrical wire cable can be "flipped" in one direction and then "flopped" back onto itself in the opposite direction. A disadvantage of allowing such wire cables to collect in a stacked fashion on top of a batten, particularly on one end of the batten, is that the collected cables can cause the batten to be top heavy, which may cause the batten to become unbalanced and undesirably alter the orientation of the batten and/or articles attached to the batten.
In some lift systems, cables coiled about a drum can lose tension, for example, from becoming disconnected from a batten and/or article being raised and/or lowered, or the batten or article striking an object in its path. As a result of slack tension on the cables, the cables may need to be retained in position about the drum during such an event.
Lift systems often include a braking mechanism 118 to stop movement of the cables and article attached to the cables, for example, in the event of loss of power to the lift system motor or other reason the article begins to fall out of control of the lift system. Some braking mechanism 118s can be less than totally reliable, requiring redundant braking systems, and can be noisy and tend to wear out quickly.


The present invention teaches a maternity and nursing bra incorporating a one-handed fastening method that inherently allows for a stronger cup support and variable adjustment of cup size. It is accomplished by affixing parts of a fastener to the inside of an inner cup (17) to an inner band (15). Also incorporated into the inside of the inner cup (17) is an optional use nursing pad pocket (18). The bra's variable strap width adjusting band (12) and the relocatable shoulder straps (10) enables the bra to be worn with a variety of outer garment styles.

1. Field of Invention
This invention relates to maternity and nursing bras specifically to fastening and wearing means.
2. Description of Prior Art
Heretofore, maternity and nursing bras did not allow for discreet nursing of a child due to the location of the devices used to expose the nipples or to the hinderance of those devices. A two-handed operation was required of the woman who normally only had one hand available while the other hand supported the baby. Also preventing discreet nursing was the lack of support for nursing pads which often resulted in those pads falling to the floor upon release of the breast cup. Moreover, many previous types of nursing bras did not easily adjust to changes in breast size and often necessitated the need for a different sized nursing bra after the breasts adjusted to the infant's exact demand. As also has been the case in nursing, the breasts themselves may vary in size for an extended period of time especially when the child shows a preference for one breast over another. Lastly, the user was limited in the type of outer garments to wear because the previous maternity and nursing bras did not provide any means in which to alter the configuration of the supporting straps.
U.S. Pat. No. 4,640,287 issued to Anderson et al on Feb. 3, 1987 discloses an easy fastening means located longitudinally on the shoulder strap but with no variation in placement of shoulder straps nor adjustment in cup size.
U.S. Pat. No. 4,633,876 issued to Scullin on Jan. 6, 1987 shows a "foldover"panel that employs no fastening means but requires some dexterity and, therefore, length of time to expose the entire areola for comfortable nursing of an infant.
U.S. Pat. No. 4,390,024 issued to Williams on Jun. 28, 1983 makes use of a multiple adjustable means located again on the shoulder strap but with no variation of said strap.
U.S. Pat. No. 4,222,387 issued to Tetu on Sept. 16, 1980 uses a detachable securing means along the entire periphery of its cup for this prosthesis bra. To re-attach quickly in order to be discreet cannot be done should this design be incorporated into a nursing bra.
U.S. Pat. No. 3,939,845 issued to Guidoni on Feb. 24, 1976 has patented a brassiere with ties for adjustment of height, width and depth of each pouch or cup as well as lateral ties to position brassiere with respect to shoulders. However, the design does not provide overall support of breasts that is needed for lactating women.
U.S. Pat. No. 2,925,816 issued to Rosenthal on Feb. 23, 1960 shows a two-handed operation for refastening to the hook with no variation in strap placement.
U.S. Pat. No. 2,666,919 issued to Spangard on Jan. 26, 1954 shows an easily unfastened bra flap using a quick action slide fastener but not so easily refastened especially with larger breast sizes.
U.S. Pat. No. 2,585,338 issued to Meares on Feb. 12, 1952 consists of a bust supporter which has pockets for removable drip pads located inwardly on the main portion of the cup. These pockers do not secure the pad and, therefore, the pads tend to fall out of the bra.
As clearly seen in such prior art, most maternity brassieres designed with detachable means either at the front of the shoulder straps or in the center front of the brassiere have failed in providing an expedient, discreet manner in which to open and close cups for nursing and have failed more so in providing a well-fitting bra during all phases of the wearing due to the normal fluctuations in breast size.

Maternity and nursing brassiere with strap variations


A cardboard carton is constructed that is particularly useful for holding a stack of paper so that individual cut sheets from the stack may be readily removed. The carton bottom has an open top and substantially open ends and closed sides, while the carton top has a Z-fold top panel, and one or more tear strips between adhesive connecting the carton top to the carton bottom and the main part of the carton top. The carton bottom, with its open top facing downwardly, is either moved over a stack of paper, or formed over the stack of paper. Then it is rotated 180.degree. about a horizontal axis (as by pivoting a U-shaped continuous conveyor about a horizontal axis), and conveyed to a station where it is moved with respect to a carton top so that the open bottom of the carton top goes over the carton bottom, and then is glued in place. Two opposite flaps on the carton lid may be glued to the bottom surface of the carton bottom panel to provide a lifting space beneath the carton. The side and end flaps of the carton bottom may be connected to the bottom panel by perforations to allow ready detachment.

Users of high speed page printers, both of laser and conventional type, and users of high speed office copiers, spend a substantial amount of time unwrapping reams of wrapped cut singles before placing them in a printer or photocopier. There are further disadvantages associated with ream wrapping: ream wrapping the paper requires ream wrap machines which have a substantial capital cost; the paper wrap itself has a substantial cost and may not be readily recyclable in offices which merely recycle conventional white paper; and there is a power cost for wrapping the reams.
Users of cut single sheets also wish to be able to quickly lift out a handful of sheets from a carton to place in a printing or photocopying machine, and many users desire a reusable carton made of recyclable material, preferably of only one type (that is not plastic bands or plastic wraps), but at the same time need to protect the cut sheets from edge damage, dust, dirt and moisture penetration.
According to the present invention carton components which fulfill these desired objectives are provided. Also, according to the present invention a method of packaging a stack of paper in a cardboard carton is provided, as well as apparatus for practicing that method.
According to a first aspect of the present invention, a combination of cut paper sheets packaged in a cardboard carton is provided. The combination comprises: At least one thousand cut unwrapped sheets of paper of the same length and width, provided in a stack having a stack height. A cardboard carton packaging the sheets and allowing ready dispensing therefrom, the carton comprising: first and second channel shaped side walls, each formed by a base and a pair of legs substantially perpendicular to the base, the legs of the channels facing each other, and the channels each having a first height greater than the stack height; a bottom panel; first and second end flaps having a second height less than half of the first height; the bases of the channel shaped sides and the end flaps integral with the bottom panel; and fastener means for holding the end flaps to the channel legs to form a carton with an open top and primarily open ends and substantially closed sides.
The fastener means for holding the end flaps to the channel legs preferably comprise adhesive disposed on the inside faces of the side flaps. A user of the cut paper sheets may reach into the primarily open ends of the cardboard carton and remove any desired number of sheets, while the carton protects the edges of the sheets, and is reusable, and is substantially entirely of recyclable material. The bases of the channel shaped sides and end flaps may be connected to the bottom panel by lines of weakness (e.g. perforations).
While the carton as described above may be packaged merely by providing plastic straps around the side walls, or a plastic wrap around the entire carton, preferably it comprises a carton bottom, and a cardboard carton lid is associated with the cardboard carton bottom and cut sheets. An exemplary cardboard carton lid may comprise the following elements: Closed first through fourth sides. A Z-fold closure top. An open bottom. And panel extensions of at least two of the sides, each extension comprising first and second parallel lines of weakness and a removable strip between them, and a bottom fastening section, below the lines of weakness, having sufficient dimension to be securely attached to a carton bottom. A pull tab may be associated with the removable strip, and either two opposite extensions, or four extensions, may be provided.
While the carton lid and carton bottom combination as described above is particularly suited for packaging of cut paper sheets, it may also be utilized to package wrapped reams, or continuous form paper, even though some of the advantages of the invention are thereby compromised.
The invention also relates to a method of packaging a stack of paper in a cardboard carton having a bottom with an open top. The method comprises the steps of automatically: (a) Providing the paper in a stack having a height at least as great as the depth of the carton bottom. (b) Providing the carton bottom over the stack of paper so that the open top of the carton bottom faces downwardly. (c) Rotating the carton bottom with paper stack therein, approximately 180.degree. about a horizontal axis so that the open top of the carton bottom faces upwardly. And (d) securing a covering on the carton bottom so that the paper is held within the carton bottom.
Step (b) may be practiced in one of two ways: by forming the cardboard carton bottom so that its top faces upwardly, automatically grasping an exterior portion of the carton, rotating the carton bottom 180.degree. about the horizontal axis, and pushing the carton bottom over the paper in the stack; or by placing a cardboard blank for construction of the cardboard carton bottom over the top of the paper in the stack, applying adhesive to selected portions of the blank, and deforming the blank so that it forms the carton bottom over the stack of paper, and is held in place by the adhesive.
Step (a) is preferably practiced by providing at least a thousand unwrapped cut sheets of paper. Step (d) is preferably practiced by placing a cardboard carton lid, having an open bottom, over the open top of the carton bottom, and securing the carton top to the carton bottom with adhesive and is further practiced by utilizing a carton top that has extending portions extending downwardly from the closed sides thereof, supplying glue to the extension portions, and then bending over the extension portions so that they engage and seal with the carton bottom, preferably the lowest surface of the carton bottom bottom panel, so as to provide a lifting space facilitating lifting of the carton.
The invention also comprises particular automatic apparatus for practicing the method as set forth above. The apparatus comprises the following elements: Means for providing a cardboard carton bottom over a stack of paper so that the open top of the carton bottom faces downwardly. Means for rotating the carton bottom with paper stacked therein approximately 180.degree. about a horizontal axis so that the open top of the carton bottom faces upwardly. And means for securing a covering on the carton bottom so that the paper is held within the carton bottom.
The means for rotating preferably comprises a substantially U-shaped continuous belt conveyor mounted for pivotal movement about a horizontal axis so that it can be pivoted from a first position in which a first leg of the U is horizontal and at the bottom, to a position in which the second leg of the U is horizontal and at the bottom. There also is preferably provided means for conveying the carton bottom with a stack of paper therein from the rotating means to the covering and securing means. The covering securing means may comprise means for moving a cardboard carton top having an open bottom with respect to the carton bottom having a stack of paper therein and an open top so that the carton top covers the carton bottom, and means for securing the carton top to the carton bottom. The means for providing a cardboard carton bottom over a stack of paper may comprise a vacuum gripper mounted for pivotal motion about a horizontal axis, and mounted for reciprocatory movement in a vertical dimension. A conveying means may be provided for conveying the carton bottom over a stack of paper from the vacuum gripper means to the rotating means. And, the means for providing the cardboard carton bottom over a stack of paper may comprise means for placing a blank cardboard carton bottom on the top of said stack of papers, and means for deforming the cardboard carton blank over the stack of papers so that the carton bottom is formed over the stack.
It is a primary object of the present invention to provide for the simple yet effective delivery of paper for users of high speed page printers and office copiers, particularly cut sheets. This and other objects of the invention will become clear from all inspection of the detailed description of the invention and from the appended claims.


An inventory verification device (“IVD”) provides automatic inventory verification and detection of inventory discrepancies. The IVD automatically verifies the quantity of items in a container based on weight and/or height measurements obtained for the items in the container using two or more sensors of the IVD. The IVD may also automatically updated tracked inventory of an item based on detected changes to the weight and/or height of the items in the container as a result of a worker adding items to the container or removing items from the container without the working providing confirmation for each addition and/or removal. The IVD autoatmically verifies whether correct items are stored in a container by performing feature matching of various characteristics for items imaged in the container against expected characteristics for items that should be stored in the container.

Inventory management may involve accurately tracking quantity, location, and/or other characteristics of stored items. Improper inventory management can lead to improper order fulfillment, delayed order fulfillment, and additional costs.
Inventory discrepancies may occur as a result of replenishing a first container containing a first item with one or more units of an incorrect second item. A customer order for the first item may then be incorrectly filled with one or more units of the second item from the first container. Also, time and resources may be wasted detecting and correcting the item misplacement.
Inventory discrepancies may also occur as a result of placing the first container in an incorrect storage location, and placing a different second container in an expected storage location of the first container. A customer order for the first item may then be incorrectly filled as a result of retrieving the second container with one or more other items instead of the first container because of the container misplacement. Here again, time and resources may be wasted detecting and correcting the container misplacement.
Inventory discrepancies may also result from improper tracking of item quantity. For instance, a quantity of a first item may not be decremented when one or more units of the first item are used to fulfill a customer order, or when one or more units of the first item are damaged, lost, stolen, misplaced, or are incorrectly counted to begin with. When a customer order for the first item is received, actual inventory of the first item may be less than the expected inventory which may lead to having an insufficient quantity on hand to fulfill a customer order.


A chain has pairs of inner sheets and pairs of outer sheets. Each sheet has two rings. An annular flange is formed on each ring. An inner surface of an opposite end to a free edge of each annular flange is rounded so as to form a recess. Each annular flange of the outer sheet is received in the recess of one inner sheet. A pin is inserted through the annular flanges of a pair of inner sheets and a pair of outer sheets. A head of the pin is received in the recess of the outer sheet. The other end of the pin is deformed so as to be received in the recess of the other outer sheet.

The present invention relates to a chain, and more particularly to a coupling portion of a chain.
Chain is widely used as chain transmission in bicycle or motorcycle. A conventional chain is shown in FIGS. 4 and 5 and comprises a plurality pairs of inner sheets I and a plurality pairs of outer sheets O alternatively coupled together. A pair of bushes B are coupled between every pair of inner sheets I. A roller R is rotatably provided on each bush B. A pin P passes each bush B and is fixed between each pair of outer sheets O. Both ends of each pin P extend beyond the outer sheets O. The ends of the pin P are disc shaped so that the sheets I and O are coupled together. The protruded ends of the pins P affect the shifting of the gears of the bicycle which has multispeeds.
The present invention has arisen to mitigate and/or obviate the afore-described disadvantages of the conventional chains.


Novel flavin-containing monooxygenase in substantially pure form is provided. Also disclosed are the cDNA and the reduced amino acid sequences, and fragments and derivatives thereof. The enzymes are useful in metabolism studies, in screening of compounds for biological or pharmacological activity, as well as serving as a bio-indicator of disease states or susceptibility to disease states.

The present invention relates to the drug screening, diagnostic, and synthesis uses of the first recombinant derived adult human liver flavin-containing monooxygenase (form 3), also referred to as adult human liver FMO (form 3) or HLFMO 3.
The mammalian flavin-containing monooxygenase (FMO, EC 22.214.171.124, Dimethylaniline N-oxidase) is a widely distributed enzyme that catalyzes the NADPH-dependent oxygenation of a wide variety of nucleophilic nitrogen-, sulfur-, and phosphorous-containing drugs, chemicals, and xenobiotics (Cashman, Chem. Res. Toxicol. 8:165-181 (1995); Ziegler, Enzymatic Basis of Detoxication 1:201-225 (1980); and Ziegler, Drug Metab. Rev. 6:1-32 (1988)). To dates, many of the investigations examining hepatic FMO have been performed with animal tissues, possibly because of the thermal instability of adult human liver FMO preparations. In contrast to adult human liver cytochromes P-450, almost nothing is known about the structure of adult human liver FMO. Adult human liver FMO has been designated FMO3 (Lawton et al., Arch. Biochem. Biophys. 308: 254-257 (1994)). A few studies with adult human liver microsomes have demonstrated FMO-like enzyme activity (Gold et al., Xenobiotica 3:179-189 (1973) Lemoine et al., Arch. Biochem. Biophys. 276:336-342 (1990); McManus et al., Drug Metab. Dispos. 15:256-261 (1987)) and immunoreactivity with the antibody against pig liver FMO1 (Lemoine et al., Arch. Biochem. Biophys. 276:336-342 (1990); Dannan et al., Mol. Pharmacol. 22:787-794 (1982)). Dimethylaniline N-oxygenation was observed in adult (Gold et al., Xenobiotica 3:179-189 (1973)) and fetal (Rane, Clin. Pharmacol. Ther. 15:32-38 (1973)) human liver microsome preparations. In contrast to dimethylaniline N-oxygenation, which was observed in both kidney and liver tissues, imipramine N-oxygenation was only observed in microsome preparations from human kidney, but not from human liver (Lemoine et al., Arch. Biochem. Biophys. 276:336-342 (1990)). The conclusion from these studies was that FMO was present in human liver tissue, albeit with low specific activity and possibly as multiple enzyme forms. This has been verified with the cloning of five forms of FMO cDNA from human liver cDNA libraries (Phillips et al., Chem. Biol. Interact. 96:17-32 (1995)).
In animals, FMO has been reported to be present as at least one pulmonary form (Williams et al., Biochem. Biophys. Res. Commun. 124:116-122 (1984); Tynes et al., Biochem. Biophys. Res. Commun. 126:1069-1075 (1985)) and as two or more hepatic forms (e.g., forms 1 and 3) (Yamada et al., Arch. Biochem. Biophys. 280:305-312 (1990); Ozols, J. Biol. Chem. 265:10289-10299 (1990)). It is more recently recognized that FMOs are present in multiple tissues and xe2x80x9chepaticxe2x80x9d and xe2x80x9cpulmonaryxe2x80x9d forms are misnomers. In rabbit liver, form 1 and 3 are only 55% identical to one another, but the amino acid sequence identity between hog liver FMO1 and rabbit liver FMO form 1 is approximately 87% (Ozols, Arch. Biochem. Biophys. 290:103-115 (1991)). Although studies are limited, forms 1 and 3 FMO apparently differ in many important properties including substrate specificity (Yamada et al., Arch. Biochem. Biophys. 280:305-312 (1990)), enzyme stability (Ozols, Arch. Biochem. Biophys. 290:103-115 (1991)) and other physical properties.
For example, hepatic form 1 FMO activity is stimulated by primary aliphatic alkylamines and form 1 FMO catalyzes the N-oxygenation of secondary and tertiary amines (Ziegler, Enzymatic Basis of Detoxication 1, 201-225 (1980)). In contrast, form 3 FMO apparently N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines (Yamada et al., Arch. Biochem. Biophys. 280:305-312. (1990)). Aliphatic primary amines are sequentially N-oxygenated by FMO3 to hydroxylamine and oximes. The pharmacological activity of these metabolities are largely unknown but if FMO3 catalyzes efficient oxime formation from endogenous amines, this could be important in cellular homeostasis. Abnormal amine metabolism by FMO3 could be important in numerous disease states that are associated with abnormal amine metabolism. Some aliphatic tertiary amines such as chlorpromazine are preferentially N-oxygenated by form 3 FMO (Yamada et al., Arch. Biochem. Biophys. 280:305-312 (1990)) but a detailed description of animal FMO3 activity has not been described.
FMO has been purified to homogeneity from a number of sources (Ziegler, Drug Metab. Rev. 19:1-32 (1988)) and it is the pig liver enzyme (FMO form I) which has been the subject of the most extensive studies. Using probes directed against the pig liver FMO and using a fetal human liver cDNA library, a cDNA encoding a FMO has been cloned (Dolphin et al., J. Biol. Chem. 266:12379-12385 (1991)). Thus, fetal human liver flavin-containing monooxygenase (FMO) shares approximately 86% identity with pig liver FMO and 87% identity with rabbit liver FMO form I deduced from the cDNA data (ibid.). Fetal human liver FMO has been designated form 1. Substrate specificity differences are apparent for hepatic form 1 and 3 FMOs from in vitro animal liver enzyme studies (Yamada et al., Arch. Biochem. Biophys. 280:305-312 (1990)), but almost nothing is known about the human liver enzymes.
A number of studies have shown that adult human liver microsomes are capable of tertiary amine N-oxygenation (Gold and Ziegler, Xenobiotica 3:179-189 (1973); McManus et al., Drug Metab. Dispos. 15:256-261 (1987); Lemoine et al., Arch. Biochem. Biophys. 276:336-342 (1990); Rane, Clin. Pharmacol. Ther. 15:32-38 (1973)) and thiobenzamide S-oxygenation (McManus et al., Drug Metab. Dispos. 15:256-261 (1987)).
Adult human liver FMO-dependent N- and S-oxygenation activity is quite thermally labile and activity is maximal at pH 8.4 (Gold and Ziegler, supra; McManus et al., supra; and Lemoine et al., supra, although considerable intersample variation has been observed. Most physical properties of animal FMOs are shared by human liver FMO forms although differences in substrate specificity have not been extensively examined. For example, human liver microsomes did not N-oxygenate imipramine even though imipramine was an excellent substrate for pig liver FMO form I (Lemoine et al., supra). Immunoquantitation of human liver FMO has relied on antibodies directed against animal FMOs. Thus, polyclonal antibodies prepared against pig liver FMO recognized a 60,000 Da human liver protein, although the immunoblot was characterized as very faint. Antisera raised against rat liver FMO recognized an adult human kidney protein, but did not recognize anything in the adult human liver (Lemoine et al., supra (1990)). This is another indication that multiple forms of FMO are present in the adult human liver and kidney.
For over 25 years, the literature has described a few people who, instead of N-oxygenating trimethylamine (TMA) to the polar, readily excreted trimethylamine N-oxide (TMANO), excreted large amounts of unmetabolized TMA in the urine and secreted the volatile and malodorous TMA in their breath, sweat and skin (Humbert, et al., Lancet i:770-771 (1970); Higgins et al., Biochem. Med. 6:392-396 (1972); Danks et al., N. Engl. J. Med. 25:962 (1976)). TMA smells like the essence of rotting fish and people who suffer from this apparent metabolic disorder have what is referred to as the xe2x80x9cfish-odor syndrome.xe2x80x9d In humans, trimethylaminuria is an autosomal recessive disorder involving deficient N-oxygenation of TMA (Al-Waiz et al., Br. J. Clin. Pharmacol. 25:664p-665p (1993); Ayesh, et al., Br. Med. J., 655-657 (1993); Ayesh and Smith, Pharmacol. Ther. 45:387-401 (1990)). Normally, over 95% of a dose of TMA from dietary sources or otherwise is converted to TMANO that is excreted in the urine. The ability to N-oxygenate TMA is apparently distributed polymorphically (at least in some Caucasian populations evaluated thus far) and people with xe2x80x9cfish-odor syndromexe2x80x9d are apparently homozygous for an allele that determines an individuals ability to carry out the N-oxygenation reaction (Ayesh et al., Br. J. Clin. Pharmacol. 25:664p-665p (1993). The molecular defect in trimethylaminuria has not yet been defined although it has been attributed to a deficiency in human FMO1 (Dolphin et al., J. Biol. Chem. 266:12379-12385 (1991); Dolphin et al., Biochem J. 287:261-267 (1992). It is now known, however, in contrast to what has been previously described (Dannan and Guengerich, Mol. Pharmacol. 22:787-794 (1982)), that human FMO1 is not expressed to a measurable extent in adult human liver and it is adult humans that have been associated with the disease. It is not likely that other monooxygenases form TMANO from TMA, based on existing studies (Gut and Conney, Drug Metab. Drug Interacts. 9:201-208 (1991) and the fact that TMA is a very good substrate for FMO from rat liver (Horori and Benoit, Biochem. Biophys. Res. Commun. 212:820-826 (1995). As described herein, cDNA-expressed human FMO3 is a good catalyst for the formation of TMANO from TMA in vitro. It is likely that human FMO3 is largely responsible for the N-oxygenation of TMA.
The deficiency of human FMO3 as an explanation for trimethylaminuria is probably more prevalent than previously realized (Treacy et al., J. Inher. Dis. 18:306-312 (1995) and the fish-odor syndrome is a major social handicap to patients who are usually anxious to obtain treatment. In addition to the psychosocial consequences of trimethylaminuria (i.e., anxiety, clinical depression, paranoia, suicidal personality and addiction to cigarettes, alcohol and drugs) on drug and endogenous amine metabolism as a result of altered or deficient human FMO3 activity (Chen and Aiello Am. J. Med. Genet. 45:335-339 (1993)), the possibly more important consequences of trimethylaminuria is that it may foretell about other more serious human diseases. For example if human FMO3 is involved in biogenic or other endogenous amine metabolism, a deficiency of human FMO3 may have profound consequences for a wide spectrum of diseases related to abnormal amine metabolism including cardiovascular disease and associated disorders, hypertension, and central nervous system diseases including but not limited to depression, stress, epilepsy, Huntington""s, Parkinson""s and Alzheimers disease and infectious diseases.
In adult human liver microsomes, in addition to FMO there are numerous other enzymes present including esterases and other monooxygenases. In some cases the other esterases and monooxygenases compete with the adult human liver FMO for substrate activity. For example, an esterase that converts a methyl ester to a carboxylic acid could make that compound unusable as a substrate for the FMO. Other monooxygenases present in the adult human liver could also compete with FMO for substrate activity. Microsomes also generate hydrogen peroxide and alkyl peroxide. Peroxide generated by microsomes could oxidize substrates of FMO such as sulfur, nitrogen, and phosphorous-containing chemicals. Therefore, the presence of such peroxides and other monooxygenases make it difficult to determine the true enzymatic activity and substrate specificity for adult human liver FMO. For this FMO to have any practical use in the research and industrial areas, it must be obtained in a form that is free of human liver microsomal monooxygenases and peroxides generated from these preparations.
The present invention provides adult human liver flavin-containing monooxygenase (form 3) in substantially pure form. The invention also includes mutants, variants, and fusion products of adult human liver flavin-containing monooxygenase (form 3). The invention also concerns a DNA sequence, and fragments and derivatives thereof, encoding adult human liver flavin-containing monooxygenase (form 3), and host cells involved in the expression of the adult human liver flavin-containing monooxygenase (form 3).
Another aspect of the invention includes methods for in vitro screening of compounds for biological or pharmacological activity. These methods include incubating a monooxygenase with the compound to detect the amount of oxygen consumed, the amount of NADPH consumed, or products formed.
A further aspect of the invention involves methods for detecting cancer in liver cells. This involves generating antibodies that react with the fetal human liver flavin-containing monooxygenase (form 1) and not FMO (form 3). Another method for detecting cancer in liver cells is the use of oligonucleotide probes that bind to the mRNA of the fetal human liver flavin-containing monooxygenase (form 1) and not FMO (form 3) gene. An additional method for detecting liver cancer uses the technique of PCR to amplify the cDNA of the fetal human liver flavin-containing monooxygenase (form 1) gene for hybridization with a probe.
Another aspect of the invention includes a method of selectively oxidizing a nucleophilic compound by incubating a monooxygenase with the nucleophilic compound.
An additional aspect of the invention involves a method of producing a nucleophilic compound with a center of chirality by incubating a monooxygenase with a substrate. This can be coupled in an asymmetric chemi-enzymatic synthesis of a chiral chemical or drug by reacting the resulting oxidized substrate with a strong base and an electiophilic compound.
Another aspect of the invention includes a method of assembling a native or active protein or peptide by incubating a monooxygenase capable of forming disulfides with an unfolded protein or peptide.
A further aspect of the invention involves a method of expressing a monooxygenase in a cDNA expression system to act as a catalyst for the renaturation of proteins or peptides by facilitating disulfide bond formation and protein folding.

DNA sequence encoding flavin-containing monooxygenase


A method of programming a memory unit having a plurality of dual cell core memory devices and at least one dual cell dynamic reference device. The memory unit is subjected to an erase configuration operation such that each cell of the core memory devices is in a blank state and such that a threshold voltage of the at least one dynamic reference device is less than a charged program level threshold voltage. Thereafter, the at least one dynamic reference and the core memory devices are programmed using a page programming routine.

The present invention relates generally to the field of non-volatile memory devices and, more particularly, to a method of improving dynamic reference tracking for a memory unit having, for example, a plurality of charge trapping dielectric flash memory devices.
A pervasive trend in modern integrated circuit manufacture is to increase the amount of data stored per unit area on an integrated circuit memory unit, such as a flash memory unit. Memory units often include a relatively large number of core memory devices (sometimes referred to as core memory cells). For instance, a conventional dual cell memory device, such as a charge trapping dielectric flash memory device, can store data in a xe2x80x9cdouble-bitxe2x80x9d arrangement. That is, one bit can be stored using a memory cell on a first xe2x80x9csidexe2x80x9d of the memory device and a second bit can be stored using a complimentary memory cell on a second xe2x80x9csidexe2x80x9d of the memory device.
The memory unit can also be provided with one or more dynamic reference memory devices having charge storing cells similar to the charge storing cells of the core memory devices. The dynamic reference devices assist in reading the core memory devices. More specifically, the dynamic references are used as indicators of the data level (e.g., charge storage) behavior of the core memory. The dynamic reference cells are programmed to store an amount of charge such that the dynamic reference has a certain threshold voltage. Over time, the charge amount stored by the dynamic reference cells and other factors contributing to the threshold voltage of the dynamic reference device may change. These factors cause a corresponding change in the threshold voltage of the dynamic reference device. The change in dynamic reference device threshold voltage can be used by a logic circuit associated with the memory unit to account for drift in threshold voltage of the core memory devices.
In the past, the dynamic reference devices have been programmed prior to programming of the core memory devices. More specifically, the dynamic references are initially programmed during an erase configuration operation. The erase configuration operation xe2x80x9csets upxe2x80x9d the core memory cells (e.g., places all core cells in a blank or erased state) for subsequent programming by a customer of the memory unit. As a result, the dynamic reference cells tend to age differently than the core cells. Also, the current loading when programming the dynamic references may not be the same as the current loading when programming the core cells. Since the dynamic references are programmed at a different time and under different conditions than the core cells, read margins of the dynamic reference devices versus the core memory devices may differ and read operation accuracy can suffer as a consequence. This is especially problematic over repeating program/erase (P/E) cycling of the memory unit.
As indicated, dynamic reference cells have conventionally been programmed during a erase configuration operation. Such an operation includes pre-programming core memory cells and the dynamic reference cells. Pre-programming of the cells can involve injecting a charge into charge storing regions of the cells. Thereafter, all of the programmed cells are erased. If any of the cells were over-erased, those over-erased cells can be soft-programmed such that each cell has an amount of charge corresponding to a predetermined blank state threshold voltage distribution. The erase configuration operation can conclude by programming the dynamic reference cells to store an appropriate amount of charge. At this point the memory unit is ready for use. For example, the core cells can be programmed. Programming the core cells can be carried out by a page program technique where groups of core cells (e.g., a selected number of core cells, such as about eight core cells) are sequentially programmed until all core cells to be programmed have been programmed. Following programming (e.g., in preparation for a read operation), the threshold voltages of the dynamic reference cells can be verified. If the threshold voltages have fallen below a specified value, the dynamic references can be refreshed. Refreshing the dynamic references may increase the above-mentioned difference in read margins between the dynamic references and core memory devices, especially over P/E cycling and/or aging where charge loss may occur in the various memory devices.
In view of the foregoing, there is a need in the art for improved dynamic reference device tracking with associated core memory devices of a flash memory unit.
According to one aspect of the invention, the invention is directed to a method of programming a memory unit having a plurality of dual cell core memory devices and at least one dual cell dynamic reference device. The method can include providing the memory unit, wherein the memory unit has been subjected to an erase configuration operation such that each cell of the core memory devices is in a blank state and wherein a threshold voltage of the at least one dynamic reference device is less than a charged program level threshold voltage; and programming the at least one dynamic reference and the core memory devices using a page programming routine.
According to another aspect of the invention, the invention is directed to a method of programming a memory unit having a plurality of dual cell core memory devices and at least one dual cell dynamic reference device. The method can include providing the memory unit, wherein the memory unit has been subjected to an erase configuration operation such that each cell of the core memory devices and of the at least one dynamic reference is in a blank state; pre-reading the at least one dynamic reference; and programming at least one cell of the at least one dynamic reference device and at least one cell of at least one core memory device with a program pulse.
According to yet another aspect of the invention, the invention is directed to a method of programming a memory unit having a plurality of dual cell core memory devices and at least one dual cell dynamic reference device. The method can include providing the memory unit, wherein the memory unit has been subjected to an erase configuration operation such that each cell of the core memory devices is in a blank state and wherein an amount of charge has been injected into at least one cell of the at least one dynamic reference device, the amount of charge establishing a threshold voltage of the dynamic reference device that falls between a blank program state and a charged program state; programming the at least one cell of the at least one dynamic reference device to the charged program state; and programming at least one cell of at least one core memory device to the charged program state.

Method of improving dynamic reference tracking for flash memory unit


It is disclosed a control node (40; 50) capable of deciding in which computing nodes to execute a plurality of subqueries of a real-time continuous query, and a method therefore. The plurality of subqueries are executed (210; 302) in two or more computing nodes and properties of at least one of: the one or more data centers comprising the computing nodes, execution of the plurality of subqueries, and the data streams, are monitored (212; 304). A subquery is selected, after which this is executed (214; 306) in an alternative computing node. Properties are monitored (214, 308) during this second execution, and if monitored properties from this execution indicate an improved performance, the subquery may be transferred (218; 310) to said alternative computing node. It is an advantage that real-time queries may be optimized, by determining in which computing node to execute what subqueries of a query for best performance.

In execution of a data query, optimization of the query is often an important component. Query optimization is well documented in relation to traditional relational database management systems (RDBMS). Such query optimization generally consists of parsing and optimization.
Parsing may verify that a structured query language (SQL) query is syntactically correct, that tables and query attributes exist, and that a user thereof has appropriate permissions. Parsing also translates the SQL query into a set of simpler query trees, wherein operators can be based on, for instance, relational algebra.
Optimization of a query may, via an optimizer, generate query trees which are equivalent and built bottom up. For each query tree generated, an optimizer may produce a query plan by selecting algorithms for each operator, estimate a cost of the plan and choose the plan having the lowest cost among plans considered.
Query optimization is equally important in real time data streaming management systems (DSMS). Ideally, latencies in actual worst case would be used in query optimization. However, such metrics are not easily measured in sufficiently short time range to be useful for a typical real time application.
Analytics applications may be composed of multiple parts for fulfilling a use case. In a situation in which an application depends on multiple data streams from different sources of a network, which data streams are to be considered, it is of relevance to deploy, run and compute selected parts of an analytics application at physical locations, for instance data centers, to achieve data co-locality and to instantiate a data stream management systems (DSMS) when/where required.
In a distributed cloud, this may imply launching virtual machines (VMs) running these analytics applications at certain locations, having adequate resources, and proper connectivity between other VMs of a single data center (DC), as well as VMs in other DCs without disrupting existing applications in any of the DCs.
It is pointed out that the term DC wherever used herein, represents any aggregate of computing nodes connected through a communication network which is physically located in a single location.
FIG. 1 presents DCs providing virtualized central processing units (CPUs), random access memory (RAM), network connectivity, storage memory. Two of the DCs (DC1, DC2) are situated at an edge of the network, whereas another (DC3) is situated at facilities of a DC provider.
DC1, DC2, DC3, and DCx, may comprise actual radio systems or network functions producing data such as network key performance indicators (KPIs), weather data.
Some real-time operations like real-time continuous queries may need to be executed over a distributed cloud of data producers. Each link between the different DCs may be associated with a specific latency cost.
Main computing capabilities may be located in a main DC where it can be assumed that computational resources are unlimited. Datacenters being located at an edge of the network, for example DC1 and DC2 in FIG. 1, may generally be constrained in terms of computational resources.
A challenge may be to determine where to instantiate a particular part of an analytics application to fulfil a real-time analytics use case. This may comprise to evaluate an impact on on-going simultaneous applications. This may also comprise to certify that conditions are met and potential latency costs are within boundaries to instantiate the VMs, connectivities and resource allocation, in order to fulfil any continuous query (CQ) requirements.
Patent document US20100030896 A1 relates to estimating worst case latencies for query optimization in distributed stream processing, when all nodes belong to one data stream management system (DSMS). This document is restricted as it focuses on latency only, estimates latencies for a worst case only, and only when all nodes belong to a single DSMS.
There is a need for an alternative solution being more applicable for determining how to distribute parts of a query for an optimal or best performance, addressing the issues as discussed above.

Method and device for deciding where to execute subqueries of an analytics continuous query


A reusable bag incorporating a foldable support structure, used for containment of item(s) for carrying by a person, comprising a bag made of a flexible, durable material removably attached to a pair of essentially U-shape, semi-rigid support members, that extend under opposite ends of the bag and up opposite sides at an angle which causes them to intersect just above the mouth of the bag where they are swingably attached to a rigid handle which straddles the mouth of the bag. Attached to the inside of the bag is a rigid bottom panel which lies horizontal on the bottom of the bag when in use and drops to a vertical position when the bag is inverted for folding. Two closure straps with snaps, located on one end near the top edge of the bag whose corresponding snap components are located on the opposite end, are used to maintain the bag in a folded condition. By virtue of this configuration, this bag is free-standing and stable whether empty or full, and may be folded flat when not in use.

1. Field of Invention
This invention relates to flexible bags, specifically to reusable bags which are used primarily as, but not limited to, grocery shopping bags.
2. Description of Prior Art
Grocery stores and supermarkets commonly supply consumers with bags to carry their purchases from the store to their vehicle or to their home.
Traditionally, these bags have been made of paper and, more recently, plastic bags have become common. With the environment a matter of great concern, many stores have offered for sale a reusable, canvas type tote bag that consumers will bring to the store each time they shop.
Although this reusable bag does address the environmental problem, each of the above mentioned bags suffer from a number of disadvantages:
(a) The paper bags in present use don't offer any type of handle, making them difficult to carry. PA1 (b) The paper bags and plastic bags in present use have negative effects on the environment: discarded usually after a single use, these disposable bags are wasting trees and adding to already overflowing landfills. PA1 (c) The canvas type tote bags in present use are not freestanding, making them more difficult to fill than a bag that is free-standing. Plastic bags are only free-standing with the assistance of a separate piece of equipment. PA1 (d) These paper, plastic and canvas bags in present use are very unstable when they are filled and being transported in a vehicle. They tend to topple over at stops, starts and turns. PA1 (e) Grocery bags in present use don't offer rigid support at the bag bottom. Thus, when a heavy item is put in, the bag tends to sag, thereby causing the other items in the bag to fall in and possibly become damaged. PA1 (a) To provide a bag to be used primarily as, but not limited to, a grocery shopping bag that is comfortable and easy to carry. PA1 (b) To provide a bag that is reusable, durable and can be used for many years, thus reducing the need for disposable bags that are harmful to the environment. PA1 (c) To provide a bag that is free-standing for easy filling and removal of items. PA1 (d) To provide a bag that is very stable when filled and being transported in a vehicle. PA1 (e) To provide a bag that supports the items inside and distributes the weight over the entire bottom thus eliminating sagging, unstable loads and reducing the possibility of damaged items.
Objects and Advantages:
Accordingly, several objects and advantages of my invention are:
Further objects and advantages are to provide a bag which is completely washable, which can be folded flat when not in use, and which can be disassembled and parts replaced if necessary.

Reusable, flexible bag with foldable support structure


Receiving an indication of a frequency ratio of first and second clocks; generating an indication of a number of clock pulses of the second clock occurring between first and second clock pulses of the first clock; and generating an indication of a time offset between (1) a clock pulse of the second clock occurring between the second clock pulse and a third clock pulse of the first clock, and (2) the second clock pulse of the first clock. Also, receiving an input data word representing a fractional number, a first part of the input data word comprising an integer portion of the fractional number and a second part comprising a decimal portion of the fractional number; providing a first output data word that is either the first part of the input data word or an increment by one of the first part; and providing a second output data word that is an integer multiple of the second part.

Digital circuits may comprise multiple components working on different frequency clocks. For a proper operation of such digital circuits, information on the different frequency clocks and their interdependencies is desirable.
Numerically controlled oscillators (NCO) are used in a wide range of timing applications. Conventional NCOs synthesize a range of frequencies in response to a digital signal. Here, the range of frequencies generated by an NCO is related to the bit resolution of the input digital signal and the clock used to control the NCO.

Apparatus and method using first and second clocks


Various embodiments for remote presentation of an interface of a computing device, such as a PC, are described herein. In particular, in various illustrated embodiments, a local device such as a Digital Media Adapter (DMA), mobile device, cellular telephone, etc. may be used to receive input from a remote control, where the local device provides human perceptible feedback, such as a sound, visual response, etc., responsive to use of the remote control. In some embodiments, the local device may contain a memory or cache for locally storing particular feedback data for human perceptible feedback. In various embodiments, a communication protocol is provided for storing, triggering, deleting, etc. feedback data in the memory or cache. Other embodiments may be disclosed or claimed.

With the recent availability of ubiquitous network connections, and easily accessible digital devices, such as digital cameras, personal video recorders, MP3 audio players, HDTV displays, telephones and other communication devices, digital set-top boxes, new generations of mobile devices and media center PCs, and the like, it was realized a framework was required for manipulating and sharing the growing variety of digital media content consumers are acquiring for these devices. For example, if one has a home network including a stereo, computer display, and a networked camera or memory containing image data from the camera, one should be able to share easily music, photos, video, etc. on a variety of connected devices on a network.
But, to do so, a standard way of integrating these devices is required. Towards this end, in June 2003 Intel, Sony, and Microsoft founded the "Digital Home Working Group" (DHWG) to promote development of a common interoperability framework for digital devices. See, for example, Uniform Resource Locator (URL) http://developer-intel-com/technology/digitalhome and related linked documents. (Note, to prevent inadvertent hyperlinks herein, periods in the preceding URL were replaced with hyphens.) To further DHWG efforts, Intel Corporation has also put forth the Intel Networked Media Product Requirements (NMPR), a comprehensive set of requirements for network media interoperability at the protocol level.
The Intel NMPR describes a "capability stack" defining how network devices and/or consumer entertainment devices may be combined to deliver an end-user experience. NMPR provides a framework for managing issues such as user control, media formats, media transports, media distribution and control, device discovery and control, network data transfer, and the physical network. For more information regarding NMPR. One component of the NMPR is a "Digital Media Adapter" (DMA), also sometimes referred to as a "Digital Media Receiver" (DMR) or "digital home adapter." A DMA is a device that renders content sourced from another device. For example, a DMA may enable a personal computer (PC) on a network to distribute digital content such as photos, music, etc., or a user interface, to another networked device, such as a television, stereo, etc. The DMA is typically an inexpensive device proximate to a device to receive content.
With NMPR (or an equivalent) the DMA may be configured to allow a remote-capable application with a Universal Plug and Play (UPnP) Remote User Interface (also known as Remote I/O) client control point to setup and control a remote interface using (extended PC Remoting Technology) (XRT), a command encapsulation protocol for passing messages back and forth between two network devices (nodes). The commands encoded in the messages may include, for example, display drawing commands and user input commands. Hence, the commands in the messages may be used to locally present a user interface of a remote device, such as a graphical user interface of a remote PC on a television or other output device associated with the DMA. For more information about UPnP Remote User Interface, see URL http://www-intel-com/technology/itj/2002/volume06issue04/art03_remote_io/p02_intro-htm, or see URL www-upnp-com. (Note, to prevent inadvertent hyperlinks, periods in the preceding URLs were replaced with hyphens.) Note also marks referenced herein are the property of their respective owners; in particular, the term UPnP is a trademark of The UPnP Implementers Corporation (UIC).
Unfortunately, while the XRT protocol (and related remoting techniques) allows a remote PC user interface to be displayed on a local output device such as a television, the XRT protocol does not provide for immediate real-time user feedback to let a user know a particular user action has been recognized by the remote PC. That is, while the XRT protocol does support the PC sending messages containing audio or other feedback to be presented on the television responsive to a user action, significant delays inherent to transferring the response data from the PC over the network, e.g., delays due to network congestion, poor wireless links, etc., may make the remote user interface appear sluggish or non-responsive.
It should be appreciated by one skilled in the art that the drawings and accompanying description refer to exemplary embodiments.


A transformer hydrogen gas monitoring system according to an embodiment of the present invention may comprise: a sensor module, which is disposed to allow at least a part thereof to meet hydrogen gas in a transformer and measures a resistance value of a member having a variable resistance value according to a hydrogen concentration in the transformer; and a multi-task module for receiving a sensing result of the sensor module, generating hydrogen concentration information corresponding to resistance value information included in the sensing result, and remotely transmitting information corresponding to the generated hydrogen concentration information.

As an aging failure phenomenon in transformers installed in the field has increased recently, the necessity of establishing a preventive diagnosis system in preparation for aging failure is increasing. A transformer preventive diagnosis may be performed through gas chromatograph (GC) in the transformer.
Conventional transformer preventive diagnosis was performed by a method of extracting gas from the transformer through a filter (membrane) and analyzing the extracted gas. Such a method is expensive for maintenance, such as filter replacement, which leads to longer transformer preventive diagnosis cycle. The aging failure of the transformer may frequently occur during the transformer preventive diagnosis cycle.

Transformer hydrogen gas monitoring system, device, and method


Systems and methods for machine learning-based power capping and virtual machine placement in cloud platforms are disclosed. A method includes applying a machine learning model to predict whether a request for deployment of a virtual machine corresponds to deployment of a user-facing (UF) virtual machine or a non-user-facing (NUF) virtual machine. The method further includes sorting a list of candidate servers based on both a chassis score and a server score for each server to determine a ranked list of the candidate servers, where the server score depends at least on whether the request for the deployment of the virtual machine is determined to be a request for a deployment of a UF virtual machine or a request for a deployment of an NUF virtual machine. The method further includes deploying the virtual machine to a server with highest rank among the ranked list of the candidate servers.

The public cloud includes a global network of servers that perform a variety of functions, including storing and managing data, running applications, and delivering content or services, such as streaming videos, provisioning electronic mail, providing office productivity software, or handling social media. The servers and other components may be located in data centers across the world. While the public cloud offers services to the public over the Internet, businesses may use private clouds or hybrid clouds. Both private and hybrid clouds also include a network of servers housed in data centers.
Managing power in a data center is difficult because of the variable demand for power from the servers. In addition, the various customer workloads vary in terms of their resource utilization, lifetime, and other aspects.

Machine learning-based power capping and virtual machine placement in cloud platforms


Methods and systems for linking input control signals, such as control signals used to control aspects of aircraft operation. In one embodiment, the method includes receiving first and second force signals corresponding to first and second forces applied to first and second controllers. The method can further include directing first and second position signals to the first and second controllers to move the first and second controllers to approximately the same positions. Each force signal is transmitted along a signal path, and the signal paths can be linked at a point where the signals on each path correspond to a quantity other that a position of a controller. The signal paths can be linked such that only one of the forces must exceed a threshold value for both controllers to be moved, and if one of the forces is outside a selected limit range, that force can be at least partially discounted.

Early commercial aircraft include two sets of mechanically linked controls for pilots sitting in the left and right (or front and back) seats of the flight deck. These mechanical control systems include cables connected between the pilots' controllers and the aircraft control surfaces, such as the aircraft ailerons and elevators. The controllers for the two pilots are mechanically linked so that each pilot feels the effect of the other pilot's input, and the resultant force applied to the control surfaces corresponds to the sum of the forces applied by each pilot.
More modern aircraft and aircraft flight simulators include fly-by-wire systems in which the controller position or the force each pilot applies to a controller, such as a yoke or control stick, is translated into an electrical signal which directs a servo actuator to move the aircraft control surface. A servo motor coupled to the controller moves the controller to a position that corresponds to the amount of force applied by the pilot. The motor also provides resistance to the pilot's force on the controller. In one conventional arrangement shown in FIG. 1A, a system 140 includes a dynamic response model 141 that receives an input pilot force signal F and outputs a controller position demand signal D. A servo motor system 170 receives the position demand signal D and actuates the controller, moving it to position P. A summing junction 144 provides a feedback loop that accounts for friction (calculated by a friction model 142) and controller feel (calculated by a feel profile module 143) to produce characteristics at the controller that mimic those produced by a mechanical system.
FIG. 1B illustrates a typical feel profile which illustrates feedback force as a function of position for a typical feel profile module 143. The feedback force (i.e., the resistance the pilot feels when exerting a force on the controller to change a position of the controller) increases rapidly for small deflections, until the pilot surpasses a breakout point 123. The profile then has a generally smooth, curved shape until the pilot approaches a stop point 124, beyond which any additional attempts to change the controller position result in a very large feedback force.
FIG. 2A illustrates another existing system 240 that receives the pilot force input signal F, applies an inverse feel profile model 243 to produce a static controller position, then applies a second order dynamic response model 241 to produce the final controller position demand signal D. FIG. 2B illustrates an associated inverse feel profile curve having a breakout point 223 and a stop point 224.
One challenge associated with fly-by-wire systems has been to link the controllers for left and right seat pilots in a manner that simulates a mechanical system. For example, FIG. 3 illustrates an existing arrangement having linked control modules 360 (shown as a left control module 360a and a right control module 360b). Each control module 360 receives an input force signal F, applies a dynamic response model 341, provides feedback generated by a friction model 342 and a feel profile model 343 and implemented by a summing junction 344 to produce a corresponding controller position demand signal D. Each control module 360 further includes a linking function 345 that inputs the output controller position demand signals and provides additional feedback via the summing junction 344.
FIG. 4 schematically illustrates yet another existing arrangement having dual control modules 460 (shown as modules 460a and 460b) that each receive a pilot force input F and, via a lookup table 446, produce a position demand signal 452, which corresponds to a static position for the corresponding controller. The position demand signals 452 are linked via linking functions 445 and the resulting signals are passed to stick systems 441 which actuate the controllers to position P. Systems having an arrangement generally similar to that shown in FIG. 4 are available from Stirling Dynamics, Ltd. of Clifton, Bristol, England.
One drawback with at least some of the foregoing systems is that they may not accurately simulate the feel and behavior of mechanically linked pilot controls. For example, some of the foregoing systems may not accurately simulate the feel that one pilot has upon seizing the controls when the other pilot has already exceeded the breakout point. Furthermore, these foregoing systems may not accurately simulate the result obtained when two pilots provide large, opposite inputs. Yet another drawback with some of the foregoing systems is that they may not be versatile enough to allow the simulated link between pilot input forces to be easily updated to take advantage of simulation improvements.

Control system and method with multiple linked inputs